{ "meta": { "title": "Epilepsy Board Review", "note": "Original teaching notes written for NeuroLogic from primary guidelines and position papers. Not a summary of any single textbook.", "parts": 9, "sections": 48, "questions": 143, "cards": 716, "bank": 463 }, "parts": [ { "id": "basics", "n": "1", "title": "Mechanisms and the EEG signal", "short": "EEG basics", "sections": [ { "id": "seizure-mechanisms", "n": "1", "title": "How seizures start and stop", "tags": [ "eeg-fundamentals", "seizure-management" ], "updated": false, "goals": [ "Relate excitation and inhibition to the drugs that act on them", "explain why absence seizures behave differently from focal seizures", "describe why status epilepticus becomes harder to stop with time" ], "blocks": [ { "type": "p", "text": "A seizure is a transient burst of abnormally excessive or synchronous neuronal activity that produces signs or symptoms. Two things have to go wrong at once: neurons become too easy to fire, and the network lets that firing recruit its neighbors in lockstep. Almost every antiseizure medication (ASM) acts on one side of that balance." }, { "type": "h3", "text": "Excitation and inhibition" }, { "type": "li", "text": "**Glutamate** drives excitation. AMPA receptors give fast depolarization; NMDA receptors, held shut by magnesium until the membrane depolarizes, let calcium in and sustain firing; kainate receptors contribute in the hippocampus." }, { "type": "li", "text": "**GABA** drives inhibition. GABA-A receptors are chloride channels: benzodiazepines increase how often they open, barbiturates how long they stay open. GABA-B receptors are G-protein coupled and act slowly through potassium channels." }, { "type": "li", "text": "**In the newborn** high intracellular chloride (the importer NKCC1 outweighs the exporter KCC2) can make GABA-A depolarizing. This is one reason neonatal seizures respond less reliably to GABAergic drugs; adding bumetanide to block NKCC1 failed in the NEMO trial." }, { "type": "li", "text": "**Intrinsic excitability** is set by ion channels: sodium channels start action potentials, potassium channels (the KCNQ2/3 M-current, KCNT1) end them and set the resting state, and T-type calcium channels in the thalamus let relay neurons fire in bursts." }, { "type": "li", "text": "**One drug class, opposite effects.** In Dravet syndrome, loss-of-function SCN1A variants reduce sodium current in GABAergic inhibitory interneurons, which depend on Nav1.1, but not in excitatory pyramidal cells. A sodium channel blocker then silences the remaining inhibition, so carbamazepine, oxcarbazepine, phenytoin and lamotrigine often make seizures worse. Gain-of-function SCN8A variants make Nav1.6, which is concentrated at the axon initial segment where action potentials start, overactive and drive excess firing; blocking sodium channels counters that defect, often at high doses." }, { "type": "p", "text": "Questions may name the channel protein instead of the gene:" }, { "type": "table", "head": [ "Protein", "Gene", "Where it comes up" ], "rows": [ [ "Nav1.1", "SCN1A", "Dravet syndrome (loss of function)" ], [ "Nav1.2", "SCN2A", "Self-limited neonatal-infantile epilepsy; early-onset encephalopathy that responds to sodium channel blockers" ], [ "Nav1.6", "SCN8A", "Developmental and epileptic encephalopathy (mostly gain of function)" ], [ "Cav3.2", "CACNA1H", "T-type calcium channel" ], [ "Kv7.2", "KCNQ2", "M-current; self-limited familial neonatal epilepsy and KCNQ2 encephalopathy" ], [ "Kv1.1", "KCNA1", "Voltage-gated potassium channel" ] ] }, { "type": "note", "label": "Try it", "text": "Watch the resting potential, the action potential and the summation of postsynaptic potentials animated in [Ions, channels and membrane voltage](eeg-fundamentals.html#basics-membrane-voltage)." }, { "type": "h3", "text": "From one cell to a seizure" }, { "type": "p", "text": "The **paroxysmal depolarizing shift** is the intracellular signature of an interictal spike: a large, prolonged depolarization crowned by a burst of action potentials and followed by hyperpolarization. The hyperpolarization and the ring of inhibition around the focus (surround inhibition) normally contain it. A seizure starts when that restraint fails and recurrent excitatory connections recruit neighboring cortex. Extracellular potassium rises and calcium falls as it goes, which makes spread easier still." }, { "type": "note", "label": "Try it", "text": "An animation in [Interictal epileptiform discharges](eeg-fundamentals.html#waveforms-interictal-discharges) follows paroxysmal depolarizing shifts in many neurons as they add up to one scalp spike." }, { "type": "p", "text": "Seizures end actively, not by exhaustion. Inhibitory interneurons, adenosine release, acidosis and potassium currents all push the network back down. The same processes explain postictal slowing and Todd paralysis." }, { "type": "p", "text": "**Why a temporal seizure can take away awareness.** The fast seizure discharge may stay in the temporal lobes, yet when responsiveness is lost, intracranial recordings show bilateral 1–2 Hz slow waves over frontal and parietal association cortex, and their power tracks the temporal seizure activity. The network inhibition hypothesis explains this: the seizure spreads to subcortical arousal systems in the brainstem and diencephalon and suppresses them, and the frontoparietal cortex drops into a sleep-like slow state. Consciousness can therefore be lost without the seizure discharge itself spreading through both hemispheres." }, { "type": "h3", "text": "Two circuits worth knowing" }, { "type": "li", "text": "**Absence seizures** come from a thalamocortical loop between the cortex, thalamic relay neurons and the GABAergic reticular nucleus. When relay neurons are hyperpolarized, T-type calcium channels let them fire in bursts, and the loop locks into roughly 3-Hz spike-and-wave. Ethosuximide blocks T-type channels. Drugs that deepen that hyperpolarization (vigabatrin, tiagabine) or that act mainly on sodium channels (carbamazepine, oxcarbazepine, phenytoin) can make absences worse." }, { "type": "li", "text": "**Mesial temporal lobe epilepsy** with hippocampal sclerosis shows neuronal loss (most marked in CA1 and CA4), loss of hilar interneurons and **mossy fiber sprouting**: dentate granule cell axons turn back and synapse on other granule cells, building a recurrent excitatory circuit that was not there before." }, { "type": "li", "text": "**Granule cell dispersion** is a common companion: instead of a tight, narrow layer, the granule cell bodies spread into the molecular layer, often in columns. In the study that described it, 11 of 15 temporal lobe specimens showed it, in step with hilar cell loss and often after severe febrile or infectious seizures in early childhood." }, { "type": "li", "text": "**mTOR and sprouting.** In rodent models after status epilepticus, rapamycin, which blocks mechanistic target of rapamycin (mTOR) signaling, suppresses mossy fiber sprouting while it is given, but sprouting returns when it stops, established sprouting is not reversed, and blocking sprouting almost completely did not reduce seizures in a mouse model. Sprouting may therefore not be necessary for epileptogenesis." }, { "type": "h3", "text": "Epileptogenesis" }, { "type": "p", "text": "After an injury such as trauma, stroke, infection or prolonged status there is often a latent period before epilepsy declares itself. Cell loss, axonal sprouting, inflammation (interleukin-1β, HMGB1) and blood–brain barrier leak (albumin activating TGF-β signaling in astrocytes) all contribute. No ASM has been shown to prevent this process in people. Phenytoin after head trauma cut seizures in the first week but did not reduce later epilepsy. Kindling, where repeated, initially subconvulsive stimulation evokes progressively stronger seizures and, after prolonged kindling, spontaneous ones, is the classic laboratory model." }, { "type": "p", "text": "Post-traumatic epilepsy has its own model: **partially isolated (\"undercut\") cortex**, in which a slab of cortex is cut away from its white matter and neighbors. After a latent period of weeks it generates epileptiform discharges. Two changes drive it: inhibitory interneurons shrink and lose synapses on pyramidal cells, so inhibition falls, and surviving pyramidal axons sprout new excitatory connections. Silencing the injured cortex with tetrodotoxin early after the cut prevents epileptogenesis in this model." }, { "type": "h3", "text": "Why status becomes self-sustaining" }, { "type": "p", "text": "Within minutes of continuous seizure activity, synaptic GABA-A receptors are pulled into the cell while NMDA and AMPA receptors move to the membrane. Inhibition falls and excitation rises as time passes. That is the biological case for giving an adequate benzodiazepine dose early, and for adding an NMDA antagonist such as ketamine in refractory status." }, { "type": "table", "head": [ "Target", "What it does", "Examples" ], "rows": [ [ "Sodium channels, fast inactivation", "Stops sustained repetitive firing", "Phenytoin, carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine" ], [ "Sodium channels, slow inactivation", "Dampens prolonged depolarization", "Lacosamide" ], [ "T-type calcium channels", "Breaks thalamic burst firing", "Ethosuximide (also zonisamide)" ], [ "α2δ subunit of calcium channels", "Reduces transmitter release", "Gabapentin, pregabalin" ], [ "Synaptic vesicle protein SV2A", "Modulates vesicle release", "Levetiracetam, brivaracetam" ], [ "GABA-A receptor", "Enhances inhibition", "Benzodiazepines, phenobarbital, ganaxolone, stiripentol, cenobamate (with a sodium-current effect)" ], [ "GABA metabolism and reuptake", "Raises synaptic GABA", "Vigabatrin (GABA transaminase), tiagabine (GAT-1)" ], [ "AMPA receptor", "Blocks fast excitation", "Perampanel" ], [ "Several mechanisms", "Broad spectrum", "Valproate, topiramate, zonisamide, felbamate, cannabidiol, fenfluramine" ] ] }, { "type": "note", "label": "Try it", "text": "Choose a drug or a target in the interactive synapse model under [ASM profiles](#asm-profiles) to see where each medication acts, or look a drug up in the [medication profiles](seizure_management.html#anti-seizure-medications)." }, { "type": "note", "label": "Board pearl", "text": "If a question asks which drug made absences or myoclonus worse, look first for carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, vigabatrin or tiagabine." }, { "type": "mcq", "id": "q-8z9g53", "stem": "A 7-year-old with childhood absence epilepsy has daily absences. A new medication is started, and within two weeks the absences are more frequent and she has an episode of absence status. Which medication was most likely started?", "options": [ "Ethosuximide", "Valproate", "Lamotrigine", "Carbamazepine", "Levetiracetam" ], "answer": 3, "explain": "Carbamazepine, oxcarbazepine and phenytoin, and GABAergic drugs that deepen thalamic hyperpolarization (vigabatrin, tiagabine), can aggravate absence and myoclonic seizures. Ethosuximide, valproate and lamotrigine all treat absence; levetiracetam is not first-line for absence but does not typically worsen it." }, { "type": "mcq", "id": "q-1cpk30l", "stem": "Why does the chance that lorazepam stops convulsive status fall the longer the seizure has lasted?", "options": [ "Hepatic enzymes are induced within minutes of seizure onset", "Synaptic GABA-A receptors are internalized while NMDA and AMPA receptors move to the membrane", "Benzodiazepine binding to albumin rises as the patient becomes acidotic", "SV2A expression falls during prolonged seizures", "Extracellular chloride falls, reversing the GABA-A current" ], "answer": 1, "explain": "Receptor trafficking during ongoing seizures removes the benzodiazepine target from the synapse and adds excitatory receptors. It is the mechanistic basis of time-dependent pharmacoresistance and of treating early with an adequate dose." }, { "type": "mcq", "id": "q-1vnbrwi", "stem": "Which change in hippocampal sclerosis creates a new recurrent excitatory circuit?", "options": [ "Dispersion of the dentate granule cell layer", "Loss of CA2 pyramidal neurons", "Mossy fiber sprouting of dentate granule cell axons onto other granule cells", "Gliosis of the alveus", "Loss of entorhinal input to CA1" ], "answer": 2, "explain": "Granule cell axons (mossy fibers) normally project to CA3. After hilar cell loss they sprout into the inner molecular layer and excite other granule cells. CA2 is relatively spared in the common form of hippocampal sclerosis." }, { "type": "cards", "items": [ { "id": "c-1mxozyg", "front": "Benzodiazepine versus barbiturate at the GABA-A receptor", "back": "Benzodiazepines increase how often the chloride channel opens; barbiturates increase how long it stays open (and open it directly at high doses)." }, { "id": "c-7uxa2k", "front": "T-type calcium channels", "back": "Thalamic relay neurons. They generate the burst firing behind 3-Hz spike-and-wave and are blocked by ethosuximide." }, { "id": "c-bcrpuj", "front": "Why GABA can excite in the newborn", "back": "High intracellular chloride (NKCC1 outweighs KCC2) makes the GABA-A current depolarizing." }, { "id": "c-ll45tb", "front": "Paroxysmal depolarizing shift", "back": "The intracellular correlate of an interictal spike: a prolonged depolarization with a burst of action potentials, then hyperpolarization." }, { "id": "c-4gbnpf", "front": "Kindling", "back": "Repeated, initially subconvulsive stimulation (for example of the amygdala) that evokes progressively stronger afterdischarges and seizures until each stimulus triggers a generalized seizure; the change is lasting, and spontaneous seizures can follow prolonged kindling. A model of epileptogenesis." }, { "id": "c-ah9t9e", "front": "Drugs that can aggravate absence or myoclonus", "back": "Carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, vigabatrin, tiagabine." }, { "id": "c-1qt8wr", "front": "Does phenytoin after head injury prevent epilepsy?", "back": "No. It reduces seizures in the first week only; no ASM prevents epileptogenesis." }, { "id": "c-ocrz3r", "front": "Why sodium channel blockers worsen SCN1A disease but help SCN8A disease", "back": "SCN1A (Nav1.1) loss of function weakens inhibitory interneurons, so blocking sodium channels removes more inhibition; SCN8A (Nav1.6) gain of function overdrives firing from the axon initial segment, so blocking sodium channels corrects it." }, { "id": "c-t2hnj4", "front": "Nav1.1, Nav1.2, Nav1.6", "back": "SCN1A, SCN2A, SCN8A." }, { "id": "c-17jst2d", "front": "Cav3.2, Kv7.2, Kv1.1", "back": "CACNA1H, KCNQ2, KCNA1." }, { "id": "c-1d4s1ee", "front": "Network inhibition hypothesis", "back": "Temporal seizures suppress subcortical arousal systems, so bilateral frontoparietal cortex slows and awareness is lost without the seizure spreading through both hemispheres." }, { "id": "c-1il7nn3", "front": "Granule cell dispersion", "back": "A widened, loosely packed dentate granule cell layer; a common histologic feature of hippocampal sclerosis." }, { "id": "c-1g3qu3y", "front": "Undercut (partially isolated) cortex", "back": "Model of post-traumatic epilepsy: lost inhibition (shrunken interneurons, fewer inhibitory synapses) plus new excitatory connections from sprouting axons." } ] } ], "sources": [ { "title": "ILAE practical clinical definition of epilepsy (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24730690/" }, { "title": "GABA-A receptor trafficking in status epilepticus (Naylor 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16120773/" }, { "title": "Phenytoin after head injury (Temkin 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2115976/" }, { "title": "Bumetanide for neonatal seizures, NEMO (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25765333/" }, { "title": "Reduced sodium current in interneurons in an Scn1a mouse (Yu 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16921370/" }, { "title": "SCN8A encephalopathy: research progress (Meisler 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27270488/" }, { "title": "SCN8A genotype–phenotype correlations (Johannesen 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/34431999/" }, { "title": "ILAE syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "HUGO Gene Nomenclature Committee", "url": "https://www.genenames.org/" }, { "title": "IUPHAR nomenclature of voltage-gated sodium channels (Catterall 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16382098/" }, { "title": "Impaired consciousness in temporal lobe seizures (Englot 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/21081551/" }, { "title": "Granule cell dispersion in temporal lobe epilepsy (Houser 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/1705855/" }, { "title": "mTOR inhibition suppresses mossy fiber sprouting (Buckmaster 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19553465/" }, { "title": "High-dose rapamycin blocks sprouting but not seizures (Heng 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23848506/" }, { "title": "Epilepsy following cortical injury (Prince 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19187292/" }, { "title": "Undercut model of post-traumatic epileptogenesis (Xiong 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21946525/" } ], "words": 1718, "bank": 11 }, { "id": "eeg-generators", "n": "2", "title": "What the scalp can see", "tags": [ "eeg-fundamentals", "epilepsy-surgery" ], "updated": false, "goals": [ "Name the generator of the scalp EEG", "predict how dipole orientation changes what EEG and MEG record", "explain why normal scalp EEG never excludes a focal seizure" ], "blocks": [ { "type": "p", "text": "The scalp EEG is the summed **postsynaptic potentials** of cortical pyramidal neurons, not their action potentials. Postsynaptic currents last tens to hundreds of milliseconds and overlap in time; action potentials last about a millisecond and cancel out. Pyramidal cells in layers III and V are lined up with their apical dendrites perpendicular to the cortical surface, so their currents add into an open field that reaches the scalp." }, { "type": "h3", "text": "What it takes to reach the scalp" }, { "type": "li", "text": "**Synchrony.** Millions of neurons have to change together." }, { "type": "li", "text": "**Orientation.** Cells aligned in parallel sum; randomly oriented cells cancel." }, { "type": "li", "text": "**Area.** Comparisons of simultaneous intracranial and scalp recordings suggest that most scalp-visible spikes involve at least about 10 cm² of synchronously active cortex, and many involve more. Smaller discharges stay invisible from the scalp." }, { "type": "li", "text": "**Distance and the skull.** The skull attenuates and blurs the field. Over a skull defect the EEG is higher in amplitude and sharper (a breach rhythm), which is easy to over-read." }, { "type": "note", "label": "Try it", "text": "Spread the timing or flip half the cells in the [summation lab](eeg-fundamentals.html#basics-synaptic-summation) to see why synchrony and alignment decide what reaches the scalp." }, { "type": "h3", "text": "Dipoles" }, { "type": "p", "text": "A patch of active cortex behaves like a dipole: negative at one end, positive at the other." }, { "type": "li", "text": "A **radial** dipole, on the crown of a gyrus, points at the scalp. EEG sees a single negative maximum over it." }, { "type": "li", "text": "A **tangential** dipole, on the wall of a sulcus, lies parallel to the scalp. EEG shows a negative end and a positive end at separate electrodes; the centrotemporal spikes of self-limited epilepsy with centrotemporal spikes typically show this pattern, negative centrotemporally and positive frontally." }, { "type": "li", "text": "**MEG** records the magnetic field around the current and is most sensitive to tangential sources, and it is not smeared by the skull. EEG and MEG are complementary rather than redundant." }, { "type": "li", "text": "**Paradoxical lateralization.** A generator on the mesial (interhemispheric) surface often points obliquely across the midline, so its scalp maximum can sit at the vertex or over the opposite hemisphere. Interictal and ictal discharges from parasagittal frontal, central (leg area), parietal and medial occipital cortex can therefore appear on the wrong side. The normal tibial somatosensory evoked potential, largest over the hemisphere on the same side as the stimulated leg, is the everyday example. Check the side against semiology and MRI, and use source modeling or MEG when they disagree." }, { "type": "note", "label": "Try it", "text": "Tilt a source from radial to tangential, change its depth and add an opposing source in the [dipole explorer](eeg-fundamentals.html#basics-dipole-orientation)." }, { "type": "table", "head": [ "Feature", "EEG", "MEG" ], "rows": [ [ "What it measures", "Potentials from extracellular volume currents", "Magnetic field of the intracellular (primary) dendritic current" ], [ "Reference", "Needed, and can contaminate the record", "None needed" ], [ "Skull and scalp", "Attenuate and blur the field", "Pass the field undistorted" ], [ "Orientation", "Radial and tangential sources", "Mainly tangential (sulcal) sources; blind to purely radial ones, though little of the cortex is purely radial" ], [ "Depth", "Better for deep sources such as mesial temporal cortex", "Signal falls off steeply with distance; in one study comparing it with later subdural recordings, MEG showed about a quarter of mesial temporal spikes but 90% or more of interhemispheric and orbitofrontal spikes" ], [ "Cortex needed for a spike", "About 10 cm² or more", "A smaller synchronous patch" ] ] }, { "type": "p", "text": "MEG is strongest over fissural cortex, where currents run tangential to the skull: interhemispheric, opercular and insular sources can show on MEG when the scalp EEG is silent. Such \"MEG-unique\" spikes can point to an epileptic region no other test has shown." }, { "type": "p", "text": "**Source localization** works back from the scalp field to its generator. This inverse problem has no unique solution, so every method adds assumptions. An **equivalent current dipole** models the discharge as one or a few point sources. **Distributed source imaging** spreads current across the cortex and picks one solution, for example the one with the least total current (the minimum norm estimate) or a noise-normalized version of it (dynamic statistical parametric mapping, standardized low-resolution electromagnetic tomography). In practice, average many spikes of one type and model the rising phase, because by the peak the discharge has already spread. Spatial sampling and the head model matter most: in 152 operated patients, 128 to 256 electrodes with the patient's own MRI as head model placed the source in the resection with 84% sensitivity and 88% specificity, against 57% and 59% with fewer than 32 electrodes and a template head. On a routine array, add the inferior temporal chain and use the patient's MRI. Modeled spike sources mark the irritative zone, which is not always the seizure-onset zone." }, { "type": "h3", "text": "Polarity does not tell you excitation from inhibition" }, { "type": "p", "text": "Excitation near the surface and inhibition deep in the cortex both make the surface negative; the reverse pair makes it positive. Most epileptiform discharges are surface negative, but positive spikes occur with sulcal generators, over skull defects, and in newborns (positive rolandic sharp waves in intraventricular hemorrhage)." }, { "type": "note", "label": "Try it", "text": "Put an excitatory or an inhibitory synapse on the apical dendrite or near the cell body in the [ion-flow lab](eeg-fundamentals.html#basics-ion-flow) and see which way the scalp deflects." }, { "type": "h3", "text": "Why scalp EEG misses seizures" }, { "type": "p", "text": "Mesial temporal, insular, orbitofrontal, interhemispheric and deep sulcal cortex are far from the electrodes or oriented badly. Focal seizures with preserved consciousness often have no scalp correlate at all. The first change seen at the scalp may be propagated activity rather than the true onset, which is why intracranial recording exists." }, { "type": "note", "label": "Board pearl", "text": "A normal scalp EEG during a typical focal seizure with preserved consciousness does not make the event nonepileptic." }, { "type": "mcq", "id": "q-4u8749", "stem": "Which structure's activity is most likely to be missed entirely by scalp EEG but detected by MEG?", "options": [ "A spike on the crown of a lateral frontal gyrus", "A spike confined to the wall of a sulcus, generating a tangential dipole", "Generalized 3-Hz spike-and-wave", "A posterior dominant rhythm at 10 Hz", "Vertex waves of stage N2 sleep" ], "answer": 1, "explain": "MEG is most sensitive to tangential (sulcal) sources and is not attenuated by the skull. EEG favors radial sources at the gyral crown. A small sulcal source can be invisible on EEG yet clear on MEG." }, { "type": "mcq", "id": "q-1q85bzj", "stem": "During video-EEG a patient has her typical aura of rising epigastric discomfort and déjà vu, fully aware throughout. The scalp EEG shows no change. What is the best interpretation?", "options": [ "The event is not epileptic", "The electrodes were placed incorrectly", "A focal seizure with preserved consciousness often has no scalp correlate", "She should be diagnosed with functional seizures", "The montage should be changed to a common average reference to reveal it" ], "answer": 2, "explain": "Small, deep or mesial seizures frequently produce no scalp change. The history, stereotypy and any later evolution matter more than the absence of an ictal scalp pattern for an aura." }, { "type": "cards", "items": [ { "id": "c-1tbccoa", "front": "Generator of the scalp EEG", "back": "Summed postsynaptic potentials of pyramidal neurons (layers III and V), not action potentials." }, { "id": "c-4mwisu", "front": "Radial versus tangential dipole", "back": "Radial (gyral crown) points at the scalp and gives one negative maximum; tangential (sulcal wall) gives separate negative and positive ends and is best seen with MEG." }, { "id": "c-1qriaq0", "front": "How much cortex for a scalp spike", "back": "At least about 10 cm² of synchronous cortex for most scalp-visible spikes." }, { "id": "c-i6eazs", "front": "Breach rhythm", "back": "Higher-amplitude, sharper, faster activity over a skull defect. A normal finding after craniotomy, not epileptiform." }, { "id": "c-1dikdrj", "front": "Does surface negativity mean excitation?", "back": "No. Superficial excitation and deep inhibition both produce surface negativity." }, { "id": "c-1vuiziv", "front": "What EEG and MEG each measure", "back": "EEG: potentials from extracellular volume currents (needs a reference, blurred by skull). MEG: the magnetic field of intracellular primary currents (no reference, undistorted by skull, weaker for deep sources)." }, { "id": "c-1lwm0kw", "front": "Paradoxical lateralization", "back": "An oblique mesial (parasagittal or interhemispheric) generator projects its scalp maximum to the vertex or the opposite side, so the EEG points to the wrong hemisphere." }, { "id": "c-1i309y1", "front": "Where MEG is weakest", "back": "Deep sources, above all mesial temporal cortex, and purely radial sources." }, { "id": "c-2ih5t7", "front": "Equivalent current dipole versus distributed source imaging", "back": "A dipole models one or a few point sources; distributed methods (minimum norm estimate and its normalized versions) spread current over the whole cortex." }, { "id": "c-1k32hpz", "front": "Which part of the spike to model", "back": "An average of many similar spikes, at the rising phase; the peak already includes spread." } ] } ], "sources": [ { "title": "Intracranial correlates of scalp interictal spikes (Tao 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15857432/" }, { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "IFCN practical guidelines for clinical MEG (Hari 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29724661/" }, { "title": "Practical fundamentals of clinical MEG in epilepsy (Laohathai 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34721261/" }, { "title": "MEG: basic principles (Singh 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24791076/" }, { "title": "Interictal MEG and the irritative zone in the electrocorticogram (Agirre-Arrizubieta 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19498089/" }, { "title": "Paradoxical lateralization in medial occipital epilepsy (Gavaret 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24005334/" }, { "title": "Paradoxical lateralization of parasagittal spikes (Oishi 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11790396/" }, { "title": "Paradoxical lateralization of ictal EEG in extratemporal epilepsy (Catarino 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22130039/" }, { "title": "Source analysis of the tibial nerve evoked potential (Baumgärtner 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9872431/" }, { "title": "Electric source imaging in 152 operated patients (Brodbeck 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21975586/" }, { "title": "Dynamic statistical parametric mapping (Dale 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10798392/" }, { "title": "sLORETA technical details (Pascual-Marqui 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12575463/" }, { "title": "The standardized EEG electrode array of the IFCN (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28778476/" } ], "words": 1326, "bank": 6 }, { "id": "eeg-technique", "n": "3", "title": "Recording technique", "tags": [ "eeg-fundamentals", "acns-terminology" ], "updated": true, "goals": [ "Localize a discharge from a bipolar and a referential montage", "choose filter, sensitivity and sampling settings and predict what changing them does", "list the technical requirements for a study of suspected electrocerebral inactivity" ], "blocks": [ { "type": "h3", "text": "Amplifiers and polarity" }, { "type": "p", "text": "Every channel is a differential amplifier that displays input 1 minus input 2. By convention, when input 1 is **negative** relative to input 2 the trace goes **up**. The amplifier rejects what is common to both inputs, which is how mains interference is removed. Rejection fails when the two electrode impedances differ, so 60-Hz noise in a single channel usually means one poor electrode, not a bad ground." }, { "type": "h3", "text": "Montages and localization" }, { "type": "li", "text": "**Bipolar chains** (longitudinal or transverse) compare neighboring electrodes. A discharge is localized by **phase reversal**: for a surface-negative maximum at T7 in the chain F7–T7, T7–P7, the channel above deflects down and the channel below deflects up, so the two point toward each other. A positive maximum points them away from each other." }, { "type": "li", "text": "**End of the chain.** A maximum at the first or last electrode of a chain (Fp1, O1) has no neighbor on one side and shows no phase reversal. Check it in a referential montage." }, { "type": "li", "text": "**Referential montages** compare every electrode with one reference (ear, Cz, the common average, or a weighted Laplacian). The maximum is the largest deflection, as long as the reference itself is quiet. An ear reference picks up temporal discharges, which then appear inverted and widespread across every channel that uses it." }, { "type": "li", "text": "Bipolar montages sharpen local detail and cancel shared noise but can hide a widespread field. Referential montages preserve true waveform and amplitude but are only as good as the reference." }, { "type": "note", "label": "Try it", "text": "Work the subtraction for five electrodes in [Bipolar math](eeg-fundamentals.html#montages-bipolar-math), then move one discharge through four montages in [One discharge, four montages](eeg-fundamentals.html#montages-four-montages). The videos [Bipolar math and phase reversal](eeg_videos.html#phase-reversal) and [Referential montages](eeg_videos.html#referential) cover the same ground." }, { "type": "h3", "text": "Filters, sensitivity and time base" }, { "type": "table", "head": [ "Setting", "Routine standard", "What changing it does" ], "rows": [ [ "Low-frequency filter (high-pass)", "1 Hz, a time constant of about 0.16 s", "Raising it removes slow waves, including real delta and slow sweat artifact" ], [ "High-frequency filter (low-pass)", "70 Hz", "Lowering it smooths muscle into rhythmic sharp activity that can mimic beta or spikes" ], [ "Notch filter", "60 Hz (50 Hz outside North America)", "Hides mains noise without fixing the electrode that caused it; use sparingly" ], [ "Sensitivity", "7 µV/mm (5–10 in adults)", "A smaller number means more gain; 2 µV/mm for suspected electrocerebral inactivity" ], [ "Time base", "30 mm/s, 10 s per page", "15 mm/s in neonates and for long reviews compresses slow activity" ] ] }, { "type": "p", "text": "A filter can make epileptiform activity easier to see by removing competing frequencies. It cannot amplify it, and aggressive filtering creates sharp-looking transients of its own. A filter setting names its cutoff, the frequency at which about 71% of the amplitude still passes (−3 dB), so a filter slopes rather than cuts: some activity beyond the setting gets through, and some inside it is reduced." }, { "type": "figure", "html": "filter-response", "caption": "How much of each frequency passes the low-frequency filter, the high-frequency filter and the 60 Hz notch. Change a setting to see what it removes, from slow drift and delta to line noise and fast muscle.", "n": 1 }, { "type": "note", "label": "Try it", "text": "Change the filters and the sensitivity on a running trace in the [filter lab](eeg-fundamentals.html#montages-filters-sensitivity)." }, { "type": "h3", "text": "Sampling and aliasing" }, { "type": "p", "text": "The sampling rate must be more than twice the highest frequency present (the Nyquist limit), and in practice about three to five times the high-frequency filter setting. An analogue anti-aliasing filter has to act before digitization, because an aliased signal cannot be separated afterward. A 60-Hz signal sampled at 100 Hz reappears as a false 40-Hz wave. Routine studies sample at 256–512 Hz; recording high-frequency oscillations needs 2 kHz or more." }, { "type": "note", "label": "Try it", "text": "Sample one rhythm at 100, 120, 256 and 512 Hz and watch it alias in the [sampling lab](eeg-fundamentals.html#montages-digital-recording)." }, { "type": "h3", "text": "Electrodes" }, { "type": "li", "text": "The 10–20 system places electrodes at 10% or 20% of skull distances. In the modified combinatorial (10–10) names, T3/T4 became **T7/T8** and T5/T6 became **P7/P8**." }, { "type": "li", "text": "An inferior temporal chain (F9/F10, T9/T10, P9/P10) samples basal temporal cortex better than the standard array and is part of the IFCN 25-electrode array." }, { "type": "li", "text": "Sphenoidal and nasopharyngeal electrodes add little over the inferior chain and are rarely used now." }, { "type": "li", "text": "Keep impedances low (under about 5 kΩ) and, more importantly, balanced. A near-zero impedance between two electrodes suggests a salt bridge." }, { "type": "note", "label": "Try it", "text": "Place all 21 electrodes yourself in the [placement lab](eeg-fundamentals.html#practice-tab-all), or review the landmarks on the [10–20 map](eeg-fundamentals.html#montages-10-20-map)." }, { "type": "h3", "text": "Safety" }, { "type": "p", "text": "Use a single ground per patient and hospital-grade equipment, keep leakage current minimal, and never let the patient be grounded through several devices at once, which creates ground loops." }, { "type": "h3", "text": "Suspected electrocerebral inactivity" }, { "type": "p", "text": "The American Clinical Neurophysiology Society (ACNS) 2016 protocol calls for a full set of scalp electrodes, including the midline (Fz, Cz, Pz), never a single- or two-channel device; impedances between 100 and 10,000 ohms; montages with interelectrode distances of 10 cm or more; sensitivity of 2 µV/mm for at least 30 minutes; and a test of the integrity of the whole system, by touching each electrode to make an artifact. It also requires:" }, { "type": "li", "text": "**Filters** no narrower than 1 Hz (low-frequency) to 30 Hz (high-frequency). Use the notch filter only after troubleshooting, and record some segments without it." }, { "type": "li", "text": "**An ECG channel in every study**, because ECG artifact is almost always present at this gain. Add other monitors as needed: a noncephalic pair of electrodes on the back of the hand, a respiration or movement monitor, and video." }, { "type": "li", "text": "**Unexplained activity blocks the conclusion.** If the reader cannot say with confidence whether residual activity above 2 µV is cerebral or artifact, the record is reported as uncertain, not as electrocerebral inactivity (ECI), and repeated (as soon as 6 hours later in adults, after at least 24 hours in neonates and children)." }, { "type": "li", "text": "**No reactivity to intense stimuli**: somatosensory, auditory and visual. An electroretinogram can persist with photic stimulation and is not cerebral." }, { "type": "li", "text": "**Confounders recorded**: temperature, blood pressure, oxygen saturation and drugs, because hypothermia, sedatives, hypotension and hypoxemia can flatten the EEG reversibly." }, { "type": "p", "text": "ECI is a reliable sign of cortical death. It says nothing about the brainstem, which may still function." }, { "type": "p", "updated": true, "label": "Brain death", "text": "The 2023 AAN/AAP/CNS/SCCM guideline does not accept EEG as an ancillary test for brain death/death by neurologic criteria. EEG reflects cortical activity, not brainstem function. Electrocerebral inactivity is an EEG finding, not a determination of death." }, { "type": "p", "text": "Under the 2023 guideline an ancillary test is used only when part of the examination or the apnea test cannot be completed or interpreted, after everything that can be done has been done. Only tests of cerebral blood flow qualify: four-vessel catheter angiography and radionuclide perfusion studies at any age, and transcranial Doppler in adults only, because it has not been validated in children. CT angiography and MRI or magnetic resonance angiography are not accepted. EEG was dropped because it tests the hemispheres and not the brainstem, while the usual reason for ancillary testing is that the brainstem cannot be fully examined; evoked potentials sample too little of the brainstem to make up for this. EEG also disagrees with the clinical examination in both directions: some patients who meet clinical criteria still show EEG activity (a few percent in a recent series, about one in five in an older one), and some children without cerebral blood flow on a radionuclide scan still have EEG activity." }, { "type": "mcq", "id": "q-12316rx", "stem": "In a longitudinal bipolar chain Fp1–F7, F7–T7, T7–P7, P7–O1, a sharp transient deflects downward in F7–T7 and upward in T7–P7 at the same instant. Where is its maximum and what is its polarity?", "options": [ "F7, surface positive", "T7, surface negative", "T7, surface positive", "P7, surface negative", "The finding cannot be localized in a bipolar montage" ], "answer": 1, "explain": "With T7 the most negative electrode, F7–T7 (F7 minus T7) is positive and deflects down, and T7–P7 is negative and deflects up. Deflections pointing toward each other mark a negative phase reversal at the shared electrode." }, { "type": "mcq", "id": "q-1ypi2j3", "stem": "A spike is largest in the channel Fp2–F8 of the longitudinal bipolar montage and does not phase-reverse anywhere. What is the best next step?", "options": [ "Report a right frontal spike with a positive field", "Increase the low-frequency filter to 5 Hz", "Review it in a referential montage, because the maximum may be at the end of the chain", "Discard it as eye movement", "Switch the notch filter off" ], "answer": 2, "explain": "A maximum at the first electrode of a chain has no neighbor on one side, so no phase reversal appears. A referential montage shows whether Fp2 carries the maximum. Eye movement is a possibility to consider, but not the conclusion before checking the field." }, { "type": "mcq", "id": "q-12n8sj6", "stem": "A 60-Hz signal is digitized at 100 samples per second without an anti-aliasing filter. What appears in the recording?", "options": [ "A 60-Hz sine wave of reduced amplitude", "A flat line", "A spurious 40-Hz wave", "A spurious 160-Hz wave", "Nothing; the notch filter removes it after digitization" ], "answer": 2, "explain": "Frequencies above half the sampling rate fold back. With a 100-Hz sampling rate a 60-Hz input appears at 100 − 60 = 40 Hz. It cannot be removed after digitization, which is why the anti-aliasing filter must act first." }, { "type": "match", "id": "match-eeg-settings", "prompt": "Match each recording parameter to its usual value", "pairs": [ [ "Low-frequency filter, routine adult study", "1 Hz" ], [ "High-frequency filter, routine adult study", "70 Hz" ], [ "Sensitivity, routine adult study", "7 µV/mm" ], [ "Sensitivity, suspected electrocerebral inactivity", "2 µV/mm" ], [ "Time base", "30 mm/s" ], [ "Sampling for high-frequency oscillations", "2 kHz or more" ] ] }, { "type": "cards", "items": [ { "id": "c-1g4y4yv", "front": "EEG polarity convention", "back": "Input 1 negative relative to input 2 deflects the trace up." }, { "id": "c-1i4jikl", "front": "Negative phase reversal in a bipolar chain", "back": "The two channels sharing the electrode deflect toward each other." }, { "id": "c-1tc18bf", "front": "End-of-chain problem", "back": "A maximum at the first or last electrode of a chain shows no phase reversal; check a referential montage." }, { "id": "c-ctn4jy", "front": "60-Hz noise in one channel", "back": "Impedance mismatch at one electrode, not a bad ground." }, { "id": "c-10ls9d7", "front": "Time constant of a 1-Hz low-frequency filter", "back": "About 0.16 s (τ = 1 ÷ (2π × 1 Hz))." }, { "id": "c-1qps833", "front": "Renamed 10–20 electrodes", "back": "T3/T4 → T7/T8 and T5/T6 → P7/P8." }, { "id": "c-92k3xp", "front": "Aliasing rule", "back": "Sample at more than twice the highest frequency (in practice three to five times the high-frequency filter), with an anti-aliasing filter before digitization." }, { "id": "c-1oyxxu3", "front": "Filters for suspected electrocerebral inactivity", "back": "Low-frequency filter no higher than 1 Hz, high-frequency filter no lower than 30 Hz." }, { "id": "c-3w7th6", "front": "Mandatory monitor in an ECI study", "back": "ECG, plus other monitors (hand electrodes, respiration, movement, video) as needed to identify artifact." }, { "id": "c-13wpaqe", "front": "Residual activity that cannot be confidently called artifact", "back": "The record cannot be classified as electrocerebral inactivity; report the uncertainty and repeat." }, { "id": "c-6eyfbr", "front": "Electrodes for suspected electrocerebral inactivity (ACNS 2016)", "back": "A full set of scalp electrodes, including Fz, Cz and Pz, not a reduced array; impedances 100 to 10,000 ohms; pairs at least 10 cm apart." }, { "id": "c-tdncr1", "front": "Ancillary tests accepted for brain death (2023)", "back": "Four-vessel catheter angiography and radionuclide perfusion at any age; transcranial Doppler in adults only. Not EEG, evoked potentials, CT angiography or MRI." }, { "id": "c-ymgmy3", "front": "Why EEG was dropped as an ancillary test", "back": "It tests the hemispheres, not the brainstem, and EEG activity can persist in some patients who meet clinical criteria." } ] } ], "sources": [ { "title": "ACNS minimum technical standards for EEG (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27482788/" }, { "title": "ACNS electrode position nomenclature (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27482794/" }, { "title": "2023 US brain death consensus guideline", "url": "https://pubmed.ncbi.nlm.nih.gov/37821233/" }, { "title": "ACNS Guideline 6: EEG in suspected cerebral death (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27482789/" }, { "title": "EEG activity after clinical brain death (Grigg 1987)", "url": "https://pubmed.ncbi.nlm.nih.gov/3619714/" } ], "words": 1788, "bank": 9 } ], "intro": [ "How seizures start, spread and stop, and why the scalp sees some of it and misses the rest. Everything later in the review leans on these three sections." ] }, { "id": "normal", "n": "2", "title": "Normal EEG, variants and artifacts", "short": "Normal EEG", "sections": [ { "id": "normal-adult", "n": "1", "title": "The normal adult EEG, awake and asleep", "tags": [ "eeg-fundamentals" ], "updated": false, "goals": [ "Describe the normal awake rhythms and how they react", "recognize the markers of each sleep stage", "know which asymmetries are allowed" ], "blocks": [ { "type": "h3", "text": "Awake" }, { "type": "li", "text": "**Posterior dominant rhythm (alpha).** 8.5–13 Hz in adults, maximal occipitally with eyes closed, and attenuated by eye opening and mental effort. A PDR below 8.5 Hz in an awake adult is abnormal. Amplitude is often higher on the right; an amplitude asymmetry over about 50%, or a frequency difference over 1 Hz, is abnormal. The side that fails to attenuate with eye opening is usually the abnormal one. This one-sided failure of alpha to block with eye opening is the **Bancaud phenomenon**; failure to block during mental arithmetic means the same thing. In a series of 120 patients whose alpha failed to attenuate on one side during mental arithmetic, 113 had lateralized EEG abnormalities, lesions or other dysfunction on that side." }, { "type": "li", "text": "**Slow and fast alpha variants.** A posterior rhythm at about half the alpha frequency (mostly 4–5 Hz), often notched, that alternates with alpha and blocks with eye opening and mental effort exactly as alpha does is the **slow alpha variant**. It is normal and should not be reported as posterior slowing. The **fast alpha variant** runs at about twice the alpha frequency (14–20 Hz), with the same posterior field and the same reactivity, and is also normal." }, { "type": "li", "text": "**Beta.** Frontocentral fast activity, increased by benzodiazepines and barbiturates. A focal loss of beta suggests cortical dysfunction or fluid between cortex and electrode; a focal increase is expected over a skull defect." }, { "type": "li", "text": "**Mu rhythm.** 7–11 Hz arch-shaped (arciform) central rhythm that attenuates with movement, or the thought of movement, of the opposite limb, not with eye opening." }, { "type": "li", "text": "**Lambda waves.** Positive occipital sharp transients while the eyes scan a patterned scene. They disappear with eye closure." }, { "type": "li", "text": "**Theta.** Small amounts of frontocentral theta are normal in drowsiness, and mild temporal theta is common in older adults." }, { "type": "note", "label": "Try it", "text": "Count the cycles of the posterior rhythm on six unannotated cases in the [posterior dominant rhythm lab](eeg-fundamentals.html#waveforms-bg-pdr), or watch the video [The posterior dominant rhythm](eeg_videos.html#pdr)." }, { "type": "h3", "text": "Asleep" }, { "type": "table", "head": [ "Stage", "What identifies it" ], "rows": [ [ "N1 (drowsiness)", "Alpha drops out; slow roving eye movements; vertex sharp waves; positive occipital sharp transients of sleep (POSTS)" ], [ "N2", "Sleep spindles (about 11–16 Hz, central) and K-complexes" ], [ "N3", "High-amplitude delta (over 75 µV) filling at least 20% of the epoch" ], [ "REM", "Low-voltage mixed frequencies, rapid eye movements, sawtooth waves, loss of chin muscle tone" ] ] }, { "type": "p", "text": "Spindles are generated in the thalamus, paced by the reticular nucleus. REM sleep in the first minutes of a routine EEG is unusual and suggests sleep deprivation, narcolepsy, or withdrawal from REM-suppressing drugs." }, { "type": "note", "label": "Try it", "text": "Step through N1, N2, N3 and REM in the [sleep explorer](eeg-fundamentals.html#waveforms-sleep-architecture), or watch the video [Drowsiness and light sleep](eeg_videos.html#light-sleep)." }, { "type": "p", "text": "Photic stimulation normally produces **photic driving**: occipital activity time-locked to the flash rate or its harmonics. Its absence is not abnormal." }, { "type": "note", "label": "Board pearl", "text": "Sleep is the best activator of focal interictal discharges. NREM sleep increases their frequency and field; REM sleep narrows the field, so a discharge that persists in REM is usually close to the focus." }, { "type": "mcq", "id": "q-435kho", "stem": "A central 9-Hz arch-shaped rhythm on the left does not change with eye opening but attenuates when the patient is asked to make a fist with her right hand. What is it?", "options": [ "Posterior dominant rhythm spreading forward", "Mu rhythm", "Wicket spikes", "Breach rhythm", "A focal seizure" ], "answer": 1, "explain": "Mu rhythm is a central arciform rhythm that attenuates with movement, or planned movement, of the contralateral limb and not with eye opening. It is a normal finding." }, { "type": "mcq", "id": "q-1kriaho", "stem": "Which finding in an adult's awake EEG is abnormal?", "options": [ "A 10-Hz posterior rhythm 30% higher in amplitude on the right", "Beta activity that increases after lorazepam", "A posterior dominant rhythm of 7 Hz", "Lambda waves while reading", "Mu rhythm over the left central region" ], "answer": 2, "explain": "An adult posterior dominant rhythm below 8.5 Hz is slow and suggests a diffuse encephalopathy or medication effect. The other findings are normal." }, { "type": "cards", "items": [ { "id": "c-i30ip7", "front": "Normal adult posterior dominant rhythm", "back": "8.5–13 Hz, occipital, attenuates with eye opening. Below 8.5 Hz in an awake adult is abnormal." }, { "id": "c-8qamoc", "front": "Abnormal alpha asymmetry", "back": "Amplitude difference over about 50%, or frequency difference over 1 Hz." }, { "id": "c-1masxz8", "front": "Mu rhythm reacts to", "back": "Movement or planned movement of the opposite limb, not eye opening." }, { "id": "c-g7ai9o", "front": "Lambda waves", "back": "Positive occipital sharp transients during visual scanning with the eyes open." }, { "id": "c-21zrqx", "front": "N2 sleep markers", "back": "Sleep spindles and K-complexes." }, { "id": "c-164j1kl", "front": "N3 sleep", "back": "Delta over 75 µV in at least 20% of the epoch." }, { "id": "c-9g0krw", "front": "REM markers", "back": "Low-voltage mixed activity, rapid eye movements, sawtooth waves, atonia." }, { "id": "c-e0cvr0", "front": "Where spindles come from", "back": "The thalamus, paced by the reticular nucleus." }, { "id": "c-j04it8", "front": "Bancaud phenomenon", "back": "Alpha fails to block with eye opening on one side; a sign of dysfunction on the unreactive side." }, { "id": "c-gsuuid", "front": "Slow alpha variant", "back": "Notched posterior rhythm at about half the alpha frequency (mostly 4–5 Hz) that reacts exactly like alpha. Normal; not posterior slowing." }, { "id": "c-1owfjmy", "front": "Fast alpha variant", "back": "Posterior rhythm at about twice the alpha frequency (14–20 Hz) with alpha's reactivity. Normal." } ] } ], "sources": [ { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "ACNS minimum technical standards (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27482788/" }, { "title": "Defective alpha reactivity with mental concentration (Westmoreland 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9821069/" }, { "title": "ILAE seminar: normal and abnormal scalp EEG patterns (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40782030/" } ], "words": 798, "bank": 8 }, { "id": "benign-variants", "n": "2", "title": "Normal variants that look epileptiform", "tags": [ "eeg-fundamentals", "acns-terminology" ], "updated": false, "goals": [ "Recognize the variants most often misread as spikes", "apply the IFCN criteria for a true interictal discharge", "explain the cost of over-reading" ], "blocks": [ { "type": "p", "text": "A variant is a pattern that looks unusual but carries no link to epilepsy. The trap is that most of them appear in drowsiness and light sleep, just when real discharges are also activated." }, { "type": "table", "head": [ "Variant", "Who and when", "How to recognize it" ], "rows": [ [ "Small sharp spikes (benign epileptiform transients of sleep)", "Adults, drowsiness and light sleep", "Under 50 µV and under 50 ms, mono- or diphasic, often bilateral independent; at most a small after-wave, no prominent slow wave; vanish in deeper sleep" ], [ "Wicket spikes", "Older adults, drowsiness", "6–11 Hz arch-shaped temporal waves singly or in trains; no slow wave, no background disruption" ], [ "14- and 6-Hz positive bursts (formerly ctenoids)", "Adolescents, light sleep", "Positive comb-like bursts posterior temporal; best seen with a contralateral ear reference. Also recorded in comatose children, first described in Reye syndrome" ], [ "6-Hz spike-and-wave (phantom)", "Adolescents and adults", "Brief, low-amplitude 5–7 Hz bursts. The **WHAM** form (waking, high-amplitude, anterior, male) is seen mainly in people with seizures; the **FOLD** form (female, occipital, low-amplitude, drowsy) mainly in people without them" ], [ "Rhythmic mid-temporal theta of drowsiness (formerly psychomotor variant)", "Young adults, drowsiness", "5–7 Hz notched, flat-topped temporal theta; no evolution" ], [ "Subclinical rhythmic electrographic discharge of adults (SREDA)", "Over about 50", "Abrupt rhythmic theta–delta, usually parietal–posterior temporal, lasting tens of seconds; the patient is unaffected and there is no postictal slowing" ], [ "Midline theta (Ciganek rhythm)", "Adults, wake or drowsiness", "5–7 Hz rhythmic theta at Cz" ], [ "Hypnagogic hypersynchrony", "Children, about 3 months to 13 years", "Bursts of high-amplitude 3–5 Hz activity at sleep onset, sometimes with sharp components" ], [ "Post-arousal (hypnopompic) hypersynchrony", "Young children, waking from sleep", "Diffuse, rhythmic, high-voltage sinusoidal delta on arousal; the waking counterpart of hypnagogic hypersynchrony. Seen mainly in young children but still occurs in adolescents, where it can mimic a seizure" ], [ "Posterior slow waves of youth", "Children and adolescents", "Delta mixed into the posterior rhythm, attenuating with eye opening" ], [ "Breach rhythm", "After craniotomy", "Sharper, faster, higher-amplitude activity over the bone defect" ] ] }, { "type": "figure", "html": "variant-gallery", "caption": "The variants drawn at one scale. Small sharp spikes are tiny and brief; wicket spikes and the positive bursts are arch- or comb-shaped trains; SREDA starts and stops abruptly with no slowing afterward. Synthetic sketches, not recordings.", "n": 2 }, { "type": "note", "label": "Try it", "text": "Switch between mu, wicket spikes, small sharp spikes, rhythmic mid-temporal theta of drowsiness and positive occipital sharp transients on full pages in the [variant explorer](eeg-fundamentals.html#waveforms-physiological-variants)." }, { "type": "h3", "text": "When is a sharp wave a real discharge?" }, { "type": "p", "text": "The IFCN lists six features of an interictal epileptiform discharge:" }, { "type": "li", "text": "Di- or triphasic waveform with a sharp or spiky morphology" }, { "type": "li", "text": "A different duration from the surrounding background (shorter or longer)" }, { "type": "li", "text": "An asymmetric waveform: a steep phase on one side and a slower phase on the other" }, { "type": "li", "text": "An aftergoing slow wave" }, { "type": "li", "text": "Disruption of the background around it" }, { "type": "li", "text": "A field over the scalp that fits a real cortical source" }, { "type": "figure", "html": "ied-criteria", "caption": "The six features marked on a left temporal spike-and-wave, and a wicket spike train, which has only the sharp look and a field.", "n": 3 }, { "type": "p", "text": "In a clinical validation study, requiring at least five of the six gave specificity above 95%; four of six was a little more sensitive but less specific. Spike means 20–70 ms and sharp wave 70–200 ms; the distinction is duration only and carries no clinical weight." }, { "type": "note", "label": "Board pearl", "text": "If in doubt, do not call it. A false \"epileptiform\" report is one of the commonest routes to a wrong epilepsy diagnosis, lifelong medication, and loss of a driving license." }, { "type": "case", "id": "case-sharp-transient", "title": "Is this spike real?", "intro": [ "A 58-year-old man is referred after one episode of transient confusion. His routine EEG was read elsewhere as \"left temporal epileptiform discharges\"." ], "steps": [ { "narrative": [ "You review the study. In drowsiness there are trains of 8-Hz arch-shaped waves over the left mid-temporal region, each wave sharp-looking. None has an aftergoing slow wave and the background between them is normal." ], "stem": "What is the most likely pattern?", "options": [ "Left temporal spikes", "Wicket spikes, a normal variant", "Rhythmic mid-temporal theta of drowsiness", "Small sharp spikes", "Lambda waves" ], "answer": 1, "explain": "Wicket spikes are 6–11 Hz arch-shaped temporal waves in older adults during drowsiness, singly or in trains, without an aftergoing slow wave or background disruption." }, { "narrative": [ "He was started on levetiracetam after the first report and now feels irritable. He has had no further events." ], "stem": "What is the best next step?", "options": [ "Add lamotrigine for better control", "Obtain a PET scan to find the focus", "Revisit the diagnosis: reassess the event itself and consider stopping the ASM", "Continue levetiracetam indefinitely because the EEG was abnormal", "Order sphenoidal electrodes" ], "answer": 2, "explain": "The EEG does not support epilepsy. The diagnosis rests on the event, which needs its own work-up (transient global amnesia, syncope, TIA, a seizure). Treating a normal variant exposes the patient to side effects without benefit." } ], "outro": [ "Over-read variants, most often wicket spikes, small sharp spikes and rhythmic mid-temporal theta, are a leading cause of epilepsy misdiagnosis. The EEG report should say \"normal variant\" plainly." ] }, { "type": "mcq", "id": "q-jdf0y4", "stem": "Which feature best distinguishes small sharp spikes from a true interictal epileptiform discharge?", "options": [ "They appear only in wakefulness", "They are always unilateral", "They are low in amplitude and very brief, with at most a small after-wave, and disappear in deeper sleep", "They are followed by a prominent slow wave", "They phase-reverse at a single electrode" ], "answer": 2, "explain": "Small sharp spikes are under 50 µV and 50 ms, occur in drowsiness and light sleep, are often bilateral independent, have no prominent aftergoing slow wave (at most a small theta wave) and disappear in deep sleep." }, { "type": "mcq", "id": "q-1fd7jbl", "stem": "A 70-year-old woman has a 40-second run of abrupt rhythmic 5-Hz activity over the parietal regions during wakefulness. She keeps talking normally throughout, and there is no slowing afterward. What is it?", "options": [ "Subclinical rhythmic electrographic discharge of adults (SREDA)", "A focal seizure with preserved consciousness", "Rhythmic mid-temporal theta of drowsiness", "Lateralized rhythmic delta activity", "Hypnagogic hypersynchrony" ], "answer": 0, "explain": "SREDA occurs in older adults, is abrupt and rhythmic, lasts tens of seconds, has no clinical accompaniment and no postictal change. It can be mistaken for a seizure because it has a start and an end." }, { "type": "match", "id": "match-variants", "prompt": "Match each variant to its defining feature", "pairs": [ [ "Wicket spikes", "Arch-shaped 6–11 Hz temporal trains in older adults" ], [ "14- and 6-Hz positive bursts", "Positive comb-like posterior temporal bursts in adolescents" ], [ "Mu rhythm", "Attenuates with movement of the opposite limb" ], [ "Lambda waves", "Occipital positive transients during visual scanning" ], [ "Hypnagogic hypersynchrony", "High-amplitude 3–5 Hz bursts at sleep onset in children" ], [ "Breach rhythm", "Sharper, faster activity over a skull defect" ] ] }, { "type": "cards", "items": [ { "id": "c-1r0vkxv", "front": "IFCN features of an interictal epileptiform discharge", "back": "Sharp di- or triphasic waveform, different duration from background, asymmetric phases, aftergoing slow wave, background disruption, plausible scalp field." }, { "id": "c-18nktj0", "front": "How many IFCN criteria for high specificity", "back": "At least five of six (specificity above 95% in validation)." }, { "id": "c-j04qke", "front": "Spike versus sharp wave", "back": "Spike 20–70 ms; sharp wave 70–200 ms. Duration only; no clinical difference." }, { "id": "c-aj4yc6", "front": "6-Hz spike-and-wave more linked to epilepsy", "back": "Waking, high-amplitude, anterior, in men (WHAM), versus female, occipital, low-amplitude, drowsy (FOLD)." }, { "id": "c-d3y9kg", "front": "SREDA", "back": "Older adults; abrupt rhythmic theta–delta posteriorly lasting tens of seconds, no clinical change, no postictal slowing." }, { "id": "c-7bw0os", "front": "Ctenoids", "back": "Older name for 14- and 6-Hz positive bursts; also seen in comatose children, historically with Reye syndrome." }, { "id": "c-k4lg4b", "front": "Psychomotor variant", "back": "Older name for rhythmic mid-temporal theta of drowsiness, a normal variant." }, { "id": "c-117r6fw", "front": "Post-arousal hypersynchrony", "back": "Diffuse rhythmic high-voltage delta on waking in young children; normal, the arousal counterpart of hypnagogic hypersynchrony." } ] } ], "sources": [ { "title": "IFCN glossary and IED criteria (Kane 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "Validation of the IFCN criteria (Kural 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32321764/" }, { "title": "Two forms of the 6/sec spike and wave complex (Hughes 1980)", "url": "https://pubmed.ncbi.nlm.nih.gov/6153962/" }, { "title": "14 and 6 c/sec positive bursts in comatose patients (Yamada 1976)", "url": "https://pubmed.ncbi.nlm.nih.gov/57050/" }, { "title": "14-and-6 Hz positive bursts in childhood encephalopathies (Drury 1989)", "url": "https://pubmed.ncbi.nlm.nih.gov/2471616/" }, { "title": "Visual scoring of sleep and arousal in infants and children (Grigg-Damberger 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17557427/" }, { "title": "Post-arousal hypersynchrony mimicking ictal EEG (Gelisse 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41311906/" } ], "words": 1135, "bank": 14 }, { "id": "artifacts", "n": "3", "title": "Artifacts", "tags": [ "eeg-fundamentals" ], "updated": false, "goals": [ "Identify eye, muscle, cardiac and electrode artifacts from their field", "name the ICU artifacts that mimic seizures", "use video and extra channels to settle doubt" ], "blocks": [ { "type": "p", "text": "The single most useful question is whether the field makes sense. Brain activity spreads to neighboring electrodes with a gradient; an electrode artifact stays in one place, and a cardiac artifact keeps time with the ECG." }, { "type": "h3", "text": "Physiological artifacts" }, { "type": "li", "text": "**Eyes.** The cornea is positive relative to the retina. On a blink the upper lid slides down over the positively charged cornea, and with eye closure the eyes also roll up (Bell phenomenon); both make Fp1/Fp2 go positive. Looking left brings the cornea toward F7, which goes positive while F8 goes negative. **Lateral rectus spikes** are brief muscle potentials at F7 or F8 at the start of each horizontal saccade. Slow lateral roving eye movements mark drowsiness." }, { "type": "li", "text": "**Muscle.** Very fast, spiky activity over the frontalis and temporalis muscles; rhythmic bursts with chewing. Lowering the high-frequency filter makes muscle look like rhythmic beta or spikes." }, { "type": "li", "text": "**Glossokinetic.** The tongue is also a dipole (tip negative). Talking and swallowing produce frontotemporal slow waves." }, { "type": "li", "text": "**Cardiac.** ECG artifact is time-locked to the QRS complex, often most obvious in referential montages to the ear and in people with short, thick necks. Pulse artifact is a slow wave at one electrode over an artery, about 200 ms after the QRS." }, { "type": "li", "text": "**Sweat.** Very slow (under 0.5 Hz) drifting potentials." }, { "type": "note", "label": "Try it", "text": "Move the eyes and blink in the [eye lab](eeg-fundamentals.html#waveforms-artifact-biophysics) to see why the frontal channels swing the way they do." }, { "type": "h3", "text": "Electrodes and equipment" }, { "type": "li", "text": "**Electrode pop.** Abrupt, steep transient confined to one electrode with no field." }, { "type": "li", "text": "**Salt bridge.** Paste joins two electrodes; the channel between them goes nearly flat." }, { "type": "li", "text": "**Mains interference.** 60 Hz (50 Hz in Europe); in one channel, a high-impedance electrode." }, { "type": "li", "text": "**ICU sources.** Ventilator (rhythmic slow waves at the breathing rate), IV pumps and drips, bed vibration and percussion, chest physiotherapy, ECMO and pacemakers. Check the rate against the device and look at the video before calling a seizure." }, { "type": "note", "label": "Try it", "text": "Switch muscle, mains, blink, ECG, electrode pop and sweat on and off in [Artifact Hunter](eeg-fundamentals.html#waveforms-artifact-hunter), compare them on real pages in the [artifact gallery](eeg-fundamentals.html#waveforms-artifact-gallery), and see [Troubleshoot before filtering](eeg-fundamentals.html#montages-technical-troubleshooting) for the technical causes." }, { "type": "mcq", "id": "q-nj37c8", "stem": "A patient in the ICU has rhythmic 0.3-Hz sharp slow waves in all channels. They occur 18 times a minute, which matches the ventilator setting, and do not evolve. What should you do first?", "options": [ "Load levetiracetam", "Correlate with the ventilator and video; this is most likely ventilator artifact", "Call it generalized periodic discharges", "Report electrographic status epilepticus", "Increase the low-frequency filter to 5 Hz and report what remains" ], "answer": 1, "explain": "A rhythmic pattern at exactly the device rate, without evolution or a cerebral field, is artifact until proven otherwise. Treating artifact exposes the patient to unnecessary drugs and sedation." }, { "type": "mcq", "id": "q-160pwme", "stem": "On eye opening and closing, which electrodes show the largest positive deflection from a blink?", "options": [ "Fp1 and Fp2", "F7 and F8", "T7 and T8", "O1 and O2", "Cz" ], "answer": 0, "explain": "During a blink the upper lid slides down over the positively charged cornea, and with closure the eyes also roll upward (Bell phenomenon); both make the frontopolar electrodes, Fp1 and Fp2, go positive." }, { "type": "cards", "items": [ { "id": "c-j7fhnb", "front": "Cornea polarity", "back": "Positive relative to the retina." }, { "id": "c-mhi3jp", "front": "Blink artifact", "back": "Positive at Fp1 and Fp2, from the lid sliding over the positive cornea and the eyes rolling up." }, { "id": "c-1p7uu3t", "front": "Looking to the left", "back": "F7 goes positive, F8 negative." }, { "id": "c-1ct9m9c", "front": "Lateral rectus spike", "back": "Brief muscle potential at F7 or F8 at the start of a horizontal saccade." }, { "id": "c-2ni7k0", "front": "Pulse artifact", "back": "Slow wave at one electrode over an artery about 200 ms after the QRS." }, { "id": "c-dlrw7f", "front": "Electrode pop", "back": "Abrupt transient confined to one electrode, with no field." }, { "id": "c-1h559pm", "front": "Salt bridge", "back": "Near-flat channel between two electrodes joined by paste." } ] } ], "sources": [ { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" } ], "words": 594, "bank": 13 }, { "id": "maturation", "n": "4", "title": "From preterm to adolescence", "tags": [ "eeg-fundamentals" ], "updated": false, "goals": [ "Date a neonatal EEG from its patterns", "recognize abnormal neonatal backgrounds", "know when the posterior rhythm and sleep markers appear in childhood" ], "blocks": [ { "type": "p", "text": "Neonatal EEG is read against **postmenstrual age** (gestational age plus weeks since birth), because the brain matures on its own schedule whether the baby is inside or outside the womb. A background that lags two weeks or more behind the expected age is **dysmature**." }, { "type": "h3", "text": "Neonatal landmarks" }, { "type": "table", "head": [ "Postmenstrual age", "What you expect" ], "rows": [ [ "Under about 30 weeks", "Discontinuous background (tracé discontinu) with long, very flat interburst intervals; little difference between states" ], [ "About 24–34 weeks", "Temporal theta bursts (temporal sawtooth), most abundant around 29–32 weeks" ], [ "About 24 weeks to term", "Delta brushes (fast activity riding on delta), usually seen from 28–30 weeks, most prominent around 32–34 weeks and rare at term" ], [ "About 34–44 weeks", "Frontal sharp transients (encoches frontales) in transitional sleep, alongside rhythmic frontal delta (anterior dysrhythmia), which starts from about 32–36 weeks" ], [ "Term", "Continuous in wake and active sleep; tracé alternant (bursts with lower-voltage, not flat, intervals) in quiet sleep" ], [ "About 44–46 weeks", "Tracé alternant gives way to continuous slow-wave sleep" ] ] }, { "type": "h3", "text": "Continuity and discontinuity" }, { "type": "p", "text": "Discontinuity is normal in the preterm brain and shortens with age, so judge the longest interburst intervals (usually in quiet sleep) against postmenstrual age:" }, { "type": "table", "head": [ "Postmenstrual age", "Longest acceptable interburst interval" ], "rows": [ [ "Under 30 weeks", "About 35 seconds" ], [ "About 30–33 weeks", "About 20 seconds" ], [ "34–36 weeks", "About 10 seconds" ], [ "37–40 weeks", "About 6 seconds" ] ] }, { "type": "p", "text": "Three discontinuous patterns are easily confused:" }, { "type": "li", "text": "**Tracé discontinu**: high-amplitude bursts (up to about 300 µV) regularly interrupted by low-voltage intervals under 25 µV. Normal in preterm infants: in all states until about 30 weeks, then only in quiet sleep, and rare by 38 weeks." }, { "type": "li", "text": "**Tracé alternant**: quiet sleep from about 34–36 weeks to about a month after term. Bursts of 50–150 µV alternate with intervals of about 25–50 µV that are lower but never flat. At term the intervals last no more than about 6 seconds." }, { "type": "li", "text": "**Burst-suppression**: invariant and unreactive, with bursts that lack normal features and intervals below about 5 µV. It is never a normal maturational pattern." }, { "type": "p", "text": "Intervals that are too long or too low for age, in a record whose bursts still contain normal elements and whose states still change, are **excessive discontinuity**, an abnormal background short of burst-suppression. The next section, [Reading a neonatal EEG](#neonatal-eeg), takes the background, states and transients feature by feature." }, { "type": "mcq", "id": "q-1kev0de", "stem": "A neonate at 35 weeks' postmenstrual age has a discontinuous quiet-sleep EEG. The bursts contain delta brushes and frontal sharp transients, sleep states cycle and the record reacts to stimulation, but interburst intervals reach 18 seconds and stay below 15 µV. What is the best interpretation?", "options": [ "Tracé discontinu, normal for this age", "Tracé alternant, normal for this age", "Excessive discontinuity for age", "Burst-suppression", "A low-voltage, invariant background" ], "answer": 2, "explain": "At 34–36 weeks the longest acceptable interburst interval is about 10 seconds, so 18-second intervals are too long. The bursts contain normal maturational elements and the record cycles and reacts, so it is not burst-suppression, which is invariant, unreactive and built of abnormal bursts over near-flat intervals." }, { "type": "h3", "text": "Abnormal neonatal backgrounds" }, { "type": "li", "text": "Burst-suppression or a persistently low-voltage, invariant background (the strongest markers of poor outcome after hypoxic-ischemic injury)" }, { "type": "li", "text": "Absent sleep–wake cycling at an age when it should be present" }, { "type": "li", "text": "Persistent asymmetry or focal attenuation" }, { "type": "li", "text": "Positive rolandic sharp waves, which point to white matter injury" }, { "type": "li", "text": "Excessive multifocal sharp transients for age" }, { "type": "h3", "text": "Childhood" }, { "type": "table", "head": [ "Age", "Landmark" ], "rows": [ [ "About 6–8 weeks after term", "Sleep spindles appear (asynchronous until about age 2)" ], [ "About 3–4 months", "Posterior rhythm about 4 Hz; hypnagogic hypersynchrony begins to appear" ], [ "About 5–6 months", "Vertex waves and K-complexes" ], [ "About 12 months", "Posterior rhythm about 6 Hz" ], [ "About 3 years", "Posterior rhythm reaches 8 Hz" ], [ "Later childhood", "9–10 Hz, with posterior slow waves of youth common into adolescence" ] ] }, { "type": "figure", "html": "maturation", "caption": "The landmarks in the two tables above as timelines. Neonatal patterns are dated by postmenstrual age; the posterior rhythm speeds up through childhood. Point at or tab to a bar or point for its age range.", "n": 4 }, { "type": "mcq", "id": "q-1br7nj1", "stem": "An EEG in an infant shows frequent delta brushes in all states, temporal sawtooth theta, and a discontinuous background without clear state differentiation. What postmenstrual age fits best?", "options": [ "24 weeks", "30 weeks", "38 weeks", "44 weeks", "3 months after term" ], "answer": 1, "explain": "Temporal theta bursts are most abundant around 29–32 weeks, and delta brushes, usually seen from 28–30 weeks, are frequent by then; the background is still discontinuous without clear state change. At term, delta brushes are sparse and quiet sleep shows tracé alternant." }, { "type": "mcq", "id": "q-14g2t79", "stem": "At what age does the posterior dominant rhythm typically first reach 8 Hz?", "options": [ "4 months", "12 months", "About 3 years", "8 years", "15 years" ], "answer": 2, "explain": "The posterior rhythm is about 4 Hz at 3–4 months, 6 Hz at a year and 8 Hz by about 3 years, rising to 9–10 Hz through childhood." }, { "type": "cards", "items": [ { "id": "c-1x2n14x", "front": "Postmenstrual age", "back": "Gestational age at birth plus weeks since birth; the age a neonatal EEG is read against." }, { "id": "c-1pw0ask", "front": "Dysmaturity", "back": "A background lagging two weeks or more behind postmenstrual age." }, { "id": "c-1qh37ko", "front": "Delta brushes peak", "back": "About 32–34 weeks; largely gone by term." }, { "id": "c-rmouc9", "front": "Tracé alternant", "back": "Term quiet sleep: bursts alternating with lower-voltage (not flat) intervals; gone by about 44–46 weeks." }, { "id": "c-1u2boax", "front": "Encoches frontales", "back": "Frontal sharp transients in transitional sleep, about 34–44 weeks." }, { "id": "c-g98ynu", "front": "Positive rolandic sharp waves", "back": "Marker of white matter injury in the preterm brain." }, { "id": "c-kha5l0", "front": "When spindles appear", "back": "About 6–8 weeks after term; synchronous by about age 2." }, { "id": "c-1h00ozh", "front": "Longest acceptable interburst interval by postmenstrual age", "back": "Under 30 weeks about 35 s; 30–33 weeks about 20 s; 34–36 weeks about 10 s; 37–40 weeks about 6 s." }, { "id": "c-1v7a04", "front": "Tracé discontinu", "back": "Normal preterm pattern: high-amplitude bursts separated by intervals under 25 µV; in all states until about 30 weeks, then quiet sleep only." }, { "id": "c-vq7q9d", "front": "Tracé alternant versus burst-suppression", "back": "Tracé alternant is normal: bursts alternate with intervals of 25–50 µV that are never flat. Burst-suppression is invariant and unreactive, with abnormal bursts and intervals under about 5 µV." }, { "id": "c-1twjbu2", "front": "Excessive discontinuity", "back": "Interburst intervals too long or too low for postmenstrual age, with normal burst content and preserved state change." } ] } ], "sources": [ { "title": "ACNS standardized neonatal EEG terminology (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23545767/" }, { "title": "ACNS guideline on continuous EEG in neonates (2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/22146359/" }, { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "Interrater agreement for the ACNS neonatal terminology (Wusthoff 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28166364/" }, { "title": "ACNS teaching slides: neonatal EEG background, with longest acceptable interburst intervals", "url": "https://www.acns.org/UserFiles/file/NeonatalEEGBackground.pdf" } ], "words": 971, "bank": 11 }, { "id": "neonatal-eeg", "n": "5", "title": "Reading a neonatal EEG", "tags": [ "eeg-fundamentals", "acns-terminology" ], "updated": false, "goals": [ "Record a newborn so the study can answer the question", "describe the background feature by feature in the ACNS neonatal terms", "tell normal neonatal transients from abnormal sharp waves and brief rhythmic discharges", "know what the background predicts after hypoxic–ischemic injury" ], "blocks": [ { "type": "p", "text": "This section follows the neonatal terminology of the American Clinical Neurophysiology Society (ACNS) and the neonatal seizure classification of the International League Against Epilepsy (ILAE). Read a newborn's EEG in a fixed order: the age, then the state, then the background, then the transients, then anything rhythmic. Discontinuity, asynchrony, little reactivity and scattered sharp transients would all be abnormal in an adult, but each is normal at the right postmenstrual age. That is why the age comes first." }, { "type": "h3", "text": "Recording a newborn" }, { "type": "li", "text": "**Electrodes.** The full 10–20 array is allowed, but a reduced set is acceptable, especially on a small premature head. At a minimum it includes Fp1, Fp2, C3, Cz, C4, T3, T4, O1, O2 and the two ears or mastoids. **Cz is always included**, because positive rolandic (vertex) sharp waves and some seizures may be detected only there. The montage needs a transverse chain (T3–C3–Cz–C4–T4) as well as longitudinal ones." }, { "type": "li", "text": "**Extra channels.** Electrocardiogram (ECG) and respiration, which the ACNS requires, and usually eye-movement leads just above and below the outer corners of the eyes and chin muscle activity (electromyography, EMG). In a newborn, state cannot be judged from the EEG alone, and these channels also identify the commonest artifacts." }, { "type": "li", "text": "**Settings.** A low-frequency filter of 0.3–0.6 Hz rather than the adult 1 Hz, so the slow components are not trimmed; sensitivity usually 7 µV/mm. Neonatal records are usually displayed at **15 mm/s**, which compresses each wave and makes ordinary activity look sharper than it would at 30 mm/s." }, { "type": "li", "text": "**No sedation, no photic stimulation.** Schedule the study for a feed: apply the electrodes, then feed, because babies tend to sleep afterwards." }, { "type": "li", "text": "**Length.** Twenty to thirty minutes is usually too short. A routine study runs about an hour, long enough for a **full epoch of quiet sleep**. To screen a high-risk newborn for seizures, the ACNS's 2011 guideline recommends 24 hours of conventional video-EEG, continued until the baby has been free of seizures for 24 hours once any are found. Cooled babies are commonly monitored through cooling and rewarming: most seizures start on the first day, but in one series of 114 cooled babies 12% started later, all in babies whose early background was moderately or severely abnormal, and seizures can recur around rewarming. The ACNS revised its indications for neonatal monitoring in 2025 using graded evidence; because the evidence is weak, all of its recommendations are conditional." }, { "type": "li", "text": "**Documentation.** Gestational age at birth, chronological age and postmenstrual age in weeks; medications; and whether the baby is being cooled, with the temperature. Drugs and cooling change the background: in one small study, a midazolam load briefly (for under 2 hours) depressed the amplitude-integrated EEG, whereas suppression that persisted reflected the severity of the injury. Use \"postmenstrual age\". \"Conceptional age\", strictly about 2 weeks lower, was often used in older EEG papers to mean postmenstrual age, so check which one a paper means." }, { "type": "p", "text": "A baby born at 34 weeks who is now 4 weeks old is 38 weeks' postmenstrual age. A baby born at 28 weeks who is 3 weeks old is 31 weeks." }, { "type": "h3", "text": "The background, feature by feature" }, { "type": "p", "text": "The ACNS neonatal terminology describes each feature separately." }, { "type": "table", "head": [ "Feature", "How it is defined", "What changes with age, or counts as abnormal" ], "rows": [ [ "Continuity", "Continuous: no attenuation below 25 µV lasting 2 seconds or more. An interburst interval is attenuation lasting 2 seconds or more", "The longest acceptable interval shortens with age (see the table in the section above). Too long or too low for age is excessive discontinuity" ], [ "Voltage (term)", "Normal: most activity 25 µV or more in all states", "Borderline low: continuous at 10–25 µV with some normal patterns. Low voltage suppressed: under 10 µV, invariant and unreactive. Electrocerebral inactivity: nothing of 2 µV or more" ], [ "Symmetry", "Homologous regions compared", "Abnormal: a persistent voltage difference over 2:1, or a clear difference in frequencies or normal patterns" ], [ "Synchrony", "A burst is synchronous when it starts in both hemispheres within 1.5 seconds", "Almost fully synchronous before about 27–29 weeks; about 70% synchronous at 29–30 weeks; nearly 100% at term. No substantial asynchrony should remain by 38 weeks" ], [ "Variability", "Spontaneous change in the background", "Present by 25 weeks and well established by 30–31 weeks" ], [ "Reactivity", "A change in the background with stimulation", "First appears at 30–32 weeks, and not with every stimulus. An unreactive record before then is not abnormal" ], [ "Maturity", "Compared with the expected patterns for postmenstrual age", "Dysmature: a record that would be normal for a baby 2 or more weeks younger" ] ] }, { "type": "p", "text": "**Burst-suppression** in the ACNS sense is invariant and unreactive, with interburst intervals below 5 µV and bursts that contain no normal patterns (no delta brushes, no occipital delta). A discontinuous record whose bursts still carry normal patterns, and which changes state or reacts, is excessive discontinuity instead." }, { "type": "note", "label": "Board pearl", "text": "Very preterm bursts are synchronous, then asynchrony appears around 29–30 weeks and fades towards term. Asynchrony is normal at 30 weeks; the same proportion of asynchronous bursts at 39 weeks is abnormal." }, { "type": "h3", "text": "States" }, { "type": "p", "text": "Behavioral state is read from the eyes, breathing and movements on video and the extra channels, and confirmed on the EEG. A state counts when its features last at least a minute." }, { "type": "table", "head": [ "State", "Eyes, breathing and movement", "EEG at term" ], "rows": [ [ "Awake", "Eyes open; irregular breathing; movement", "Continuous low-to-medium voltage (25–50 µV) mixed theta and delta with some faster activity: *activité moyenne*" ], [ "Active sleep", "Eyes closed with rapid eye movements; irregular breathing, sometimes brief pauses; small movements", "*Activité moyenne*, the same as wakefulness" ], [ "Quiet sleep", "Eyes closed and still; regular breathing; few movements", "*Tracé alternant*, often giving way later in the same quiet-sleep period to continuous high-voltage (50–150 µV) delta and theta; by about 46 weeks only the continuous slow pattern remains" ], [ "Indeterminate", "The features do not agree", "A small amount is normal; a large share at term is abnormal" ] ] }, { "type": "li", "text": "**Sleep starts in active sleep.** A newborn falls from wakefulness straight into active sleep, the precursor of REM sleep; this pattern lasts for the first months after term. At term, active sleep takes up about 50–60% of sleep and quiet sleep 30–40%, in cycles of about 40–70 minutes." }, { "type": "li", "text": "**Before term.** Rudimentary cycling appears around 25 weeks, and some periods have all the features of active sleep by 28–31 weeks. Until about 30 weeks tracé discontinu fills every state; after that it belongs mainly to quiet sleep, and from 34 weeks active sleep is consistently continuous. Until about 32–34 weeks, wakefulness is defined by open eyes." }, { "type": "note", "label": "Try it", "text": "See how the posterior rhythm and sleep develop after the newborn period in [How normal EEG changes with age](eeg-fundamentals.html#waveforms-developmental-orientation)." }, { "type": "h3", "text": "Normal patterns of prematurity and term" }, { "type": "p", "text": "Each of these is normal within its age range and becomes a sign of dysmaturity if it persists beyond it. Their presence inside bursts, together with variability or reactivity, is also what separates excessive discontinuity from burst-suppression." }, { "type": "table", "head": [ "Pattern", "What it looks like", "Postmenstrual age" ], "rows": [ [ "Monorhythmic occipital delta", "Rhythmic high-voltage delta (up to about 200 µV), occipital, temporal or central; usually synchronous and symmetric, often surface-positive", "24–34 weeks" ], [ "Temporal theta (temporal sawtooth)", "Sharply contoured 4.5–6 Hz bursts of about 2 seconds over the temporal regions, often asynchronous between sides", "24–34 weeks, most at about 29–32" ], [ "Occipital theta", "Faster, lower and more often one-sided than temporal theta", "Most abundant around 25 weeks; gone by term" ], [ "Delta brushes", "Slow delta waves (0.3–1.5 Hz, 50–250 µV) with fast activity of about 8–22 Hz riding on them", "Can appear from 24 weeks, usually seen from 28–30; peak at about 32–34; move from diffuse to occipital; mostly in quiet sleep from about 34 weeks; gone by about 38–42 weeks" ], [ "Anterior dysrhythmia", "Single or brief runs of frontal delta, 50–100 µV, synchronous and symmetric, in transitional and quiet sleep", "From about 32 weeks in the ACNS terminology (about 36 in some other sources) to 44" ], [ "Frontal sharp transients (*encoches frontales*)", "Broad diphasic frontal waves (a small negative then a larger positive phase), 50–100 µV and about 0.5–0.75 seconds; synchronous and symmetric; most in the change from active to quiet sleep", "About 34–44 weeks" ] ] }, { "type": "p", "text": "Prominent delta brushes in both sleep states at term are mildly abnormal: a sign of dysmaturity worth a follow-up EEG. Frontal sharp transients are bilateral and synchronous by definition; a sharp wave that keeps appearing over one frontal region is judged by the rules for sharp waves below." }, { "type": "h3", "text": "Sharp waves: normal or not" }, { "type": "p", "text": "Spikes last under 100 ms and sharp waves 100–200 ms. Count them in the continuous parts of the record, wakefulness and active sleep, not inside the bursts of tracé alternant." }, { "type": "p", "text": "**Normal neonatal sharp transients** are surface-negative, 100–200 ms long, mostly central, mid-temporal or centrotemporal, single (a few in brief runs), and scattered over both sides. Healthy term newborns have them: in one study of healthy newborns, term babies averaged about 12 an hour, with wide variation." }, { "type": "p", "text": "**Abnormal sharp waves** show one or more of:" }, { "type": "li", "text": "**Persistence in one place**: concentrated over one region or one hemisphere" }, { "type": "li", "text": "**Unusual sites** in the ACNS terminology: frontal (other than frontal sharp transients), vertex or occipital, although one study found frontopolar sharp transients common in healthy newborns" }, { "type": "li", "text": "**Runs or trains**, rather than single waves" }, { "type": "li", "text": "**Excess for age**: the ACNS gives more than 11 an hour in preterm and more than 13 an hour in term babies. These figures sit close to the averages in that study of healthy babies, so read them as a guide rather than a hard limit" }, { "type": "li", "text": "**Positive polarity** at the central or vertex electrodes, or excessive positive mid-temporal sharp waves at term" }, { "type": "li", "text": "**An abnormal background** around them" }, { "type": "p", "text": "**Positive rolandic sharp waves** are surface-positive sharp waves at C3, C4 or Cz, often maximal at the vertex. In premature babies they mark **white matter injury, above all periventricular leukomalacia**, and can appear before the cysts are visible on ultrasound. In a series of 765 premature babies they were seen in about 7%, always preceded the cysts, and were almost 100% specific for periventricular leukomalacia; they were sensitive for it in babies born at 28–32 weeks but missed most cases in those born before 28 weeks. The more frequent they are, the higher the risk of later motor disability: in one series of babies with periventricular echogenicity on ultrasound, no more than 0.1 a minute carried a low risk of poor outcome. They were first described with intraventricular hemorrhage." }, { "type": "note", "label": "Board pearl", "text": "In one study, three experts read 60 records of term babies with hypoxic–ischemic encephalopathy. They agreed very well on seizures (kappa 0.93) and well on the overall background category (0.70), but poorly on negative sharp waves, brief rhythmic discharges and symmetry (kappa under 0.2). Weigh seizures and the background most, and be cautious about conclusions resting on a few negative sharp waves; positive rolandic sharp waves were not tested." }, { "type": "h3", "text": "Brief rhythmic discharges, and other rhythmic patterns" }, { "type": "li", "text": "**Brief rhythmic discharges** look like a seizure but last **under 10 seconds**: sharply contoured rhythmic activity, evolving in the ACNS definition, with or without evolution in the ILAE one. Those that evolve may be very brief seizures. They are rare in an otherwise normal record and usually occur alongside an abnormal background or seizures. They mark a newborn at high risk of seizures, so after brief rhythmic discharges on a routine recording, **longer or repeat monitoring** should be considered. In one series of 340 neonates, which defined them by duration alone, they were linked to periventricular leukomalacia and hypoglycemia and to abnormal later development." }, { "type": "li", "text": "**A rhythmic pattern lasting over 10 seconds that does not evolve** is not a seizure. It is described as rhythmic or periodic activity." }, { "type": "li", "text": "**Periodic discharges** are uncommon in newborns; they occur with herpes simplex encephalitis, stroke and global hypoxia–ischemia." }, { "type": "li", "text": "**Normal rhythmic delta** includes monorhythmic occipital delta and anterior dysrhythmia." }, { "type": "h3", "text": "Artifacts in the neonatal intensive care unit" }, { "type": "p", "text": "Many artifacts here are rhythmic and can mimic seizures:" }, { "type": "li", "text": "**Caregivers:** patting; chest physiotherapy" }, { "type": "li", "text": "**The baby:** sucking on a pacifier or endotracheal tube; a pulsatile fontanelle" }, { "type": "li", "text": "**Devices:** conventional and high-frequency ventilators; the pump of extracorporeal membrane oxygenation (ECMO)" }, { "type": "li", "text": "**Signals:** ECG; electrical interference" }, { "type": "p", "text": "Video, a bedside log of care and procedures, and the ECG and respiration channels sort most of them out. During cooling, shivering can lift an amplitude-integrated EEG into a falsely normal band, and high-voltage ECG artifact can do the same over a near-flat raw EEG." }, { "type": "h3", "text": "The background after hypoxic–ischemic injury" }, { "type": "p", "text": "The background is graded with the same terms: normal, excessively discontinuous, burst-suppression, low voltage suppressed, or electrocerebral inactivity. Its meaning depends on **when** it is recorded, especially during therapeutic hypothermia:" }, { "type": "table", "head": [ "Finding", "What it means" ], "rows": [ [ "An abnormal background in the first 6 hours of life", "Not reliable on its own, especially with cooling. In one study, an abnormal amplitude-integrated EEG at 3–6 hours of age was followed by poor outcome in 84% of babies kept at normal temperature but only 59% of cooled babies" ], [ "Normal or near-normal background early", "Strongly favorable" ], [ "Background returning to normal", "Babies with good outcomes recovered by about 24 hours without cooling and by about 48 hours with it" ], [ "Burst-suppression or extremely low voltage persisting beyond 24 hours, and still more beyond 48 hours", "Increasingly specific: in cooled babies, an abnormal trace that persists predicts death or disability far better than the same trace in the first hours, and in another study these patterns became specific for brain injury on MRI only after 24 hours" ], [ "Sleep–wake cycling", "Its return is favorable; in one study of cooled and uncooled babies, never developing it always meant a poor outcome" ], [ "Inactivity persisting at 3 days", "Death in every case in one series" ] ] }, { "type": "p", "text": "A record that is merely discontinuous early in cooling is often followed by a good outcome. Repeat or continuous recording through rewarming tells you more than any single early hour." }, { "type": "p", "text": "Burst-suppression in a newborn **without** an asphyxial history points elsewhere: early infantile developmental and epileptic encephalopathy, nonketotic hyperglycinemia, or a vitamin B6-dependent epilepsy (see [Neonatal and infantile onset](#syndromes-infancy) and [Immune, infectious and metabolic causes](#immune-infectious-metabolic))." }, { "type": "h3", "text": "Amplitude-integrated EEG" }, { "type": "p", "text": "Amplitude-integrated EEG filters one or two channels (usually across P3–P4, or C3–P3 and C4–P4) to about 2–15 Hz, rectifies and smooths them, and plots the band on a semilogarithmic scale at about 6 cm an hour. Neonatologists use it at the bedside to read the background and its sleep–wake cycling." }, { "type": "li", "text": "**Voltage.** A lower margin above 5 µV with an upper margin above 10 µV is normal. A lower margin at or below 5 µV with the upper margin still above 10 µV is moderately abnormal. Both margins low (upper below 10 µV, lower below 5 µV) is suppressed." }, { "type": "li", "text": "**Pattern names.** Continuous normal voltage; discontinuous normal voltage; burst-suppression; continuous low voltage; flat trace. Before cooling was standard, the last three at 3–6 hours of life predicted poor outcome." }, { "type": "li", "text": "**Sleep–wake cycling.** A smooth, wave-like rise and fall of the band as the background alternates between more and less continuous." }, { "type": "li", "text": "**Seizures.** It is a screen, not a substitute. A single channel without the raw EEG detects under half of individual seizures and misses brief, focal and low-amplitude ones; the ACNS does not recommend it alone for seizure detection when conventional EEG is available." }, { "type": "mcq", "id": "q-524yg3", "stem": "A term newborn, now 2 days old, has a 25-minute EEG with ECG but no eye, chin or respiration channels. The baby is awake and then in active sleep, the background is continuous and of normal voltage, and nothing abnormal is seen. Which limitation matters most?", "options": [ "The low-frequency filter should have been 1 Hz", "Photic stimulation was not performed", "No quiet sleep was recorded, and without the extra channels the states cannot be confirmed", "The display should have been 30 mm/s", "Sedation should have been given to obtain sleep" ], "answer": 2, "explain": "A neonatal study should run long enough, usually about an hour, to include a full epoch of quiet sleep, and needs eye, chin and respiration channels to judge state. Discontinuity, tracé alternant and many transients are judged in quiet sleep. Newborns are recorded with a 0.3–0.6 Hz low-frequency filter, usually at 15 mm/s, without sedation or photic stimulation." }, { "type": "mcq", "id": "q-8b2oio", "stem": "A baby born at 29 weeks is 10 days old. Her EEG shows an age-appropriate discontinuous background, with delta brushes and temporal theta in the bursts, and frequent surface-positive sharp waves maximal at Cz and C4, about two a minute. Cranial ultrasound is normal so far. What do the sharp waves most strongly suggest?", "options": [ "A normal maturational transient of this age", "Evolving white matter injury such as periventricular leukomalacia", "Neonatal seizures needing an antiseizure medication", "Encoches frontales recorded at the vertex", "Artifact from the high-frequency ventilator" ], "answer": 1, "explain": "Positive rolandic sharp waves, often maximal at the vertex, are the EEG marker of white matter injury in premature babies and can precede the cysts of periventricular leukomalacia on ultrasound. They are not seizures and are not a normal pattern of prematurity; frequent ones carry a higher risk of later motor disability." }, { "type": "mcq", "id": "q-g5puz5", "stem": "A newborn at 39 weeks' postmenstrual age has a continuous, normal-voltage background with normal sleep–wake cycling. In quiet sleep, about 40% of the bursts of tracé alternant begin in one hemisphere more than 2 seconds before the other. How should this be reported?", "options": [ "Normal: asynchrony is a feature of neonatal quiet sleep", "Normal: synchrony is not assessed after 37 weeks", "Abnormal: excessive asynchrony for age", "Burst-suppression", "Dysmature by more than 4 weeks" ], "answer": 2, "explain": "Bursts count as synchronous when they start within 1.5 seconds on both sides. Synchrony rises from about 70% at 29–30 weeks to nearly 100% at term, and no substantial asynchrony should remain by 38 weeks. Asynchrony of this degree would be normal around 30 weeks but is abnormal at 39." }, { "type": "match", "id": "match-neonatal-patterns", "prompt": "Match each neonatal pattern to its age range or meaning", "pairs": [ [ "Temporal theta (temporal sawtooth)", "About 24–34 weeks, most at 29–32" ], [ "Delta brushes", "Usually from 28–30 weeks, peak about 32–34, gone by about 38–42" ], [ "Frontal sharp transients (encoches frontales)", "About 34–44 weeks, synchronous and diphasic" ], [ "Monorhythmic occipital delta", "About 24–34 weeks, a normal pattern inside preterm bursts" ], [ "Positive rolandic sharp waves", "White matter injury in premature babies" ], [ "Brief rhythmic discharges", "Seizure-like runs under 10 seconds; consider monitoring longer" ] ] }, { "type": "cards", "items": [ { "id": "c-1jt9rn8", "front": "Minimum reduced neonatal electrode set", "back": "Fp1, Fp2, C3, Cz, C4, T3, T4, O1, O2 and the two ears or mastoids; Cz always." }, { "id": "c-8wshzu", "front": "Why Cz is always recorded in a newborn", "back": "Positive rolandic (vertex) sharp waves and some seizures may be detected only there." }, { "id": "c-3dfrei", "front": "Extra channels for a neonatal EEG", "back": "ECG and respiration (required), usually eye-movement leads and chin muscle, to judge state and identify artifact." }, { "id": "c-1s89jt6", "front": "Neonatal filter and display", "back": "Low-frequency filter 0.3–0.6 Hz; usually 15 mm/s, which makes waves look sharper." }, { "id": "c-hcufh0", "front": "Length of a routine neonatal EEG", "back": "About an hour, including a full epoch of quiet sleep; 20–30 minutes is usually too short." }, { "id": "c-1efrpt5", "front": "Seizure screening in a high-risk newborn (ACNS 2011)", "back": "24 hours of conventional video-EEG; if seizures occur, continue until 24 hours seizure-free. Cooled babies are commonly monitored through rewarming." }, { "id": "c-1dqnvto", "front": "Interburst interval (ACNS)", "back": "Attenuation below 25 µV lasting 2 seconds or more." }, { "id": "c-sa7n2y", "front": "Neonatal voltage categories (term)", "back": "Normal 25 µV or more; borderline low 10–25 µV; low voltage suppressed under 10 µV; electrocerebral inactivity under 2 µV, called so only on a recording that meets the inactivity standards." }, { "id": "c-99dsis", "front": "Neonatal asymmetry", "back": "A persistent voltage difference over 2:1, or a clear difference in frequencies or patterns." }, { "id": "c-qumtco", "front": "Synchronous burst", "back": "Starts in both hemispheres within 1.5 seconds." }, { "id": "c-do9ue2", "front": "Synchrony by age", "back": "Almost complete before about 27–29 weeks; about 70% at 29–30 weeks; nearly 100% at term; none substantial by 38 weeks." }, { "id": "c-z4hc5", "front": "When reactivity appears", "back": "About 30–32 weeks' postmenstrual age." }, { "id": "c-c8crzx", "front": "Activité moyenne", "back": "Continuous 25–50 µV mixed-frequency activity of wakefulness and active sleep at term." }, { "id": "c-w3kzrt", "front": "How a newborn falls asleep", "back": "Straight into active sleep." }, { "id": "c-hx65b2", "front": "Monorhythmic occipital delta", "back": "High-voltage rhythmic delta of 24–34 weeks; a normal pattern inside preterm bursts." }, { "id": "c-1iq7twx", "front": "Delta brushes prominent in both sleep states at term", "back": "Mildly abnormal (dysmaturity); repeat the EEG." }, { "id": "c-1f6qbul", "front": "Abnormal neonatal sharp waves", "back": "One region, unusual site (frontal, vertex, occipital), in runs, excessive for age, positive, or on an abnormal background." }, { "id": "c-6og6hj", "front": "What positive rolandic sharp waves mark", "back": "White matter injury, above all periventricular leukomalacia; they can precede the cysts on ultrasound." }, { "id": "c-1331l3y", "front": "Brief rhythmic discharges", "back": "Seizure-like rhythmic runs under 10 seconds; they mark a high risk of seizures, so consider longer or repeat monitoring." }, { "id": "c-1ktljmw", "front": "Rhythmic pattern over 10 seconds without evolution", "back": "Not a seizure; rhythmic or periodic activity." }, { "id": "c-wvx3kv", "front": "Normalization of the background with cooling", "back": "Good-outcome babies recover by about 48 hours with hypothermia (24 hours without)." }, { "id": "c-1kim26y", "front": "Single-channel amplitude-integrated EEG without raw EEG", "back": "Detects under half of neonatal seizures." } ] } ], "sources": [ { "title": "ACNS standardized neonatal EEG terminology (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23545767/" }, { "title": "ACNS guideline on continuous EEG in neonates (2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/22146359/" }, { "title": "ACNS Guideline 5: minimum technical standards for pediatric EEG (2016)", "url": "https://www.acns.org/UserFiles/file/Guideline5-MinimumTechnicalStandardsforPediatricEEG_v1.pdf" }, { "title": "EEG features of brain maturation in premature infants (Pavlidis 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28627083/" }, { "title": "Sleep EEG in preterm and term neonates (Dereymaeker 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28711233/" }, { "title": "Delta brushes in premature infants (Whitehead 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214965/" }, { "title": "Sharp transients in healthy neonates (Scher 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/7511499/" }, { "title": "Positive rolandic sharp waves and periventricular leukomalacia (Baud 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9602191/" }, { "title": "Positive rolandic sharp waves and outcome (Vermeulen 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12948325/" }, { "title": "Brief rhythmic discharges in neonates (Oliveira 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10964078/" }, { "title": "Interrater agreement for the ACNS neonatal terminology (Wusthoff 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28166364/" }, { "title": "aEEG and outcome during hypothermia (Thoresen 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20566612/" }, { "title": "EEG prognosis during hypothermia (Nash 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21300971/" }, { "title": "EEG in neonatal encephalopathy during cooling (Hamelin 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21316017/" }, { "title": "aEEG voltage classification (al Naqeeb 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10353940/" }, { "title": "aEEG at 3 and 6 hours and outcome (Toet 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10375357/" }, { "title": "Occipital theta of prematurity (Hughes 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2335042/" }, { "title": "Pitfalls of aEEG during cooling (Marics 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24268061/" }, { "title": "ACNS guideline on indications for neonatal continuous EEG (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39752571/" }, { "title": "Early background and duration of monitoring in cooled newborns (Benedetti 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32222256/" }, { "title": "Seizures through cooling and rewarming (Shah 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24443407/" }, { "title": "Midazolam and amplitude-integrated EEG in asphyxiated newborns (van Leuven 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15384888/" } ], "words": 3377, "bank": 4 }, { "id": "activation", "n": "6", "title": "Activation procedures", "tags": [ "eeg-fundamentals" ], "updated": false, "goals": [ "Know what hyperventilation, photic stimulation and sleep add", "tell a photoparoxysmal from a photomyogenic response", "list the contraindications to hyperventilation" ], "blocks": [ { "type": "h3", "text": "Hyperventilation" }, { "type": "p", "text": "Three to five minutes of deep breathing, ideally eyes closed. It reliably provokes absences in untreated childhood and juvenile absence epilepsy, so a routine EEG without hyperventilation can miss the diagnosis. Slow, high-amplitude **buildup** is normal in children and in hypoglycemia; it should settle within about a minute of stopping. Avoid hyperventilation after recent stroke, TIA or intracranial hemorrhage, in moyamoya, sickle cell disease or trait, significant cardiopulmonary disease and raised intracranial pressure." }, { "type": "h3", "text": "Photic stimulation" }, { "type": "p", "text": "Flashes at a range of frequencies, typically about 1 to 30 Hz, with eyes open, closing and closed. Eye closure is the most provocative moment." }, { "type": "li", "text": "**Photoparoxysmal response.** Generalized spike- or polyspike-and-wave evoked by the flashes: a cortical, epileptic response most common in juvenile myoclonic epilepsy and eyelid myoclonia with absences." }, { "type": "li", "text": "**Grades of photoparoxysmal response (Waltz types).** Responses run from spikes within the occipital rhythm (type 1) and parieto-occipital spikes with a slow wave (type 2), through posterior discharges that spread forward (type 3), to generalized spike- or polyspike-and-wave (type 4). The generalized end carries the link to epilepsy: in the family study that introduced the grades, only type 4 was more common in probands with epilepsy and their siblings than in controls, and the IFCN glossary counts types 3 and 4 as the responses strongly associated with epilepsy. Responses confined to the back of the head are weak evidence. Stop the flashes as soon as generalized discharges appear." }, { "type": "li", "text": "**Self-limited versus prolonged responses.** Generalized responses that stop with the flashes still carry an excess of seizures. Those that outlast the train carry more, but mostly because the same patients more often have other epileptiform abnormalities." }, { "type": "li", "text": "**Photomyogenic (photomyoclonic) response.** Frontal muscle jerks time-locked to the flash that stop when the flashes stop. It reflects muscle, often with anxiety, alcohol or sedative withdrawal, not epilepsy." }, { "type": "li", "text": "**Photic driving** at the flash rate is normal." }, { "type": "figure", "html": "activation-model", "caption": "Hyperventilation and photic stimulation on four channels. Switch the procedure, the flash rate and the response to compare normal buildup and photic driving with an absence seizure and a photoparoxysmal response.", "n": 5 }, { "type": "h3", "text": "Sleep and sleep deprivation" }, { "type": "p", "text": "Sleep increases interictal discharges, especially in NREM. Sleep deprivation raises the yield further, partly independently of the sleep it produces. A sleep-deprived EEG is the usual next step after a normal routine study when suspicion remains." }, { "type": "mcq", "id": "q-2jcui6", "stem": "During photic stimulation there are frontal spike-like potentials time-locked to each flash, with visible eyelid and forehead twitching. They stop the moment the stimulator is switched off. What is this?", "options": [ "Photoparoxysmal response", "Photomyogenic response", "Photic driving", "Occipital spikes of photosensitive epilepsy", "Eyelid myoclonia" ], "answer": 1, "explain": "A photomyogenic response is muscle activity time-locked to the flash in the frontal regions that ends with the stimulus. It is not an epileptic response." }, { "type": "mcq", "id": "q-fpimni", "stem": "In which patient should hyperventilation be omitted?", "options": [ "A 7-year-old with suspected absence seizures", "A 25-year-old with suspected juvenile myoclonic epilepsy", "A 16-year-old with sickle cell disease", "A 40-year-old with focal seizures and a normal MRI", "A 70-year-old with transient confusion and no cardiopulmonary disease" ], "answer": 2, "explain": "Hyperventilation lowers cerebral blood flow and is avoided in sickle cell disease or trait, moyamoya, recent stroke, TIA or hemorrhage, significant cardiopulmonary disease and raised intracranial pressure." }, { "type": "cards", "items": [ { "id": "c-w9whss", "front": "Hyperventilation duration", "back": "Three to five minutes." }, { "id": "c-1a8wo1u", "front": "Normal hyperventilation buildup", "back": "High-amplitude slowing, common in children and with low glucose; settles within about a minute." }, { "id": "c-vvzih1", "front": "Contraindications to hyperventilation", "back": "Recent stroke, TIA or hemorrhage; moyamoya; sickle cell disease or trait; significant cardiopulmonary disease; raised intracranial pressure." }, { "id": "c-17gkuwn", "front": "Most provocative moment in photic stimulation", "back": "Eye closure." }, { "id": "c-1n48vo8", "front": "Photoparoxysmal response", "back": "Generalized spike-wave evoked by flashes; epileptic; most common in JME and eyelid myoclonia with absences." }, { "id": "c-fcsaaf", "front": "Photomyogenic response", "back": "Frontal muscle time-locked to flashes, stops with the stimulus; not epileptic." }, { "id": "c-16nl5yy", "front": "Waltz types of photoparoxysmal response", "back": "1, spikes within the occipital rhythm; 2, parieto-occipital spike and slow wave; 3, posterior discharge spreading forward; 4, generalized spike- or polyspike-and-wave. The generalized end carries the link to epilepsy." }, { "id": "c-1ubg3eg", "front": "When to stop photic stimulation", "back": "As soon as generalized epileptiform discharges appear, whether or not they outlast the flashes." } ] } ], "sources": [ { "title": "ACNS minimum technical standards (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27482788/" }, { "title": "ILAE idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" }, { "title": "Patterns of the photoparoxysmal response: a genetic study (Waltz 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1378379/" }, { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "Prolonged versus self-limited photoparoxysmal responses (Puglia 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1532400/" }, { "title": "CSCN guidelines for visual-sensitive EEG testing (2008)", "url": "https://doi.org/10.1017/S0317167100008532" } ], "words": 651, "bank": 5 } ], "intro": [ "Most EEG errors are over-reading: a normal variant or an artifact called epileptiform, and a patient treated for epilepsy they do not have. This part is about knowing normal well enough to leave it alone." ] }, { "id": "abnormal", "n": "3", "title": "Epileptiform and ictal EEG", "short": "Epileptiform EEG", "sections": [ { "id": "ieds", "n": "1", "title": "Interictal epileptiform discharges", "tags": [ "eeg-fundamentals", "ilae-classification" ], "updated": false, "goals": [ "Weigh an interictal discharge by its location and the clinical question", "estimate the yield of routine, repeat and sleep-deprived EEG", "recognize the nonepileptiform abnormalities that still localize" ], "blocks": [ { "type": "h3", "text": "What a discharge means" }, { "type": "p", "text": "An interictal epileptiform discharge (IED) raises the probability that a person who has had a seizure has epilepsy and predicts recurrence after a first unprovoked seizure. It does not diagnose epilepsy on its own: a small percentage of healthy adults and a few percent of healthy children have them, most often centrotemporal or generalized discharges in children." }, { "type": "p", "text": "Location matters:" }, { "type": "li", "text": "**Anterior temporal spikes** are strongly associated with seizures." }, { "type": "li", "text": "**Centrotemporal spikes** are common in school-age children, and most children who have them never have a seizure." }, { "type": "li", "text": "**Occipital spikes** in young children, particularly with fixation-off sensitivity, often belong to self-limited syndromes. They are not specific: they also occur with structural occipital epilepsy, in children with migraine, and in children who never have a seizure (one in five in one series of occipital spike-wave paroxysms). Very sharp, brief \"needle-like\" occipital spikes in blind or severely visually impaired children are a recognized pattern that is often over-read as epileptic." }, { "type": "li", "text": "**Temporal lateralized rhythmic delta activity** (temporal LRDA, long called TIRDA) carries roughly the same meaning as temporal spikes in temporal lobe epilepsy." }, { "type": "li", "text": "**Generalized spike-and-wave** at 3 Hz with a normal background points to an idiopathic generalized epilepsy; even brief subclinical bursts can impair attention in a child." }, { "type": "p", "text": "In temporal lobe epilepsy, bilateral independent temporal spikes are common. When about 80% or more come from one side, seizures usually start on that side." }, { "type": "p", "text": "**EEG traits run in families.** Unaffected first-degree relatives of people with childhood absence epilepsy, juvenile myoclonic epilepsy and self-limited epilepsy with centrotemporal spikes often have abnormal EEGs (about a fifth to two-fifths across studies), though the signature trait itself (generalized spike-and-wave, centrotemporal spikes) is found in fewer. Even identical genes do not guarantee seizures: in Lennox's twin series, about 80% of the identical co-twins of people with idiopathic generalized epilepsy also had epilepsy, against none of the non-identical co-twins. A spike in a symptom-free sibling is an inherited trait, not a diagnosis." }, { "type": "h3", "text": "Yield" }, { "type": "li", "text": "A first routine EEG shows IEDs in roughly a third to a half of people with epilepsy." }, { "type": "li", "text": "Yield rises with repeat studies, sleep and sleep deprivation, and recording soon (within a day or two) after a seizure." }, { "type": "li", "text": "Prolonged ambulatory or inpatient video-EEG is the definitive test when routine studies are unhelpful." }, { "type": "h3", "text": "Abnormal but not epileptiform" }, { "type": "li", "text": "**Focal polymorphic delta**, continuous and arrhythmic, localizes a structural lesion, usually involving white matter." }, { "type": "li", "text": "**Focal attenuation** means dysfunctional cortex or something between cortex and electrode (subdural fluid, hematoma)." }, { "type": "li", "text": "**Frontally predominant generalized rhythmic delta** (GRDA, formerly FIRDA) is nonspecific: encephalopathy, raised pressure or deep lesions." }, { "type": "li", "text": "**Occipital intermittent rhythmic delta** (OIRDA, still the ILAE term; occipitally predominant GRDA in ACNS terms) in a child is supportive of absence epilepsy." }, { "type": "note", "label": "Try it", "text": "Compare focal polymorphic slowing with periodic patterns on real pages in [Slowing and periodic patterns](eeg-fundamentals.html#waveforms-pathology-showcase)." }, { "type": "mcq", "id": "q-1dzwm1h", "stem": "A 34-year-old has a first unprovoked generalized convulsion. Neurological examination and MRI are normal. A routine EEG the next day is normal. What is the best interpretation?", "options": [ "Epilepsy is excluded", "The event was psychogenic", "A normal EEG lowers but does not remove the chance of epilepsy; a sleep-deprived EEG can raise the yield", "ASM treatment is mandatory", "An intracranial EEG is indicated" ], "answer": 2, "explain": "A single routine EEG misses interictal discharges in about half or more of people with epilepsy. Repeat or sleep-deprived recordings increase the yield; the decision to treat rests on the whole picture of recurrence risk." }, { "type": "mcq", "id": "q-1pld4a8", "stem": "Which interictal finding on a routine EEG has the weakest association with actually having seizures?", "options": [ "Right anterior temporal spikes in an adult", "Centrotemporal spikes in an 8-year-old evaluated for headaches", "Left temporal lateralized rhythmic delta activity (temporal LRDA)", "Generalized 3-Hz spike-and-wave in a 7-year-old with staring spells", "Right frontal spikes in a patient with nocturnal hypermotor events" ], "answer": 1, "explain": "Centrotemporal spikes are common in healthy school-age children and most never have seizures. The other findings are strongly linked to epilepsy in their clinical context." }, { "type": "cards", "items": [ { "id": "c-nnrfh1", "front": "Does an IED diagnose epilepsy?", "back": "No. It raises the probability and predicts recurrence, but healthy people can have them." }, { "id": "c-dzefhd", "front": "Yield of a first routine EEG in epilepsy", "back": "About a third to a half." }, { "id": "c-ue49ao", "front": "How to raise EEG yield", "back": "Repeat studies, sleep, sleep deprivation, early recording after a seizure, prolonged video-EEG." }, { "id": "c-1noi6zh", "front": "Temporal LRDA (formerly TIRDA)", "back": "Rhythmic temporal delta; as significant as temporal spikes for temporal lobe epilepsy." }, { "id": "c-nvbj9y", "front": "Frontally predominant GRDA (formerly FIRDA)", "back": "Nonspecific (encephalopathy, deep lesions)." }, { "id": "c-925jyu", "front": "OIRDA", "back": "Occipital intermittent rhythmic delta; supports absence epilepsy in a child." }, { "id": "c-1lnpby8", "front": "Continuous polymorphic delta", "back": "Localizes a structural lesion, usually involving white matter." }, { "id": "c-46uvhu", "front": "Occipital spikes in a child", "back": "Nonspecific: self-limited occipital syndromes, structural epilepsy, migraine, or no seizures at all. Needle-like occipital spikes in blind children are not by themselves evidence of epilepsy." }, { "id": "c-128fi8t", "front": "Generalized spike-and-wave or centrotemporal spikes in a healthy sibling", "back": "An inherited EEG trait, not a diagnosis of epilepsy." } ] }, { "type": "note", "label": "Try it", "text": "[Interictal discharges in EEG Fundamentals](eeg-fundamentals.html#waveforms-interictal-discharges) shows each defining feature on a tracing." } ], "sources": [ { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "AAN/AES first unprovoked seizure guideline (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25901057/" }, { "title": "Clinical manifestations with occipital spike-wave paroxysms (Talwar 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1628582/" }, { "title": "Occipital epileptiform abnormalities in epilepsy and migraine (Brinciotti 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10840629/" }, { "title": "Occipital spikes of the blind (Dema 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41874475/" }, { "title": "Needle-like occipital spikes in visual impairment (Nascimento 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35918165/" }, { "title": "EEG of asymptomatic first-degree relatives: meta-analysis (Tashkandi 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30767897/" }, { "title": "Centrotemporal sharp wave EEG trait (Strug 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19172991/" }, { "title": "Epilepsy in twins: the Lennox series (Vadlamudi 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15079012/" }, { "title": "ILAE idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" } ], "words": 800, "bank": 9 }, { "id": "ictal-scalp", "n": "2", "title": "Seizures on the EEG", "tags": [ "eeg-fundamentals", "epilepsy-surgery" ], "updated": false, "goals": [ "Recognize evolution as the core of an ictal pattern", "use onset patterns and postictal signs to localize", "know which seizures scalp EEG misses" ], "blocks": [ { "type": "h3", "text": "Evolution is the signature" }, { "type": "p", "text": "A seizure pattern changes as it goes: its frequency, shape or location shifts in sequence, usually building then fading. Artifact and rhythmic encephalopathic patterns tend to stay the same. In the ICU the ACNS 2021 definition makes this operational: discharges averaging more than 2.5 Hz for at least 10 seconds, or any pattern with definite evolution lasting at least 10 seconds (see the critical care part)." }, { "type": "note", "label": "Try it", "text": "Drag through onset, evolution and the postictal period in the [seizure timeline](eeg-fundamentals.html#waveforms-seizure-dynamics)." }, { "type": "h3", "text": "Scalp onset patterns" }, { "type": "li", "text": "**Mesial temporal onset** typically shows a regular 5–9 Hz rhythm over the inferior temporal electrodes, appearing within about 30 seconds of clinical onset." }, { "type": "li", "text": "**Neocortical temporal onset** tends to be slower, more irregular and less well lateralized." }, { "type": "li", "text": "**Frontal lobe seizures** are often brief, from sleep and hypermotor; the scalp EEG is frequently hidden by movement artifact or shows little change." }, { "type": "li", "text": "**Attenuation (electrodecrement)**, rhythmic spiking and rhythmic delta are other common onset forms." }, { "type": "h3", "text": "When the scalp misleads" }, { "type": "p", "text": "Scalp ictal EEG localizes temporal seizures more often than extratemporal ones. In an analysis of 486 seizures:" }, { "type": "li", "text": "**Occipital seizures** were falsely localized or lateralized in 28%. They spread quickly, above or below the sylvian fissure and to either side, so the scalp onset and the later semiology can both look temporal once the visual aura has passed." }, { "type": "li", "text": "**Parietal seizures** were falsely localized or lateralized in 16%." }, { "type": "li", "text": "**Mesial frontal seizures** most often looked generalized at onset. This is expected and does not argue against a mesial frontal lesion." }, { "type": "p", "text": "A **focal beta-frequency onset** is uncommon in frontal lobe epilepsy (about a quarter of surgical candidates), but when present it localizes well: at least 90% of such patients became seizure-free after surgery. **Paradoxical lateralization** also occurs: parasagittal generators can project to the opposite side, and in children with a large destructive hemispheric lesion acquired early in life, the ictal rhythm can appear over the healthy hemisphere. Such children still did well after hemispherectomy when the deficit, semiology and MRI pointed to the damaged side." }, { "type": "mcq", "id": "q-1r4nqp2", "stem": "A 7-year-old has a dense left hemiparesis from a perinatal right middle cerebral artery stroke and daily drug-resistant seizures that begin with stiffening of the left arm. MRI shows extensive right hemispheric encephalomalacia and a normal left hemisphere. On video-EEG the ictal rhythm of each seizure is most prominent over the left hemisphere. What is the best interpretation?", "options": [ "The seizures arise from the left hemisphere, so surgery on the right is not an option", "The epilepsy is generalized", "The scalp EEG is paradoxically lateralized; the deficit, semiology and MRI still point to the damaged right hemisphere", "The left-sided rhythm is a breach rhythm", "The events are not epileptic" ], "answer": 2, "explain": "Children with a large hemispheric lesion acquired early in life can show their ictal rhythm over the healthy hemisphere. When the hemiparesis, seizure semiology and MRI all point to the damaged side, this discordant scalp pattern is still compatible with seizure freedom after hemispherectomy. A breach rhythm needs a skull defect and is not ictal." }, { "type": "h3", "text": "Intracranial onset patterns" }, { "type": "p", "text": "**Low-voltage fast activity** at onset marks the seizure-onset zone and is associated with better surgical outcome when that tissue is resected. A **hypersynchronous onset** of repetitive high-amplitude spikes is typical of hippocampal sclerosis. Widespread onset across many contacts, or clinical signs before any EEG change, suggest you are recording spread rather than onset." }, { "type": "p", "text": "A **burst of high-amplitude polyspikes followed by low-voltage fast activity** is associated with focal cortical dysplasia and a focal epileptogenic zone. Between seizures, dysplastic cortex often shows near-continuous rhythmic spiking: such continuous or repetitive discharges were recorded in about two-thirds of patients with dysplasia but in only 1 of 40 with other lesions, and removing that tissue predicted a good outcome. Still, no onset pattern belongs to one pathology. In a depth-electrode study each pattern appeared across several lesion types; only periodic spikes at onset (seen only with mesial temporal sclerosis) and delta brush (seen only with dysplasia) were confined to one." }, { "type": "h3", "text": "After the seizure" }, { "type": "p", "text": "Lateralized postictal slowing points to the side of onset. Postictal aphasia points to the dominant hemisphere, and postictal nose-wiping is usually done with the hand on the same side as the focus." }, { "type": "note", "label": "Board pearl", "text": "A normal scalp EEG during a focal seizure with preserved consciousness is expected, not suspicious. Focal seizures with preserved consciousness show a scalp correlate in only a minority of cases." }, { "type": "mcq", "id": "q-k3iqvi", "stem": "During video-EEG, a patient has a seizure with an epigastric aura, staring and oral automatisms. Twenty seconds after clinical onset a regular 6-Hz rhythm appears over F7, T7 and the inferior temporal electrode T9. What does this pattern suggest?", "options": [ "Mesial temporal onset on the left", "Left frontal onset", "Neocortical lateral temporal onset", "A generalized seizure", "Artifact from chewing" ], "answer": 0, "explain": "A regular 5–9 Hz inferior temporal rhythm within about 30 seconds of clinical onset is typical of hippocampal onset. Neocortical temporal onsets are slower, more irregular and less lateralized." }, { "type": "mcq", "id": "q-189jvr", "stem": "Which intracranial seizure-onset pattern best marks the seizure-onset zone and predicts a good surgical outcome if resected?", "options": [ "Rhythmic delta starting in several lobes at once", "Attenuation appearing 20 seconds after clinical onset", "Low-voltage fast activity confined to a few contacts", "Periodic spikes after a clinical seizure has started", "Slowing without evolution" ], "answer": 2, "explain": "Focal low-voltage fast activity is the classic marker of the true onset zone. Onsets that are widespread, late, or after clinical onset suggest propagated activity." }, { "type": "cards", "items": [ { "id": "c-6bu0fg", "front": "What makes a pattern ictal", "back": "Evolution: sequential change in frequency, morphology or location." }, { "id": "c-ncr6bm", "front": "Mesial temporal scalp onset", "back": "Regular 5–9 Hz inferior temporal rhythm within about 30 seconds of clinical onset." }, { "id": "c-5vn7qs", "front": "Intracranial marker of the onset zone", "back": "Focal low-voltage fast activity." }, { "id": "c-1gxasxp", "front": "Hypersynchronous onset", "back": "Repetitive high-amplitude spikes at onset; typical of hippocampal sclerosis." }, { "id": "c-4dmkrl", "front": "Postictal aphasia", "back": "Dominant hemisphere." }, { "id": "c-n2ioiy", "front": "Postictal nose-wiping", "back": "Usually with the hand on the side of the focus." }, { "id": "c-5290hb", "front": "Occipital seizure with a temporal scalp onset", "back": "Usually spread: occipital seizures are the ones most often falsely localized or lateralized on scalp EEG." }, { "id": "c-g3rp4m", "front": "Mesial frontal seizure that looks generalized", "back": "Expected; in mesial frontal epilepsy the scalp onset most often looks generalized." }, { "id": "c-gxw8k6", "front": "Focal ictal beta on scalp EEG in frontal lobe epilepsy", "back": "Uncommon (about a quarter), but when present at least 90% are seizure-free after surgery." }, { "id": "c-1jxrt7n", "front": "Ictal rhythm over the healthy hemisphere after a large early lesion", "back": "Paradoxical lateralization; does not exclude hemispherectomy if the other data are concordant." }, { "id": "c-1gith9y", "front": "Polyspike burst then low-voltage fast activity", "back": "Intracranial onset associated with focal cortical dysplasia." }, { "id": "c-2ij1wi", "front": "Near-continuous rhythmic spiking on intracranial EEG", "back": "Typical of dysplastic cortex." } ] } ], "sources": [ { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "ILAE 2025 seizure classification", "url": "https://pubmed.ncbi.nlm.nih.gov/40264351/" }, { "title": "Localizing value of ictal EEG in focal epilepsy (Foldvary 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11739820/" }, { "title": "Occipital lobe epilepsy: spread patterns and surgery (Williamson 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1543348/" }, { "title": "Focal ictal beta discharge in frontal lobe epilepsy surgery (Worrell 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11906513/" }, { "title": "Paradoxical lateralization of ictal EEG in extratemporal epilepsy (Catarino 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22130039/" }, { "title": "Paradoxical ictal EEG lateralization with unilateral encephaloclastic lesions (Garzon 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19740718/" }, { "title": "Repertoire of seizure-onset patterns (Lagarde 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30426477/" }, { "title": "Intrinsic epileptogenicity of dysplastic cortex (Palmini 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7717684/" }, { "title": "Seizure-onset patterns and pathology (Perucca 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24176980/" } ], "words": 1062, "bank": 10 }, { "id": "generalized-eeg", "n": "3", "title": "Generalized patterns and what they predict", "tags": [ "eeg-fundamentals", "ilae-classification" ], "updated": false, "goals": [ "Match generalized EEG signatures to syndromes", "recognize the patterns of the developmental and epileptic encephalopathies", "avoid being misled by focal features in generalized epilepsy" ], "blocks": [ { "type": "table", "head": [ "Pattern", "Typical frequency and context", "Points toward" ], "rows": [ [ "Generalized spike-and-wave", "About 3 Hz, abrupt start and stop, normal background, provoked by hyperventilation", "[Childhood absence epilepsy](ilae_classification.html#syndrome-21); [juvenile absence epilepsy](ilae_classification.html#syndrome-29) (often a little faster, with polyspikes)" ], [ "Generalized polyspike-and-wave", "Irregular, about 3–5.5 Hz, on awakening, frequently photosensitive", "[Juvenile myoclonic epilepsy](ilae_classification.html#syndrome-30)" ], [ "Slow spike-and-wave", "Under 2.5 Hz, with a slow background", "[Lennox–Gastaut syndrome](ilae_classification.html#syndrome-25)" ], [ "Generalized paroxysmal fast activity", "About 10 Hz or faster, mostly in NREM sleep, with or without tonic seizures", "Lennox–Gastaut syndrome" ], [ "Hypsarrhythmia", "Chaotic, very high-amplitude slowing with multifocal spikes", "[Infantile epileptic spasms syndrome](ilae_classification.html#syndrome-4)" ], [ "Burst-suppression", "Bursts separated by near-flat periods, from the first weeks of life", "[Early infantile developmental and epileptic encephalopathy](ilae_classification.html#syndrome-5)" ], [ "Spike-wave activation in sleep", "Near-continuous spike-and-wave in NREM sleep", "[Developmental and epileptic encephalopathy (or epileptic encephalopathy) with spike-wave activation in sleep](ilae_classification.html#syndrome-26)" ] ] }, { "type": "figure", "html": "generalized-ladder", "caption": "Generalized patterns on one time base and one scale. Count the complexes in a second to separate 3-Hz spike-and-wave, faster polyspike-and-wave and slow spike-and-wave. Synthetic sketches, not recordings.", "n": 6 }, { "type": "note", "label": "Try it", "text": "Each syndrome in the table opens in the [ILAE syndrome lookup](ilae_classification.html#syndromes-tab), with a summary, the EEG findings, a link to its criteria in the 2022 paper and, for most, an illustrative tracing." }, { "type": "h3", "text": "Details that get tested" }, { "type": "li", "text": "An **epileptic spasm** on EEG is usually a high-amplitude slow wave followed by attenuation, sometimes with superimposed fast activity." }, { "type": "li", "text": "In **epilepsy with myoclonic absences**, 3-Hz spike-and-wave is accompanied by rhythmic jerks of the shoulders and arms." }, { "type": "li", "text": "**Idiopathic generalized epilepsies can look focal.** Fragments of generalized discharges often appear maximal on one side, and myoclonic or tonic–clonic seizures may start asymmetrically. Mistaking this for focal epilepsy leads to sodium channel blockers that worsen absences and myoclonus." }, { "type": "li", "text": "The background is normal in idiopathic generalized epilepsy. A slow, disorganized background with generalized discharges argues for a developmental and epileptic encephalopathy." }, { "type": "li", "text": "**The typical absence discharge** is bilaterally synchronous and usually maximal frontally. Its rate often slows toward the end of the burst, so judge it in the first second: about 3 Hz (range 2.5–4 Hz) in childhood absence epilepsy, where an onset at 4 Hz is common. Hyperventilation provokes it in most untreated children, and drowsiness, sleep and sleep deprivation increase it. Longer, higher-amplitude bursts more often impair task performance when responsiveness is tested; very brief ones may leave it intact. Recovery is immediate, apart from a moment of reorientation, though brief slowing after the burst is common on the EEG." }, { "type": "li", "text": "**Secondary bilateral synchrony**: a focal spike consistently leads into bilaterally synchronous spike-and-wave. The leading region is almost always the most active spike focus (91% in one series), and focal slowing, lateralized seizure features or examination findings, when present, point the same way. It marks a focal epilepsy, most often frontal (about half of cases in that series). Contrast it with an idiopathic generalized epilepsy, whose fragments can look focal but shift from side to side and do not consistently lead the bursts, and with a truly generalized onset, which is bilateral from the first complex." }, { "type": "h3", "text": "Hypsarrhythmia and the BASED score" }, { "type": "p", "text": "Hypsarrhythmia is an interictal EEG pattern, not a diagnosis. Infantile epileptic spasms syndrome needs epileptic spasms with hypsarrhythmia or with multifocal or focal epileptiform discharges; if the interictal EEG shows none of these, a spasm must be recorded. Standard treatment should not be withheld because hypsarrhythmia is absent." }, { "type": "li", "text": "**Elements**: very high-amplitude (often over 200–300 µV), irregular, disorganized slow waves; abundant multifocal spikes and sharp waves over both hemispheres; little interhemispheric synchrony." }, { "type": "li", "text": "**Modified (atypical) hypsarrhythmia**: increased interhemispheric synchrony, asymmetry, a consistent focus, episodes of voltage attenuation, or mostly slow waves with few spikes." }, { "type": "li", "text": "**State**: clearest in NREM sleep, then wakefulness; reduced or absent in REM sleep, relatively normal right after arousal, and attenuated during a cluster of spasms. Record NREM sleep." }, { "type": "li", "text": "A consistent focal discharge or focal fast activity suggests a structural cause." }, { "type": "p", "text": "Because readers agree poorly on whether hypsarrhythmia is present, the **BASED score** (Burden of AmplitudeS and Epileptiform Discharges) grades the most epileptic 5-minute sleep epoch in children 1–24 months old (corrected age) from 0 (normal) to 5. It counts independent spike foci and how much of the epoch they occupy, channels with abnormally high-amplitude background (200 µV or more; 300 µV or more posterior temporal), and two special features: grouped multifocal spikes and paroxysmal voltage attenuations. A score of 4 suggests and 5 strongly suggests an epileptic encephalopathy (earlier versions said probable and definite). It is used at diagnosis and to judge response: after treatment, a pretreatment score of 4 or 5 must fall to 3 or less to count as electrographic remission. Agreement between readers is good, but the score supports clinical judgment rather than replacing it." }, { "type": "mcq", "id": "q-1gow6x2", "stem": "A 6-month-old with infantile epileptic spasms syndrome had a pretreatment EEG with a BASED score of 5. After two weeks of high-dose prednisolone the spasms have stopped. A sleep EEG now shows a single right central spike focus, no high-amplitude background, no grouped multifocal spikes and no voltage attenuations, for a BASED score of 2. What is the best interpretation?", "options": [ "Persistent epileptic encephalopathy, because spikes remain", "Electroclinical remission", "Remission cannot be judged without hypsarrhythmia on the first EEG", "Clinical remission only; the EEG has not improved enough", "The score is invalid because the EEG included sleep" ], "answer": 1, "explain": "Electroclinical remission needs both cessation of spasms and loss of the EEG features of an epileptic encephalopathy. With a pretreatment score of 4 or 5, a fall to 3 or less counts as remission, and a single spike focus scores 2. The BASED score is meant to be applied to sleep, and it does not depend on whether the first EEG was called hypsarrhythmia." }, { "type": "mcq", "id": "q-1dgmxqb", "stem": "A 15-year-old has morning jerks of her arms, one generalized convulsion after an all-night party, and a routine EEG with 4–5 Hz generalized polyspike-and-wave that is activated by photic stimulation. Some discharges are maximal on the right. What is the diagnosis and the key treatment pitfall?", "options": [ "Right frontal lobe epilepsy; start carbamazepine", "Juvenile myoclonic epilepsy; avoid carbamazepine and oxcarbazepine", "Childhood absence epilepsy; start ethosuximide", "Lennox–Gastaut syndrome; start rufinamide", "Juvenile absence epilepsy; start phenytoin" ], "answer": 1, "explain": "Morning myoclonus, a convulsion after sleep deprivation, and photosensitive generalized polyspike-and-wave define juvenile myoclonic epilepsy. Asymmetric discharges are common and should not redirect the diagnosis. Carbamazepine and oxcarbazepine can worsen myoclonus and absences." }, { "type": "mcq", "id": "q-1b48ify", "stem": "Which EEG finding best fits Lennox–Gastaut syndrome?", "options": [ "3-Hz spike-and-wave provoked by hyperventilation with a normal background", "Slow spike-and-wave under 2.5 Hz and bursts of fast activity in sleep, with a slow background", "Hypsarrhythmia", "Centrotemporal spikes activated by sleep", "Generalized polyspike-and-wave provoked by photic stimulation" ], "answer": 1, "explain": "Lennox–Gastaut syndrome is defined by multiple seizure types including tonic seizures, slow spike-and-wave, and generalized paroxysmal fast activity in sleep, with cognitive impairment." }, { "type": "match", "id": "match-generalized-eeg", "prompt": "Match each EEG pattern to the syndrome it points to", "pairs": [ [ "3-Hz spike-and-wave with a normal background", "Childhood absence epilepsy" ], [ "Photosensitive polyspike-and-wave on awakening", "Juvenile myoclonic epilepsy" ], [ "Slow spike-and-wave with paroxysmal fast activity in sleep", "Lennox–Gastaut syndrome" ], [ "Hypsarrhythmia", "Infantile epileptic spasms syndrome" ], [ "Burst-suppression in the first weeks of life", "Early infantile developmental and epileptic encephalopathy" ], [ "Near-continuous spike-and-wave in NREM sleep", "Spike-wave activation in sleep (DEE-SWAS or EE-SWAS)" ] ] }, { "type": "cards", "items": [ { "id": "c-rzbb3e", "front": "Childhood absence epilepsy EEG", "back": "About 3-Hz generalized spike-and-wave with abrupt onset, normal background, provoked by hyperventilation." }, { "id": "c-6dbqns", "front": "Juvenile myoclonic epilepsy EEG", "back": "Irregular 3–5.5 Hz generalized polyspike-and-wave and spike-and-wave, frequently photosensitive." }, { "id": "c-1ndbgmm", "front": "Lennox–Gastaut EEG", "back": "Slow spike-and-wave under 2.5 Hz plus paroxysmal fast activity in sleep, slow background." }, { "id": "c-z6w0ke", "front": "Hypsarrhythmia", "back": "Chaotic, very high-amplitude slowing with multifocal spikes; infantile epileptic spasms syndrome." }, { "id": "c-ib3x1x", "front": "EEG of an epileptic spasm", "back": "High-amplitude slow wave followed by attenuation, sometimes with fast activity." }, { "id": "c-vwusst", "front": "Focal-looking discharges in a teenager with morning myoclonus", "back": "Still juvenile myoclonic epilepsy; asymmetry is common in generalized epilepsies." }, { "id": "c-nuf6db", "front": "Where to measure the rate of an absence discharge", "back": "In the first second; the rate often slows toward the end. About 3 Hz (2.5–4 Hz) in childhood absence epilepsy." }, { "id": "c-40ry7y", "front": "Field of typical 3-Hz spike-and-wave", "back": "Bilaterally synchronous, usually maximal frontally." }, { "id": "c-1mdh4my", "front": "Secondary bilateral synchrony", "back": "A consistent focal spike lead-in to bilateral spike-and-wave, usually from the most active spike focus; a focal (often frontal) epilepsy." }, { "id": "c-1e9pb3w", "front": "Elements of hypsarrhythmia", "back": "Very high-amplitude disorganized slow waves, multifocal spikes, little interhemispheric synchrony." }, { "id": "c-1n8qy4x", "front": "Hypsarrhythmia and sleep state", "back": "Clearest in NREM sleep; reduced or absent in REM sleep, after arousal and during a cluster of spasms." }, { "id": "c-ormu8r", "front": "BASED score of 4 or 5", "back": "4 suggests, 5 strongly suggests an epileptic encephalopathy. Remission: a pretreatment 4–5 must fall to 3 or less." } ] } ], "sources": [ { "title": "ILAE idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" }, { "title": "ILAE syndromes with onset in childhood (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503717/" }, { "title": "ILAE syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "Electroclinical features of absence seizures (Sadleir 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16894100/" }, { "title": "Impaired consciousness in absence seizures (Guo 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27839650/" }, { "title": "Secondary bilateral synchrony (Blume 1985)", "url": "https://pubmed.ncbi.nlm.nih.gov/4076066/" }, { "title": "IFCN glossary of EEG terms (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/30214992/" }, { "title": "Hypsarrhythmia: variations on the theme (Hrachovy 1984)", "url": "https://pubmed.ncbi.nlm.nih.gov/6539199/" }, { "title": "The 2021 BASED score (Mytinger 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33839516/" }, { "title": "BASED score training and interrater reliability (Mytinger 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40009427/" }, { "title": "Inter-rater agreement for hypsarrhythmia with the BASED score (Mytinger 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26280806/" } ], "words": 1370, "bank": 10 }, { "id": "neonatal-seizures", "n": "4", "title": "Neonatal seizures", "tags": [ "ilae-classification", "seizure-management", "eeg-fundamentals" ], "updated": true, "goals": [ "Apply the ILAE 2021 neonatal classification", "know why EEG confirmation is required", "follow the 2023 ILAE treatment recommendations" ], "blocks": [ { "type": "p", "updated": true, "label": "ILAE 2021", "text": "Neonatal seizures have their own classification. They are defined on EEG, because many neonatal seizures have no clinical sign and many odd neonatal movements are not seizures. Events without an EEG correlate are not classified as seizures." }, { "type": "h3", "text": "Classification" }, { "type": "p", "text": "Neonatal seizures are almost always focal in onset, so the classification does not ask focal versus generalized. A seizure is either **with clinical signs**, described by its predominant feature (automatisms, clonic, epileptic spasms, myoclonic, tonic, autonomic, behavioral arrest, or sequential), or **electrographic only**." }, { "type": "h3", "text": "On the EEG" }, { "type": "p", "text": "In the ACNS neonatal terminology, an electrographic seizure is a sudden, repetitive, evolving pattern lasting at least 10 seconds, and neonatal status epilepticus is seizure activity adding up to at least half of any one-hour period. The ILAE 2021 classification sets no minimum duration, only one long enough to show evolution, so evolving runs shorter than 10 seconds can count as very brief seizures. After an ASM, clinical signs often stop while electrographic seizures continue (**electroclinical uncoupling**), which is why monitoring must continue after treatment. Continuous conventional EEG is the gold standard; amplitude-integrated EEG is a useful screen but misses brief, focal and low-amplitude seizures." }, { "type": "p", "text": "What neonatal seizures look like on the EEG:" }, { "type": "li", "text": "**Almost always focal at onset.** Newborns rarely have truly generalized, synchronous seizures; the International League Against Epilepsy (ILAE) notes that a few rare conditions, such as spasms or myoclonic seizures in inborn errors of metabolism, can engage both hemispheres quickly. A widespread seizure usually involves both sides out of step (\"diffuse\"); seizures can also migrate, arise independently on each side, or be **multifocal** (three or more independent foci, at least one on each side)." }, { "type": "li", "text": "**Mostly central, temporal or vertex.** In one series of 851 seizures, 81% began at central, temporal or vertex electrodes. This is why C3, C4, Cz and the temporal electrodes are never left out." }, { "type": "li", "text": "**Typically brief.** The median is about a minute and three quarters last 2.5 minutes or less, but the range runs from 10 seconds to over 40 minutes." }, { "type": "li", "text": "**Rhythmic sharp waves, spikes or sharp-and-slow waves** in term babies; **rhythmic delta** more often in premature ones. Frequency and shape often change as the discharge spreads. Some discharges are low in amplitude or slow and easy to overlook. In one series, low-amplitude discharges were linked to higher mortality and discharges under 2 Hz to more disability." }, { "type": "li", "text": "**Evolution is required**, in frequency, voltage, shape or location. A rhythmic pattern that does not evolve is not a seizure however long it lasts, and two seizures count separately only if 10 seconds or more apart." }, { "type": "li", "text": "**Most have no clinical sign.** In hypoxic–ischemic encephalopathy 50–80% are electrographic only. At the bedside, in one small study (526 seizures in 9 babies), staff documented only 9% of EEG seizures correctly, and only about a quarter of the events they suspected were seizures." }, { "type": "li", "text": "**Movements with and without an EEG seizure.** Focal clonic and focal tonic movements were consistently accompanied by an EEG seizure in Mizrahi and Kellaway's classic video-EEG study. Some myoclonic seizures were too. Generalized tonic posturing and most subtle movements (mouthing, eye movements, bicycling) usually were not, and were thought to be nonepileptic because stimulation provoked them and restraint stopped them." }, { "type": "li", "text": "**Seizure burden** is the total seizure time in an hour. A burden above about 30–60 seconds an hour has been suggested as a threshold for treatment, although the ILAE notes there is still no agreed definition of neonatal status epilepticus." }, { "type": "li", "text": "**A channelopathy signature.** In neonatal epilepsies due to KCNQ2, KCNQ3 or SCN2A variants, seizures typically begin with brief attenuation over both hemispheres, then rhythmic discharges, then several seconds of postictal suppression. On amplitude-integrated EEG this shows as a brief dip, a quick rise and a postictal fall. In one multicenter study it was not seen in babies with hypoxic–ischemic encephalopathy, so recognizing it supports starting a sodium channel blocker before the genetic result returns." }, { "type": "p", "text": "Brief rhythmic discharges, normal neonatal transients and the background terms are covered in [Reading a neonatal EEG](#neonatal-eeg)." }, { "type": "h3", "text": "Causes" }, { "type": "li", "text": "Hypoxic-ischemic encephalopathy is the commonest cause in term neonates, followed by stroke, hemorrhage, infection and metabolic disturbances (glucose, calcium, magnesium, sodium)." }, { "type": "li", "text": "**Neonatal-onset epilepsies**: [self-limited (familial) neonatal epilepsy](ilae_classification.html#syndrome-0) with KCNQ2 or KCNQ3 variants, [self-limited neonatal-infantile epilepsy](ilae_classification.html#syndrome-1) (often SCN2A), [KCNQ2 developmental and epileptic encephalopathy](ilae_classification.html#syndrome-9), and [early infantile developmental and epileptic encephalopathy](ilae_classification.html#syndrome-5)." }, { "type": "li", "text": "**Vitamin-responsive epilepsies**: [pyridoxine-dependent epilepsy](ilae_classification.html#syndrome-13) (ALDH7A1) and [PNPO deficiency](ilae_classification.html#syndrome-14)." }, { "type": "h3", "text": "Treatment (ILAE 2023)" }, { "type": "li", "text": "**Phenobarbital first line**, whatever the cause. The exception is a likely channelopathy (a family history, for example), when phenytoin or carbamazepine is preferred." }, { "type": "li", "text": "**Second line**: phenytoin, levetiracetam, midazolam or lidocaine. Levetiracetam is preferred with cardiac disease." }, { "type": "li", "text": "**Treat electrographic-only seizures too**: a lower seizure burden may improve outcome." }, { "type": "li", "text": "**Stop ASMs before discharge** after acute provoked seizures that have resolved, even if the MRI or EEG is abnormal." }, { "type": "li", "text": "**Therapeutic hypothermia** reduces seizure burden in hypoxic-ischemic encephalopathy." }, { "type": "li", "text": "**Try pyridoxine** when features suggest a B6-dependent epilepsy and seizures continue after second-line drugs." }, { "type": "li", "text": "**How to run the vitamin trial.** Give pyridoxine 100 mg intravenously (or by mouth) with ventilatory support at hand and the EEG running, because apnea, hypotension and flattening of the EEG can follow. Continue about 30 mg/kg/day for 3–5 days before calling the trial negative, since responses can be delayed. An immediate EEG change neither confirms nor excludes pyridoxine-dependent epilepsy. Send α-aminoadipic semialdehyde and genetic testing, and keep treating until the results return." }, { "type": "li", "text": "**A failed pyridoxine trial does not end the search.** Pyridox(am)ine 5′-phosphate oxidase (PNPO) deficiency may respond only to pyridoxal 5′-phosphate, so if a vitamin B6-dependent epilepsy is still suspected, give pyridoxal 5′-phosphate (about 30 mg/kg/day in three doses for 3–5 days). Folinic acid-responsive seizures turned out to be pyridoxine-dependent epilepsy (ALDH7A1). Pyridoxine is the treatment; folinic acid can be added but does not replace it." }, { "type": "li", "text": "**Genetic neonatal-onset epilepsies**: sodium channel blockers (carbamazepine, phenytoin) are the targeted choice for KCNQ2 encephalopathy and for early-onset SCN2A and SCN8A disease, often at high doses. They can worsen seizures in the rare neonatal-onset loss-of-function SCN1A disease." }, { "type": "p", "text": "In the NEOLEV2 trial, phenobarbital stopped seizures more often than levetiracetam as a first drug." }, { "type": "case", "id": "case-neonatal", "title": "A term newborn with HIE", "intro": [ "A term neonate is born after placental abruption, with Apgar scores of 1 and 4 and a cord pH of 6.9. Therapeutic hypothermia is started at 3 hours of age. At 14 hours the nurse notices intermittent lip-smacking and a few seconds of rhythmic left-arm jerking." ], "steps": [ { "narrative": [], "stem": "What is the most important next step?", "options": [ "Treat on clinical grounds and skip EEG to save time", "Start continuous conventional EEG, and treat seizures confirmed on EEG", "Obtain amplitude-integrated EEG only and stop if it is normal", "Obtain an MRI before any treatment", "Observe; neonatal movements are rarely seizures" ], "answer": 1, "explain": "Neonatal seizures are defined on EEG. Continuous conventional EEG is the gold standard in high-risk neonates such as those with HIE on hypothermia. aEEG alone can miss brief or focal seizures." }, { "narrative": [ "cEEG shows a 90-second right central seizure with evolving rhythmic sharp waves, followed by two more within the hour." ], "stem": "Which ASM should be given first?", "options": [ "Phenobarbital", "Levetiracetam", "Lorazepam infusion", "Topiramate", "Carbamazepine" ], "answer": 0, "explain": "The ILAE 2023 guideline recommends phenobarbital as first-line whatever the cause, unless a channelopathy is likely. It outperformed levetiracetam in NEOLEV2." }, { "narrative": [ "After phenobarbital, the arm jerking stops but the EEG still shows seizures every 20 minutes." ], "stem": "What does this represent, and what next?", "options": [ "Artifact from hypothermia; no action needed", "Electroclinical uncoupling; give a second-line ASM", "Treatment success; stop the EEG", "Nonepileptic events; stop phenobarbital", "Brain death; discuss withdrawal of care" ], "answer": 1, "explain": "After an ASM, clinical signs often disappear while electrographic seizures continue. Electrographic-only seizures should still be treated; phenytoin, levetiracetam, midazolam or lidocaine are second-line options." }, { "narrative": [ "Seizures stop on day 2. MRI on day 5 shows bilateral basal ganglia and thalamic injury. The EEG no longer shows seizures." ], "stem": "What should happen to her ASMs before discharge?", "options": [ "Continue phenobarbital for at least a year because the MRI is abnormal", "Switch to levetiracetam for six months", "Stop them before discharge, because the seizures were acute provoked", "Continue both drugs until the EEG normalizes", "Start vigabatrin prophylaxis against infantile spasms" ], "answer": 2, "explain": "The ILAE 2023 guideline recommends stopping ASMs before discharge after acute provoked neonatal seizures without evidence of neonatal-onset epilepsy, regardless of MRI or EEG findings." } ], "outro": [ "Hypoxic-ischemic encephalopathy is the commonest cause of neonatal seizures at term. The pattern to remember: EEG confirms, phenobarbital first, treat what the EEG shows, and stop provoked-seizure treatment before home." ] }, { "type": "mcq", "id": "q-1ygztfh", "stem": "A 3-day-old term boy with normal pregnancy and delivery has brief tonic seizures with apnea. His father had \"fits\" as a newborn that stopped by six months. Interictal EEG is normal between seizures. Which drug do the ILAE 2023 recommendations favor first?", "options": [ "Phenobarbital", "A sodium channel blocker such as carbamazepine or phenytoin", "Levetiracetam", "Vigabatrin", "Pyridoxine" ], "answer": 1, "explain": "A family history of self-limited neonatal seizures suggests a KCNQ2/KCNQ3 channelopathy. For a likely channelopathy the guideline recommends phenytoin or carbamazepine first rather than phenobarbital." }, { "type": "cards", "items": [ { "id": "c-1as1b9y", "front": "Minimum duration of a neonatal electrographic seizure", "back": "10 seconds in the ACNS neonatal terminology; the ILAE 2021 classification sets no minimum beyond enough time to show evolution." }, { "id": "c-d6g9js", "front": "Neonatal status epilepticus (ACNS)", "back": "Seizures totaling at least half (50% or more) of any one-hour period." }, { "id": "c-1mmq1wq", "front": "Electroclinical uncoupling", "back": "Clinical signs stop after an ASM while electrographic seizures continue." }, { "id": "c-1qkl70p", "front": "First-line ASM for neonatal seizures (ILAE 2023)", "back": "Phenobarbital, unless a channelopathy is likely (then phenytoin or carbamazepine)." }, { "id": "c-19qr2h6", "front": "Second-line neonatal ASMs", "back": "Phenytoin, levetiracetam, midazolam or lidocaine; levetiracetam if cardiac disease." }, { "id": "c-p0xqjy", "front": "Acute provoked neonatal seizures at discharge", "back": "Stop ASMs before discharge, whatever the MRI or EEG." }, { "id": "c-nir2qs", "front": "Commonest cause of seizures in term neonates", "back": "Hypoxic-ischemic encephalopathy." }, { "id": "c-hn7mxk", "front": "Pyridoxine trial in a neonate", "back": "100 mg intravenously with ventilatory support and EEG, then about 30 mg/kg/day for 3–5 days; watch for apnea and EEG flattening." }, { "id": "c-1k6esk3", "front": "Pyridoxine trial fails but B6 dependency is still suspected", "back": "Give pyridoxal 5′-phosphate; PNPO deficiency may respond only to it." }, { "id": "c-10rgdl5", "front": "Folinic acid-responsive seizures", "back": "A form of pyridoxine-dependent epilepsy (ALDH7A1); treat with pyridoxine, with folinic acid at most an add-on." }, { "id": "c-5cqd78", "front": "Where neonatal seizures start", "back": "Almost always focal; mostly at central, temporal or vertex electrodes." }, { "id": "c-12sudv2", "front": "Typical neonatal seizure duration", "back": "Brief: median about 1 minute, three quarters 2.5 minutes or less; range 10 seconds to over 40 minutes." }, { "id": "c-cp23ot", "front": "Neonatal movements reliably accompanied by an EEG seizure", "back": "Focal clonic, focal tonic and some myoclonic; generalized tonic posturing and most subtle movements usually are not." }, { "id": "c-jmy22g", "front": "Neonatal seizures with no clinical sign in hypoxic–ischemic encephalopathy", "back": "About 50–80%." }, { "id": "c-iaipuu", "front": "Ictal pattern of KCNQ2, KCNQ3 and SCN2A neonatal seizures", "back": "Bilateral attenuation at onset, rhythmic discharges, then postictal suppression; on amplitude-integrated EEG a dip, a rise and a fall. Favors an early sodium channel blocker." } ] } ], "sources": [ { "title": "ILAE classification of seizures in the neonate (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33522601/" }, { "title": "ILAE treatment of neonatal seizures (2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37655702/" }, { "title": "NEOLEV2 trial (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32385134/" }, { "title": "ACNS neonatal EEG terminology (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23545767/" }, { "title": "ILAE syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "EEG response to intravenous pyridoxine (Bok 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20887371/" }, { "title": "Folinic acid-responsive seizures are pyridoxine-dependent epilepsy (Gallagher 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19142996/" }, { "title": "Where and how neonatal seizures start (Shellhaas and Clancy 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17765607/" }, { "title": "Duration of neonatal seizures (Clancy and Legido 1987)", "url": "https://pubmed.ncbi.nlm.nih.gov/3653058/" }, { "title": "Ictal EEG patterns in preterm and term newborns (Patrizi 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12907278/" }, { "title": "Ictal discharge features and outcome (Nagarajan 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21723453/" }, { "title": "Clinical recognition of neonatal seizures (Murray 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/17626147/" }, { "title": "Characterization of neonatal seizures by video-EEG (Mizrahi and Kellaway 1987)", "url": "https://pubmed.ncbi.nlm.nih.gov/3683874/" }, { "title": "Ictal EEG and aEEG pattern in SCN2A and KCNQ3 neonatal epilepsy (Pijpers 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37429183/" } ], "words": 1624, "bank": 13 } ], "intro": [ "What an abnormal EEG adds to the diagnosis, and what it cannot do. Interictal discharges raise or lower the probability of epilepsy; the seizure pattern, when you capture one, tells you where and what kind." ] }, { "id": "icu", "n": "4", "title": "Critical care EEG", "short": "Critical care", "sections": [ { "id": "acns-terminology", "n": "1", "title": "ACNS 2021 terminology", "tags": [ "acns-terminology" ], "updated": true, "goals": [ "Name rhythmic and periodic patterns with main terms and modifiers", "describe the background in standard terms", "apply the ACNS definitions of electrographic and electroclinical seizures and status" ], "blocks": [ { "type": "p", "updated": true, "label": "ACNS 2021", "text": "The old labels are retired. PLEDs are now LPDs, BIPLEDs are BIPDs, GPEDs are GPDs, and triphasic waves are GPDs with triphasic morphology. \"Epileptiform\" was dropped because these patterns sit on a spectrum and naming them should not presume they are seizures." }, { "type": "h3", "text": "Building a name" }, { "type": "p", "text": "A rhythmic or periodic pattern gets two main terms and any modifiers." }, { "type": "li", "text": "**Main term 1, where:** generalized (G), lateralized (L), bilateral independent (BI), unilateral independent (UI), multifocal (Mf)." }, { "type": "li", "text": "**Main term 2, what:** periodic discharges (PDs), rhythmic delta activity (RDA), spike-and-wave or sharp-and-wave (SW)." }, { "type": "li", "text": "**Plus modifiers:** +F superimposed fast activity (PDs or RDA), +R superimposed rhythmic activity (PDs only), +S superimposed sharp waves or spikes (RDA only). Plus features raise the likelihood that a pattern is ictal." }, { "type": "li", "text": "**Other modifiers:** prevalence, duration, frequency, number of phases, sharpness, amplitude, polarity, stimulus-induced (SI-), evolving or fluctuating, triphasic morphology, and anterior–posterior lag." }, { "type": "p", "text": "**Periodic or rhythmic?** In ACNS terms, **periodic** means the same waveform repeats with a clearly visible interval between one discharge and the next, at nearly regular intervals: the cycle length changes by less than 50% from one cycle to the next in most cycle pairs. **Rhythmic** means the same waveform repeats with no interval between waves, under the same less-than-50% rule; irregular or polymorphic delta is not RDA. RDA runs at 0.5 to 4 Hz. A **discharge** lasts under 0.5 seconds, or longer with no more than three phases; a longer waveform with four or more phases is a burst. **Spike-and-wave** requires each slow wave to run straight into the next spike. If an interval follows each complex, the pattern is PDs, and each spike-and-wave complex counts as one discharge." }, { "type": "figure", "html": "rhythm-periodic", "caption": "Shape first, then timing: does the waveform repeat, and is there an interval between one wave and the next? Move the sliders to see when a pattern is periodic, rhythmic or neither.", "n": 7 }, { "type": "p", "text": "**Six cycles.** A pattern counts as rhythmic or periodic only if it continues for at least six consecutive cycles, so the shortest qualifying run depends on its frequency: 12 seconds at 0.5 Hz, 6 seconds at 1 Hz, 2 seconds at 3 Hz, 1.5 seconds at 4 Hz. Brief potentially ictal rhythmic discharges (BIRDs) also need at least six waves at a regular rate, but they apply only to activity faster than 4 Hz and must also last at least 0.5 seconds, which is the binding limit above 12 Hz. No rhythmic or periodic pattern in the terminology is faster than 4 Hz: an abnormal rhythmic or periodic pattern above 4 Hz that lasts 0.5 seconds or more is BIRDs if it lasts under 10 seconds and an electrographic seizure if it lasts 10 seconds or more. Normal rhythms and benign variants, such as alpha, are excluded." }, { "type": "p", "text": "Try it in the [ACNS name builder](acns_criteria.html#name-builder-section)." }, { "type": "h3", "text": "Prevalence and duration" }, { "type": "table", "head": [ "Prevalence term", "Share of the record", "Duration term", "Length of a run" ], "rows": [ [ "Continuous", "90% or more", "Very long", "1 hour or more" ], [ "Abundant", "50–89%", "Long", "10–59 minutes" ], [ "Frequent", "10–49%", "Intermediate", "1–9.9 minutes" ], [ "Occasional", "1–9%", "Brief", "10–59 seconds" ], [ "Rare", "Under 1%", "Very brief", "Under 10 seconds" ] ] }, { "type": "note", "label": "Try it", "text": "Type the share of the record or the length of a run and get the ACNS term from [Numbers into ACNS words](acns_criteria.html#acns-quantifiers)." }, { "type": "h3", "text": "The background" }, { "type": "li", "text": "**Continuity:** continuous (under 1% of the record attenuated or suppressed); nearly continuous (1–9%); discontinuous (10–49%); burst-attenuation or burst-suppression (50–99%); attenuation or suppression (over 99%)." }, { "type": "li", "text": "**Suppression** means under 10 µV; **attenuation** means 10 µV or more but under half the background voltage." }, { "type": "figure", "html": "continuity-model", "caption": "The continuity scale as a slider: set the share of the record that is suppressed or attenuated and read its ACNS name. A synthetic 20-second trace; the shaded stretches are the low-voltage periods.", "n": 8 }, { "type": "li", "text": "**Reactivity** is a change in cerebral activity with stimulation. Muscle or eye artifact alone does not count, and a response made up only of stimulus-induced patterns is reported separately, as \"SIRPIDs only\", not as reactive." }, { "type": "li", "text": "**Testing reactivity:** ACNS 2021 strongly encourages a standard protocol of escalating stimuli, recording the type and strength of each: auditory (clapping, calling the patient's name), then light touch, then noxious stimuli (nail-bed pressure, sternal rub, trapezius squeeze, nostril tickle, suctioning). An international consensus for patients after cardiac arrest adds: do not stimulate the patient beforehand, give each stimulus at least three times for at least 5 seconds, and record the sedatives and analgesics on board. If the EEG seems unreactive after one round, repeat a standardized noxious round from the unstimulated state, and if the patient is sedated or paralyzed, say so in the impression." }, { "type": "li", "text": "**Why reactivity matters:** a response needs intact sensory pathways, the ascending arousal systems of the upper brainstem that project to thalamus and cortex, and working thalamocortical circuits; damage anywhere along that chain can abolish it. Across causes of coma, a reactive EEG goes with survival and recovery, and an unreactive one with death or poor outcome. After cardiac arrest, absent reactivity alone has too inconsistent a specificity to predict poor outcome, and the 2021 European guidelines stopped using it for that purpose. It does strengthen a highly malignant pattern: among 845 patients in the second Targeted Temperature Management trial (TTM2), the specificity of a highly malignant EEG for poor outcome rose from 93% to 97% when the record was also unreactive." }, { "type": "li", "text": "Also describe symmetry, the dominant frequency, the presence of sleep transients and state changes, and whether bursts are **highly epileptiform** or **identical**." }, { "type": "figure", "html": "reactivity-model", "caption": "Reactivity has to be provoked. Apply the stimulus and compare the background before and after: eye opening in an awake adult, then a reactive and an unreactive record in the critically ill.", "n": 9 }, { "type": "h3", "text": "What counts as a seizure" }, { "type": "table", "head": [ "Term", "Definition" ], "rows": [ [ "Electrographic seizure", "Epileptiform discharges averaging more than 2.5 Hz for 10 seconds or more, or any pattern with definite evolution lasting 10 seconds or more" ], [ "Electrographic status epilepticus", "Electrographic seizure for 10 continuous minutes or more, or for 20% or more of any 60-minute period" ], [ "Electroclinical seizure", "Any EEG pattern with a definite time-locked clinical correlate (any duration), or EEG and clinical improvement after a parenteral ASM" ], [ "Electroclinical status epilepticus", "Electroclinical seizure for 10 continuous minutes or more, or 20% or more of any hour; 5 continuous minutes if there is bilateral tonic–clonic activity" ], [ "Possible electroclinical status", "A pattern on the ictal–interictal continuum for 10 minutes or 20% of an hour that improves on EEG, but not clinically, after a parenteral ASM" ] ] }, { "type": "mcq", "id": "q-jfnqq4", "stem": "Which is the current ACNS name for a pattern formerly called \"BIPLEDs with superimposed rhythmic activity\"?", "options": [ "BIRDs", "BIPDs+R", "BI-LRDA+S", "GPDs+R", "BIPLEDs are still the preferred term" ], "answer": 1, "explain": "Bilateral independent periodic epileptiform discharges are now bilateral independent periodic discharges (BIPDs). Superimposed rhythmic activity on PDs is the +R modifier." }, { "type": "mcq", "id": "q-pjxhsc", "stem": "A comatose patient has static lateralized rhythmic delta at 1.5 Hz for three hours, without evolution, fluctuation or plus features. By ACNS 2021 criteria, what is this?", "options": [ "Electrographic status epilepticus", "An electrographic seizure", "On the ictal–interictal continuum", "LRDA that meets neither seizure nor IIC criteria as described", "BIRDs" ], "answer": 3, "explain": "Rhythmic delta does not count toward the 2.5 Hz rule and has no evolution. Lateralized RDA reaches the continuum only above 1 Hz with a plus modifier or fluctuation. It still carries an increased seizure risk and warrants continued monitoring." }, { "type": "mcq", "id": "q-b48zfv", "stem": "A patient has repetitive left face twitching, each twitch time-locked to a right central periodic discharge at 0.8 Hz, lasting 15 minutes. What is the diagnosis by ACNS criteria?", "options": [ "LPDs, interictal", "Ictal–interictal continuum only", "Electroclinical status epilepticus", "Electrographic seizure without clinical correlate", "Artifact" ], "answer": 2, "explain": "Any EEG pattern with a definite time-locked clinical correlate is an electroclinical seizure regardless of frequency. Lasting 10 continuous minutes or more, it is electroclinical status epilepticus (here, focal motor status)." }, { "type": "cards", "items": [ { "id": "c-1puuw3n", "front": "Main term 1 options", "back": "Generalized, lateralized, bilateral independent, unilateral independent, multifocal." }, { "id": "c-b8r4jm", "front": "Main term 2 options", "back": "Periodic discharges, rhythmic delta activity, spike-and-wave or sharp-and-wave." }, { "id": "c-e9o25t", "front": "+R and +S", "back": "+R superimposed rhythmic activity applies to PDs; +S superimposed sharp waves applies to RDA." }, { "id": "c-jk8gqz", "front": "Electrographic seizure (ACNS 2021)", "back": "Discharges averaging over 2.5 Hz for 10 s or more, or definite evolution for 10 s or more." }, { "id": "c-m3c7nu", "front": "Electrographic status epilepticus", "back": "10 continuous minutes, or 20% of any hour." }, { "id": "c-1wyw37r", "front": "Electroclinical status with convulsions", "back": "5 continuous minutes of bilateral tonic–clonic activity." }, { "id": "c-47tfhq", "front": "Suppression versus attenuation", "back": "Suppression under 10 µV; attenuation 10 µV or more but under half of background." }, { "id": "c-bqbbak", "front": "Do SIRPIDs count as a reactive background?", "back": "No. ACNS 2021 reports this response as its own category, \"SIRPIDs only\"." }, { "id": "c-1j5jct6", "front": "Periodic (ACNS)", "back": "A repeating waveform with a clear interval between discharges, recurring at nearly regular intervals (cycle length varies by under 50% between most consecutive cycles)." }, { "id": "c-cup81d", "front": "Rhythmic (ACNS)", "back": "A repeating waveform with no interval between waves." }, { "id": "c-1dzoz1y", "front": "Spike-and-wave with an interval after each complex", "back": "PDs; each spike-and-wave complex is one discharge." }, { "id": "c-1e95qn", "front": "Shortest run that counts as rhythmic or periodic", "back": "Six consecutive cycles: 6 s at 1 Hz, 2 s at 3 Hz." }, { "id": "c-173dowq", "front": "Fastest rhythmic or periodic pattern in the terminology", "back": "4 Hz. An abnormal rhythmic or periodic pattern above 4 Hz lasting 0.5 s or more is BIRDs (under 10 s) or a seizure (10 s or more)." }, { "id": "c-eabmmt", "front": "Reactivity testing", "back": "Quiet baseline; escalating auditory, touch and noxious stimuli, each repeated; a second noxious round if unreactive; note the sedatives." }, { "id": "c-8nuhc2", "front": "Does absent reactivity alone predict poor outcome after cardiac arrest?", "back": "No. Its specificity is inconsistent; it adds weight to a highly malignant pattern." } ] }, { "type": "note", "label": "Try it", "text": "Name patterns on synthetic 16-channel strips in [Read the Strip](acns_criteria.html#strip-drill-section), then turn your findings into ACNS wording in [Write the Report](acns_criteria.html#report-builder-section)." } ], "sources": [ { "title": "ACNS standardized critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "ACNS 2021 terminology document", "url": "https://www.acns.org/UserFiles/file/ACNSStandardizedCriticalCareEEGTerminology_rev2021.pdf" }, { "title": "International consensus on EEG reactivity testing after cardiac arrest (Admiraal 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30056156/" }, { "title": "Value and mechanisms of EEG reactivity in impaired consciousness (Azabou 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30071861/" }, { "title": "ERC–ESICM post-resuscitation care guidelines (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33765189/" }, { "title": "Highly malignant EEG patterns after cardiac arrest in TTM2 (Turella 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38172300/" } ], "words": 1555, "bank": 11 }, { "id": "iic-and-birds", "n": "2", "title": "The ictal–interictal continuum and seizure risk", "tags": [ "acns-terminology", "seizure-management" ], "updated": false, "goals": [ "Apply the IIC criteria", "recognize BIRDs", "estimate seizure risk with 2HELPS2B", "decide when an antiseizure trial is reasonable" ], "blocks": [ { "type": "h3", "text": "Which patterns carry seizure risk" }, { "type": "p", "text": "In a multicenter cohort of 4772 critically ill adults, lateralized periodic discharges, lateralized rhythmic delta and generalized periodic discharges were associated with seizures; generalized rhythmic delta, including frontally predominant GRDA (the old FIRDA), was not. Higher frequency and plus features raised the risk, and the frequency at which risk begins differs by pattern:" }, { "type": "table", "head": [ "Pattern", "When it carries seizure risk" ], "rows": [ [ "Lateralized periodic discharges (LPDs)", "At every frequency; 58% had seizures when plus features were present" ], [ "Bilateral independent periodic discharges (BIPDs)", "A high risk close to that of LPDs: seizures in 45%, against 52% with LPDs and 8% with no periodic discharges, in a matched case–control study" ], [ "Generalized periodic discharges (GPDs)", "From 1.5 Hz (24% at 1.5–2 Hz, 32% at 2 Hz or faster), or at any frequency with a plus feature" ], [ "Lateralized rhythmic delta activity (LRDA)", "From 1.5 Hz (24% at 1.5–2 Hz, 40% at 2 Hz or faster), or at any frequency with a plus feature" ], [ "Generalized rhythmic delta activity (GRDA)", "No added risk: 13%, no different from patients with no rhythmic or periodic pattern" ] ] }, { "type": "p", "text": "A higher prevalence of LPDs or GPDs also raised the risk. Stimulus-induced patterns carried no risk beyond that of the underlying pattern." }, { "type": "h3", "text": "The ictal–interictal continuum (IIC)" }, { "type": "p", "text": "A pattern is on the IIC if it does not meet seizure criteria and, over at least 10 seconds, it is:" }, { "type": "li", "text": "PDs or spike-and-wave averaging more than 1 and up to 2.5 Hz; or" }, { "type": "li", "text": "PDs or spike-and-wave at 0.5–1 Hz with a plus modifier or fluctuation; or" }, { "type": "li", "text": "lateralized rhythmic delta above 1 Hz with a plus modifier or fluctuation." }, { "type": "figure", "html": "iic-map", "caption": "The same criteria by average frequency over 10 seconds, next to the seizure threshold. Point at or tab to a band for its criterion.", "n": 10 }, { "type": "p", "text": "GRDA never qualifies. The IIC is a description, not a diagnosis. Whether to treat depends on the clinical picture, imaging, and sometimes a monitored trial." }, { "type": "note", "label": "Try it", "text": "Set a pattern's frequency, plus modifiers and evolution in the [ACNS name builder](acns_criteria.html#name-builder-section) and see when it meets continuum or seizure criteria." }, { "type": "h3", "text": "Brief potentially ictal rhythmic discharges (BIRDs)" }, { "type": "p", "text": "Rhythmic activity faster than 4 Hz, at least six waves, lasting 0.5 to under 10 seconds, not a normal variant and not part of burst-suppression. **Definite BIRDs** evolve, or match the patient's seizures or interictal discharges; **possible BIRDs** are only sharply contoured. BIRDs are strongly associated with seizures." }, { "type": "h3", "text": "A treatment trial" }, { "type": "p", "text": "When a pattern on the IIC might be causing the patient's impairment, a trial of a parenteral ASM (a small benzodiazepine dose, or a nonsedating drug such as levetiracetam, valproate or lacosamide) with EEG and bedside examination can help. Clear clinical and EEG improvement makes it an electroclinical seizure. EEG improvement alone is ambiguous, especially after a benzodiazepine that also sedates." }, { "type": "h3", "text": "2HELPS2B" }, { "type": "p", "text": "Six items from the first hours of EEG and the history estimate the risk of seizures during monitoring. In a later validation, a score of 0 after the first hour identified patients at low enough risk that a shorter recording may suffice." }, { "type": "calc", "name": "twohelps2b" }, { "type": "case", "id": "case-iic", "title": "Periodic discharges after a stroke", "intro": [ "A 71-year-old is admitted with a left MCA infarct and is more confused on day 2 than expected. Continuous EEG shows left hemispheric periodic discharges at 1.5 Hz, sharply contoured, with intermittent superimposed rhythmic activity. No evolution is seen." ], "steps": [ { "narrative": [], "stem": "How are these discharges named, and where do they sit?", "options": [ "GPDs, interictal", "LPDs+R at 1.5 Hz, on the ictal–interictal continuum", "Electrographic status epilepticus", "LRDA+S, not on the continuum", "BIRDs" ], "answer": 1, "explain": "They are lateralized periodic discharges with superimposed rhythmic activity (+R). PDs above 1 and up to 2.5 Hz are on the IIC even without plus features; they do not meet seizure criteria without evolution or a rate above 2.5 Hz." }, { "narrative": [ "Her 2HELPS2B items: LPDs present, plus features present, frequency not above 2 Hz, no sporadic discharges, no prior seizure, no BIRDs." ], "stem": "What is her score and estimated seizure risk?", "options": [ "1, about 12%", "2, about 27%", "3, about 50%", "4, about 73%", "0, under 5%" ], "answer": 1, "explain": "LPDs (1) plus features (1) = 2, an estimated seizure risk of about 27% in the derivation cohort. Continue monitoring for at least 24 hours." }, { "narrative": [], "stem": "The team wonders whether her confusion is ictal. What is the most reasonable test?", "options": [ "Load phenobarbital to burst-suppression", "Ignore the pattern; LPDs are always interictal", "A monitored trial of a nonsedating parenteral ASM, watching both the EEG and her examination", "Repeat MRI", "Lumbar puncture" ], "answer": 2, "explain": "Clear EEG and clinical improvement after a parenteral ASM would make this an electroclinical seizure and justify treatment. A nonsedating drug avoids confusing sedation with improvement." } ], "outro": [ "LPDs after a cortical stroke are common. Name them precisely, estimate risk, monitor long enough, and treat on the combination of EEG, examination and trial response rather than the pattern alone." ] }, { "type": "mcq", "id": "q-nnam9c", "stem": "Which pattern meets the ACNS 2021 criteria for the ictal–interictal continuum?", "options": [ "GRDA at 2 Hz with superimposed fast activity", "GPDs at 2 Hz without plus features", "LRDA at 1 Hz with superimposed sharp waves", "LPDs at 0.7 Hz without plus features or fluctuation", "LPDs at 3 Hz for 12 seconds" ], "answer": 1, "explain": "PDs averaging more than 1 and up to 2.5 Hz qualify on frequency alone. GRDA never qualifies; LRDA needs to be above 1 Hz; PDs at 0.5–1 Hz need a plus modifier or fluctuation; LPDs above 2.5 Hz for 10 seconds or more are an electrographic seizure." }, { "type": "cards", "items": [ { "id": "c-iu7ouw", "front": "IIC criterion 1", "back": "PDs or spike-and-wave averaging more than 1 and up to 2.5 Hz over 10 s." }, { "id": "c-jo6hxt", "front": "IIC criterion 2", "back": "PDs or spike-and-wave at 0.5–1 Hz with a plus modifier or fluctuation." }, { "id": "c-je6w8u", "front": "IIC criterion 3", "back": "Lateralized RDA above 1 Hz with a plus modifier or fluctuation." }, { "id": "c-qd6itz", "front": "Does GRDA qualify for the IIC?", "back": "Never." }, { "id": "c-1yihzir", "front": "BIRDs", "back": "Rhythmic activity over 4 Hz, at least six waves, 0.5 to under 10 s, not a variant or part of burst-suppression." }, { "id": "c-s37kwl", "front": "Heaviest 2HELPS2B item", "back": "BIRDs (2 points)." }, { "id": "c-199jqe6", "front": "2HELPS2B risk bands", "back": "0 about 5%; 1 12%; 2 27%; 3 50%; 4 73%; 5 88%; 6–7 over 95%." }, { "id": "c-1ywf6eb", "front": "Which rhythmic ICU pattern is not linked to seizures?", "back": "GRDA, including frontally predominant GRDA." }, { "id": "c-4w95fv", "front": "Frequency at which GPDs and LRDA start to carry seizure risk", "back": "1.5 Hz, or any frequency with a plus feature." }, { "id": "c-1awz1l4", "front": "LPDs and seizure risk by frequency", "back": "Associated with seizures at every frequency." }, { "id": "c-h7e63e", "front": "BIPDs and seizure risk", "back": "High, close to LPDs (45% versus 52%)." } ] } ], "sources": [ { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "2HELPS2B derivation (Struck 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29052706/" }, { "title": "Periodic and rhythmic patterns and seizure risk (Rodriguez Ruiz 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27992625/" }, { "title": "BIPDs, electrographic seizures and outcome (Osman 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30227348/" } ], "words": 973, "bank": 10 }, { "id": "coma-prognosis", "n": "3", "title": "Coma, cardiac arrest and prognosis", "tags": [ "acns-terminology", "seizure-management" ], "updated": false, "goals": [ "Grade encephalopathy on EEG", "interpret EEG after cardiac arrest within a multimodal framework", "avoid the confounders that make early prognosis wrong" ], "blocks": [ { "type": "h3", "text": "Encephalopathy on EEG" }, { "type": "p", "text": "As encephalopathy deepens, the EEG usually slows from theta to delta, loses reactivity and state changes, becomes discontinuous, and finally suppresses. GPDs with triphasic morphology and generalized rhythmic delta are common along the way. Sedatives, hypothermia and metabolic derangement do the same, which is why the background must be read with the drug chart and temperature in hand." }, { "type": "p", "text": "One grading scale used in ICU research scores the background in the patient's most awake state:" }, { "type": "table", "head": [ "Grade", "Background in the most awake state" ], "rows": [ [ "I, mild", "Posterior dominant rhythm in the alpha range, regular and reactive, with intermittent theta" ], [ "II, mild to moderate", "Mostly theta, often reactive, with or without alpha; intermittent delta" ], [ "III, moderate to moderately severe", "Widespread delta, reactive or not; or spindle coma" ], [ "IV, severe", "Burst-suppression; alpha, beta or theta coma; diffuse attenuation under 20 µV" ], [ "V", "Continuous suppression, with no definite activity over 2 µV" ] ] }, { "type": "p", "text": "Sleep architecture is not part of the grade but tracks it. Among delirious medical ICU patients, those without K-complexes or sleep spindles had more severe encephalopathy and higher odds of death. On routine EEG, the amount of generalized theta or delta slowing tracked delirium severity and predicted longer stays, worse function and higher mortality." }, { "type": "h3", "text": "After cardiac arrest" }, { "type": "p", "text": "EEG is one part of a multimodal assessment. European resuscitation and intensive care guidelines advise prognosticating no earlier than 72 hours after return of circulation, once sedation, hypothermia and metabolic confounders have been dealt with. Poor outcome is considered likely when at least two of these are present:" }, { "type": "li", "text": "no pupillary and corneal reflexes at 72 hours or later" }, { "type": "li", "text": "bilaterally absent N20 somatosensory evoked potentials at 24 hours or later" }, { "type": "li", "text": "a highly malignant EEG after 24 hours" }, { "type": "li", "text": "neuron-specific enolase above 60 µg/L at 48 and/or 72 hours" }, { "type": "li", "text": "status myoclonus within 72 hours" }, { "type": "li", "text": "diffuse, extensive anoxic injury on CT or MRI" }, { "type": "p", "text": "**Highly malignant** EEG patterns are a suppressed background with or without periodic discharges, and burst-suppression. **Identical bursts** after arrest are especially ominous. A continuous, reactive background is a favorable sign." }, { "type": "note", "label": "Try it", "text": "Measure voltage and time on real pages of focal attenuation, discontinuity, a suppressed background and burst suppression in [Continuity, attenuation and suppression](eeg-fundamentals.html#waveforms-continuity-attenuation)." }, { "type": "p", "text": "**Timing cuts both ways.** A favorable EEG is most informative early. In a five-center cohort of 850 comatose patients, a continuous background at 12 hours predicted good recovery with 91% specificity and 50% sensitivity; from 24 hours on, its specificity fell below 90%. Propofol lowered EEG amplitude, continuity and dominant frequency in the same program but did not change the chance of a favorable or unfavorable pattern, so the early EEG stays usable under the sedation of routine post-arrest care. European guidelines likewise count a benign EEG within 24 hours (continuous, reactive, not suppressed, without epileptiform discharges) as a sign of potential recovery. A poor prognosis has to wait: a highly malignant EEG counts only after 24 hours, and only as one predictor in the multimodal assessment at 72 hours or later." }, { "type": "p", "text": "**Rhythmic and periodic patterns.** Periodic discharges after arrest, including generalized periodic discharges (GPDs), are linked to poor outcome but with limited specificity, and the background beneath them matters more. On a suppressed background they are part of a highly malignant pattern; on a continuous, reactive background they should not be read as a sign of poor outcome. In an EEG substudy of the original Targeted Temperature Management trial, a single malignant feature, such as a rhythmic or periodic pattern, had only 48% specificity for poor outcome; two malignant features raised it to 96%. Suppressing these patterns does not help. In the TELSTAR trial, 172 comatose survivors with rhythmic or periodic patterns were randomized to stepwise antiseizure treatment for at least 48 hours or to standard care: poor outcome at 3 months was 90% versus 92%, and the treated group stayed slightly longer in intensive care. Guidelines suggest levetiracetam or valproate for clear post-arrest seizures." }, { "type": "p", "text": "**Self-fulfilling prophecy.** When the treating team knows a test result and uses it to decide on withdrawing life-sustaining treatment, patients predicted to do badly die whether or not they could have recovered, and the test looks more accurate than it is. A 2013 systematic review found 88% of prognostic studies after cardiac arrest at risk of this bias. The guideline safeguards answer it: wait at least 72 hours, exclude sedation, temperature and metabolic confounders, and require at least two concordant predictors, so that no single result decides." }, { "type": "p", "text": "**Temperature.** Routine cooling to 32–36 °C is no longer the standard after cardiac arrest. In the TTM2 trial (2021), 1900 comatose adults after out-of-hospital arrest did no better at 33 °C than with fever prevention alone, and European guidelines now recommend monitoring core temperature and preventing fever (above 37.7 °C) for at least 72 hours. The 2025 AHA guideline accepts a target anywhere from 32 to 37.5 °C for at least 36 hours. In a patient who is still cooled, hypothermia is one more confounder of the early EEG." }, { "type": "h3", "text": "Myoclonus after cardiac arrest" }, { "type": "p", "text": "Early myoclonus is common after arrest, and the EEG beneath it separates two very different groups. In a cohort of 401 comatose patients, 69 had early myoclonus:" }, { "type": "li", "text": "**Burst-suppression with high-amplitude polyspikes** in lockstep with the jerks (48 patients): none survived with a favorable outcome." }, { "type": "li", "text": "**A continuous background with narrow, vertex-maximal spike-and-wave** in lockstep with the jerks (8 patients): half survived, all with a favorable outcome, although they stayed comatose for 1 to 2 weeks." }, { "type": "p", "text": "European guidelines define status myoclonus as continuous, generalized myoclonus lasting 30 minutes or more, and count it only within 72 hours and alongside other predictors. They suggest an EEG in any patient with post-arrest myoclonus, to find epileptiform activity and to look for a continuous or reactive background that signals potential recovery. Generalized myoclonus with epileptiform discharges may be early Lance–Adams syndrome, which is compatible with awakening and a good outcome. In one registry, such patients had preserved brainstem reflexes, evoked potentials and a reactive EEG, and first showed awareness 3 to 23 days after the arrest. Myoclonus alone should not drive withdrawal of care." }, { "type": "p", "text": "**Lance–Adams syndrome** proper is chronic post-hypoxic myoclonus: multifocal action and intention myoclonus of cortical origin that appears days to weeks after the hypoxic event, once the patient has regained consciousness, often with dysarthria and ataxia. It is disabling and usually persists. Treatment targets cortical myoclonus with antiseizure medications: levetiracetam, valproate or clonazepam, alone or in combination." }, { "type": "mcq", "id": "q-50mnv0", "stem": "A patient is comatose 36 hours after cardiac arrest, off sedation and normothermic, with frequent jerks of the face and arms. Which EEG finding beneath the jerks most argues for continuing full care?", "options": [ "Burst-suppression with high-amplitude polyspikes time-locked to each jerk", "A suppressed background with generalized periodic discharges", "Burst-suppression with identical bursts", "A continuous, reactive background with narrow vertex spike-and-wave time-locked to each jerk", "A suppressed, unreactive background with no discharges" ], "answer": 3, "explain": "A continuous background with narrow vertex-maximal spike-and-wave in lockstep with the jerks is the phenotype in which survivors recovered well, and it may herald Lance–Adams syndrome. The other four are highly malignant patterns." }, { "type": "h3", "text": "Classic coma patterns" }, { "type": "table", "head": [ "Pattern", "Meaning" ], "rows": [ [ "Burst-suppression", "Deep anesthesia, hypothermia, or severe anoxic injury; identical, highly epileptiform bursts after arrest are malignant" ], [ "Alpha coma", "Diffuse, nonreactive alpha-frequency activity, most often after cardiac arrest or a brainstem (pontine) stroke; then usually a poor sign" ], [ "Spindle coma", "Sleep-like spindles in coma; often trauma or brainstem lesions, with a better outlook than alpha coma" ], [ "Beta coma", "Diffuse, frontally predominant beta activity in coma: the typical pattern of sedative-hypnotic (barbiturate or benzodiazepine) intoxication; reversible when the drug clears if there was no hypoxia" ], [ "Electrocerebral inactivity", "No cerebral activity over 2 µV with the technical protocol met" ], [ "Posterior alpha rhythm that blocks with eye opening and reacts to sound or light, in an apparently comatose patient", "Not alpha coma: consider locked-in syndrome or functional (psychogenic) unresponsiveness" ] ] }, { "type": "p", "text": "**Cause and reactivity, not the pattern's name, set the prognosis.** In a meta-analysis of 335 published cases of alpha coma, 76% died overall and 88% after cardiorespiratory arrest, but only 8% of the 25 drug-induced cases. In the same study's own patients, EEG reactivity predicted survival: most with a reactive record woke up, and most without died. Beta coma behaves like drug-induced alpha coma: in a small series of sedative intoxications without hypoxia, patients in alpha or beta coma all recovered fully once the drug was withdrawn. In comatose children, alpha, spindle, theta and beta coma patterns shared similar causes and outcomes, and reactive records tended to do better. Read any rhythmic coma pattern with the cause and the reactivity in hand." }, { "type": "p", "text": "**When the EEG looks awake.** A wakeful EEG in a patient who seems comatose should raise two diagnoses before alpha coma. **Locked-in syndrome**, most often from an acute ventral pontine lesion, leaves awareness and vertical eye and eyelid movements intact: ask the patient to look up or to blink. In 23 EEGs from 8 patients, the record was normal or minimally slow in all but one patient and always reactive. **Functional (psychogenic) unresponsiveness** is an involuntary coma-like state without structural or metabolic brain damage; resistance to passive eye opening is a bedside clue, and laboratory tests, imaging and EEG are unremarkable. The reverse mismatch matters too: a flat EEG says nothing about the brainstem, which is why EEG is no longer an ancillary test for brain death (see Recording technique in the EEG basics part)." }, { "type": "case", "id": "case-cardiac-arrest", "title": "Unresponsive after cardiac arrest", "intro": [ "A 58-year-old is resuscitated after 25 minutes of out-of-hospital arrest with a non-shockable rhythm. He is sedated with propofol, and fever is actively prevented." ], "steps": [ { "narrative": [ "At 12 hours the EEG shows burst-suppression with long flat periods." ], "stem": "What is the correct interpretation at this point?", "options": [ "Prognosis is poor; discuss withdrawal of care today", "Burst-suppression at 12 hours on propofol is not interpretable in isolation; reassess after confounders clear", "He is brain dead", "Start a pentobarbital infusion", "Fever prevention explains the EEG, so no follow-up is needed" ], "answer": 1, "explain": "Propofol can itself cause burst-suppression, as can hypothermia in a patient who is still cooled. Guidelines place EEG within multimodal assessment no earlier than 72 hours after return of circulation, and a highly malignant EEG counts only after 24 hours." }, { "narrative": [ "At 80 hours, off sedation and normothermic, he has absent pupillary and corneal reflexes, bilaterally absent N20 responses, and an EEG with a suppressed background and no reactivity." ], "stem": "How should these findings be weighed?", "options": [ "Each alone is enough to predict poor outcome", "Several concordant predictors make a poor neurological outcome very likely", "They cannot be interpreted until day 14", "The EEG outweighs the other findings", "Obtain a Wada test" ], "answer": 1, "explain": "Poor outcome is considered likely when at least two robust predictors agree after 72 hours with confounders excluded. Here the examination, SSEPs and EEG agree." } ], "outro": [ "Multimodal, delayed and confounder-free: that is the framework. A single early EEG under sedation should never drive a prognosis on its own." ] }, { "type": "mcq", "id": "q-1gcaoer", "stem": "Which EEG finding after cardiac arrest is a favorable prognostic sign?", "options": [ "Burst-suppression with identical bursts at 36 hours", "Suppressed background with periodic discharges at 48 hours", "A continuous background that reacts to stimulation", "Alpha coma that does not react to stimulation", "Electrocerebral inactivity at 72 hours" ], "answer": 2, "explain": "A continuous, reactive background early after arrest is associated with good recovery. The other patterns are malignant or highly malignant." }, { "type": "cards", "items": [ { "id": "c-1o3csw6", "front": "Earliest multimodal prognosis after cardiac arrest", "back": "72 hours after return of circulation, with confounders excluded." }, { "id": "c-1a13gtz", "front": "Highly malignant EEG after arrest", "back": "Suppressed background with or without periodic discharges, or burst-suppression." }, { "id": "c-158qmne", "front": "Identical bursts after arrest", "back": "A particularly malignant pattern." }, { "id": "c-v2rcff", "front": "Favorable EEG after arrest", "back": "Continuous, reactive background." }, { "id": "c-1ahf1jf", "front": "Temperature after cardiac arrest", "back": "Prevent fever (above 37.7 °C) for at least 72 hours; routine cooling to 32–36 °C is no longer the standard." }, { "id": "c-1bhxrtd", "front": "NSE threshold in prognosis guidance", "back": "Above 60 µg/L at 48 and/or 72 hours." }, { "id": "c-1b1aj3b", "front": "Alpha coma after anoxia", "back": "Diffuse nonreactive alpha activity; usually poor prognosis." }, { "id": "c-gr2nbc", "front": "Spindle coma", "back": "Often trauma or brainstem lesions; better outlook than alpha coma." }, { "id": "c-yb67y3", "front": "Mild encephalopathy on EEG (grade I)", "back": "A regular, reactive alpha-range posterior dominant rhythm with intermittent theta." }, { "id": "c-1g8dxa3", "front": "Severe encephalopathy on EEG (grade IV)", "back": "Burst-suppression; alpha, beta or theta coma; or diffuse attenuation under 20 µV." }, { "id": "c-tmoddi", "front": "Favorable EEG after arrest: when is it most informative?", "back": "Early. A continuous background at 12 hours had 91% specificity for good outcome, less from 24 hours." }, { "id": "c-1h4b1b6", "front": "TELSTAR", "back": "Suppressing rhythmic and periodic EEG patterns after cardiac arrest for at least 48 hours did not improve 3-month outcome (90% versus 92% poor)." }, { "id": "c-1fg16o2", "front": "Periodic discharges after arrest on a continuous, reactive background", "back": "Not a sign of poor outcome by themselves." }, { "id": "c-z2crx6", "front": "Two EEG phenotypes of early post-arrest myoclonus", "back": "Burst-suppression with high-amplitude polyspikes (no favorable outcomes) versus a continuous background with narrow vertex spike-and-wave (half survived, all well)." }, { "id": "c-19ddvvd", "front": "Status myoclonus (ERC–ESICM)", "back": "Continuous, generalized myoclonus lasting 30 minutes or more." }, { "id": "c-16sb1gu", "front": "Lance–Adams syndrome", "back": "Chronic cortical action myoclonus after hypoxia in a patient who has woken; treat with levetiracetam, valproate or clonazepam." }, { "id": "c-74jami", "front": "Self-fulfilling prophecy", "back": "Withdrawing care because a test predicts a poor outcome makes that test look falsely accurate." }, { "id": "c-1dwt2ym", "front": "Alpha coma mortality by cause", "back": "About 88% after cardiorespiratory arrest; 8% when drug induced." }, { "id": "c-1vq008d", "front": "Beta coma", "back": "Diffuse beta in coma from sedative-hypnotic intoxication; usually reversible without hypoxia." }, { "id": "c-87eofj", "front": "Reactive posterior alpha rhythm in apparent coma", "back": "Consider locked-in syndrome (test vertical gaze and blinking) or functional unresponsiveness." } ] } ], "sources": [ { "title": "ERC–ESICM post-resuscitation care guidelines (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41123621/" }, { "title": "ERC–ESICM post-resuscitation care guidelines (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33765189/" }, { "title": "ERC–ESICM guidelines on temperature control after cardiac arrest (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35089409/" }, { "title": "Hypothermia versus normothermia after out-of-hospital cardiac arrest: TTM2 (Dankiewicz 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34133859/" }, { "title": "AHA 2025 guidelines: post-cardiac arrest care", "url": "https://pubmed.ncbi.nlm.nih.gov/41122894/" }, { "title": "Standardized EEG after cardiac arrest (Westhall 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26865516/" }, { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "Loss of N2 sleep features and EEG grade of encephalopathy in ICU delirium (Knauert 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30179762/" }, { "title": "EEG slowing and delirium severity (Kimchi 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31467255/" }, { "title": "Early EEG for outcome prediction of postanoxic coma (Ruijter 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31155751/" }, { "title": "Propofol and early EEG after cardiac arrest (Ruijter 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31163372/" }, { "title": "Treating rhythmic and periodic EEG patterns after cardiac arrest: TELSTAR (Ruijter 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35196426/" }, { "title": "EEG phenotypes of early myoclonus after cardiac arrest (Elmer 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27351833/" }, { "title": "Early Lance–Adams syndrome after cardiac arrest (Aicua Rapun 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28342959/" }, { "title": "Post-hypoxic myoclonus: concepts, neurophysiology and treatment (Gupta 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27708982/" }, { "title": "Withdrawal of life-sustaining therapies after cardiac arrest (Tam 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40762583/" }, { "title": "Etiology and prognosis in alpha coma (Kaplan 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10210610/" }, { "title": "Alpha and beta coma in drug intoxication (Carroll 1979)", "url": "https://pubmed.ncbi.nlm.nih.gov/88336/" }, { "title": "EEG assessment of coma (Husain 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16751721/" }, { "title": "Rhythmic coma patterns in children (RamachandranNair 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16408585/" }, { "title": "EEG in locked-in syndrome (Markand 1976)", "url": "https://pubmed.ncbi.nlm.nih.gov/57041/" }, { "title": "Locked-in syndrome revisited (Schnetzer 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37006459/" }, { "title": "Locked-in syndrome (Laureys 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16186044/" }, { "title": "Functional coma: cases and review (Ryznar 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31053419/" }, { "title": "Pediatric and adult brain death consensus guideline (Greer 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37821233/" } ], "words": 2109, "bank": 10 }, { "id": "periodic-by-cause", "n": "4", "title": "Periodic patterns by cause", "tags": [ "acns-terminology", "ilae-classification" ], "updated": false, "goals": [ "Link characteristic periodic patterns to their causes", "recognize drug-induced encephalopathies that mimic status", "know when a periodic pattern should change the work-up" ], "blocks": [ { "type": "table", "head": [ "Pattern", "Typical period", "Think of" ], "rows": [ [ "Temporal LPDs with fever and confusion", "About 1–2 s", "Herpes simplex encephalitis; start acyclovir while waiting for PCR" ], [ "Generalized periodic sharp waves, often with startle myoclonus", "About 0.5–2 s", "Sporadic Creutzfeldt–Jakob disease; they appear as the illness progresses and fade late and in sleep" ], [ "Very high-amplitude stereotyped complexes with time-locked myoclonus", "Every 4–15 s", "Subacute sclerosing panencephalitis" ], [ "Periodic long-interval diffuse discharges (PLIDDs), the category the SSPE complexes belong to", "Long, as in SSPE", "Subacute sclerosing panencephalitis (SSPE); also reported with phencyclidine intoxication and trypanosomiasis. Contrast the short-interval diffuse discharges of Creutzfeldt–Jakob disease" ], [ "GPDs with triphasic morphology and anterior–posterior lag", "About 1–2 Hz", "Hepatic, renal or septic encephalopathy; lithium, baclofen, cefepime (especially in renal failure)" ], [ "Extreme delta brush", "Continuous rhythmic delta with superimposed beta", "Anti-NMDA receptor encephalitis" ], [ "LPDs after an acute lesion", "Variable", "Stroke, tumor, abscess, trauma" ] ] }, { "type": "note", "label": "Try it", "text": "Compare lateralized and generalized periodic discharges with focal slowing on real pages in [Slowing and periodic patterns](eeg-fundamentals.html#waveforms-pathology-showcase)." }, { "type": "h3", "text": "Triphasic morphology: metabolic or ictal?" }, { "type": "p", "text": "ACNS 2021 defines **triphasic morphology** strictly: three phases, negative–positive–negative, each longer than the one before, with the second (positive) phase the largest. If the first negative phase is too small to see, a positive–negative biphasic wave still qualifies. A discharge whose largest phase is negative is not triphasic. An **anterior–posterior lag** is a consistent delay of more than 100 ms from the most anterior to the most posterior channel showing the discharge." }, { "type": "p", "text": "The label tells you little. In a blinded study, 11 experts agreed only fairly on which generalized periodic discharges (GPDs) were triphasic (kappa 0.33). Patients whose GPDs were called triphasic had seizures as often as those with other GPDs (25% versus 26%) and were less, not more, likely to have a toxic-metabolic encephalopathy (55% versus 79%)." }, { "type": "p", "text": "GPDs with triphasic morphology used to be read as metabolic by default. Features that favor a toxic-metabolic cause are frontal predominance, an anterior-to-posterior lag, a slower rate, and reactivity to stimulation. None is decisive. Clinical and EEG improvement after a benzodiazepine suggests nonconvulsive status, but benzodiazepines also dampen metabolic patterns and sedate the patient, so EEG improvement alone proves little. Cefepime neurotoxicity in renal failure can produce frank nonconvulsive status." }, { "type": "p", "text": "**Cefepime.** Cefepime crosses the blood–brain barrier and antagonizes GABA in a concentration-dependent way. That fits its picture of depressed consciousness, myoclonus, triphasic GPDs and nonconvulsive status epilepticus (NCSE), and explains why toxicity tracks drug levels: in a systematic review of 135 cases, 80% had renal dysfunction and 48% had been overdosed, although 26% became toxic on appropriate doses. A quarter of those with an EEG had NCSE. Symptoms resolved a median of 2 days after the drug was stopped, an antiseizure medication was given, or the patient was dialyzed." }, { "type": "h3", "text": "Drug effects to recognize" }, { "type": "li", "text": "Benzodiazepines and barbiturates: excess beta." }, { "type": "li", "text": "Anesthetics (propofol, barbiturates) and hypothermia: slowing, then burst-suppression." }, { "type": "li", "text": "Clozapine, lithium, and high-dose baclofen can produce generalized discharges and myoclonus." }, { "type": "li", "text": "Ifosfamide, a chemotherapy drug for sarcoma, lymphoma and other tumors, causes an encephalopathy, usually from 12 hours to 6 days after starting high-dose treatment, attributed to its metabolite chloroacetaldehyde. In the largest EEG series (16 patients), GPDs, often triphasic, were the commonest finding; a distinctive pattern of GPDs separated by 2–4-second stretches of background attenuation appeared in 5. Background slowing and intermittent rhythmic delta were also seen, and only one patient had NCSE. Six patients had orofacial myoclonus (grimacing, chewing, eye opening and closing) with no EEG correlate. Stop or slow the drug and give supportive care; methylene blue and thiamine are used, with varying efficacy. Symptoms usually improve within 48–72 hours of stopping the drug, but 5 of the 16 died." }, { "type": "mcq", "id": "q-1cq7dgi", "stem": "A 66-year-old with end-stage renal disease is started on cefepime for pneumonia. Two days later she is confused with multifocal myoclonus. EEG shows continuous generalized periodic discharges with triphasic morphology at 2 Hz. What is the most appropriate step?", "options": [ "Attribute it to uremia and observe", "Recognize possible cefepime neurotoxicity: stop or change the antibiotic, consider dialysis, and consider a monitored benzodiazepine or ASM trial", "Start a propofol infusion to burst-suppression", "Diagnose Creutzfeldt–Jakob disease", "Order an MRI and wait for the result before any change" ], "answer": 1, "explain": "Cefepime accumulates in renal failure and can cause encephalopathy with triphasic GPDs and nonconvulsive status. Removing the drug (and dialysis) is the key step; a monitored trial helps decide whether seizures are present." }, { "type": "mcq", "id": "q-rcwl2", "stem": "A 62-year-old has three months of rapidly progressive dementia, ataxia and startle-sensitive myoclonus. EEG shows generalized periodic sharp waves about once a second. What is the most likely diagnosis?", "options": [ "Subacute sclerosing panencephalitis", "Sporadic Creutzfeldt–Jakob disease", "Herpes simplex encephalitis", "Hepatic encephalopathy", "Anti-NMDA receptor encephalitis" ], "answer": 1, "explain": "Roughly 1-Hz generalized periodic sharp waves with rapidly progressive dementia and myoclonus is the classic picture of sporadic CJD. SSPE complexes recur every 4–15 seconds." }, { "type": "match", "id": "match-periodic", "prompt": "Match each pattern to its most likely cause", "pairs": [ [ "Temporal LPDs with fever and aphasia", "Herpes simplex encephalitis" ], [ "Generalized periodic sharp waves about 1 Hz with rapid dementia", "Sporadic Creutzfeldt–Jakob disease" ], [ "Complexes every 4–15 seconds with time-locked jerks", "Subacute sclerosing panencephalitis" ], [ "Extreme delta brush", "Anti-NMDA receptor encephalitis" ], [ "Triphasic GPDs after an antibiotic in renal failure", "Cefepime neurotoxicity" ] ] }, { "type": "cards", "items": [ { "id": "c-1r4soy6", "front": "HSV encephalitis EEG", "back": "Temporal LPDs, often about 1–2 s apart." }, { "id": "c-dzcjeu", "front": "Sporadic CJD EEG", "back": "Generalized periodic sharp waves about 0.5–2 s apart, appearing as the disease progresses." }, { "id": "c-9rrkgn", "front": "SSPE EEG", "back": "High-amplitude stereotyped complexes every 4–15 s with time-locked myoclonus." }, { "id": "c-1b6p9sx", "front": "Extreme delta brush", "back": "Anti-NMDA receptor encephalitis." }, { "id": "c-1e9fdqg", "front": "Features favoring a metabolic triphasic pattern", "back": "Frontal predominance, anterior–posterior lag, slower rate, reactivity." }, { "id": "c-lzdd37", "front": "Cefepime neurotoxicity", "back": "Encephalopathy, myoclonus, triphasic GPDs or NCSE, mostly in renal failure." }, { "id": "c-qask9z", "front": "Mechanism of cefepime neurotoxicity", "back": "Concentration-dependent GABA antagonism; reversed by stopping the drug or dialysis." }, { "id": "c-dsh71d", "front": "Triphasic morphology (ACNS 2021)", "back": "Negative–positive–negative, each phase longer than the last, the positive phase the largest." }, { "id": "c-jz7c9z", "front": "Discharge whose largest phase is negative", "back": "Not triphasic morphology." }, { "id": "c-1hz8ih4", "front": "Do triphasic GPDs mean a metabolic cause and low seizure risk?", "back": "No. Blinded raters agreed poorly, and seizure risk matched other GPDs (25% versus 26%)." }, { "id": "c-1798iqf", "front": "Periodic long-interval diffuse discharges", "back": "The category of SSPE complexes; also phencyclidine intoxication and trypanosomiasis." }, { "id": "c-nhg3zc", "front": "Ifosfamide encephalopathy EEG", "back": "GPDs, often triphasic, sometimes with 2–4 s stretches of attenuation; orofacial myoclonus." } ] } ], "sources": [ { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "Periodic and rhythmic patterns and seizure risk (Rodriguez Ruiz 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27992625/" }, { "title": "Autoimmune-associated seizures and epilepsy, ILAE (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32544279/" }, { "title": "GPDs and \"triphasic waves\": a blinded evaluation (Foreman 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26294138/" }, { "title": "Cefepime-induced neurotoxicity: a systematic review (Payne 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29137682/" }, { "title": "Clinical and EEG characteristics of ifosfamide-related encephalopathy (Gusdon 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30694943/" }, { "title": "Periodic EEG patterns: classification (Brenner 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2187023/" }, { "title": "Pseudoperiodic and paroxysmal EEG activities (Dunand 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11915484/" } ], "words": 1004, "bank": 7 }, { "id": "qeeg-trends", "n": "5", "title": "Quantitative EEG trends", "tags": [ "acns-terminology", "seizure-management" ], "updated": true, "goals": [ "Explain what the common qEEG trends compute", "use trends to find events and confirm them on the raw EEG", "recognize the alpha/delta ratio warning after subarachnoid hemorrhage" ], "blocks": [ { "type": "h3", "text": "What trends are for" }, { "type": "p", "text": "Quantitative EEG (qEEG) compresses hours of recording into displays of power, rhythmicity, amplitude and symmetry over time. Trends show where to look; they do not replace reading the raw EEG. Spectrogram-guided review cut the time to review 24 hours of EEG from 38 to 8 minutes, with 87% sensitivity for seizures. But when experts read trends without the raw EEG, they missed about a third of seizures and raised false alarms at about one an hour. An automated seizure detector found only about a quarter of seizures." }, { "type": "h3", "text": "The common trends" }, { "type": "li", "text": "**Power spectrogram (CDSA)**: time across, frequency up, power as color. Seizures often appear as a flame, an abrupt rise in power with smooth edges." }, { "type": "li", "text": "**Rhythmicity spectrogram**: power belonging to rhythmic activity only; seizures show a band that drifts in frequency." }, { "type": "li", "text": "**Amplitude-integrated EEG**: upper and lower amplitude margins on a semi-logarithmic scale. The lower margin rises in seizures and falls toward zero in burst suppression." }, { "type": "li", "text": "**Suppression percentage**: the share of each epoch below a low voltage threshold, high in burst suppression." }, { "type": "li", "text": "**Asymmetry spectrogram**: the difference between the hemispheres at each frequency." }, { "type": "li", "text": "**Alpha/delta ratio (ADR) and relative alpha variability**: trended over days after subarachnoid hemorrhage." }, { "type": "figure", "html": "qeeg-trends", "caption": "Each trend in turn, drawn as a teaching sketch by the same models as the Persyst trend lab, not from a recording. Choose a trend to see what it plots and what the sketch shows.", "n": 11 }, { "type": "h3", "text": "Naming spectrogram patterns" }, { "type": "p", "text": "A shared vocabulary helps a team describe a spectrogram before anyone opens the raw EEG. A **solid flame** (an abrupt rise in power with smooth edges) is the most recognizable seizure pattern. **Choppy flames** are irregular and less stereotyped, and usually reflect changes of state rather than seizures. **Broadband monotonous** power spans more than 5 Hz without change and corresponds to long, unchanging status epilepticus or periodic discharges; **narrowband monotonous** power stays below 5 Hz and is typical of encephalopathy. **Stripes** are bursts of power alternating with suppression, and a **suppressed** spectrogram is low power throughout. Artifact appears suddenly and lacks the evolution of a seizure." }, { "type": "figure", "html": "qeeg-patterns", "caption": "The pattern names, each drawn as a small power spectrogram (time across, frequency up, power as color). Teaching sketches from the trend lab's models; each name points to what the raw EEG usually shows, never to a diagnosis on its own.", "n": 12 }, { "type": "h3", "text": "Pitfalls" }, { "type": "p", "text": "Slow, low-amplitude and very focal seizures, and seizures on a background of periodic discharges, are the ones trends miss. Chewing, patting and ventilator artifact add power and rhythmicity. A single bad electrode makes a false asymmetry." }, { "type": "p", "updated": true, "label": "ADR after subarachnoid hemorrhage", "text": "In poor-grade subarachnoid hemorrhage, a post-stimulation ADR that falls by more than 10% from baseline for six consecutive readings, or by more than 50% in any single reading, was associated with delayed cerebral ischemia. In a prospective study, prespecified EEG alarms (falling alpha variability, falling ADR, worsening focal slowing, new epileptiform abnormalities) preceded DCI by a median of about two days." }, { "type": "note", "label": "Try it", "text": "Read six ICU panels, and check the raw EEG under each finding, in the [Persyst trend lab](natus_instructions.html#pq-lab-section)." }, { "type": "mcq", "id": "q-ni4vk2", "stem": "A seizure detector alarms twice an hour in a ventilated patient. The spectrogram shows brief vertical bands of power, mostly above 15 Hz, on both sides at once, with abrupt onset and offset. What is the next step?", "options": [ "Load an antiseizure medication", "Review the raw EEG at each alarm; this pattern suggests muscle or movement artifact", "Increase the detector sensitivity", "Order an MRI", "Ignore all further alarms" ], "answer": 1, "explain": "Seizures build and evolve; artifact starts and stops abruptly and fills the fast frequencies on both sides. Every alarm needs the raw EEG before anyone acts on it." }, { "type": "mcq", "id": "q-jmj2yn", "stem": "On day 5 after a poor-grade subarachnoid hemorrhage, the right-sided post-stimulation alpha/delta ratio has fallen by 55% from baseline over 12 hours, and the left is unchanged. What does this suggest?", "options": [ "Right hemisphere seizures", "Normal day-to-night variation", "Possible delayed cerebral ischemia in the right hemisphere", "A disconnected electrode on the left", "Deepening sedation" ], "answer": 2, "explain": "A regional fall of more than 50% in the post-stimulation ADR is associated with delayed cerebral ischemia. It should prompt urgent clinical review and vascular assessment. Sedation would lower the ADR on both sides." }, { "type": "cards", "items": [ { "id": "c-138c6ta", "front": "Solid flame on a spectrogram", "back": "An abrupt rise in power with smooth edges; the typical seizure signature." }, { "id": "c-1bit9ew", "front": "Stripes on a spectrogram", "back": "Alternating power and suppression: burst suppression." }, { "id": "c-1li6xgk", "front": "Broadband monotonous spectrogram", "back": "Sustained high power across a wide band: ongoing status or continuous periodic discharges." }, { "id": "c-i4h9c9", "front": "Clue that a spectrogram event is artifact", "back": "Abrupt onset and offset, fast frequencies, both sides at once, no evolution." }, { "id": "c-1tudwif", "front": "aEEG in burst suppression", "back": "The lower margin falls toward zero." }, { "id": "c-1paqbyt", "front": "ADR thresholds for DCI", "back": "A fall of more than 10% for six consecutive readings, or more than 50% in any single reading." }, { "id": "c-11zwtaw", "front": "Sensitivity of an automated seizure detector in the ICU", "back": "About 26% in one multi-reader study; always read the raw EEG." } ] } ], "sources": [ { "title": "Spectrogram screening of adult EEGs (Moura 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24857926/" }, { "title": "Sensitivity of qEEG for seizure identification in the ICU (Haider 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27466474/" }, { "title": "qEEG panels read by non-neurophysiologists (Swisher 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26241242/" }, { "title": "ADR and delayed cerebral ischemia (Claassen 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15546778/" }, { "title": "cEEG predicts delayed cerebral ischemia (Rosenthal 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29659050/" }, { "title": "qEEG in the ICU with Persyst (Veciana de las Heras 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39335433/" } ], "words": 799, "bank": 6 } ], "intro": [ "Continuous EEG in the ICU finds seizures that nobody can see, and it produces patterns that are neither clearly seizures nor clearly safe. This part covers the ACNS vocabulary, the criteria that decide what to treat, and what the EEG says about prognosis." ] }, { "id": "diagnosis", "n": "5", "title": "Diagnosis and classification", "short": "Diagnosis", "sections": [ { "id": "definitions", "n": "1", "title": "Definitions that change management", "tags": [ "ilae-classification", "seizure-management" ], "updated": false, "goals": [ "Apply the ILAE 2014 practical definition of epilepsy", "separate acute symptomatic from unprovoked seizures", "define resolved and drug-resistant epilepsy" ], "blocks": [ { "type": "h3", "text": "Epilepsy (ILAE 2014)" }, { "type": "p", "text": "Epilepsy is present when any of these apply:" }, { "type": "li", "text": "at least two unprovoked (or reflex) seizures occurring more than 24 hours apart" }, { "type": "li", "text": "one unprovoked (or reflex) seizure with a probability of further seizures similar to the recurrence risk after two, at least 60% over the next 10 years" }, { "type": "li", "text": "a diagnosis of an epilepsy syndrome" }, { "type": "p", "text": "The middle criterion is where judgment comes in. A remote structural cause (an old stroke or injury) together with epileptiform discharges usually puts the risk high enough. The 60% figure was chosen to match the risk of a further seizure after two unprovoked seizures, which is far higher than after one (the numbers are under [The first seizure](#first-seizure))." }, { "type": "h3", "text": "Acute symptomatic (provoked) seizures" }, { "type": "p", "text": "A seizure in close time relation to an acute brain insult is **acute symptomatic**, not epilepsy, however many occur. Working time windows:" }, { "type": "li", "text": "within a week of stroke, traumatic brain injury, anoxia or intracranial surgery" }, { "type": "li", "text": "during the active phase of CNS infection or autoimmune inflammation" }, { "type": "li", "text": "within 24 hours of a severe metabolic derangement, for example glucose under 36 mg/dL (2.0 mmol/L), sodium under 115 mmol/L, calcium under 5 mg/dL, or magnesium under 0.8 mg/dL" }, { "type": "li", "text": "alcohol withdrawal, typically 7–48 hours after the last drink, and drug intoxication or withdrawal" }, { "type": "p", "text": "Drugs are a common cause. In a poison-center series of drug-related seizures, bupropion led, followed by diphenhydramine, tricyclic antidepressants, tramadol, amphetamines, isoniazid and venlafaxine. Theophylline toxicity causes seizures and arrhythmias and is more often fatal after chronic overmedication than after a single overdose. Among the carbapenem antibiotics, imipenem carries the clearest excess seizure risk. Isoniazid overdose calls for intravenous pyridoxine (vitamin B6), given gram for gram with the amount taken." }, { "type": "p", "text": "Seizures after the acute period (a late seizure a year after a stroke, for example) are **unprovoked**, and a single one carries a high recurrence risk. The difference is large. In a population study of stroke, traumatic brain injury and brain infection, people whose first seizure was acute symptomatic had a higher 30-day mortality but were 80% less likely over 10 years to have a later unprovoked seizure than people whose first seizure was remote symptomatic from the same causes. That is why acute symptomatic seizures are not epilepsy and do not, by themselves, call for long-term antiseizure medication (ASM)." }, { "type": "h3", "text": "Resolved" }, { "type": "p", "text": "Epilepsy is considered resolved when someone with an age-dependent syndrome is past the applicable age, or has been seizure-free for 10 years with the last 5 off ASMs. \"Resolved\" was chosen over \"cured\" because the underlying tendency may persist." }, { "type": "h3", "text": "Drug-resistant epilepsy (ILAE 2010)" }, { "type": "p", "text": "Failure of adequate trials of two tolerated, appropriately chosen and appropriately used ASM schedules, as monotherapy or in combination, to achieve sustained seizure freedom. Sustained means 12 months, or three times the longest pre-treatment interval between seizures, whichever is longer. A drug stopped early for side effects, used at a low dose, or not taken does not count as a failed trial." }, { "type": "note", "label": "Try it", "text": "The [drug-resistant epilepsy pathway](seizure_management.html#refractory-epilepsy) on the Seizure Management page follows this definition through referral and the presurgical evaluation." }, { "type": "calc", "name": "definition-check" }, { "type": "mcq", "id": "q-92ulmp", "stem": "A 58-year-old had a left MCA stroke two years ago. She now has a first unprovoked focal seizure with impaired consciousness, and her EEG shows left temporal sharp waves. Which statement best reflects the ILAE 2014 definition?", "options": [ "She cannot have epilepsy until a second seizure occurs", "She can be diagnosed with epilepsy after one seizure, because her recurrence risk is at least 60%", "This is an acute symptomatic seizure", "Epilepsy requires an MRI lesion that has grown", "The diagnosis depends on whether she is treated" ], "answer": 1, "explain": "One unprovoked seizure with a recurrence risk of at least 60% over 10 years meets the practical definition. A remote stroke plus epileptiform discharges is the typical example. Two years after the stroke, the seizure is not acute symptomatic." }, { "type": "mcq", "id": "q-1rjb2mt", "stem": "A 45-year-old has had three generalized convulsions, each within 36 hours of stopping heavy drinking. Between these episodes he is well. What is the correct classification?", "options": [ "Epilepsy, because he has had more than two seizures", "Acute symptomatic seizures related to alcohol withdrawal", "Juvenile myoclonic epilepsy", "Drug-resistant epilepsy", "Reflex epilepsy" ], "answer": 1, "explain": "Seizures within the withdrawal window are provoked. Their number does not make them epilepsy; management is withdrawal treatment and abstinence support, not long-term ASMs." }, { "type": "mcq", "id": "q-v9cmld", "stem": "Which patient meets the ILAE definition of drug-resistant epilepsy?", "options": [ "Failed levetiracetam at 250 mg twice daily and lamotrigine stopped after a rash on day 10", "Seizures continue on carbamazepine; he admits taking it only occasionally", "Seizures continue after adequate, tolerated trials of lamotrigine and then levetiracetam at therapeutic doses", "Seizure-free for 18 months on the second drug", "Absence seizures continue on carbamazepine and phenytoin" ], "answer": 2, "explain": "Drug resistance requires two appropriate, tolerated, adequately used trials. Low doses, early withdrawal for side effects and non-adherence do not count, and carbamazepine and phenytoin are not appropriate for absence seizures." }, { "type": "cards", "items": [ { "id": "c-86047f", "front": "ILAE 2014: epilepsy after one seizure", "back": "One unprovoked seizure with a recurrence risk of at least 60% over 10 years." }, { "id": "c-b0c0ra", "front": "Resolved epilepsy", "back": "Past the age of an age-dependent syndrome, or seizure-free 10 years with the last 5 off ASMs." }, { "id": "c-3gs9ji", "front": "Drug-resistant epilepsy", "back": "Failure of two tolerated, appropriate, adequately used ASM trials to give sustained seizure freedom." }, { "id": "c-q3ihry", "front": "Sustained seizure freedom", "back": "12 months, or three times the longest pre-treatment interseizure interval, whichever is longer." }, { "id": "c-18iqxst", "front": "Acute symptomatic window after stroke or head injury", "back": "Within one week." }, { "id": "c-1jjwtfd", "front": "Alcohol withdrawal seizure window", "back": "Typically 7–48 hours after the last drink." }, { "id": "c-13k1bwu", "front": "Are reflex seizures provoked?", "back": "Yes, by a specific stimulus, but unlike acute symptomatic seizures they count toward epilepsy: the ILAE 2014 definition says \"unprovoked (or reflex)\" seizures." }, { "id": "c-148p4we", "front": "Later unprovoked seizures after a first acute symptomatic seizure", "back": "About 80% less likely than after a first remote symptomatic seizure from the same cause (stroke, head injury, brain infection)." }, { "id": "c-cro4yv", "front": "Leading drug causes of seizures in poison-center data", "back": "Bupropion, then diphenhydramine, tricyclic antidepressants, tramadol, amphetamines, isoniazid and venlafaxine." }, { "id": "c-17mdok2", "front": "Antidote for isoniazid seizures", "back": "Intravenous pyridoxine (vitamin B6), gram for gram with the isoniazid taken." }, { "id": "c-juuks", "front": "Carbapenem most clearly linked to seizures", "back": "Imipenem." } ] } ], "sources": [ { "title": "ILAE practical clinical definition of epilepsy (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24730690/" }, { "title": "ILAE definition of drug-resistant epilepsy (2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19889013/" }, { "title": "ILAE definition of acute symptomatic seizures (2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19732133/" }, { "title": "Is a first acute symptomatic seizure epilepsy? (Hesdorffer 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19374657/" }, { "title": "Drug-induced seizures reported to a poison control system (Thundiyil 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/18072153/" }, { "title": "Life-threatening events after theophylline overdose (Shannon 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10326941/" }, { "title": "The risk of seizures among the carbapenems: a meta-analysis (Cannon 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24744302/" }, { "title": "Single high-dose pyridoxine for isoniazid overdose (Wason 1981)", "url": "https://pubmed.ncbi.nlm.nih.gov/7265398/" } ], "words": 982, "bank": 5 }, { "id": "seizure-classification", "n": "2", "title": "Classifying the seizure (ILAE 2025)", "tags": [ "ilae-classification" ], "updated": true, "goals": [ "Place a seizure in one of the four classes", "apply consciousness as a classifier correctly", "describe semiology in the basic and expanded formats" ], "blocks": [ { "type": "p", "updated": true, "label": "ILAE 2025", "text": "The update keeps the 2017 structure but makes consciousness, judged by awareness and responsiveness together, the classifier for focal seizures and seizures of unknown origin (unknown whether focal or generalized); \"onset\" has been dropped from the class names. Motor versus non-motor onset is now a descriptor rather than a class, and negative myoclonus is recognized as a generalized seizure type." }, { "type": "h3", "text": "Four classes" }, { "type": "li", "text": "**Focal** seizures begin in networks within one hemisphere. Classify consciousness as preserved or impaired if you can; if you cannot tell, stay with \"focal seizure\". A focal seizure that spreads to both sides is a **focal to bilateral tonic–clonic** seizure." }, { "type": "li", "text": "**Generalized** seizures engage bilateral networks rapidly. They are grouped into absence seizures (typical, atypical, myoclonic absence, eyelid myoclonia), generalized tonic–clonic seizures, and other generalized seizures (myoclonic, myoclonic–atonic, atonic, clonic, tonic, negative myoclonic, epileptic spasms). Consciousness is not used to classify them." }, { "type": "li", "text": "**Unknown** whether focal or generalized: some features are known but the onset is not." }, { "type": "li", "text": "**Unclassified**: the event is considered epileptic but there is too little information to go further." }, { "type": "note", "label": "Try it", "text": "Open each class with its subtypes and examples under [seizure types](ilae_classification.html#seizure-types) on the ILAE page." }, { "type": "p", "text": "The update lists 21 seizure types in all. Neonatal seizures have their own classification." }, { "type": "h3", "text": "Describing what happened" }, { "type": "p", "text": "The basic version records whether the seizure had **observable** manifestations or not. The expanded version lists signs in the order they occurred: observable (motor signs, automatisms, autonomic signs, behavioral arrest) and non-observable (sensory, cognitive, emotional). The sequence often localizes better than the class." }, { "type": "h3", "text": "Older names you will still meet" }, { "type": "p", "text": "Older papers and many question stems use the 1981 or 2017 names. They map onto the 2025 terms like this:" }, { "type": "table", "head": [ "1981", "2017", "2025" ], "rows": [ [ "Simple partial seizure", "Focal aware seizure", "Focal seizure with preserved consciousness" ], [ "Complex partial seizure", "Focal impaired awareness seizure", "Focal seizure with impaired consciousness" ], [ "Secondarily generalized tonic–clonic seizure", "Focal to bilateral tonic–clonic seizure", "Focal to bilateral tonic–clonic seizure" ], [ "Partial seizure with motor or sensory signs", "Focal motor onset or focal non-motor onset seizure (a seizure type)", "Focal seizure, with motor or other features as descriptors" ], [ "Absence seizure", "Generalized non-motor (absence) seizure", "Absence seizure" ], [ "(no equivalent)", "Unknown onset seizure", "Seizure of unknown origin (unknown whether focal or generalized)" ] ] }, { "type": "p", "text": "The 2010 word \"dyscognitive\" was also dropped in 2017. The 2017 classifier was awareness, meaning recall of the event; 2025 replaced it with consciousness judged by awareness and responsiveness together, because \"awareness\" translated poorly and ignored responsiveness. Under both rules, impairment at any point makes the whole seizure \"impaired\"." }, { "type": "h3", "text": "Generalized seizure types at the bedside and on EEG" }, { "type": "table", "head": [ "Type", "What you see", "Ictal EEG" ], "rows": [ [ "Typical absence", "Sudden stare and arrest lasting seconds (median about 7 s), often with automatisms or eyelid twitching; immediate return to normal; often provoked by hyperventilation", "Regular generalized spike-and-wave at about 3 Hz, starting and stopping abruptly" ], [ "Atypical absence", "Gradual onset or offset, usually longer, more change in tone (a head drop); seen in Lennox–Gastaut syndrome", "Irregular spike-and-wave slower than 2.5 Hz, sometimes with fast activity" ], [ "Myoclonic", "Lightning-fast jerk (under 100 ms), mostly of the arms; can cause a fall", "Generalized polyspike-and-wave time-locked to the jerk" ], [ "Atonic", "Sudden loss of tone without a preceding jerk: head drop or fall, about 1 second", "Generalized electrodecrement or slow waves" ], [ "Tonic", "Sustained stiffening, usually in extension, median about 8 s; may be subtle in sleep (eyes rolling up); required for Lennox–Gastaut syndrome", "Diffuse decrement, then bilateral fast activity of 10 Hz or more that builds up (a recruiting rhythm)" ], [ "Tonic–clonic", "Tonic phase, then clonic jerks that slow as the silent periods lengthen; median about 80 s; may open with myoclonic jerks or an absence", "Fast spikes in the tonic phase (often hidden by muscle), spike-and-slow-wave bursts with the jerks, then postictal suppression or diffuse slowing" ] ] }, { "type": "p", "text": "**Absence or focal seizure with impaired consciousness?** Both cause staring and unresponsiveness, and automatisms occur in most patients with typical absences, so automatisms do not make a seizure focal. An absence lasts seconds, starts and stops abruptly, has no warning and ends with immediate recovery. A focal seizure with impaired consciousness often begins with an aura, lasts a minute or more and is followed by confusion. The EEG settles it." }, { "type": "mcq", "id": "q-1m5djyp", "stem": "A 9-year-old with developmental delay has nightly events. On video-EEG during sleep, his eyes roll up and both arms rise and stiffen for 8 seconds. The EEG shows diffuse flattening followed by bilateral fast activity at about 15 Hz that grows in amplitude. What seizure type is this?", "options": [ "Atonic seizure", "Tonic seizure", "Myoclonic seizure", "Atypical absence seizure", "Epileptic spasm" ], "answer": 1, "explain": "Stiffening that lasts seconds, with a diffuse decrement and then building fast activity of 10 Hz or more, is a generalized tonic seizure, the seizure type required for Lennox–Gastaut syndrome. Atonic seizures are a loss of tone with decrement or slow waves; myoclonic jerks last under 100 ms with polyspike-and-wave; atypical absences show slow spike-and-wave; an epileptic spasm lasts about a second, with a high-amplitude slow wave and then a decrement." }, { "type": "mcq", "id": "q-1ie5sym", "stem": "A woman describes a seizure beginning with a rising epigastric sensation. Her husband says she then stared and fumbled with her clothes and did not answer him; afterwards she could not recall the episode. How is this classified under ILAE 2025?", "options": [ "Focal seizure with preserved consciousness", "Focal seizure with impaired consciousness", "Generalized absence seizure", "Seizure of unknown origin", "Unclassified seizure" ], "answer": 1, "explain": "The epigastric aura indicates focal onset. She was unresponsive and could not recall the event, so consciousness was impaired. Automatisms and the aura are descriptors listed in sequence." }, { "type": "mcq", "id": "q-1ysovbr", "stem": "A seizure is witnessed only in its convulsive phase; no one knows how it began, and the EEG and MRI are normal. How should it be classified?", "options": [ "Generalized tonic–clonic seizure", "Focal to bilateral tonic–clonic seizure", "Bilateral tonic–clonic seizure of unknown origin", "Unclassified seizure", "Focal seizure with impaired consciousness" ], "answer": 2, "explain": "When the onset is not known but the seizure clearly became bilateral tonic–clonic, it is classified as a bilateral tonic–clonic seizure of unknown origin (unknown whether focal or generalized). \"Unclassified\" is kept for events with too little information to characterize at all." }, { "type": "cards", "items": [ { "id": "c-mbyp02", "front": "The four seizure classes (ILAE 2025)", "back": "Focal; generalized; unknown whether focal or generalized; unclassified." }, { "id": "c-1bb4m06", "front": "Classifier for focal seizures and seizures of unknown origin", "back": "Consciousness (impaired or preserved), judged by awareness and responsiveness." }, { "id": "c-j7dlaq", "front": "If consciousness cannot be determined", "back": "Use the parent term, for example \"focal seizure\"." }, { "id": "c-b48xja", "front": "Does consciousness classify generalized seizures?", "back": "No." }, { "id": "c-wxmkuu", "front": "New generalized seizure type in 2025", "back": "Negative myoclonus." }, { "id": "c-105456k", "front": "Basic versus expanded description", "back": "Basic: with or without observable manifestations. Expanded: the chronological sequence of semiology." }, { "id": "c-o8r0gw", "front": "Number of seizure types in the 2025 classification", "back": "21." }, { "id": "c-uitjcb", "front": "Complex partial seizure (1981)", "back": "2017: focal impaired awareness seizure. 2025: focal seizure with impaired consciousness." }, { "id": "c-2jke2r", "front": "Simple partial seizure (1981)", "back": "2017: focal aware seizure. 2025: focal seizure with preserved consciousness." }, { "id": "c-1si7t31", "front": "Secondarily generalized seizure (1981)", "back": "Focal to bilateral tonic–clonic seizure." }, { "id": "c-ptbksf", "front": "Typical absence EEG", "back": "Regular generalized spike-and-wave at about 3 Hz, abrupt onset and offset." }, { "id": "c-13i5gzg", "front": "Atypical absence EEG", "back": "Irregular spike-and-wave slower than 2.5 Hz; gradual onset or offset." }, { "id": "c-yxpj6u", "front": "Tonic seizure EEG", "back": "Diffuse decrement, then building bilateral fast activity of 10 Hz or more." }, { "id": "c-1lenazh", "front": "Atonic seizure EEG", "back": "Generalized electrodecrement or slow waves, with a loss of tone lasting about a second." }, { "id": "c-6xre26", "front": "Myoclonic seizure EEG", "back": "Generalized polyspike-and-wave time-locked to the jerk." }, { "id": "c-31o3kw", "front": "Do automatisms make a staring spell focal?", "back": "No. Most patients with typical absences have them." } ] }, { "type": "note", "label": "Try it", "text": "Classify an event step by step on the [ILAE Classification page](ilae_classification.html)." } ], "sources": [ { "title": "ILAE updated classification of epileptic seizures (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40264351/" }, { "title": "Practical guide to the 2025 classification", "url": "https://pubmed.ncbi.nlm.nih.gov/41081650/" }, { "title": "ILAE operational classification of seizure types (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28276060/" }, { "title": "Instruction manual for the ILAE 2017 seizure classification", "url": "https://pubmed.ncbi.nlm.nih.gov/28276064/" } ], "words": 1218, "bank": 7 }, { "id": "epilepsy-classification", "n": "3", "title": "Classifying the epilepsy (ILAE 2017)", "tags": [ "ilae-classification" ], "updated": false, "goals": [ "Work through the three levels of the framework", "name the six etiology groups", "use the terms developmental and epileptic encephalopathy and self-limited correctly" ], "blocks": [ { "type": "h3", "text": "Three levels, with etiology throughout" }, { "type": "li", "text": "**Level 1, seizure type** (as above). Diagnosis can stop here when there is not enough information." }, { "type": "li", "text": "**Level 2, epilepsy type**: focal, generalized, combined generalized and focal, or unknown. Combined epilepsy is real and easy to miss: Dravet and Lennox–Gastaut syndromes both belong here." }, { "type": "li", "text": "**Level 3, epilepsy syndrome**: a characteristic cluster of seizure types, EEG and imaging features, age at onset and course. Not every epilepsy fits a syndrome." }, { "type": "note", "label": "Try it", "text": "Work through epilepsy type, syndrome and etiology on the [ILAE epilepsy tab](ilae_classification.html#epilepsy-tab)." }, { "type": "p", "text": "At every level, ask about **etiology**: structural, genetic, infectious, metabolic, immune or unknown. More than one can apply (tuberous sclerosis is both structural and genetic). Consider **comorbidities** (learning, psychiatric, behavioral, sleep) at every level too." }, { "type": "h3", "text": "Terms that changed" }, { "type": "li", "text": "**Developmental and epileptic encephalopathy** (DEE): impairment comes from both the underlying cause and the epileptic activity. **Epileptic encephalopathy**: the epileptic activity itself causes the impairment." }, { "type": "li", "text": "**Self-limited** (likely to remit spontaneously) and **pharmacoresponsive** replaced \"benign\"." }, { "type": "li", "text": "**Genetic** does not mean inherited: many pathogenic variants in DEEs arise de novo." }, { "type": "li", "text": "**Idiopathic, symptomatic and cryptogenic** (1989) meant presumed genetic, secondary to a known or presumed brain disorder, and \"presumed symptomatic\" but unproven. In 2010 they became genetic, structural-metabolic and unknown; in 2017, the six etiology groups above. \"Idiopathic\" was judged imprecise now that genes are being found, and \"symptomatic generalized epilepsy\" had lumped together very different patients. **Cryptogenic** therefore now reads as **unknown**." }, { "type": "li", "text": "**Idiopathic generalized epilepsy** survives only as the name for four syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and generalized tonic–clonic seizures alone. \"Genetic generalized epilepsy\" may be used when a genetic cause is judged likely." }, { "type": "h3", "text": "The 2010 revision" }, { "type": "p", "text": "The 2010 report bridged the 1989 and 2017 classifications. It redefined generalized seizures as arising in, and rapidly engaging, bilaterally distributed networks, and focal seizures as arising in networks limited to one hemisphere. The 2025 definitions keep this and add that generalized networks need not include the whole cortex and that the onset can look asymmetric or even focal. It also named some recognizable lesion-based pictures as distinctive **constellations**: mesial temporal lobe epilepsy with hippocampal sclerosis, Rasmussen syndrome, gelastic seizures with hypothalamic hamartoma, and hemiconvulsion–hemiplegia–epilepsy. In the 2022 ILAE syndrome papers, mesial temporal lobe epilepsy with hippocampal sclerosis and Rasmussen syndrome are syndromes with onset at a variable age, and gelastic seizures with hypothalamic hamartoma is an etiology-specific syndrome in the neonatal and infantile paper." }, { "type": "mcq", "id": "q-wplidv", "stem": "A 6-year-old with Dravet syndrome has generalized tonic–clonic, myoclonic and focal seizures. What is her epilepsy type in the 2017 framework?", "options": [ "Focal", "Generalized", "Combined generalized and focal", "Unknown", "Unclassified" ], "answer": 2, "explain": "Dravet syndrome has both generalized and focal seizure types, which places it in combined generalized and focal epilepsy, as does Lennox–Gastaut syndrome." }, { "type": "mcq", "id": "q-1gcq7nq", "stem": "A child with tuberous sclerosis complex has focal seizures from a cortical tuber. How is the etiology best classified?", "options": [ "Structural only", "Genetic only", "Structural and genetic", "Unknown", "Immune" ], "answer": 2, "explain": "Etiology categories are not exclusive. Tuberous sclerosis is caused by TSC1 or TSC2 variants (genetic) and produces tubers (structural)." }, { "type": "cards", "items": [ { "id": "c-n5b7f3", "front": "Three levels of the ILAE 2017 framework", "back": "Seizure type, epilepsy type, epilepsy syndrome." }, { "id": "c-1m13fch", "front": "Epilepsy types", "back": "Focal; generalized; combined generalized and focal; unknown." }, { "id": "c-220paf", "front": "Six etiology groups", "back": "Structural, genetic, infectious, metabolic, immune, unknown." }, { "id": "c-1wxnq4c", "front": "Developmental and epileptic encephalopathy", "back": "Impairment from both the underlying cause and the epileptic activity." }, { "id": "c-18z5jrw", "front": "What replaced \"benign\"", "back": "Self-limited and pharmacoresponsive." }, { "id": "c-14ln29f", "front": "Syndromes with combined generalized and focal epilepsy", "back": "Dravet and Lennox–Gastaut syndromes." }, { "id": "c-1dz3l8k", "front": "Idiopathic, symptomatic, cryptogenic (1989)", "back": "Became genetic, structural-metabolic, unknown (2010), then the six 2017 etiology groups." }, { "id": "c-pbo7l6", "front": "Cryptogenic (1989)", "back": "\"Presumed symptomatic\"; now unknown etiology." }, { "id": "c-1th3od1", "front": "Where \"idiopathic\" survives", "back": "Idiopathic generalized epilepsy: childhood absence, juvenile absence, juvenile myoclonic epilepsy, and generalized tonic–clonic seizures alone." }, { "id": "c-192kjke", "front": "2010 \"constellations\"", "back": "Mesial temporal lobe epilepsy with hippocampal sclerosis, Rasmussen syndrome, gelastic seizures with hypothalamic hamartoma, hemiconvulsion–hemiplegia–epilepsy." } ] } ], "sources": [ { "title": "ILAE classification of the epilepsies (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28276062/" }, { "title": "ILAE syndrome classification overview (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503715/" }, { "title": "ILAE revised terminology and concepts (Berg 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20196795/" }, { "title": "ILAE 2010 terminology summary", "url": "https://ilae.org/files/dmfile/ilae-handoutv10.pdf" }, { "title": "Practical guide to the 2025 classification", "url": "https://pubmed.ncbi.nlm.nih.gov/41081650/" }, { "title": "ILAE syndromes with onset at a variable age (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503725/" }, { "title": "ILAE syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" } ], "words": 617, "bank": 4 }, { "id": "first-seizure", "n": "4", "title": "The first seizure", "tags": [ "seizure-management", "ilae-classification" ], "updated": false, "goals": [ "Work up a first seizure efficiently", "estimate recurrence risk from the factors that predict it", "share the decision about starting an ASM" ], "blocks": [ { "type": "h3", "text": "Work-up" }, { "type": "li", "text": "**History from a witness** is the most valuable test: onset, sequence, duration, recovery, triggers, and any earlier events that may have been seizures (morning jerks, auras, staring spells)." }, { "type": "li", "text": "**Blood tests** guided by the situation: glucose, sodium, calcium, magnesium, and toxicology." }, { "type": "li", "text": "**EEG**, ideally early and including sleep." }, { "type": "li", "text": "**MRI** with an epilepsy protocol. CT is for the emergency question (bleeding, mass, trauma) or when MRI is not possible." }, { "type": "li", "text": "**MRI is not routinely needed** for a typical idiopathic generalized epilepsy (NICE also exempts self-limited epilepsy with centrotemporal spikes). Image when the picture is atypical, new features appear, or first-line treatment fails. The ILAE imaging task force favors MRI in new generalized as well as focal epilepsy, so practice varies." }, { "type": "li", "text": "**Lumbar puncture** if infection or inflammation is suspected." }, { "type": "h3", "text": "Will it happen again?" }, { "type": "p", "text": "After a first unprovoked seizure in an adult, the risk of recurrence is greatest in the first two years, in the range of roughly 20–45%. Four factors raise it:" }, { "type": "li", "text": "a prior brain insult (remote symptomatic cause)" }, { "type": "li", "text": "epileptiform discharges on EEG" }, { "type": "li", "text": "a significant abnormality on brain imaging" }, { "type": "li", "text": "a seizure from sleep" }, { "type": "p", "text": "The American Academy of Neurology and American Epilepsy Society guideline rates the evidence as strongest (Level A) for a prior brain insult and an epileptiform EEG, and weaker (Level B) for an imaging abnormality and a seizure from sleep." }, { "type": "p", "text": "A second unprovoked seizure changes the outlook. In a prospective cohort of 204 people followed from a first unprovoked seizure, 33% had a second. Of those, 73% had a third within 4 years, and after a third, 76% had a fourth, so the risk barely rises after the second seizure. Most recurrences came within a year. The risk after two seizures is the benchmark for the ILAE's 60% threshold for diagnosing epilepsy after one." }, { "type": "h3", "text": "To treat or not" }, { "type": "p", "text": "Starting an antiseizure medication (ASM) right away reduces the recurrence risk over the next two years by roughly a third. It does not improve the chance of long-term remission. Adverse effects are common but usually mild. The decision rests on recurrence risk and on what a second seizure would cost the patient (driving, work, safety), and is best made together." }, { "type": "p", "text": "Two randomized trials are behind this:" }, { "type": "li", "text": "**First Seizure Trial (FIRST)**: about 400 people after a first tonic–clonic seizure. Relapse by 2 years was 25% with immediate treatment and 51% when treatment waited for a second seizure, yet the chance of 1 or 2 seizure-free years later was the same, and about half of those left untreated never had a second seizure." }, { "type": "li", "text": "**Multicentre Study of Early Epilepsy and Single Seizures (MESS)**: 1,443 people with a single seizure or early epilepsy. Immediate treatment delayed the first, second and first tonic–clonic recurrence, but freedom from seizures 3–5 years later (76% versus 77%), quality of life and serious complications did not differ." }, { "type": "p", "text": "The guideline adds that immediate treatment may not improve quality of life (Level C) and that adverse effects, reported in 7–31%, are mostly mild and reversible (Level B)." }, { "type": "case", "id": "case-first-seizure", "title": "A first convulsion at 23", "intro": [ "A 23-year-old graduate student had a generalized convulsion at 7 a.m. after a week of little sleep before exams. His roommate says he went stiff, then jerked for about a minute, and was confused for 20 minutes. He bit the side of his tongue." ], "steps": [ { "narrative": [], "stem": "What single question is most likely to change the diagnosis?", "options": [ "Whether he drinks coffee", "Whether he has had morning jerks or brief staring spells before", "Whether he has headaches", "Whether a parent has migraine", "Whether he has ever fainted at the dentist" ], "answer": 1, "explain": "A history of morning myoclonus or absences turns an apparently first seizure into juvenile myoclonic epilepsy, which changes the EEG expected, the drug choice and the prognosis." }, { "narrative": [ "He reports years of occasional arm jerks when tired in the morning. EEG shows 4–5 Hz generalized polyspike-and-wave with a photoparoxysmal response. MRI is normal." ], "stem": "What is the diagnosis?", "options": [ "Acute symptomatic seizure from sleep deprivation", "Focal epilepsy with bilateral spread", "Juvenile myoclonic epilepsy", "Childhood absence epilepsy", "Epilepsy with generalized tonic–clonic seizures alone" ], "answer": 2, "explain": "Morning myoclonus, a convulsion after sleep deprivation, and photosensitive generalized polyspike-and-wave make this juvenile myoclonic epilepsy. Sleep deprivation is a trigger, not an acute brain insult, so the seizure is not acute symptomatic." }, { "narrative": [], "stem": "Which ASM is the best first choice for a man with this syndrome?", "options": [ "Valproate", "Carbamazepine", "Phenytoin", "Gabapentin", "Oxcarbazepine" ], "answer": 0, "explain": "Valproate is the most effective drug for idiopathic generalized epilepsy, and SANAD II confirmed its advantage over levetiracetam. In women who could become pregnant, levetiracetam or lamotrigine is usually preferred because of valproate's teratogenicity. Carbamazepine, oxcarbazepine, phenytoin and gabapentin can worsen myoclonus." }, { "narrative": [], "stem": "What advice matters most for his safety now?", "options": [ "He may drive as usual once treatment starts", "He must follow his state's driving restrictions, and avoid sleep deprivation and binge drinking", "He can stop the ASM after a year seizure-free", "He needs a helmet at all times", "He should avoid all screens" ], "answer": 1, "explain": "Driving rules follow local law. Sleep deprivation and alcohol are the main modifiable triggers in juvenile myoclonic epilepsy, which usually needs long-term treatment; relapse after withdrawal is common." } ], "outro": [ "The history of earlier minor seizures is the most frequently missed piece of a \"first seizure\" work-up." ] }, { "type": "mcq", "id": "q-1t7eucx", "stem": "Which factor does NOT independently raise recurrence risk after a first unprovoked seizure in adults, according to the AAN/AES guideline?", "options": [ "A prior brain insult such as stroke", "Epileptiform discharges on EEG", "A significant abnormality on brain imaging", "A seizure arising from sleep", "Postictal confusion lasting 30 minutes" ], "answer": 4, "explain": "The guideline identifies prior brain insult, epileptiform EEG, significant imaging abnormality and nocturnal seizure. Postictal confusion is common and does not predict recurrence." }, { "type": "cards", "items": [ { "id": "c-6m6quv", "front": "Recurrence risk after a first unprovoked seizure", "back": "About 20–45% within two years, greatest early." }, { "id": "c-5go5gv", "front": "Four predictors of recurrence", "back": "Prior brain insult, epileptiform EEG, significant imaging abnormality, seizure from sleep." }, { "id": "c-1mibqej", "front": "Effect of immediate ASM treatment", "back": "Cuts early recurrence by about a third; does not change long-term remission." }, { "id": "c-orbtdg", "front": "Imaging for a first seizure", "back": "MRI with an epilepsy protocol; CT for emergencies or if MRI is impossible." }, { "id": "c-15td032", "front": "The most missed part of first-seizure history", "back": "Earlier minor seizures such as morning jerks, auras or absences." }, { "id": "c-1ae2oao", "front": "Strongest-evidence predictors of recurrence (Level A)", "back": "Prior brain insult and an epileptiform EEG." }, { "id": "c-1hk5xue", "front": "Recurrence after a second unprovoked seizure", "back": "About 73% within 4 years, against about 33% after a first (Hauser 1998)." }, { "id": "c-m0rim1", "front": "FIRST trial", "back": "Immediate treatment after a first tonic–clonic seizure halved 2-year relapse (25% versus 51%) but did not change later remission." }, { "id": "c-1tkv305", "front": "MESS trial", "back": "Immediate versus deferred treatment: fewer early seizures, same remission at 3–5 years, same quality of life." }, { "id": "c-nnu625", "front": "MRI in typical idiopathic generalized epilepsy", "back": "Not routinely needed (NICE); image if atypical, new features appear or first-line treatment fails." } ] } ], "sources": [ { "title": "AAN/AES guideline: first unprovoked seizure in adults (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25901057/" }, { "title": "SANAD II, generalized and unclassifiable epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838758/" }, { "title": "Risk of recurrent seizures after two unprovoked seizures (Hauser 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9459646/" }, { "title": "FIRST trial: treatment after a first tonic–clonic seizure (1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8450987/" }, { "title": "FIRST trial: treatment does not improve prognosis (Musicco 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9339678/" }, { "title": "MESS: immediate versus deferred treatment (Marson 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15950714/" }, { "title": "NICE NG217: epilepsies in children, young people and adults (2022)", "url": "https://www.ncbi.nlm.nih.gov/books/NBK581165/" }, { "title": "ILAE recommendations for structural MRI in epilepsy (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31135062/" } ], "words": 990, "bank": 9 }, { "id": "semiology", "n": "5", "title": "Semiology: localizing and lateralizing", "tags": [ "epilepsy-surgery", "ilae-classification" ], "updated": false, "goals": [ "Localize a seizure from its first sign and sequence", "use lateralizing signs with their reliability in mind", "recognize frontal and insular seizures that mimic other disorders" ], "blocks": [ { "type": "h3", "text": "The first sign localizes; the sequence tells the path" }, { "type": "table", "head": [ "Region", "Typical features" ], "rows": [ [ "Mesial temporal", "Rising epigastric sensation, déjà vu, fear, smell or taste; motionless stare; oral then manual automatisms; lasts one to two minutes; postictal confusion" ], [ "Lateral temporal", "Auditory aura (Heschl gyrus), vertigo, complex hallucinations; earlier clonic signs and faster spread" ], [ "Frontal: orbitofrontal and cingulate", "Brief hypermotor seizures from sleep in clusters; thrashing, bicycling, pelvic thrusting, vocalization; fast recovery" ], [ "Supplementary motor area", "Abrupt asymmetric bilateral tonic posturing (fencing), often with preserved consciousness" ], [ "Primary motor", "Contralateral clonic jerks, sometimes marching (Jacksonian)" ], [ "Parietal", "Contralateral tingling, pain, distorted body image, vertigo; may be silent until spread" ], [ "Occipital", "Colored shapes or flashes, ictal blindness, eye deviation, blinking; postictal headache" ], [ "Occipitotemporal and anterior temporal (visual)", "Complex (formed) visual hallucinations and tunnel vision; elementary flashes, illusions and visual loss can also occur here, so they do not prove occipital onset" ], [ "Insula and operculum", "Throat constriction, perioral or widespread unpleasant sensations, hypersalivation, dysarthria; can mimic temporal or hypermotor frontal seizures" ], [ "Hypothalamic hamartoma", "Gelastic seizures (laughter without mirth) starting in early childhood" ], [ "Cortex (no hamartoma)", "Gelastic seizures can also arise from cingulate, frontal, temporal, insular or orbitofrontal cortex" ], [ "Temporal, autonomic", "Pilomotor seizures (goose bumps), mostly temporal; consider limbic encephalitis, especially with LGI1 antibodies" ] ] }, { "type": "note", "label": "Try it", "text": "Find the mesial temporal, insulo-opercular and medial frontal regions, with the stereo-EEG electrodes that sample them, in the 3D [Epilepsy Brain Atlas](eeg_atlas.html)." }, { "type": "p", "text": "Two rules sit behind the table. Primary cortex gives elementary symptoms and association cortex complex ones: in a surgical series, complex visual hallucinations never came from occipital-onset seizures. And a sign shows where the seizure is when the sign appears (the symptomatogenic zone), not necessarily where it began (the epileptogenic zone), which is why the same sign, such as laughter, can come from different onsets." }, { "type": "h3", "text": "Frontal, mesial frontal and cingulate seizures" }, { "type": "p", "text": "Frontal seizures follow a front-to-back gradient. In a stereo-EEG study of 54 patients, elementary motor signs came from precentral and premotor cortex; elementary signs mixed with nonintegrated gestures from premotor plus prefrontal cortex; integrated gestures with distal stereotypies from anterior lateral and medial prefrontal cortex; and fearful behavior from ventromedial prefrontal (paralimbic) cortex. The further forward the onset, the more organized the behavior." }, { "type": "p", "text": "On the mesial surface:" }, { "type": "li", "text": "**Supplementary motor area**: brief asymmetric tonic posturing with consciousness kept, the commonest sign though present in under half of patients; speech arrest is reported in about one patient in ten." }, { "type": "li", "text": "**Negative motor areas**: some frontal or central seizures stop movement or speech, or weaken the opposite arm, while awareness is kept (focal akinetic seizures). Test recall before calling such a patient unconscious." }, { "type": "li", "text": "**Anterior cingulate**: fear, emotional facial expressions including ictal pouting, autonomic signs, vocalization and sudden hypermotor behavior, often with awareness kept; brief seizures clustered in sleep with immediate recovery, easily taken for a parasomnia." }, { "type": "li", "text": "**Midcingulate**: rarely recorded; reported seizures are motor, including hypermotor onset, with early spread to motor and premotor cortex." }, { "type": "li", "text": "**Posterior cingulate**: silent at onset; spread to mesial temporal structures gives staring and automatisms, so the picture can look temporal (\"pseudotemporal\"). Consider it before a temporal resection in a nonlesional case." }, { "type": "p", "text": "The cingulate lies deep, so scalp EEG is often nonlocalizing. Damage to both anterior cingulate gyri can cause akinetic mutism." }, { "type": "h3", "text": "Lateralizing signs" }, { "type": "table", "head": [ "Sign", "Side of onset" ], "rows": [ [ "Dystonic posturing of one limb", "Opposite side" ], [ "Unilateral manual automatisms (with dystonia of the other hand)", "Same side" ], [ "Forced, sustained head version before generalization", "Opposite side" ], [ "Figure-of-4 posture", "Opposite to the extended arm" ], [ "Last clonic jerks of a convulsion", "Same side" ], [ "Todd paralysis", "Opposite side" ], [ "Postictal nose-wiping", "Hand on the same side" ], [ "Postictal aphasia", "Dominant hemisphere" ], [ "Preserved speech during an impaired-consciousness seizure", "Non-dominant hemisphere" ], [ "Ictal vomiting, spitting or urge to urinate", "Non-dominant temporal lobe" ], [ "Unilateral eye blinking", "Same side" ], [ "Unilateral tonic limb posturing", "Unreliable early in a focal seizure (opposite side in only 40% of temporal lobe seizures in one series, with poor observer agreement); more reliable once the seizure becomes bilateral" ], [ "Head turning late in the convulsion", "Often toward the side of onset; does not lateralize" ], [ "Unilateral piloerection (goose bumps)", "Usually same side" ] ] }, { "type": "note", "label": "Board pearl", "text": "Early, mild, non-forced head turning is unreliable and may be to the same side. Only forced, sustained version shortly before the convulsion lateralizes to the opposite hemisphere." }, { "type": "p", "text": "As a focal seizure becomes bilateral, the signs come in sequence: forced version away from the onset usually first, then asymmetric tonic posturing (the figure-of-4, or M2e, a fencing-like posture with the arm opposite the onset raised), then the clonic phase, which ends asymmetrically on the side of onset. In one blinded series of seizures becoming bilateral, version, unilateral tonic posturing, M2e, unilateral clonic jerking, an asymmetric clonic ending and Todd paresis each pointed to the correct side more than 80% of the times they appeared (positive predictive value), and two or more concordant signs were always right, but none separated temporal from extratemporal onset. A head turn at the end of the convulsion is different: it is often ipsilateral, because by then the other hemisphere is driving it." }, { "type": "match", "id": "match-lateralizing", "prompt": "Match each sign to the side of seizure onset it suggests", "pairs": [ [ "Dystonic posturing of the right hand", "Left hemisphere" ], [ "Postictal wiping of the nose with the left hand", "Left hemisphere" ], [ "Forced, sustained head version to the right just before convulsing", "Left hemisphere" ], [ "Preserved speech during a focal impaired-consciousness seizure", "Non-dominant hemisphere" ], [ "Ictal vomiting", "Non-dominant temporal lobe" ], [ "Postictal aphasia", "Dominant hemisphere" ] ] }, { "type": "mcq", "id": "q-3o7i4g", "stem": "A right-handed man's seizures begin with oral automatisms, then left-hand fumbling while the right arm becomes dystonic. Where do they most likely start?", "options": [ "Right temporal lobe", "Left temporal lobe", "Left frontal lobe", "Right parietal lobe", "Generalized onset" ], "answer": 1, "explain": "Unilateral manual automatisms are ipsilateral and dystonic posturing is contralateral to the onset. Left-hand automatisms with right-arm dystonia point to the left temporal lobe, fitting the oral automatisms of mesial temporal onset." }, { "type": "mcq", "id": "q-1pru0rr", "stem": "A 19-year-old has clusters of 30-second nocturnal episodes with violent thrashing and bicycling, several a night, with immediate recovery. Sleep specialists suspect a parasomnia. Which feature favors sleep-related hypermotor epilepsy?", "options": [ "Episodes in the first third of the night only", "Onset in early childhood with resolution by adolescence", "Highly stereotyped, brief episodes in clusters, arising from sleep at any time of night", "Complex, variable behaviors with no recall", "Walking around the house for 20 minutes" ], "answer": 2, "explain": "Hypermotor frontal seizures are brief, stereotyped, clustered and can arise at any time of night. NREM parasomnias occur mainly in the first third of the night, are variable and longer, and usually stop in adolescence." }, { "type": "cards", "items": [ { "id": "c-cmp8bj", "front": "Epigastric rising aura", "back": "Mesial temporal lobe." }, { "id": "c-177ozpj", "front": "Auditory aura", "back": "Lateral temporal neocortex (Heschl gyrus)." }, { "id": "c-ulq5z6", "front": "Fencing posture with preserved consciousness", "back": "Supplementary motor area." }, { "id": "c-1lrjq6a", "front": "Gelastic seizures from early childhood", "back": "Hypothalamic hamartoma." }, { "id": "c-vl126v", "front": "Throat constriction and perioral tingling", "back": "Insular or opercular onset." }, { "id": "c-ir8bj0", "front": "Colored circles and ictal blindness", "back": "Occipital lobe." }, { "id": "c-1m28p8o", "front": "Dystonic limb", "back": "Contralateral to onset." }, { "id": "c-xkc6hd", "front": "Unilateral manual automatisms", "back": "Ipsilateral to onset." }, { "id": "c-1ly0r6k", "front": "Figure-of-4", "back": "Onset opposite the extended arm." }, { "id": "c-1ef8mgx", "front": "Last clonic jerk of a convulsion", "back": "Ipsilateral to onset." }, { "id": "c-rif9f9", "front": "Head turn at the end of a convulsion", "back": "Often ipsilateral; does not lateralize, unlike early forced version." }, { "id": "c-1x7a5bi", "front": "Motor sequence as a focal seizure becomes bilateral", "back": "Version, then asymmetric tonic posture (figure-of-4 or M2e), then clonic phase with an asymmetric ending." }, { "id": "c-1lirsf8", "front": "Unilateral ictal piloerection", "back": "Usually ipsilateral, temporal; think of limbic encephalitis (LGI1)." }, { "id": "c-16gzjwe", "front": "Gelastic seizures without a hamartoma", "back": "Cingulate, frontal, temporal, insular or orbitofrontal onset." }, { "id": "c-abmk55", "front": "Complex visual hallucinations", "back": "Occipitotemporal or anterior temporal onset, not primary occipital cortex." }, { "id": "c-1kpamrv", "front": "Front-to-back gradient of frontal seizures", "back": "Elementary motor signs (precentral) → nonintegrated gestures → integrated gestures with distal stereotypies (anterior prefrontal) → fearful behavior (ventromedial prefrontal)." }, { "id": "c-11lm28r", "front": "Focal akinetic seizure", "back": "Cannot move or speak, or the opposite arm is weak, with awareness kept; negative motor areas." }, { "id": "c-ytlj61", "front": "Anterior cingulate seizures", "back": "Fear, ictal pouting, autonomic signs, hypermotor behavior; brief, clustered in sleep, quick recovery." }, { "id": "c-1250j50", "front": "Posterior cingulate seizures", "back": "Silent onset with spread to mesial temporal structures; can look like temporal lobe epilepsy." }, { "id": "c-152rzo", "front": "Bilateral anterior cingulate damage", "back": "Akinetic mutism." } ] } ], "sources": [ { "title": "ILAE updated classification of epileptic seizures (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40264351/" }, { "title": "Practical guide to the 2025 classification", "url": "https://pubmed.ncbi.nlm.nih.gov/41081650/" }, { "title": "Ipsilateral head and eye turning at the end of versive seizures (Wyllie 1986)", "url": "https://pubmed.ncbi.nlm.nih.gov/3748388/" }, { "title": "Lateralizing value of ictal limb posturing and version (Bleasel 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9048668/" }, { "title": "Asymmetric tonic limb posturing, the figure-4 sign (Kotagal 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10756413/" }, { "title": "Ictal motor sequences: lateralization and localization values (Marashly 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26864781/" }, { "title": "Frontal lobe seizures: from semiology to localization (Bonini 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24372328/" }, { "title": "Focal akinetic seizures (Noachtar 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10430445/" }, { "title": "Semiology of supplementary and pre-supplementary motor area epilepsy (Buonocore 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41277683/" }, { "title": "Ictal semiology in anterior cingulate epilepsy (Chassoux 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40711405/" }, { "title": "Cingulate epilepsy: three electroclinical subtypes (Alkawadri 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23753910/" }, { "title": "Mid-cingulate epilepsy studied by stereo-EEG (Alkawadri 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27919842/" }, { "title": "Posterior cingulate epilepsy (Enatsu 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/23926279/" }, { "title": "Akinetic mutism and frontal-subcortical circuits (Mega 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9359123/" }, { "title": "Localizing value of mimic ictal semiology, including gelastic seizures (Kokkinos 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40035641/" }, { "title": "Localizing value of epileptic visual auras (Bien 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10648433/" }, { "title": "Localizing and lateralizing value of ictal piloerection (Loddenkemper 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15146005/" }, { "title": "Pilomotor seizures in limbic encephalitis (Rocamora 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24890932/" } ], "words": 1295, "bank": 14 }, { "id": "mimics", "n": "6", "title": "Mimics of epilepsy", "tags": [ "ilae-classification", "seizure-management" ], "updated": false, "goals": [ "Separate syncope, functional seizures and sleep disorders from epileptic seizures at the bedside", "use video-EEG and laboratory adjuncts appropriately", "deliver a functional seizure diagnosis well" ], "blocks": [ { "type": "h3", "text": "Syncope" }, { "type": "p", "text": "A prodrome of light-headedness, warmth, sweating, tunnel vision or muffled hearing; a trigger (standing, heat, pain, venepuncture, micturition); pallor. Brief irregular jerks are common (**convulsive syncope**), usually lasting under 15 seconds and starting after the fall. Recovery of orientation is quick. Cardiac syncope (arrhythmia, structural disease, long QT) can happen during exertion or lying down and needs cardiac work-up." }, { "type": "p", "text": "**EEG during syncope.** Whatever the cause, cerebral hypoperfusion gives the same sequence: background slowing, then high-amplitude delta (maximal anteriorly), then flattening if perfusion falls further, with recovery in reverse order. In tilt-induced syncope the pattern is either \"slow\" alone or \"slow–flat–slow\", and flattening marks the deeper circulatory failure (lower blood pressure, longer pauses or asystole). There is no evolving rhythmic discharge. Jerks occur during the slow phases and tonic postures during the flat phase, and neither is epileptic. Jerks are few: fewer than 10 favors syncope and more than 20 a convulsive seizure (the \"10/20 rule\"), and limpness at the start strongly favors syncope. A temporal lobe seizure can also stop the heart (ictal asystole): pauses longer than about 6 seconds usually cause syncope, with the same slowing and flattening. Its management is under [SUDEP and mortality](#sudep-mortality)." }, { "type": "p", "text": "In children with recurrent vasovagal syncope, explanation and reassurance come first; drug treatment has only modest effect, and beta-blockers do not help (2017 American College of Cardiology and American Heart Association syncope guideline). Rarely, a child induces syncope compulsively by straining against a closed glottis (a Valsalva maneuver)." }, { "type": "h3", "text": "Functional (dissociative) seizures" }, { "type": "p", "text": "Most papers and many question stems use the older name **psychogenic nonepileptic seizures (PNES)**. Avoid \"pseudoseizures\": in surveys it is among the least preferred and most offensive terms, read as \"putting it on\". \"Functional seizures\" is neutral about cause and acceptable to patients." }, { "type": "p", "text": "Features that favor a functional seizure:" }, { "type": "li", "text": "eyes closed during the event, often resisting opening (the most reliable single sign)" }, { "type": "li", "text": "long duration, waxing and waning, pauses" }, { "type": "li", "text": "side-to-side head or body movements, asynchronous limb movements, pelvic thrusting" }, { "type": "li", "text": "ictal crying, and memory of the event despite apparent unresponsiveness" }, { "type": "li", "text": "occurring from apparent sleep, with the EEG showing wakefulness" }, { "type": "li", "text": "after a convulsion, fast, shallow breathing that settles quickly; slow, deep, noisy (stertorous) breathing instead favors a generalized tonic–clonic seizure" }, { "type": "p", "text": "Eyes open at the start favor an epileptic seizure: in one series 152 of 156 people with epileptic seizures opened their eyes, and 50 of 52 with functional seizures kept them closed. A bite on the side of the tongue favors an epileptic convulsion. No sign stands alone: pelvic thrusting and hypermotor behavior also occur in frontal lobe seizures (pelvic thrusting in 24% of patients with frontal lobe epilepsy in one series, against 17% with functional seizures)." }, { "type": "p", "text": "The diagnostic standard is **video-EEG capture of a typical event** with no ictal change and a history consistent with the diagnosis. Some people have both epilepsy and functional seizures. Explain the diagnosis clearly and without blame, taper antiseizure medications (ASMs) if there is no epilepsy, and refer for psychological treatment, where cognitive behavioral therapy (CBT)-informed therapy has the best evidence." }, { "type": "p", "text": "**Levels of diagnostic certainty (ILAE task force, LaFrance 2013).** Each level needs a history consistent with functional seizures:" }, { "type": "table", "head": [ "Level", "Event seen by", "EEG" ], "rows": [ [ "Possible", "A witness, or the patient's own description", "Routine or sleep-deprived EEG without epileptiform activity" ], [ "Probable", "A clinician, in person or on home video, with typical features", "Routine or sleep-deprived EEG without epileptiform activity" ], [ "Clinically established", "A clinician experienced with seizure disorders, in person or on video", "Routine or ambulatory EEG during a typical event, without epileptiform activity" ], [ "Documented", "A clinician experienced with seizure disorders, on video-EEG", "No epileptiform activity before, during or after a typical event" ] ] }, { "type": "p", "text": "**Who gets them.** In one monitoring series, two-thirds of patients were women and onset averaged 26 years. Psychiatric comorbidity is the rule (53–100% across studies), especially post-traumatic stress disorder, depression, anxiety and personality disorders; all but depression are more common than in epilepsy. Past trauma (44–100%) and abuse (23–77%) are frequent. The average delay to diagnosis was 7 years in 313 patients, and longer in younger patients, in those with interictal epileptiform EEG findings and in those taking ASMs. Functional seizures can also begin after epilepsy surgery (de novo in about 4% after temporal lobe surgery in one series), so new events after a seizure-free period need video-EEG." }, { "type": "p", "text": "**Not deliberate.** Factitious disorder (falsifying illness to occupy the sick role) and malingering (feigning for an external gain such as money or avoiding duty) are both intentional. Functional seizures are not." }, { "type": "p", "text": "**Course and treatment.** Outcome in adults is often poor: at a mean of 4 years after diagnosis, 71% of 164 patients still had events and more than half depended on social security. Outcomes were better with younger onset and earlier diagnosis, more education, less dramatic attacks, fewer other somatic symptoms and less dissociation. In a pilot trial, sertraline alone did not reduce events significantly more than placebo. In a multicenter pilot, CBT-informed psychotherapy cut seizures by 51% alone and 59% with sertraline, whereas sertraline alone and usual care did not. In the CODES trial of 368 adults, adding CBT to standardized care did not significantly reduce monthly seizures at 12 months, but it lengthened seizure-free periods and improved bothersomeness, quality of life and psychosocial functioning." }, { "type": "p", "text": "**Children.** Functional seizures are common but often missed in children and adolescents, and home video helps alongside video-EEG, especially when epilepsy coexists. Outcome is better than in adults: after diagnosis by video-EEG and explanation, 14 of 18 young patients (78%) were free of events at a mean of 30 months." }, { "type": "h3", "text": "Sleep disorders" }, { "type": "li", "text": "**NREM arousal disorders** (confusional arousals, sleepwalking, night terrors): childhood, first third of the night, variable, longer, often with amnesia." }, { "type": "li", "text": "**REM sleep behavior disorder**: older adults, dream enactment in the last part of the night; associated with synucleinopathies." }, { "type": "li", "text": "**Sleep-related hypermotor epilepsy**: brief, stereotyped, clustered, any time of night." }, { "type": "li", "text": "**Sleep-related rhythmic movement disorder**: head banging or body rocking repeating about once a second, usually at sleep onset, starting in infancy and often resolving in early childhood; it can be mistaken for nocturnal frontal seizures." }, { "type": "h3", "text": "Other mimics" }, { "type": "p", "text": "Migraine aura spreads over minutes rather than seconds, with positive then negative symptoms. A transient ischemic attack (TIA) gives negative symptoms. Hypoglycemia is another mimic. Transient amnesia, the paroxysmal movement disorders and the mimics of infancy (hyperekplexia, breath-holding spells, Sandifer syndrome, shuddering attacks) are set out below." }, { "type": "li", "text": "**Occipital seizure or migraine aura?** Occipital seizures cause elementary visual hallucinations lasting seconds: multiple bright, colored, mostly circular spots, often in one half of the visual field, sometimes with blindness or eye deviation and often followed by a migraine-like headache. A migraine aura spreads gradually over 5 minutes or more, each symptom lasts 5–60 minutes, and the typical pattern is a zigzag (fortification) figure near fixation with a scintillating edge that leaves a scotoma behind. Childhood occipital visual epilepsy is covered under [Childhood onset](#syndromes-childhood)." }, { "type": "li", "text": "**Limb-shaking TIA**: brief, coarse, irregular shaking of one arm, or arm and leg, often on standing or exertion, from severe stenosis or occlusion of the opposite internal carotid artery. The EEG shows no epileptic activity. It is the exception to the rule that a TIA gives only negative symptoms, and it calls for urgent imaging of the neck and head vessels." }, { "type": "li", "text": "**Transient epileptic amnesia (TEA) or transient global amnesia (TGA)?** TEA begins in later life (mean 62 years) with frequent, brief amnesic attacks (median 30–60 minutes), often on waking, and accelerated forgetting between attacks; attacks stopped with an ASM in 44 of 47 treated patients. TGA is usually a single attack lasting over an hour, often after an emotional or physical precipitant; attacks shorter than an hour, or rapidly recurring, point to epilepsy." }, { "type": "li", "text": "**Acute confusional migraine and Alice in Wonderland syndrome**: confusional migraine, mostly in children, brings confusion and agitation, usually after the headache begins, and is not listed in the International Classification of Headache Disorders (ICHD-3). Alice in Wonderland syndrome distorts body image, the size or shape of objects and the sense of time; causes include migraine and, in children, encephalitis (often Epstein–Barr virus). EEG and MRI are advised when the cause is unclear." }, { "type": "li", "text": "**Concussive (impact) convulsions**: tonic stiffening then jerking within 2 seconds of a head impact, lasting up to about 150 seconds, with rapid recovery and normal imaging. In 22 elite footballers none developed epilepsy. They are probably non-epileptic and need no ASM; a seizure later in the first week after a brain injury is an acute symptomatic seizure." }, { "type": "h3", "text": "Paroxysmal movement disorders" }, { "type": "p", "text": "These episodic disorders are mistaken for focal seizures; the trigger and the length of the attacks are the best clues." }, { "type": "table", "head": [ "Disorder", "Trigger and attacks", "Gene", "Treatment" ], "rows": [ [ "Paroxysmal kinesigenic dyskinesia", "Sudden movement; dystonia or chorea lasting under a minute, often many a day; awareness kept", "PRRT2", "Low-dose carbamazepine or another ASM" ], [ "Paroxysmal non-kinesigenic dyskinesia", "Caffeine, alcohol or emotional stress; mixed chorea and dystonia for 10 minutes to an hour; onset in infancy or early childhood", "MR-1 (also called PNKD)", "Benzodiazepines such as clonazepam" ], [ "Paroxysmal exercise-induced dyskinesia", "Prolonged exercise; chorea or dystonia, mainly of the legs; may come with generalized epilepsy", "SLC2A1 (glucose transporter 1 deficiency); low cerebrospinal fluid (CSF)-to-blood glucose ratio", "Ketogenic diet" ], [ "Episodic ataxia type 1", "Brief attacks of ataxia and slurred speech; myokymia between attacks", "KCNA1", "Acetazolamide helps some" ], [ "Episodic ataxia type 2", "Longer attacks of ataxia, slurred speech and vertigo; nystagmus between attacks", "CACNA1A", "Acetazolamide; 4-aminopyridine reduced attacks in a randomized trial" ] ] }, { "type": "mcq", "id": "q-15znkr8", "stem": "A 16-year-old has had attacks of twisting of both feet and legs for a year, each beginning after about 20 minutes of running and settling with rest. Sudden movements and caffeine do not trigger them. She also had brief absence seizures in childhood. Examination between attacks and MRI are normal. Which test is most likely to confirm the diagnosis?", "options": [ "Prolonged video-EEG to record an attack", "Paired fasting CSF and blood glucose, or SLC2A1 testing", "PRRT2 testing", "Serum creatine kinase after an attack", "KCNA1 testing" ], "answer": 1, "explain": "Dyskinesia brought on by prolonged exercise, mainly in the legs, together with generalized seizures, suggests paroxysmal exercise-induced dyskinesia from glucose transporter 1 deficiency (SLC2A1), confirmed by a low CSF-to-blood glucose ratio or genetic testing; the ketogenic diet treats it. PRRT2 causes attacks on sudden movement, KCNA1 causes episodic ataxia with myokymia, and an EEG during an attack would not identify the cause." }, { "type": "h3", "text": "Mimics in infants and children" }, { "type": "table", "head": [ "Mimic", "Clues", "What to do" ], "rows": [ [ "Benign neonatal sleep myoclonus", "Repetitive jerks in a well newborn, only in sleep, stopping on waking; provoked by rocking, increased by holding the limbs; no EEG change", "Reassure, no ASM (jerks can worsen on ASMs); usually gone by 3 months, sometimes later" ], [ "Hyperekplexia", "Stiffness from birth, worse with handling; exaggerated startle to a tap on the nose; stiffening with apnea; no epileptic EEG change; GLRA1 most often, also SLC6A5 or GLRB", "Clonazepam (helpful in about 95%); forced flexion of the head and legs toward the trunk (the Vigevano maneuver) can end a stiffening and apnea episode" ], [ "Breath-holding spells", "Onset at 6–18 months, gone by about age 5. Cyanotic: crying from anger or frustration, breath held in expiration, cyanosis. Pallid: pain or fright, little crying, pallor from vagal slowing or pause of the heart. Both can end in loss of consciousness and stiffening", "Reassure; look for iron deficiency, since iron reduced spells in a placebo-controlled trial" ], [ "Benign myoclonus of infancy and shuddering attacks", "Brief shudders or axial contractions while awake, often with excitement or frustration; normal development; no EEG change", "Separate from epileptic spasms, which cluster (often on waking) and have an ictal EEG correlate; resolve in early childhood; a link to essential tremor is unproven" ], [ "Alternating hemiplegia of childhood", "Paroxysmal eye movements in the first months, then hemiplegic attacks that switch sides or become bilateral and end with sleep; developmental delay; EEG shows slowing, not seizures", "De novo ATP1A3 variants; flunarizine is the most used preventive, with variable benefit; not Todd paralysis" ], [ "Opsoclonus–myoclonus–ataxia", "Toddler with chaotic eye movements in all directions, myoclonus, ataxia, irritability and poor sleep; jerks without EEG correlate", "Search for neuroblastoma; immunotherapy such as corticosteroids or corticotropin, not ASMs" ], [ "Sandifer syndrome", "Abnormal posturing or torticollis with gastroesophageal reflux", "Treat the reflux" ], [ "Benign paroxysmal torticollis and benign paroxysmal vertigo", "Torticollis: head tilt from the first year, lasting minutes to days, with pallor, irritability, vomiting or ataxia. Vertigo: brief attacks in young children with nystagmus, vomiting or fear, consciousness kept", "Migraine-related episodic syndromes (ICHD-3); normal examination between attacks; exclude posterior fossa lesions; the vertigo is now also called recurrent vertigo of childhood" ], [ "Motor stereotypies and gratification behavior", "Stereotypies: repetitive arm or hand movements or head nodding, in typically developing children as well as in autism, often for years. Gratification: from 3 months to 3 years, perineal pressure with leg posturing, grunting, flushing and sweating, awareness kept, stops with distraction", "Normal examination and tests; home video; reassurance" ], [ "Spasmus nutans", "Infant head nodding, head tilt and nystagmus", "MRI (chiasmal glioma in a minority) and eye examination (retinal dystrophy can look the same)" ] ] }, { "type": "mcq", "id": "q-qquwq1", "stem": "A 9-month-old has brief shudders of the head and trunk several times a day, mostly when excited. He stays alert and smiles straight afterward, and his development is normal. Video-EEG captures 12 events with no EEG change on a normal background. What is the most likely diagnosis?", "options": [ "Infantile epileptic spasms syndrome", "Benign myoclonus of infancy (shuddering attacks)", "Myoclonic epilepsy in infancy", "Benign neonatal sleep myoclonus", "Hyperekplexia" ], "answer": 1, "explain": "Brief shudders or axial contractions while awake, set off by excitement, in a developing infant with no EEG change, are benign myoclonus of infancy or shuddering attacks, which resolve in early childhood. Epileptic spasms come in clusters with an ictal EEG correlate; myoclonic epilepsy in infancy has generalized spike-and-wave with the jerks; sleep myoclonus is confined to sleep in newborns; hyperekplexia begins at birth with stiffness and exaggerated startle." }, { "type": "h3", "text": "Laboratory adjuncts" }, { "type": "p", "text": "Serum prolactin rises 10–20 minutes after a generalized tonic–clonic or focal impaired-consciousness seizure and then falls, so timing matters. A normal value does not exclude a seizure, and syncope can raise it too. Lateral tongue biting favors an epileptic seizure; incontinence does not discriminate." }, { "type": "case", "id": "case-functional", "title": "Events that do not stop", "intro": [ "A 27-year-old woman has had \"seizures\" for two years despite levetiracetam, lamotrigine and lacosamide. Events last 5–15 minutes, with her eyes shut, side-to-side head movements, and crying afterwards. She has been intubated twice in the emergency department." ], "steps": [ { "narrative": [], "stem": "What is the most important next step?", "options": [ "Add a fourth ASM", "Refer for epilepsy surgery evaluation", "Admit for video-EEG monitoring to capture typical events", "Measure prolactin at her next clinic visit", "Obtain a PET scan" ], "answer": 2, "explain": "Two failed ASMs should prompt review of the diagnosis. Video-EEG capture of typical events is the diagnostic standard for functional seizures and is required before surgery could ever be considered." }, { "narrative": [ "During monitoring she has three typical events. The EEG shows continuous posterior alpha throughout, with muscle artifact, and no ictal change. She recalls being spoken to during one event." ], "stem": "How should the diagnosis be communicated?", "options": [ "Tell her the events are \"not real\" and discharge her", "Avoid naming the diagnosis to prevent distress", "Explain that these are functional (dissociative) seizures: real, common and treatable, and not epilepsy", "Say that the test was inconclusive", "Continue all ASMs in case some events are epileptic" ], "answer": 2, "explain": "A clear, non-judgmental explanation that names the condition and emphasizes that it is real and treatable improves engagement with treatment." }, { "narrative": [], "stem": "What should happen to her ASMs and ongoing care?", "options": [ "Continue all three indefinitely", "Taper the ASMs if there is no evidence of coexisting epilepsy, and refer for psychological therapy with neurology follow-up", "Stop all three abruptly today", "Switch to a benzodiazepine for events", "Discharge from neurology care" ], "answer": 1, "explain": "Without evidence of epilepsy, ASMs add risk without benefit and are tapered. Psychological therapy (CBT-informed approaches have the best evidence) with continued neurological support gives the best outcomes." } ], "outro": [ "Two failed ASMs should always prompt a diagnostic review. About one person in five referred to epilepsy centers for drug-resistant epilepsy turns out to have functional seizures." ] }, { "type": "mcq", "id": "q-1xdojqc", "stem": "Which sign most strongly favors a functional (dissociative) seizure over an epileptic seizure?", "options": [ "Incontinence of urine", "Injury during the event", "Eyes closed during the event, resisting opening", "Occurrence during the day", "A raised creatine kinase the next day" ], "answer": 2, "explain": "Sustained eye closure during an event is one of the most reliable signs of a functional seizure; the eyes are usually open in epileptic convulsions. Incontinence and injury occur in both." }, { "type": "cards", "items": [ { "id": "c-1veric5", "front": "Most reliable bedside sign of a functional seizure", "back": "Eyes closed during the event, often resisting opening." }, { "id": "c-hw1r33", "front": "Diagnostic standard for functional seizures", "back": "Video-EEG capture of a typical event without ictal change, with a consistent history." }, { "id": "c-10yy064", "front": "Convulsive syncope", "back": "Brief irregular jerks, usually under 15 s, after the fall; quick reorientation." }, { "id": "c-xsyso5", "front": "Prolactin after a seizure", "back": "Rises 10–20 minutes after a convulsion or focal impaired-consciousness seizure; also after syncope." }, { "id": "c-1oezhe", "front": "Lateral tongue bite", "back": "Favors an epileptic seizure." }, { "id": "c-135bjv2", "front": "PRRT2 attacks triggered by sudden movement", "back": "Paroxysmal kinesigenic dyskinesia; responds to low-dose carbamazepine." }, { "id": "c-xu2pxi", "front": "Evidence-based treatment for functional seizures", "back": "Psychological therapy, especially CBT-informed approaches." }, { "id": "c-1x9wvse", "front": "EEG during syncope", "back": "Slowing, high-amplitude delta, then flattening if deeper; recovery in reverse; no evolving rhythmic discharge." }, { "id": "c-qf3cxu", "front": "The 10/20 rule", "back": "Fewer than 10 jerks favors syncope; more than 20 favors a convulsive seizure." }, { "id": "c-1f9l3b8", "front": "Older name for functional seizures", "back": "Psychogenic nonepileptic seizures (PNES); avoid \"pseudoseizures\"." }, { "id": "c-v7xaow", "front": "Levels of certainty for functional seizures (ILAE 2013)", "back": "Possible, probable, clinically established, documented." }, { "id": "c-oya5p2", "front": "Documented functional seizures", "back": "A typical event seen on video-EEG by an experienced clinician, with no epileptiform activity before, during or after." }, { "id": "c-3f97jw", "front": "Postictal stertorous breathing", "back": "Favors a generalized tonic–clonic seizure over a functional convulsion." }, { "id": "c-ds7sfy", "front": "Pelvic thrusting", "back": "Seen in functional seizures and in frontal lobe seizures; not decisive alone." }, { "id": "c-tfebhi", "front": "Average delay to a functional seizure diagnosis", "back": "About 7 years." }, { "id": "c-1coi5sq", "front": "Commonest psychiatric comorbidities in functional seizures", "back": "Post-traumatic stress disorder, depression, anxiety and personality disorders; past trauma and abuse are frequent." }, { "id": "c-1bl824v", "front": "Factitious disorder versus malingering", "back": "Both deliberate: the sick role versus an external gain. Functional seizures are not deliberate." }, { "id": "c-hqs9ov", "front": "Adult outcome of functional seizures", "back": "Most still have events years later; better with younger onset, earlier diagnosis and less dramatic attacks." }, { "id": "c-1kytj0d", "front": "CODES trial", "back": "CBT added to standardized care: no significant fall in monthly seizures, but better secondary outcomes." }, { "id": "c-1sb8q5h", "front": "Sleep-related rhythmic movement disorder", "back": "Head banging or body rocking at sleep onset in young children." }, { "id": "c-1nwvw77", "front": "Occipital seizure versus migraine aura", "back": "Seizure: seconds, colored circular spots. Aura: spreads over 5 minutes or more, lasts 5–60 minutes, zigzag figure with a scotoma." }, { "id": "c-e4bdmj", "front": "Limb-shaking TIA", "back": "Postural, irregular shaking of one limb from severe opposite carotid disease; image the vessels urgently." }, { "id": "c-1cdcv4c", "front": "Transient epileptic amnesia", "back": "Older adults; brief, recurrent amnesia, often on waking; responds to ASMs." }, { "id": "c-1aw5711", "front": "Concussive convulsion", "back": "Within seconds of impact, quick recovery, normal imaging: not epilepsy, no ASM." }, { "id": "c-1glig7g", "front": "Paroxysmal non-kinesigenic dyskinesia", "back": "Caffeine, alcohol or stress; 10 minutes to an hour; MR-1 (PNKD) gene; clonazepam." }, { "id": "c-amm2oy", "front": "Paroxysmal exercise-induced dyskinesia", "back": "After prolonged exercise; SLC2A1 (glucose transporter 1 deficiency); ketogenic diet." }, { "id": "c-6rwzpe", "front": "Episodic ataxia type 1 versus type 2", "back": "Type 1: KCNA1, brief attacks, myokymia. Type 2: CACNA1A, longer attacks, nystagmus; acetazolamide or 4-aminopyridine." }, { "id": "c-akwnvy", "front": "Benign neonatal sleep myoclonus", "back": "Jerks only in sleep, stop on waking, increase with restraint; no ASM." }, { "id": "c-wllw7u", "front": "Hyperekplexia", "back": "Stiffness, nose-tap startle, apnea; GLRA1; clonazepam; forced flexion (Vigevano) maneuver." }, { "id": "c-1i4mx4n", "front": "Pallid breath-holding spell", "back": "Pain or fright; vagal slowing or pause of the heart; check for and treat iron deficiency." }, { "id": "c-15z4mfq", "front": "Alternating hemiplegia of childhood", "back": "De novo ATP1A3; side-switching hemiplegia relieved by sleep; early eye-movement attacks; flunarizine." }, { "id": "c-oyfx9r", "front": "Opsoclonus–myoclonus–ataxia", "back": "Jerks without EEG correlate; look for neuroblastoma; immunotherapy." }, { "id": "c-1npa5ra", "front": "Spasmus nutans", "back": "Head nodding, head tilt and nystagmus in an infant; MRI for chiasmal glioma." } ] } ], "sources": [ { "title": "ILAE minimum requirements for diagnosing psychogenic nonepileptic seizures (LaFrance 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24111933/" }, { "title": "ILAE practical clinical definition of epilepsy (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24730690/" }, { "title": "Electroencephalography in syncope (Brenner 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9244159/" }, { "title": "Semiology of tilt-induced syncope and EEG changes (van Dijk 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24343112/" }, { "title": "Motor phenomena in syncope and convulsive seizures: the 10/20 rule (Shmuely 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29549227/" }, { "title": "Ictal asystole and ictal syncope (Bestawros 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25391254/" }, { "title": "ACC/AHA/HRS guideline for syncope (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28280231/" }, { "title": "Compulsively self-induced syncope by Valsalva maneuver (Aicardi 1988)", "url": "https://pubmed.ncbi.nlm.nih.gov/3134879/" }, { "title": "Terminology for psychogenic nonepileptic seizures: the case for \"functional seizures\" (Asadi-Pooya 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31986440/" }, { "title": "Preferred terminology for functional seizures (Loewenberger 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32535370/" }, { "title": "Clinical signs that distinguish psychogenic nonepileptic from epileptic seizures (Avbersek 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20581136/" }, { "title": "Postictal breathing in convulsive functional and epileptic seizures (Rosemergy 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23395834/" }, { "title": "Ictal eye closure in psychogenic nonepileptic seizures (Chung 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16769949/" }, { "title": "Oral lacerations and incontinence during convulsive events (Oliva 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18325019/" }, { "title": "Pelvic thrusting in seizures and pseudoseizures (Geyer 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10636155/" }, { "title": "Gender and emotional adjustment in nonepileptic seizures (Holmes 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/12609391/" }, { "title": "Psychiatric comorbidity in functional seizures compared with epilepsy (Diprose 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26874243/" }, { "title": "Trauma and post-traumatic stress disorder in nonepileptic seizures (Fiszman 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15582828/" }, { "title": "Diagnostic delay in psychogenic nonepileptic seizures (Reuber 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11839862/" }, { "title": "Functional seizures before and after temporal lobe surgery (González Otárula 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28867568/" }, { "title": "Factitious disorders and malingering in functional neurologic disorders (Bass 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27719868/" }, { "title": "Outcome in psychogenic nonepileptic seizures at 1–10 years (Reuber 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12601698/" }, { "title": "Pilot trial of sertraline for nonepileptic seizures (LaFrance 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20739647/" }, { "title": "Multicenter pilot treatment trial for nonepileptic seizures (LaFrance 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24989152/" }, { "title": "CODES: CBT for adults with dissociative seizures (Goldstein 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32445688/" }, { "title": "Psychogenic nonepileptic seizures in the pediatric population (Operto 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31568694/" }, { "title": "Psychogenic seizures in children and adolescents: outcome (Wyllie 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2314960/" }, { "title": "Rhythmic movement disorder in childhood (Gwyther 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27884450/" }, { "title": "Elementary visual hallucinations in occipital epilepsy versus migraine (Panayiotopoulos 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10201433/" }, { "title": "ICHD-3: migraine with aura", "url": "https://ichd-3.org/1-migraine/1-2-migraine-with-aura/" }, { "title": "Limb shaking: a carotid TIA (Baquis 1985)", "url": "https://pubmed.ncbi.nlm.nih.gov/4002258/" }, { "title": "Limb-shaking TIA: a systematic review (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37839077/" }, { "title": "The syndrome of transient epileptic amnesia (Butler 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17444534/" }, { "title": "Syndromes of transient amnesia: 153 cases (Hodges 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2266362/" }, { "title": "Transient global amnesia: 142 cases (Quinette 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16670178/" }, { "title": "Acute confusional migraine: a review (Farooqi 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29414874/" }, { "title": "Alice in Wonderland syndrome: a systematic review (Blom 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27347442/" }, { "title": "Alice in Wonderland syndrome: clinical review (Mastria 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/28116304/" }, { "title": "Concussive convulsions in elite footballers (McCrory 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9022428/" }, { "title": "Diagnostic criteria for paroxysmal kinesigenic dyskinesia (Bruno 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15623687/" }, { "title": "Paroxysmal non-kinesigenic dyskinesia: genotype and phenotype (Bruno 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17515540/" }, { "title": "Paroxysmal exercise-induced dyskinesia and SLC2A1 (Suls 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18577546/" }, { "title": "Hereditary episodic ataxia (Riant 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21492892/" }, { "title": "4-aminopyridine in episodic ataxia type 2: randomized trial (Strupp 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21734179/" }, { "title": "Benign neonatal sleep myoclonus: review (Maurer 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20351003/" }, { "title": "Benign neonatal sleep myoclonus (Daoust-Roy 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1415056/" }, { "title": "Genotype–phenotype correlations in hyperekplexia (Thomas 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24030948/" }, { "title": "Hyperekplexia in neonates (Praveen 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11524514/" }, { "title": "Startle disease: an avoidable cause of sudden infant death (Vigevano 1989)", "url": "https://pubmed.ncbi.nlm.nih.gov/2563117/" }, { "title": "Breath-holding spells: narrative review (Leung 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30421679/" }, { "title": "Iron therapy for breath-holding spells (Daoud 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9108851/" }, { "title": "Benign myoclonus of early infancy (Pachatz 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10937134/" }, { "title": "Transient infant movements (Piscitello 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34519642/" }, { "title": "Shuddering attacks are not related to essential tremor (Jan 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20519668/" }, { "title": "Alternating hemiplegia of childhood: early features (Sweney 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19254988/" }, { "title": "De novo ATP1A3 mutations cause alternating hemiplegia (Heinzen 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22842232/" }, { "title": "Alternating hemiplegia treated with topiramate and flunarizine (Aishworiya 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21575320/" }, { "title": "Opsoclonus–myoclonus–ataxia syndrome in children: international perspective (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35260471/" }, { "title": "Opsoclonus myoclonus presenting as status epilepticus (Haden 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19847000/" }, { "title": "Sandifer syndrome: systematic review (Kato 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38526644/" }, { "title": "ICHD-3: benign paroxysmal torticollis", "url": "https://ichd-3.org/1-migraine/1-6-episodic-syndromes-that-may-be-associated-with-migraine/1-6-3-benign-paroxysmal-torticollis/" }, { "title": "ICHD-3: benign paroxysmal vertigo", "url": "https://ichd-3.org/1-migraine/1-6-episodic-syndromes-that-may-be-associated-with-migraine/1-6-2-benign-paroxysmal-vertigo/" }, { "title": "Bárány Society criteria for vestibular migraine and recurrent vertigo of childhood (2021 interpretation)", "url": "https://pubmed.ncbi.nlm.nih.gov/34628805/" }, { "title": "Masturbation in infancy presenting as a movement disorder (Yang 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16322167/" }, { "title": "Nonautistic motor stereotypies (Harris 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18358406/" }, { "title": "Spasmus nutans-like nystagmus and underlying abnormalities (Kiblinger 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17548996/" } ], "words": 3094, "bank": 12 } ], "intro": [ "Before any drug is chosen the questions are the same: was it a seizure, was it provoked, is this epilepsy, and what kind. The definitions below are operational: each one changes what you do next." ] }, { "id": "syndromes", "n": "6", "title": "Syndromes, genetics and causes", "short": "Syndromes", "sections": [ { "id": "syndrome-framework", "n": "1", "title": "How the 2022 syndrome classification works", "tags": [ "ilae-classification" ], "updated": true, "goals": [ "Explain how syndromes are grouped", "use the renamed syndromes", "know what a syndrome diagnosis requires" ], "blocks": [ { "type": "p", "updated": true, "label": "ILAE 2022", "text": "For the first time the ILAE published a full syndrome classification, in four papers by age at onset: neonates and infants, childhood, variable age, and the idiopathic generalized epilepsies. Most familiar names changed, and \"benign\" and \"catastrophic\" were retired." }, { "type": "h3", "text": "The building blocks" }, { "type": "li", "text": "Syndromes are grouped by **age at onset**: neonatal and infantile (up to 2 years), childhood, and variable age (childhood or adulthood)." }, { "type": "li", "text": "Within each group they are **self-limited** (likely to remit), **developmental and epileptic encephalopathies**, or defined by a specific cause (**etiology-specific** syndromes such as KCNQ2-DEE, CDKL5-DEE or Sturge–Weber syndrome)." }, { "type": "li", "text": "The **idiopathic generalized epilepsies** are four syndromes only: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic–clonic seizures alone." }, { "type": "li", "text": "Each syndrome lists **mandatory** criteria, **exclusionary** criteria, and **alerts**: features that are rare in the syndrome and should prompt caution before diagnosing it." }, { "type": "figure", "html": "syndrome-ages", "caption": "Typical age at onset for the syndromes in this part, on a logarithmic age scale, using the ranges given in the sections that follow. Point at or tab to a bar for its EEG signature and a clue.", "n": 13 }, { "type": "h3", "text": "The rename table" }, { "type": "table", "head": [ "Older name", "2022 name" ], "rows": [ [ "Benign familial neonatal seizures", "Self-limited (familial) neonatal epilepsy (SeLNE)" ], [ "Benign familial infantile seizures", "Self-limited (familial) infantile epilepsy (SeLIE)" ], [ "Ohtahara syndrome and early myoclonic encephalopathy", "Early infantile developmental and epileptic encephalopathy (EIDEE)" ], [ "West syndrome, infantile spasms", "Infantile epileptic spasms syndrome (IESS)" ], [ "Benign epilepsy with centrotemporal spikes", "Self-limited epilepsy with centrotemporal spikes (SeLECTS)" ], [ "Panayiotopoulos syndrome", "Self-limited epilepsy with autonomic seizures (SeLEAS)" ], [ "Late-onset occipital epilepsy (Gastaut type)", "Childhood occipital visual epilepsy (COVE)" ], [ "Doose syndrome, myoclonic-astatic epilepsy", "Epilepsy with myoclonic–atonic seizures (EMAtS)" ], [ "Jeavons syndrome", "Epilepsy with eyelid myoclonia (EEM)" ], [ "Continuous spike-and-wave in sleep, Landau–Kleffner syndrome", "DEE or EE with spike-wave activation in sleep (DEE-SWAS, EE-SWAS)" ], [ "Epilepsy with generalized tonic–clonic seizures on awakening", "Epilepsy with generalized tonic–clonic seizures alone (GTCA)" ], [ "Autosomal dominant nocturnal frontal lobe epilepsy", "Sleep-related hypermotor (hyperkinetic) epilepsy (SHE)" ], [ "Autosomal dominant epilepsy with auditory features", "Epilepsy with auditory features (EAF)" ] ] }, { "type": "match", "id": "match-renames", "prompt": "Match each older name to its 2022 name", "pairs": [ [ "West syndrome", "Infantile epileptic spasms syndrome" ], [ "Panayiotopoulos syndrome", "Self-limited epilepsy with autonomic seizures" ], [ "Doose syndrome", "Epilepsy with myoclonic–atonic seizures" ], [ "Ohtahara syndrome", "Early infantile developmental and epileptic encephalopathy" ], [ "Landau–Kleffner syndrome", "Epileptic encephalopathy with spike-wave activation in sleep" ], [ "Benign rolandic epilepsy", "Self-limited epilepsy with centrotemporal spikes" ] ] }, { "type": "mcq", "id": "q-144gnmb", "stem": "Which is NOT one of the four idiopathic generalized epilepsies in the 2022 classification?", "options": [ "Childhood absence epilepsy", "Juvenile absence epilepsy", "Juvenile myoclonic epilepsy", "Epilepsy with generalized tonic–clonic seizures alone", "Epilepsy with myoclonic–atonic seizures" ], "answer": 4, "explain": "The IGEs are CAE, JAE, JME and GTCA. Epilepsy with myoclonic–atonic seizures is a generalized developmental and epileptic encephalopathy of childhood." }, { "type": "cards", "items": [ { "id": "c-c4bju7", "front": "What \"alerts\" mean in the 2022 syndrome criteria", "back": "Features rare in the syndrome that should prompt caution before diagnosing it." }, { "id": "c-19xuckd", "front": "The four idiopathic generalized epilepsies", "back": "CAE, JAE, JME and GTCA." }, { "id": "c-wv5y4c", "front": "Age groups in the 2022 syndrome papers", "back": "Neonatal and infantile, childhood, variable age (plus the IGE paper)." }, { "id": "c-1yrncyy", "front": "Etiology-specific syndrome examples", "back": "KCNQ2-DEE, CDKL5-DEE, PCDH19 clustering epilepsy, GLUT1 deficiency, Sturge–Weber syndrome, gelastic seizures with hypothalamic hamartoma." } ] } ], "sources": [ { "title": "ILAE syndrome classification overview (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503715/" }, { "title": "Syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "Syndromes with onset in childhood (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503717/" }, { "title": "Syndromes with onset at a variable age (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503725/" }, { "title": "Idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" } ], "words": 492, "bank": 2 }, { "id": "syndromes-infancy", "n": "2", "title": "Neonatal and infantile onset", "tags": [ "ilae-classification", "seizure-management" ], "updated": false, "goals": [ "Recognize the self-limited and encephalopathic syndromes of the first two years", "treat infantile spasms urgently", "spot Dravet syndrome early" ], "blocks": [ { "type": "table", "head": [ "Syndrome", "Onset", "Key features", "Genes and notes" ], "rows": [ [ "[SeLNE](ilae_classification.html#syndrome-0)", "First days of life (typically day 2–7)", "Focal tonic or clonic seizures, often with apnea, in a well baby; remits within months, but up to a third have seizures again later in life (febrile seizures, focal clusters, tonic–clonic seizures, occasionally SeLECTS)", "KCNQ2 (most), KCNQ3; autosomal dominant" ], [ "[Self-limited neonatal-infantile epilepsy](ilae_classification.html#syndrome-1)", "Days to the second year", "Clusters of focal seizures; remits", "Often SCN2A" ], [ "[SeLIE](ilae_classification.html#syndrome-2)", "First two years, peak around 6 months", "Clusters of focal seizures; development normal", "PRRT2; relatives may have paroxysmal kinesigenic dyskinesia" ], [ "[EIDEE](ilae_classification.html#syndrome-5)", "Under 3 months", "Tonic seizures, spasms, myoclonus; burst-suppression or severely abnormal EEG; severe delay", "STXBP1, KCNQ2, SCN2A, CDKL5 and structural causes" ], [ "[KCNQ2 developmental and epileptic encephalopathy](ilae_classification.html#syndrome-9)", "First week of life", "Frequent tonic (often asymmetric) seizures in an encephalopathic newborn; burst-suppression in over 60%, otherwise multifocal discharges; evolution to infantile spasms is less common than in other early encephalopathies", "De novo KCNQ2 missense variants with a stronger loss of function than in SeLNE; carbamazepine or phenytoin often stops the seizures; over half become seizure-free, but moderate to severe disability remains" ], [ "[Epilepsy of infancy with migrating focal seizures](ilae_classification.html#syndrome-6)", "First months", "Focal seizures shifting between hemispheres; developmental regression", "KCNT1 most often (gain-of-function variants, about half of cases)" ], [ "[IESS](ilae_classification.html#syndrome-4)", "1–24 months", "Epileptic spasms in clusters on waking; hypsarrhythmia or multifocal discharges; developmental plateau", "Tuberous sclerosis, hypoxic-ischemic injury, malformations, genetic and metabolic causes" ], [ "[Dravet syndrome](ilae_classification.html#syndrome-7)", "Usually 3–12 months", "Prolonged febrile and afebrile hemiclonic or generalized seizures; later myoclonic, atypical absence and focal seizures; development slows after year one", "SCN1A loss of function in most, usually de novo" ], [ "[Myoclonic epilepsy in infancy](ilae_classification.html#syndrome-3)", "Infancy", "Myoclonic seizures in a developmentally normal child; responds to treatment", "Often no cause found" ] ] }, { "type": "note", "label": "Try it", "text": "Each syndrome name opens its entry in the [ILAE syndrome lookup](ilae_classification.html#syndromes-tab), with a summary, the EEG findings, a link to its criteria in the 2022 paper and, for most, an illustrative tracing." }, { "type": "p", "text": "**How the early infantile encephalopathy evolves.** Early infantile developmental and epileptic encephalopathy often turns into infantile epileptic spasms syndrome after 3–4 months of age, as burst-suppression gives way to hypsarrhythmia, and many later meet criteria for Lennox–Gastaut syndrome. The ILAE puts that at about half of infants with a severe developmental and epileptic encephalopathy of this age, and about 30% of all infants with IESS. Older questions still use the two names it replaced. **Ohtahara syndrome**: tonic spasms, burst-suppression in waking and sleep alike, mostly structural causes, and the classic sequence from Ohtahara to West to Lennox–Gastaut syndrome. **Early myoclonic encephalopathy**: erratic myoclonus and focal seizures, burst-suppression mainly in sleep, and genetic or metabolic causes. The ILAE merged them because their features and causes overlap and the split no longer changes treatment or prognosis." }, { "type": "h3", "text": "Infantile epileptic spasms syndrome" }, { "type": "li", "text": "**West syndrome is a subset, not a synonym.** West syndrome is the triad of spasms, hypsarrhythmia and developmental stagnation or regression. IESS needs only epileptic spasms with hypsarrhythmia or with focal or multifocal discharges, so an infant without hypsarrhythmia or obvious regression still qualifies and still gets standard treatment." }, { "type": "li", "text": "Treat as an emergency. A shorter lag between onset and treatment is associated with better development." }, { "type": "li", "text": "**First-line**: hormonal therapy (ACTH or high-dose prednisolone) or vigabatrin. **Vigabatrin is preferred when the cause is tuberous sclerosis.**" }, { "type": "li", "text": "**Prednisolone or ACTH**: they work about equally well. In the UK Infantile Spasms Study (UKISS), spasms had stopped by day 14 in 70% on oral prednisolone and 76% on intramuscular tetracosactide (synthetic ACTH), and a meta-analysis of randomized trials found no difference in spasm cessation, EEG response or relapse. Prednisolone is oral, cheaper and quicker to start. Watch for hypertension, irritability, infection, cushingoid features and increased appetite. ACTH has also caused hypertrophic cardiomyopathy, so an infant who becomes hypertensive on it needs an echocardiogram." }, { "type": "li", "text": "In the ICISS trial, hormonal therapy plus vigabatrin stopped spasms more often than hormonal therapy alone, without a difference in development at 18 months." }, { "type": "li", "text": "Confirm response with EEG: resolution of hypsarrhythmia matters as well as clinical cessation." }, { "type": "li", "text": "**If spasms or hypsarrhythmia persist** on a video-EEG that includes sleep and waking, treatment has failed, even if the family no longer sees spasms. Switch to the other first-line class (vigabatrin after hormones, or hormones after vigabatrin). In the National Infantile Spasms Consortium cohort, 55% responded when the second drug was the other standard class, compared with 25% for any other choice. Spasms can also return after a first response (41% in one cohort treated with ACTH, mainly when discharges persisted on the EEG), so keep checking." }, { "type": "li", "text": "**Look for a surgical cause.** Asymmetric spasms, focal seizures or a consistent focal EEG feature suggest a structural lesion. With focal cortical dysplasia, an early-acquired lesion, or tuberous sclerosis with a tuber that matches the EEG, refer early for [surgical evaluation](#presurgical-evaluation). A generalized EEG does not rule surgery out: in one series of 50 children and young adults with early lesions whose discharges were largely generalized or bilateral, 72% became seizure-free. When refractory spasms have no known cause, repeat the MRI after myelination (about age 2) and consider fluorodeoxyglucose positron emission tomography (FDG-PET) to find a hidden dysplasia." }, { "type": "li", "text": "**Prognosis** depends mostly on the cause. It is better with no known cause, normal development before the spasms, a short lag to treatment and a prompt response. In long follow-up about a third are seizure-free and about a quarter have a favorable cognitive outcome; around 30% of all infants with IESS evolve to Lennox–Gastaut syndrome." }, { "type": "h3", "text": "Dravet syndrome" }, { "type": "li", "text": "Suspect it in an infant with **prolonged, often hemiclonic, febrile seizures** before age one, triggered by fever, warm baths or vaccination, especially when they recur." }, { "type": "li", "text": "Test for SCN1A early." }, { "type": "li", "text": "**Avoid sodium channel blockers** (carbamazepine, oxcarbazepine, phenytoin, lamotrigine), which worsen seizures." }, { "type": "li", "text": "Useful drugs: valproate, clobazam, stiripentol, fenfluramine and cannabidiol; the ketogenic diet also helps." }, { "type": "li", "text": "SUDEP risk is high. Every family needs a rescue plan for prolonged seizures." }, { "type": "case", "id": "case-dravet", "title": "Recurrent febrile status in an infant", "intro": [ "A 7-month-old girl has a 35-minute right-sided clonic seizure with a temperature of 38.4 °C, the day after her routine vaccinations. Development has been normal. MRI and CSF are normal." ], "steps": [ { "narrative": [], "stem": "Six weeks later she has a 25-minute left-sided clonic seizure during a warm bath, without fever. Which diagnosis must be considered now?", "options": [ "Simple febrile seizures", "Self-limited infantile epilepsy", "Dravet syndrome", "Infantile epileptic spasms syndrome", "Childhood absence epilepsy" ], "answer": 2, "explain": "Prolonged hemiclonic seizures of alternating side in the first year, triggered by fever, vaccination or warm baths in a previously normal infant, are the classic early picture of Dravet syndrome." }, { "narrative": [], "stem": "What is the most useful next investigation?", "options": [ "Repeat MRI in 3 months", "Genetic testing that includes SCN1A", "Lumbar puncture for lactate", "Prolonged ambulatory EEG only", "Muscle biopsy" ], "answer": 1, "explain": "More than 80% of children with Dravet syndrome have an SCN1A variant, usually de novo. Confirmation guides treatment and counseling. Early EEG and MRI are often normal." }, { "narrative": [ "She is found to carry a de novo SCN1A truncating variant. Her local doctor has started carbamazepine." ], "stem": "What is the most important change?", "options": [ "Stop carbamazepine and use valproate or clobazam, then stiripentol, fenfluramine or cannabidiol as needed", "Increase carbamazepine to a higher target level", "Add lamotrigine", "Switch to phenytoin", "Add oxcarbazepine" ], "answer": 0, "explain": "Sodium channel blockers worsen seizures in SCN1A loss-of-function Dravet syndrome. Valproate and clobazam are first-line; stiripentol, fenfluramine and cannabidiol have randomized trial evidence." }, { "narrative": [], "stem": "What must the family also have?", "options": [ "Nothing further; the drugs will control her seizures", "A written rescue plan with a rescue benzodiazepine for prolonged seizures, and counseling about SUDEP", "Advice to avoid all vaccinations", "A referral for epilepsy surgery", "Daily antipyretics" ], "answer": 1, "explain": "Prolonged seizures and SUDEP are the main dangers. Vaccination should continue, with fever management around it; vaccination may trigger the first seizure but does not cause the syndrome." } ], "outro": [ "Recurrent prolonged febrile seizures in the first year are not \"just febrile seizures\". Test early, and keep sodium channel blockers away." ] }, { "type": "mcq", "id": "q-glerh6", "stem": "A 5-month-old with tuberous sclerosis complex develops clusters of flexor spasms on waking. EEG shows hypsarrhythmia. What is the preferred first treatment?", "options": [ "Levetiracetam", "Vigabatrin", "Carbamazepine", "Wait two weeks to confirm the diagnosis", "Phenytoin" ], "answer": 1, "explain": "Vigabatrin is first-line for epileptic spasms in tuberous sclerosis. Treatment of infantile spasms should start without delay because a shorter lead time is associated with better development." }, { "type": "cards", "items": [ { "id": "c-rlm60n", "front": "SeLNE gene", "back": "KCNQ2 (most), KCNQ3." }, { "id": "c-1o9n8hi", "front": "SeLIE gene", "back": "PRRT2; relatives may have paroxysmal kinesigenic dyskinesia." }, { "id": "c-y7iugl", "front": "EIDEE replaced", "back": "Ohtahara syndrome and early myoclonic encephalopathy." }, { "id": "c-1tp333m", "front": "Migrating focal seizures of infancy gene", "back": "KCNT1 (gain-of-function variants), found in about half of cases." }, { "id": "c-1py9bo", "front": "First-line for infantile spasms", "back": "Hormonal therapy (ACTH or high-dose prednisolone) or vigabatrin; vigabatrin if tuberous sclerosis." }, { "id": "c-1cbgju7", "front": "ICISS trial finding", "back": "Hormonal therapy plus vigabatrin stopped spasms more often than hormones alone; no developmental difference at 18 months." }, { "id": "c-1039q1t", "front": "Dravet red flags", "back": "Prolonged febrile hemiclonic seizures before age one, alternating sides, triggered by fever, baths or vaccination." }, { "id": "c-1lxvf64", "front": "Drugs to avoid in Dravet syndrome", "back": "Sodium channel blockers: carbamazepine, oxcarbazepine, phenytoin, lamotrigine." }, { "id": "c-hbqbof", "front": "Drugs with trial evidence in Dravet syndrome", "back": "Stiripentol, fenfluramine, cannabidiol (plus valproate and clobazam first-line)." }, { "id": "c-ss75ow", "front": "Later seizures after SeLNE", "back": "Up to a third have seizures again later in life (febrile, focal clusters, tonic–clonic, occasionally SeLECTS)." }, { "id": "c-bjej89", "front": "KCNQ2 developmental and epileptic encephalopathy", "back": "Neonatal tonic seizures in an encephalopathic baby, burst-suppression or multifocal EEG, usually de novo; sodium channel blockers often work." }, { "id": "c-1l1fv5p", "front": "Ohtahara syndrome versus early myoclonic encephalopathy", "back": "Ohtahara: tonic spasms, burst-suppression awake and asleep, structural causes. Early myoclonic: erratic myoclonus, burst-suppression mainly in sleep, metabolic or genetic causes. Both are now EIDEE." }, { "id": "c-u05vf1", "front": "Usual evolution of early infantile encephalopathy", "back": "To infantile epileptic spasms syndrome, then often to Lennox–Gastaut syndrome." }, { "id": "c-8iumuf", "front": "West syndrome versus IESS", "back": "West syndrome is the triad of spasms, hypsarrhythmia and regression; IESS needs only spasms with hypsarrhythmia or focal or multifocal discharges." }, { "id": "c-pukpwz", "front": "Prednisolone versus ACTH for spasms", "back": "Similar efficacy in trials and meta-analysis; prednisolone is oral and cheaper; watch blood pressure, infection and irritability." }, { "id": "c-ps54rw", "front": "Spasms or hypsarrhythmia persist after the first agent", "back": "Switch to the other first-line class; refer early for surgery if a focal lesion fits." }, { "id": "c-fw5zod", "front": "Better prognosis in infantile spasms", "back": "No known cause, normal development before onset, short treatment lag, prompt response." } ] } ], "sources": [ { "title": "Syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "ICISS trial (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/27838190/" }, { "title": "Fenfluramine in Dravet syndrome (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31862249/" }, { "title": "EPISTOP, preventive vigabatrin in TSC (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33180985/" }, { "title": "Syndromes with onset in childhood (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503717/" }, { "title": "Ohtahara syndrome and early myoclonic encephalopathy (Ohtahara 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/14734930/" }, { "title": "Early treatment of KCNQ2 encephalopathy (Pisano 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25880994/" }, { "title": "Gain-of-function KCNT1 variants in migrating focal seizures (Barcia 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/23086397/" }, { "title": "UKISS, hormones versus vigabatrin (2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15541450/" }, { "title": "Corticosteroids versus ACTH for infantile spasms, meta-analysis (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31657133/" }, { "title": "Cardiac hypertrophy with ACTH therapy (1987)", "url": "https://pubmed.ncbi.nlm.nih.gov/2821097/" }, { "title": "Response to second treatment for infantile spasms (Knupp 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27615012/" }, { "title": "Relapse of spasms after ACTH (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26547521/" }, { "title": "Surgery for early lesions despite generalized EEG (Wyllie 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17646632/" }, { "title": "Surgery for tuberous sclerosis epilepsy, review (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33720022/" }, { "title": "Long-term outcome of West syndrome (Riikonen 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11701277/" }, { "title": "Infantile spasms: outcome in clinical studies (Riikonen 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32305143/" } ], "words": 1546, "bank": 14 }, { "id": "syndromes-childhood", "n": "3", "title": "Childhood onset", "tags": [ "ilae-classification", "seizure-management", "eeg-fundamentals" ], "updated": false, "goals": [ "Distinguish the self-limited focal epilepsies of childhood", "manage childhood absence epilepsy", "recognize Lennox–Gastaut syndrome and spike-wave activation in sleep" ], "blocks": [ { "type": "h3", "text": "Self-limited focal epilepsies" }, { "type": "table", "head": [ "Syndrome", "Age", "Seizures", "EEG", "Course" ], "rows": [ [ "[SeLECTS](ilae_classification.html#syndrome-17)", "About 4–10 years", "Hemifacial clonic seizures, drooling, speech arrest with preserved awareness, mostly from sleep; may become bilateral", "Centrotemporal spikes with a horizontal dipole, activated by sleep", "Remits by mid-adolescence; treatment often unnecessary" ], [ "[SeLEAS](ilae_classification.html#syndrome-18)", "About 3–6 years", "Autonomic seizures from sleep: nausea, vomiting, pallor, then eye deviation and unresponsiveness; often prolonged", "Multifocal spikes, often occipital; may be normal", "Few seizures; remits within a few years" ], [ "[COVE](ilae_classification.html#syndrome-19)", "Later childhood", "Brief elementary visual hallucinations, sometimes ictal blindness, often followed by headache", "Occipital spikes, often with fixation-off sensitivity", "Often remits; many need treatment" ], [ "[Photosensitive occipital lobe epilepsy](ilae_classification.html#syndrome-20)", "Childhood and adolescence", "Visual seizures triggered by flicker, screens or video games", "Occipital spikes; photoparoxysmal response", "Avoid triggers; often needs treatment" ] ] }, { "type": "h3", "text": "Generalized" }, { "type": "li", "text": "**[Childhood absence epilepsy](ilae_classification.html#syndrome-21)**: onset typically 4–10 years (range 2–13) in a normal child, many typical absences a day, 3-Hz spike-and-wave provoked by hyperventilation. In the CAE trial, **ethosuximide** and valproate were more effective than lamotrigine, and ethosuximide had fewer attentional side effects, making it first choice for absence-only disease. Absences that begin before age 4, or that come with a movement disorder, learning problems or drug resistance, call for testing for GLUT1 deficiency (SLC2A1 testing and a fasting lumbar puncture for the CSF-to-blood glucose ratio): it causes about 1 in 10 absence epilepsies starting before 4, and its treatment is the ketogenic diet, not an antiseizure medication (ASM)." }, { "type": "li", "text": "**[Epilepsy with myoclonic absences](ilae_classification.html#syndrome-23)** (absences with rhythmic jerks of the shoulders and arms) and **[epilepsy with eyelid myoclonia](ilae_classification.html#syndrome-22)** (eyelid jerks with upward eye deviation on eye closure, photosensitive and often persistent) are compared in the table below." }, { "type": "li", "text": "**[Epilepsy with myoclonic–atonic seizures](ilae_classification.html#syndrome-24)**: onset typically 2–6 years (range 6 months to 8 years), often in a previously normal child; myoclonic–atonic drops. The ketogenic diet is often effective; avoid carbamazepine, oxcarbazepine and phenytoin. About two thirds remit, usually within 3 years, and can stop treatment. Tonic seizures, recurrent nonconvulsive status, and an EEG with near-continuous irregular or slow spike-and-wave or paroxysmal fast activity predict a worse course. Unlike Lennox–Gastaut syndrome, development is normal before onset in two thirds, the drops are myoclonic–atonic rather than tonic, and the generalized spike-and-wave is faster (2–6 Hz) on a background that is normal at onset." }, { "type": "table", "head": [ "", "Epilepsy with myoclonic absences", "Epilepsy with eyelid myoclonia" ], "rows": [ [ "Seizure", "Absences of 10–60 seconds with rhythmic 3-Hz arm jerks and stepwise tonic raising of the arms", "Eyelid jerks with upward eye deviation lasting under 6 seconds, many times a day, with or without absence" ], [ "Trigger", "Hyperventilation; photosensitivity in only about 14%", "Eye closure and bright light (photosensitive)" ], [ "Who", "About 70% boys; peak onset about age 7", "Girls twice as often as boys; peak onset 6–8 years" ], [ "Development", "Impaired in about half at onset; intellectual disability in 70% eventually", "Often normal" ], [ "Course and treatment", "Remits in about 40%; valproate with ethosuximide, worse outlook when tonic–clonic seizures are added", "Often lifelong; eyelid myoclonia resist drugs more than the tonic–clonic seizures do" ] ] }, { "type": "h3", "text": "Developmental and epileptic encephalopathies" }, { "type": "li", "text": "**[Lennox–Gastaut syndrome](ilae_classification.html#syndrome-25)**: onset before 18 years (usually 1–8), multiple drug-resistant seizure types including **tonic seizures**, cognitive impairment, slow spike-and-wave and paroxysmal fast activity in sleep. Drop attacks cause injury. Options include valproate, clobazam, lamotrigine, rufinamide, topiramate, felbamate, cannabidiol and fenfluramine, the ketogenic diet, VNS and corpus callosotomy." }, { "type": "li", "text": "**Nonconvulsive status in Lennox–Gastaut syndrome**: about half of patients have episodes of atypical absence status (up to three quarters in some reports), with altered awareness, erratic myoclonus and atonic components, interspersed with clusters of brief tonic seizures. Because the baseline EEG already shows near-continuous slow spike-and-wave, the American Clinical Neurophysiology Society (ACNS) 2021 terminology diagnoses status in a patient with a known epileptic encephalopathy only in two situations: discharges more frequent or prominent than the patient's own baseline, with a decline in clinical state; or EEG and clinical improvement after an intravenous antiseizure medication. Intravenous benzodiazepines may stop the absence state but can bring out tonic seizures or even tonic status, possibly through the sleepiness they cause. The evidence is a handful of case reports, so keep recording after the dose rather than avoiding benzodiazepines. Experts recommend clobazam or corticosteroids, note that high-dose intravenous valproate can also work, and advise against anesthetic coma for this nonconvulsive status." }, { "type": "li", "text": "**[DEE-SWAS and EE-SWAS](ilae_classification.html#syndrome-26)**: cognitive, language or behavioral regression with marked activation of spike-and-wave in NREM sleep; **Landau–Kleffner syndrome** is the form with acquired auditory verbal agnosia. Causes, EEG and treatment are under \"Spike-wave activation in sleep\" below." }, { "type": "li", "text": "**[Febrile infection-related epilepsy syndrome (FIRES)](ilae_classification.html#syndrome-27)**: a previously healthy child develops super-refractory status days after a febrile illness. It sits within new-onset refractory status (NORSE). The ketogenic diet and anakinra are used; outcomes are often poor." }, { "type": "li", "text": "**[Hemiconvulsion–hemiplegia–epilepsy](ilae_classification.html#syndrome-28)**: prolonged febrile hemiclonic status in a young child, then hemiplegia and later focal epilepsy. The child (under 4) has a hemiparesis from the moment the status ends; it is permanent in most, but minimal or gone within a year in about 20%. MRI shows swelling, T2 hyperintensity and restricted diffusion across the affected hemisphere, then atrophy. Drug-resistant focal seizures follow, usually within 3 years. In Rasmussen syndrome, by contrast, the hemiparesis comes late and progresses. Surgery helps selected patients: in 26 operated patients, temporal lobectomy cured all 12 with seizures from the mesial temporal lobe alone, while results were poorer with neocortical or multifocal onset; hemispherotomy is an option for wider involvement." }, { "type": "mcq", "id": "q-8n2fch", "stem": "A 7-year-old boy has had three episodes in which he woke at night with twitching of the left side of his mouth, drooling and inability to speak while fully aware. EEG shows right centrotemporal spikes activated by sleep. Development and examination are normal. What is the best advice?", "options": [ "Start carbamazepine immediately and continue until age 18", "Obtain intracranial EEG", "Explain the self-limited course; treatment is optional and depends on seizure frequency and family preference", "Start a ketogenic diet", "Refer for epilepsy surgery" ], "answer": 2, "explain": "SeLECTS remits by mid-adolescence, most children have few seizures, and many need no ASM. Treatment is reasonable if seizures are frequent, prolonged or distressing." }, { "type": "mcq", "id": "q-1b5tivq", "stem": "A 4-year-old girl has an hour-long nocturnal episode of vomiting, pallor and eye deviation, then becomes unresponsive. She recovers fully. EEG shows multifocal spikes, most often occipital. What is the most likely diagnosis?", "options": [ "Childhood occipital visual epilepsy", "Self-limited epilepsy with autonomic seizures", "Migraine with aura", "Encephalitis", "Lennox–Gastaut syndrome" ], "answer": 1, "explain": "Prolonged nocturnal autonomic seizures with vomiting and pallor in a preschool child with occipital or multifocal spikes are typical of SeLEAS (formerly Panayiotopoulos syndrome). Most children have few seizures and remit." }, { "type": "mcq", "id": "q-gwncab", "stem": "Which feature is required for a diagnosis of Lennox–Gastaut syndrome?", "options": [ "Hypsarrhythmia", "Photosensitivity", "Tonic seizures", "Centrotemporal spikes", "Onset after age 18" ], "answer": 2, "explain": "Tonic seizures are a mandatory criterion, alongside at least one other seizure type, generalized slow spike-and-wave under 2.5 Hz and generalized paroxysmal fast activity in sleep (both are required, on the current or an earlier EEG), and cognitive impairment, with onset before 18." }, { "type": "h3", "text": "Spike-wave activation in sleep" }, { "type": "li", "text": "**EE-SWAS or DEE-SWAS**: the dividing rule is development before the sleep activation began. If it was normal, the diagnosis is epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS); if it was already impaired, developmental and epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS). Both need clear, persisting regression in cognition, language, behavior or motor skills, linked in time to the EEG pattern. Landau–Kleffner syndrome is the EE-SWAS form dominated by auditory verbal agnosia." }, { "type": "li", "text": "**Age and EEG**: seizures begin at 2–12 years (peak 4–5) and the activation appears 1–2 years later: slow (1.5–2 Hz) spike-and-wave, nearly continuous in non-rapid eye movement sleep, with spindles and K-complexes lost. The waking EEG can be normal and seizures can be absent, so a sleep EEG is mandatory, often overnight to reach slow-wave sleep. The old definition used a spike-wave index (the share of slow-wave sleep taken up by discharges) above 85%, but lower indices can still cause regression." }, { "type": "li", "text": "**Causes**: early thalamic injury, bilateral perisylvian polymicrogyria and other early lesions, GRIN2A variants, and evolution from SeLECTS or SeLEAS (rarely COVE)." }, { "type": "li", "text": "**Atypical evolution of SeLECTS**: suspect it with school or language decline, behavior change, negative myoclonus (lapses of tone that drop objects or cause falls), atypical absences or loss of seizure control. Carbamazepine, oxcarbazepine and phenobarbital have been linked to negative myoclonus in this setting. Get an overnight sleep EEG and neuropsychological testing even if seizures are controlled, and withdraw these drugs if the pattern is found." }, { "type": "li", "text": "**Treatment**: corticosteroids (in the RESCUE ESES trial, IQ rose by at least 11.25 points in 25% on corticosteroids and 0% on clobazam) or high-dose benzodiazepines first; sulthiame, acetazolamide and amantadine have small series; remove a causal lesion when possible. Sodium channel blockers can make it worse. In pooled data from 575 children, improvement followed steroids in 81%, benzodiazepines 68%, other ASMs 49% and surgery 90%." }, { "type": "li", "text": "**Prognosis**: seizures and the EEG pattern usually settle by adolescence, but about half are left with impairment that limits independence. Activation lasting more than 2 years and younger onset predict worse cognition, so treat promptly." }, { "type": "mcq", "id": "q-1n8o69w", "stem": "An 8-year-old boy with centrotemporal spikes, seizure-free on carbamazepine for a year, has had 3 months of falling grades, sparse speech and sudden drops of objects from his right hand. A 30-minute awake EEG is normal. What should come next?", "options": [ "Reassurance, because the awake EEG is normal", "Overnight EEG that captures non-rapid eye movement sleep, with neuropsychological testing", "Increase carbamazepine and review in 3 months", "Brainstem auditory evoked potentials", "Switch carbamazepine to oxcarbazepine" ], "answer": 1, "explain": "Regression with negative myoclonus in a child with SeLECTS suggests evolution to epileptic encephalopathy with spike-wave activation in sleep. The waking EEG can be normal, so the diagnosis needs a sleep recording, ideally overnight. Carbamazepine and oxcarbazepine have been linked to this picture and should be withdrawn if the pattern is confirmed." }, { "type": "cards", "items": [ { "id": "c-w3x4ce", "front": "SeLECTS seizures", "back": "Hemifacial clonic, drooling, speech arrest with awareness, mostly from sleep." }, { "id": "c-1ws8qf5", "front": "SeLECTS EEG", "back": "Centrotemporal spikes with a horizontal dipole, activated by sleep." }, { "id": "c-s5tjie", "front": "SeLEAS", "back": "Prolonged nocturnal autonomic seizures (vomiting, pallor) at about 3–6 years." }, { "id": "c-1k88pwy", "front": "COVE", "back": "Brief elementary visual seizures and ictal blindness with headache after; occipital spikes with fixation-off sensitivity." }, { "id": "c-12dyg6j", "front": "CAE first choice (CAE trial)", "back": "Ethosuximide: as effective as valproate, better than lamotrigine, fewer attention effects." }, { "id": "c-1s5zuq9", "front": "Epilepsy with eyelid myoclonia", "back": "Girls twice as often as boys; brief eyelid jerks with upward eye deviation on eye closure and in bright light; photosensitive; often lifelong." }, { "id": "c-q20smn", "front": "Lennox–Gastaut mandatory seizure type", "back": "Tonic seizures." }, { "id": "c-4ncyvz", "front": "Landau–Kleffner syndrome", "back": "EE-SWAS with acquired auditory verbal agnosia." }, { "id": "c-1b3i5a6", "front": "FIRES", "back": "Super-refractory status days after a febrile illness in a healthy child; part of NORSE." }, { "id": "c-dx2yp2", "front": "Absences beginning before age 4", "back": "Test for GLUT1 deficiency (SLC2A1, fasting CSF-to-blood glucose ratio); treat with the ketogenic diet." }, { "id": "c-1iuqapn", "front": "Epilepsy with myoclonic absences", "back": "Boys; rhythmic 3-Hz arm jerks with stepwise tonic arm raising; frequent intellectual disability; valproate plus ethosuximide." }, { "id": "c-134701g", "front": "Epilepsy with myoclonic–atonic seizures: prognosis", "back": "About two thirds remit within 3 years; tonic seizures and recurrent nonconvulsive status predict a worse course." }, { "id": "c-10p0o19", "front": "Status in a known epileptic encephalopathy (ACNS 2021)", "back": "More frequent or prominent discharges than the patient's baseline with clinical decline, or EEG and clinical improvement after an IV antiseizure medication." }, { "id": "c-okph9w", "front": "IV benzodiazepine in Lennox–Gastaut atypical absence status", "back": "Can provoke tonic seizures or tonic status." }, { "id": "c-kzybv1", "front": "EE-SWAS versus DEE-SWAS", "back": "Development normal before the sleep activation (EE-SWAS) versus already impaired (DEE-SWAS)." }, { "id": "c-spzmhq", "front": "Test for spike-wave activation in sleep", "back": "Overnight sleep EEG: slow 1.5–2 Hz spike-and-wave nearly continuous in non-rapid eye movement sleep; the waking EEG can be normal." }, { "id": "c-8io57c", "front": "Red flags for atypical evolution of SeLECTS", "back": "School or language decline, behavior change, negative myoclonus, atypical absences, loss of seizure control." }, { "id": "c-y4tkji", "front": "Outcome in spike-wave activation in sleep", "back": "EEG usually remits by adolescence; cognition is worse with activation lasting over 2 years and with younger onset." }, { "id": "c-1iduime", "front": "Hemiconvulsion–hemiplegia–epilepsy versus Rasmussen syndrome", "back": "Hemiconvulsion–hemiplegia–epilepsy: the hemiparesis follows the febrile status at once and does not progress. Rasmussen: the hemiparesis appears later and worsens." } ] } ], "sources": [ { "title": "Syndromes with onset in childhood (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503717/" }, { "title": "Childhood Absence Epilepsy trial (2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20200383/" }, { "title": "NORSE and FIRES consensus definitions (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29399791/" }, { "title": "Idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" }, { "title": "Glut1 deficiency syndrome: international consensus (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32913944/" }, { "title": "Epilepsy with myoclonic absences (Bureau 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15737698/" }, { "title": "ACNS critical care EEG terminology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33475321/" }, { "title": "Tonic status after IV benzodiazepine in Lennox–Gastaut syndrome (Tassinari 1972)", "url": "https://pubmed.ncbi.nlm.nih.gov/4626571/" }, { "title": "Expert opinion on managing Lennox–Gastaut syndrome (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29085326/" }, { "title": "Updated Lennox–Gastaut syndrome treatment algorithms (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39700524/" }, { "title": "RESCUE ESES trial (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38081201/" }, { "title": "Treatment of ESES, pooled analysis of 575 cases (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26337159/" }, { "title": "Sulthiame in ESES (2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22509732/" }, { "title": "Acetazolamide in ESES (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26230617/" }, { "title": "Amantadine in ESES (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29754107/" }, { "title": "Negative myoclonus in atypical rolandic epilepsy (2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/18562140/" }, { "title": "Hemiconvulsion–hemiplegia–epilepsy, 35 cases (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29414550/" }, { "title": "Surgery for delayed epilepsy in hemiconvulsion–hemiplegia–epilepsy syndrome (2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18235079/" } ], "words": 1936, "bank": 14 }, { "id": "syndromes-adult", "n": "4", "title": "Adolescence, adulthood and variable age", "tags": [ "ilae-classification", "seizure-management", "epilepsy-surgery" ], "updated": false, "goals": [ "Separate the idiopathic generalized epilepsies of adolescence", "recognize the familial focal epilepsies", "know the progressive myoclonus epilepsies" ], "blocks": [ { "type": "h3", "text": "Idiopathic generalized epilepsies of adolescence" }, { "type": "table", "head": [ "Syndrome", "Onset", "Seizures", "Notes" ], "rows": [ [ "[Juvenile absence epilepsy](ilae_classification.html#syndrome-29)", "About 9–13 years", "Absences, less frequent than in CAE; most also have tonic–clonic seizures", "Usually needs long-term treatment" ], [ "[Juvenile myoclonic epilepsy](ilae_classification.html#syndrome-30)", "About 10–24 years", "Myoclonus after waking; tonic–clonic seizures; absences in some", "Photosensitivity common; triggered by sleep loss and alcohol; relapse common after withdrawal" ], [ "[Epilepsy with generalized tonic–clonic seizures alone](ilae_classification.html#syndrome-31)", "Teens to early adulthood", "Tonic–clonic seizures only, often after waking", "Triggered by sleep loss" ] ] }, { "type": "p", "text": "Valproate is the most effective drug for idiopathic generalized epilepsy. For women who could become pregnant, levetiracetam or lamotrigine is usually preferred." }, { "type": "h3", "text": "Focal epilepsies of variable age" }, { "type": "li", "text": "**[Sleep-related hypermotor (hyperkinetic) epilepsy](ilae_classification.html#syndrome-32)**: brief, stereotyped hypermotor seizures from NREM sleep in clusters. Genetic forms involve nicotinic receptor genes (CHRNA4, CHRNB2, CHRNA2), KCNT1 and the GATOR1 genes; focal cortical dysplasia is a common structural cause. Most patients respond to first-line antiseizure medications (ASMs); low-dose carbamazepine works in some but fails in at least a third. Drug-resistant cases with a well-defined lesion, especially focal cortical dysplasia type IIb, do well with surgery." }, { "type": "li", "text": "**[Familial focal epilepsy with variable foci](ilae_classification.html#syndrome-35)**: family members have focal seizures from different lobes. DEPDC5, NPRL2 and NPRL3 (the GATOR1 complex that regulates mTOR) are the main genes, and some carriers have focal cortical dysplasia." }, { "type": "li", "text": "**[Familial mesial temporal lobe epilepsy](ilae_classification.html#syndrome-33)**: a common, usually mild syndrome beginning in adolescence or adulthood, in which every affected relative has mesial temporal seizures, above all intense déjà vu, often with a rising epigastric feeling or fear. MRI is normal and most patients become seizure-free on the first ASM; many never seek care because they think the déjà vu is normal, and a first tonic–clonic seizure often brings them in. Inheritance is complex (polygenic or multifactorial), not simple dominant. Hippocampal atrophy or T2 signal change, with antecedent febrile seizures, marks a less favorable, drug-resistant form." }, { "type": "li", "text": "**[Epilepsy with auditory features](ilae_classification.html#syndrome-36)**: auditory auras (buzzing, ringing), sometimes receptive aphasia; LGI1 variants in some families." }, { "type": "li", "text": "**[Mesial temporal lobe epilepsy with hippocampal sclerosis](ilae_classification.html#syndrome-34)**: often an early precipitating injury such as prolonged febrile seizures, a latent period, then focal impaired-consciousness seizures that frequently become drug-resistant. Surgery is highly effective." }, { "type": "li", "text": "**[Rasmussen syndrome](ilae_classification.html#syndrome-40)**: a childhood-onset, T-cell-mediated inflammation of one hemisphere with epilepsia partialis continua, progressive hemiparesis and cognitive decline, and progressive atrophy on MRI. Hemispherotomy is the definitive treatment." }, { "type": "li", "text": "**Rasmussen syndrome diagnosis (Bien criteria, 2005)**: either all three Part A criteria (focal seizures with unilateral cortical deficits; unihemispheric EEG slowing with unilateral seizure onset; unihemispheric focal cortical atrophy with high T2 signal, or with high signal or atrophy in the ipsilateral caudate head) or two of the three Part B criteria (epilepsia partialis continua or progressive unilateral cortical deficits; progressive unilateral focal atrophy on serial MRI; T-cell-dominant encephalitis on biopsy). A 2013 modification, used in the 2026 international consensus, also accepts two Part A criteria plus a positive biopsy; biopsy is needed only when the criteria are not otherwise met." }, { "type": "li", "text": "**Immunotherapy in Rasmussen syndrome** can slow the disease or buy time but does not replace hemispherotomy: IV corticosteroids for flares and status, with or without intravenous immunoglobulin (IVIG), then maintenance with IVIG, azathioprine, mycophenolate, rituximab or adalimumab, none shown better than another." }, { "type": "h3", "text": "Progressive myoclonus epilepsies" }, { "type": "p", "text": "Suspect one when myoclonus, generalized seizures and progressive cognitive and cerebellar decline occur together. Unverricht–Lundborg disease is the most frequent cause worldwide. With Lafora disease, the neuronal ceroid lipofuscinoses, mitochondrial disorders and sialidosis it accounts for most cases; dentatorubral–pallidoluysian atrophy and the other causes are rare." }, { "type": "table", "head": [ "Disease", "Gene or defect", "Clues" ], "rows": [ [ "Unverricht–Lundborg disease", "CSTB repeat expansion (autosomal recessive)", "Stimulus-sensitive action myoclonus from about 6–15 years; slower cognitive decline; phenytoin worsens it" ], [ "Lafora disease", "EPM2A or NHLRC1 (recessive)", "Teenage onset, occipital seizures with visual hallucinations, rapid dementia; Lafora bodies on axillary skin biopsy" ], [ "Neuronal ceroid lipofuscinoses", "CLN genes (mostly recessive); the only dominant form is a rare adult-onset one (DNAJC5)", "Visual failure and regression; CLN2 disease has intraventricular enzyme replacement (cerliponase alfa). CLN2 disease (deficiency of the enzyme tripeptidyl peptidase 1, TPP1) starts at about 2–4 years, most often with seizures, and speech is delayed or regressing by age 3; a photoparoxysmal response to slow 1–3 Hz flashes is an early clue" ], [ "MERRF", "Mitochondrial DNA (m.8344A>G)", "Maternal inheritance; ragged-red fibres, hearing loss, lipomas" ], [ "Sialidosis type I", "NEU1 (recessive)", "Myoclonus with a cherry-red spot, little dementia early" ], [ "DRPLA", "ATN1 CAG repeat (dominant)", "Ataxia, chorea, dementia; anticipation; more common in Japan" ] ] }, { "type": "h3", "text": "Reflex epilepsies" }, { "type": "p", "text": "Seizures reliably triggered by a stimulus: flicker (juvenile myoclonic epilepsy, eyelid myoclonia, photosensitive occipital epilepsy), reading (jaw jerks), startle (often with hemiparesis), hot water, music, eating, and thinking or manipulating objects (praxis induction, common in juvenile myoclonic epilepsy)." }, { "type": "p", "text": "**[Epilepsy with reading-induced seizures](ilae_classification.html#syndrome-37)** is a named ILAE syndrome. Onset is in the late teens (median about 17), males are affected about twice as often, and small myoclonic jerks of the jaw, lips or tongue (felt as a click or a stutter) appear while reading or doing other language tasks. If reading continues, the jerks spread and a tonic–clonic seizure can follow. MRI is normal, spontaneous seizures are not expected, and seizures respond to ASMs and to limiting the trigger." }, { "type": "mcq", "id": "q-19ga7pj", "stem": "A 16-year-old develops worsening stimulus-sensitive myoclonus and generalized seizures. Over 18 months she has visual hallucinations, occipital seizures and rapidly declining school performance. Which test is most likely to confirm the diagnosis?", "options": [ "Muscle biopsy for ragged-red fibres", "Axillary skin biopsy for Lafora bodies, or genetic testing of EPM2A and NHLRC1", "Fundoscopy for a cherry-red spot", "Serum ceruloplasmin", "CSF 14-3-3 protein" ], "answer": 1, "explain": "Teenage onset with occipital seizures, visual hallucinations and rapid dementia fits Lafora disease. Periodic acid–Schiff-positive Lafora bodies in sweat gland cells on axillary skin biopsy, or EPM2A/NHLRC1 testing, confirm it." }, { "type": "mcq", "id": "q-1saz5js", "stem": "In a patient with Unverricht–Lundborg disease, which drug should be avoided because it can worsen myoclonus and cerebellar signs?", "options": [ "Valproate", "Levetiracetam", "Clonazepam", "Phenytoin", "Piracetam" ], "answer": 3, "explain": "Phenytoin worsens Unverricht–Lundborg disease. Sodium channel blockers, gabapentin, pregabalin, vigabatrin and tiagabine can aggravate myoclonus in progressive myoclonus epilepsies." }, { "type": "cards", "items": [ { "id": "c-2yt6ue", "front": "Juvenile absence epilepsy versus CAE", "back": "Later onset (about 9–13), fewer absences, most also have tonic–clonic seizures, usually lifelong." }, { "id": "c-imfjmo", "front": "Juvenile myoclonic epilepsy triggers", "back": "Sleep deprivation, alcohol, flicker; praxis-induced jerks." }, { "id": "c-k8dsmv", "front": "SHE genes", "back": "CHRNA4, CHRNB2, CHRNA2, KCNT1, GATOR1 genes." }, { "id": "c-1r7zt8z", "front": "Familial focal epilepsy with variable foci genes", "back": "DEPDC5, NPRL2, NPRL3 (GATOR1, mTOR pathway)." }, { "id": "c-ujl2xp", "front": "Epilepsy with auditory features gene", "back": "LGI1 in some families." }, { "id": "c-1l2kjv1", "front": "Rasmussen syndrome", "back": "Unihemispheric T-cell inflammation, epilepsia partialis continua, progressive hemiparesis; hemispherotomy." }, { "id": "c-bcmkyz", "front": "Unverricht–Lundborg disease", "back": "CSTB repeat expansion; stimulus-sensitive myoclonus; avoid phenytoin." }, { "id": "c-1xqoezm", "front": "Lafora disease", "back": "EPM2A or NHLRC1; occipital seizures, rapid dementia; Lafora bodies on axillary skin biopsy." }, { "id": "c-1kh1yfg", "front": "CLN2 disease treatment", "back": "Intraventricular cerliponase alfa (enzyme replacement)." }, { "id": "c-1hzj3d", "front": "CLN2 disease early EEG clue", "back": "Photoparoxysmal response to slow (1–3 Hz) photic stimulation; the missing enzyme is TPP1." }, { "id": "c-vwlzsd", "front": "Inheritance of the neuronal ceroid lipofuscinoses", "back": "Recessive, except a rare adult-onset dominant form (DNAJC5)." }, { "id": "c-30dkrn", "front": "Most frequent progressive myoclonus epilepsy", "back": "Unverricht–Lundborg disease." }, { "id": "c-1w0jbbo", "front": "Sleep-related hypermotor epilepsy: treatment", "back": "Most respond to first-line ASMs (low-dose carbamazepine helps some, fails in at least a third); surgery for lesional cases such as focal cortical dysplasia type IIb." }, { "id": "c-1bk48vi", "front": "Familial mesial temporal lobe epilepsy", "back": "Déjà vu and epigastric auras in several relatives, normal MRI, complex inheritance, usually easy to control; hippocampal sclerosis predicts a harder course." }, { "id": "c-hm77dt", "front": "Bien criteria for Rasmussen syndrome", "back": "All three Part A (focal seizures with unilateral deficit, unihemispheric EEG slowing, unihemispheric atrophy with signal change) or two of three Part B (epilepsia partialis continua or progressive deficit, progressive atrophy, T-cell encephalitis on biopsy)." }, { "id": "c-kt3a6m", "front": "Immunotherapy in Rasmussen syndrome", "back": "Can slow progression or buy time (IV steroids, immunoglobulin, other maintenance agents) but does not replace hemispherotomy." }, { "id": "c-68tdxr", "front": "Epilepsy with reading-induced seizures", "back": "Jaw and perioral myoclonic jerks while reading or speaking, onset in the late teens, may progress to a tonic–clonic seizure if reading continues; responds to ASMs." } ] } ], "sources": [ { "title": "Idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" }, { "title": "Syndromes with onset at a variable age (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503725/" }, { "title": "SANAD II, generalized and unclassifiable epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838758/" }, { "title": "Sleep-related hypermotor epilepsy: definition and criteria (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27164717/" }, { "title": "Familial mesial temporal lobe epilepsy (Crompton 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20864493/" }, { "title": "Rasmussen encephalitis: European consensus (Bien 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15689357/" }, { "title": "Evaluation of the Bien criteria (Olson 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23980696/" }, { "title": "International consensus on Rasmussen syndrome (2026)", "url": "https://doi.org/10.1002/epi.70225" }, { "title": "Photosensitivity as an early marker of CLN2 disease (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28632327/" }, { "title": "Cerliponase alfa for CLN2 disease (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29688815/" }, { "title": "Autosomal dominant neuronal ceroid lipofuscinosis (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/32783189/" } ], "words": 1265, "bank": 9 }, { "id": "genetics", "n": "5", "title": "Genetic testing and precision treatment", "tags": [ "ilae-classification", "seizure-management" ], "updated": true, "goals": [ "Choose the first genetic test", "interpret the patterns of inheritance that matter for counseling", "match genes to treatment decisions" ], "blocks": [ { "type": "p", "updated": true, "label": "Genetic testing", "text": "The National Society of Genetic Counselors guideline (2022) strongly recommends genetic testing for everyone with unexplained epilepsy, of any age, with exome or genome sequencing (or a panel of more than 25 genes) first and chromosomal microarray after, all with pre- and post-test counseling." }, { "type": "h3", "text": "Diagnostic yield" }, { "type": "p", "text": "In a systematic review, diagnostic yield was about 48% for genome sequencing, 24% for exome sequencing, 19% for multigene panels and 9% for chromosomal microarray. Yield was highest in developmental and epileptic encephalopathies and when there were neurodevelopmental comorbidities." }, { "type": "h3", "text": "Genes that change treatment" }, { "type": "table", "head": [ "Finding", "What it changes" ], "rows": [ [ "SCN1A loss of function (Dravet syndrome)", "Avoid sodium channel blockers; use valproate, clobazam, stiripentol, fenfluramine, cannabidiol" ], [ "SCN2A or SCN8A gain of function (usually onset in the first months)", "Sodium channel blockers, sometimes at high dose, can work well" ], [ "SCN2A loss of function (later onset)", "Sodium channel blockers are unhelpful or harmful" ], [ "KCNQ2 (self-limited neonatal epilepsy or DEE)", "Sodium channel blockers such as carbamazepine often effective" ], [ "TSC1 or TSC2", "Vigabatrin for spasms; everolimus for refractory focal seizures; early surveillance EEG" ], [ "SLC2A1 (GLUT1 deficiency)", "Ketogenic diet" ], [ "ALDH7A1", "Lifelong pyridoxine, with lysine restriction" ], [ "PNPO", "Pyridoxal 5′-phosphate" ], [ "POLG", "Avoid valproate (risk of fatal liver failure)" ], [ "CDKL5", "Ganaxolone is approved for CDKL5 deficiency disorder" ], [ "KCNT1 gain of function (migrating focal seizures of infancy, severe sleep-related hypermotor epilepsy)", "Quinidine, which blocks the channel, has limited and inconsistent benefit: more than 50% seizure reduction in only 20% in a registry, and no effect in a small randomized trial. It prolongs the QT interval even at low blood levels, so ECG monitoring is required" ] ] }, { "type": "h3", "text": "Inheritance patterns that matter" }, { "type": "li", "text": "**Autosomal dominant with incomplete penetrance**: many familial focal epilepsies and self-limited syndromes (KCNQ2 neonatal, PRRT2 infantile, CHRNA4, LGI1, DEPDC5) and the GEFS+ spectrum." }, { "type": "li", "text": "**De novo dominant**: most developmental and epileptic encephalopathies (SCN1A in Dravet, STXBP1, SCN2A, SCN8A, KCNT1). Recurrence risk for parents is low but not zero, because of parental mosaicism." }, { "type": "li", "text": "**X-linked**: PCDH19 clustering epilepsy affects heterozygous girls and spares hemizygous boys (mosaic boys can be affected); CDKL5 mostly affects girls, usually de novo; DCX causes lissencephaly in boys and band heterotopia in girls; FLNA causes periventricular nodular heterotopia in women; IKBKG causes incontinentia pigmenti, seen in girls because it is usually lethal in boys." }, { "type": "li", "text": "**Autosomal recessive**: most progressive myoclonus epilepsies, pyridoxine-dependent epilepsy, POLG disease and most metabolic epilepsies." }, { "type": "li", "text": "**Maternal (mitochondrial DNA)**: MERRF, MELAS." }, { "type": "li", "text": "**Somatic (brain-only) variants**: focal cortical dysplasia type II and hemimegalencephaly (mTOR pathway genes), mild malformation with oligodendroglial hyperplasia (SLC35A2) and Sturge–Weber syndrome (GNAQ). Blood testing will miss them." }, { "type": "li", "text": "**Polygenic (complex)**: the idiopathic generalized epilepsies, where many common variants of small effect add up; a genome-wide study found 16 risk loci, most in the generalized epilepsies. Rare variants of larger effect include the T-type calcium channel gene CACNA1H (childhood absence epilepsy) and the GABA-A receptor subunit genes GABRA1 (a juvenile myoclonic epilepsy family) and GABRG2 (absence epilepsy with febrile seizures). GLUT1 deficiency (SLC2A1) remains the treatable monogenic cause of early-onset absences." }, { "type": "li", "text": "**Genes shared with other paroxysmal disorders**: CACNA1A (episodic ataxia type 2 and familial hemiplegic migraine, sometimes with epilepsy), ATP1A2 (familial hemiplegic migraine, with infantile seizures in some families), KCNA1 (episodic ataxia type 1, with or without epilepsy), SCN1A (Dravet syndrome and GEFS+, but also familial hemiplegic migraine) and HCN1 (from neonatal encephalopathy to GEFS+; a third of sporadic cases have their first seizure with fever)." }, { "type": "h3", "text": "Chromosomal disorders to recognize" }, { "type": "li", "text": "**Angelman syndrome** (loss of maternal 15q11–q13, including UBE3A): absent speech, ataxia, happy affect, and high-amplitude notched delta on EEG. Loss of the paternal region gives Prader–Willi syndrome, where seizures are uncommon." }, { "type": "li", "text": "**Ring chromosome 20**: frontal seizures and prolonged nonconvulsive status with confusion; needs a karyotype because mosaicism is missed by microarray." }, { "type": "li", "text": "**Down syndrome**: infantile spasms in infancy and late-onset myoclonic epilepsy with Alzheimer disease in adulthood." }, { "type": "li", "text": "**Wolf–Hirschhorn (4p deletion)** and **15q duplication** syndromes both have prominent epilepsy." }, { "type": "mcq", "id": "q-ikwv7n", "stem": "A 4-year-old with global developmental delay and drug-resistant focal and generalized seizures has a normal MRI and a normal chromosomal microarray. What is the most appropriate next genetic test?", "options": [ "No further testing; the microarray was normal", "Karyotype", "Exome or genome sequencing", "A single-gene test for SCN1A only", "Mitochondrial DNA testing only" ], "answer": 2, "explain": "Exome or genome sequencing has the highest diagnostic yield and is recommended first-tier for unexplained epilepsy, especially a developmental and epileptic encephalopathy. A normal microarray does not exclude a monogenic cause." }, { "type": "mcq", "id": "q-6qh9t7", "stem": "A family has two daughters with clusters of febrile and afebrile seizures and intellectual disability, both carrying a PCDH19 variant. Their father carries the same variant and is healthy. How is this explained?", "options": [ "Incomplete penetrance of an autosomal dominant variant", "Mitochondrial inheritance", "X-linked inheritance in which hemizygous males are spared and heterozygous females affected", "De novo variants in both daughters", "Autosomal recessive inheritance" ], "answer": 2, "explain": "PCDH19 clustering epilepsy follows an unusual X-linked pattern: disease results from a mixture of cells with and without the protein (cellular interference), so heterozygous females and mosaic males are affected while hemizygous males are not." }, { "type": "match", "id": "match-genes", "prompt": "Match each gene to the treatment decision it drives", "pairs": [ [ "SCN1A loss of function", "Avoid sodium channel blockers" ], [ "SLC2A1", "Ketogenic diet" ], [ "POLG", "Avoid valproate" ], [ "ALDH7A1", "Lifelong pyridoxine" ], [ "TSC2 with infantile spasms", "Vigabatrin" ], [ "CDKL5", "Ganaxolone" ] ] }, { "type": "cards", "items": [ { "id": "c-1uohy6e", "front": "First-tier genetic test for unexplained epilepsy", "back": "Exome or genome sequencing (or a panel of more than 25 genes), then chromosomal microarray." }, { "id": "c-ac2mzz", "front": "Diagnostic yields (systematic review)", "back": "Genome about 48%, exome 24%, panel 19%, microarray 9%." }, { "id": "c-1seqvbe", "front": "Who has the highest genetic yield", "back": "Developmental and epileptic encephalopathies and neurodevelopmental comorbidities." }, { "id": "c-zjrssi", "front": "PCDH19 inheritance", "back": "X-linked; heterozygous females and mosaic males affected, hemizygous males spared." }, { "id": "c-17jdd8t", "front": "Somatic variants missed on blood testing", "back": "FCD type II and hemimegalencephaly (mTOR pathway), MOGHE (SLC35A2), Sturge–Weber (GNAQ)." }, { "id": "c-1upnm0e", "front": "Angelman syndrome EEG", "back": "High-amplitude notched delta." }, { "id": "c-1tf8vq7", "front": "Ring chromosome 20 test", "back": "Karyotype, because mosaicism is missed by microarray." }, { "id": "c-mcf5lb", "front": "SCN2A gain versus loss of function", "back": "Gain (early onset) responds to sodium channel blockers; loss (later onset) does not." }, { "id": "c-hk18wj", "front": "KCNT1 and quinidine", "back": "KCNT1 variants are gain of function; quinidine helps few patients and prolongs the QT interval, so monitor the ECG." }, { "id": "c-g8k3m2", "front": "Genetic architecture of the idiopathic generalized epilepsies", "back": "Mostly polygenic; rare risk variants in CACNA1H, GABRA1 and GABRG2; SLC2A1 is the treatable monogenic cause of early absences." }, { "id": "c-2m3uw0", "front": "Epilepsy genes shared with migraine and ataxia", "back": "CACNA1A (episodic ataxia type 2, hemiplegic migraine), ATP1A2 (hemiplegic migraine), KCNA1 (episodic ataxia type 1), SCN1A (also hemiplegic migraine)." }, { "id": "c-ql1jc5", "front": "HCN1", "back": "Spectrum from neonatal encephalopathy to GEFS+; first seizures often with fever." } ] } ], "sources": [ { "title": "NSGC guideline on genetic testing for unexplained epilepsy (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36281494/" }, { "title": "Genetic testing for the epilepsies, systematic review (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/34893972/" }, { "title": "EPISTOP, preventive vigabatrin in TSC (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33180985/" }, { "title": "Gain-of-function KCNT1 variants (Barcia 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/23086397/" }, { "title": "Treatment responsiveness in KCNT1-related epilepsy (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31054119/" }, { "title": "Randomized trial of quinidine for KCNT1 epilepsy (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29196578/" }, { "title": "Idiopathic generalized epilepsy syndromes (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503716/" }, { "title": "Genome-wide mega-analysis of the common epilepsies (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30531953/" }, { "title": "CACNA1H and childhood absence epilepsy (2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12891677/" }, { "title": "GABRA1 in juvenile myoclonic epilepsy (2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11992121/" }, { "title": "GABRG2 in absence epilepsy and febrile seizures (2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11326275/" }, { "title": "ATP1A2 in hemiplegic migraine and infantile convulsions (2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12953268/" }, { "title": "SCN1A in familial hemiplegic migraine (2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16054936/" }, { "title": "CACNA1A variants in epilepsy (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35600082/" }, { "title": "KCNA1: episodic ataxia and epilepsy (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32316562/" }, { "title": "HCN1 variant spectrum (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30351409/" }, { "title": "Incontinentia pigmenti (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26564087/" }, { "title": "SLC35A2 mosaicism in MOGHE (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33407896/" } ], "words": 1046, "bank": 12 }, { "id": "febrile", "n": "6", "title": "Febrile seizures", "tags": [ "ilae-classification", "seizure-management" ], "updated": false, "goals": [ "Define simple and complex febrile seizures", "counsel on recurrence and later epilepsy", "know which investigations are and are not needed" ], "blocks": [ { "type": "p", "text": "A febrile seizure occurs with a temperature of at least 38 °C in a child aged 6 to 60 months, without CNS infection, an acute metabolic cause, or earlier afebrile seizures. They affect roughly 2–5% of children." }, { "type": "table", "head": [ "", "Simple", "Complex" ], "rows": [ [ "Duration", "Under 15 minutes", "15 minutes or longer" ], [ "Type", "Generalized", "Focal features" ], [ "Recurrence within 24 hours", "No", "Yes" ] ] }, { "type": "p", "text": "**Febrile status epilepticus** (30 minutes or more) is associated with acute hippocampal injury on MRI and, in some children, later hippocampal sclerosis. The evidence comes from the prospective **FEBSTAT** study: about 1 child in 10 had acute hippocampal T2 hyperintensity and swelling after febrile status, and on repeat MRI about a year later 10 of 14 had hippocampal sclerosis. Over 10 years, 71% of children with that acute change developed epilepsy (39% mesial temporal lobe epilepsy), against 23% when the acute MRI was normal, none of whom developed mesial temporal lobe epilepsy." }, { "type": "p", "text": "**Febrile seizures plus (FS+)** is the label for febrile seizures that persist after the sixth birthday, or that are followed by afebrile seizures. It is the commonest phenotype after simple febrile seizures in families with **genetic epilepsy with febrile seizures plus (GEFS+)**, an autosomal dominant spectrum with incomplete penetrance: relatives who share one variant range from simple febrile seizures and FS+ to FS+ with absences, myoclonic or atonic seizures, focal epilepsies, epilepsy with myoclonic–atonic seizures and Dravet syndrome. The outlook for any one relative depends on the syndrome that relative has. When FS+ is the only phenotype, seizures usually end by puberty; they respond to antiseizure medications (ASMs), and some children need no daily treatment. SCN1B was the first gene found; SCN1A variants are found in about 10% of families, and GABA-A receptor genes such as GABRG2 are among the others." }, { "type": "h3", "text": "Counseling" }, { "type": "li", "text": "**Recurrence**: about a third of children have another. The risk is higher with a first febrile seizure before about 18 months, a family history of febrile seizures, a lower temperature at the time, and a short interval between fever onset and the seizure." }, { "type": "li", "text": "**Later epilepsy**: after a simple febrile seizure the risk is only slightly above that of the general population. It rises with complex features, a family history of epilepsy, and pre-existing neurodevelopmental problems." }, { "type": "li", "text": "**Antipyretics** make the child comfortable but do not prevent recurrence. Continuous ASM prophylaxis is not recommended for simple febrile seizures. A rescue benzodiazepine can be offered for prolonged seizures." }, { "type": "h3", "text": "Investigations after a simple febrile seizure in a well child" }, { "type": "li", "text": "**Lumbar puncture** if there are meningeal signs or symptoms. Consider it between 6 and 12 months if Haemophilus influenzae type b or pneumococcal vaccination is incomplete or unknown, and when antibiotics were given beforehand." }, { "type": "li", "text": "**EEG, neuroimaging and routine blood tests** are not needed to evaluate the seizure itself." }, { "type": "calc", "name": "febrile-check" }, { "type": "mcq", "id": "q-172p2vw", "stem": "A 14-month-old has a 4-minute generalized tonic–clonic seizure on the first day of a febrile illness. She is back to normal an hour later, has no meningeal signs, and is fully vaccinated. What investigation does she need?", "options": [ "EEG within 24 hours", "MRI brain", "Lumbar puncture", "Serum electrolytes and calcium", "None directed at the seizure; evaluate the source of fever as usual" ], "answer": 4, "explain": "For a simple febrile seizure in a neurologically healthy, vaccinated child without meningeal signs, the AAP recommends against routine EEG, neuroimaging and blood tests, and LP is not routinely needed." }, { "type": "cards", "items": [ { "id": "c-6j1jlx", "front": "Febrile seizure age range", "back": "6 to 60 months." }, { "id": "c-156hgxn", "front": "Complex febrile seizure", "back": "Focal features, 15 minutes or more, or recurrence within 24 hours." }, { "id": "c-1bfftqx", "front": "Febrile status epilepticus", "back": "30 minutes or longer; linked to acute hippocampal injury." }, { "id": "c-1wvequo", "front": "Recurrence after a first febrile seizure", "back": "About one in three." }, { "id": "c-1rvib2u", "front": "Recurrence risk factors", "back": "Onset before about 18 months, family history, lower temperature, short fever-to-seizure interval." }, { "id": "c-1f9iqae", "front": "Do antipyretics prevent recurrence?", "back": "No." }, { "id": "c-1jrefkm", "front": "Workup after a simple febrile seizure", "back": "Evaluate the fever; no routine EEG, imaging or blood tests; LP only if indicated." }, { "id": "c-1c7p5ol", "front": "FEBSTAT study", "back": "Acute hippocampal T2 hyperintensity after febrile status predicts hippocampal sclerosis and later epilepsy (71% at 10 years, versus 23% with a normal acute MRI)." }, { "id": "c-ret56r", "front": "Febrile seizures plus (FS+)", "back": "Febrile seizures continuing beyond age 6, or joined by afebrile seizures." }, { "id": "c-ku72gz", "front": "GEFS+", "back": "Autosomal dominant family spectrum with incomplete penetrance, from febrile seizures and FS+ to epilepsy with myoclonic–atonic seizures and Dravet syndrome; genes include SCN1B, SCN1A, GABRG2." } ] } ], "sources": [ { "title": "AAP guideline: evaluation of the child with a simple febrile seizure (2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21285335/" }, { "title": "Syndromes with onset in childhood (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503717/" }, { "title": "Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24318290/" }, { "title": "Febrile status epilepticus and epileptogenesis: the FEBSTAT study (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40770931/" }, { "title": "Syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "Generalized epilepsy with febrile seizures plus (Scheffer 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9126059/" }, { "title": "SCN1B in GEFS+ (1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9697698/" }, { "title": "GABRG2 in a GEFS+ family (2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11326274/" } ], "words": 695, "bank": 5 }, { "id": "structural-causes", "n": "7", "title": "Structural causes", "tags": [ "epilepsy-surgery", "ilae-classification" ], "updated": false, "goals": [ "Recognize the malformations, tumors and vascular lesions that cause epilepsy", "manage seizure risk after stroke and head injury", "know when a lesion means surgery" ], "blocks": [ { "type": "h3", "text": "Malformations of cortical development" }, { "type": "li", "text": "**Focal cortical dysplasia** (ILAE classification updated in 2022): type I is abnormal cortical layering (Ia radial, Ib tangential, Ic both); type II has dysmorphic neurons (IIa) or dysmorphic neurons with balloon cells (IIb); type III sits next to another lesion (IIIa hippocampal sclerosis, IIIb tumor, IIIc vascular malformation, IIId other early-life injury). The 2022 update added **mild malformation with oligodendroglial hyperplasia (MOGHE)**. Type II is often caused by somatic mTOR-pathway variants. MRI shows blurring of the gray–white junction, cortical thickening, and in type IIb a **transmantle sign** tapering toward the ventricle. Complete resection of type II gives excellent results. MOGHE often carries a brain-only (somatic) SLC35A2 variant (45% of one surgical series); its histology shows clusters of increased oligodendroglial density, patchy hypomyelination and heterotopic neurons in the white matter." }, { "type": "li", "text": "**Heterotopia and lissencephaly**: periventricular nodular heterotopia (FLNA, mostly women); subcortical band heterotopia and lissencephaly (DCX, LIS1). Periventricular nodules match gray matter in signal and do not enhance, unlike the subependymal nodules of tuberous sclerosis, which often calcify. Subcortical band heterotopia (\"double cortex\") is a band of gray matter beneath the cortex. **The lissencephaly gradient** points to the gene: LIS1 (chromosome 17p13.3) is worse posteriorly; DCX (X-linked) is worse anteriorly and causes lissencephaly in boys and band heterotopia in girls." }, { "type": "li", "text": "**Polymicrogyria**, often bilateral perisylvian with oromotor dysfunction; **schizencephaly**; **hemimegalencephaly** (somatic mTOR variants, often treated with hemispherotomy). Polymicrogyria (excess small, overfolded gyri) can be genetic (more than 30 genes, including tubulin genes, and the 22q11.2 deletion) or acquired (congenital cytomegalovirus, prenatal ischemia). Schizencephaly is a full-thickness cleft from the cortical surface to the ventricle lined by polymicrogyric gray matter: open-lip when fluid separates the walls, closed-lip when they touch. A porencephalic cyst, by contrast, has no gray-matter lining." }, { "type": "li", "text": "**Hemimegalencephaly on MRI**: one enlarged hemisphere with an abnormal gyral pattern, increased white-matter volume with abnormal signal, and an enlarged, misshapen lateral ventricle. The other hemisphere is often smaller than normal, which helps explain poorer seizure and cognitive outcomes after hemispherotomy; seizures arising independently from the other side on EEG also predict a shorter seizure-free period. Assess both before surgery." }, { "type": "h3", "text": "Tumors" }, { "type": "p", "text": "Low-grade, slow-growing tumors are the most epileptogenic. **Ganglioglioma** (often BRAF V600E) and **dysembryoplastic neuroepithelial tumor** are the classic long-term epilepsy-associated tumors of the temporal lobe; early complete resection gives the best seizure outcomes. Metastases and high-grade gliomas cause seizures less often. In people with brain tumors who have never had a seizure, prophylactic antiseizure medications (ASMs) are not recommended. When treatment is needed, drugs without enzyme induction (such as levetiracetam) avoid interactions with chemotherapy." }, { "type": "p", "text": "On MRI a **ganglioglioma** is usually a cortically based, cystic, enhancing nodule, most often temporal, and calcifies in about half. A **dysembryoplastic neuroepithelial tumor** is cortically based and multicystic (\"bubbly\"), bright on T2, with little or no mass effect or edema, and enhances less often than a ganglioglioma." }, { "type": "p", "text": "**Hypothalamic hamartoma** is a congenital, non-neoplastic mass between the pituitary stalk and the mammillary bodies. It is isointense to slightly hypointense to gray matter on T1, iso- or hyperintense on T2, and does not enhance. Pedunculated hamartomas tend to cause central precocious puberty; sessile ones attached to the hypothalamic wall tend to cause seizures. In the ILAE syndrome of **gelastic seizures with hypothalamic hamartoma** (onset in the first year in about 85%), mirthless laughing seizures come first, then focal and generalized seizures, sometimes a Lennox–Gastaut-like picture, with drug resistance, cognitive decline, aggression and impulsivity. The hamartoma itself generates the seizures: depth electrodes record onset there and lesioning it stops them, so scalp EEG foci (often temporal or frontal) mislead and cortical resections fail. Treat the lesion early, for example by MRI-guided laser ablation, after which 93% of 71 patients were free of gelastic seizures at one year (see [ablation and disconnection](#surgical-options))." }, { "type": "h3", "text": "Vascular lesions" }, { "type": "li", "text": "**Cavernous malformations** are highly epileptogenic, through the surrounding hemosiderin; resection including the hemosiderin rim improves seizure outcome. An incidental cavernoma with no seizures needs neither an ASM nor surgery. On MRI a cavernoma has a \"popcorn\" core of blood of different ages with a dark hemosiderin rim that blooms on gradient-echo or susceptibility-weighted imaging, and little or no enhancement or edema. Use those sequences to count lesions: about 20% of patients have several, often familial (autosomal dominant KRIT1, CCM2 or PDCD10)." }, { "type": "li", "text": "**Arteriovenous malformations** present with seizures in a substantial proportion. The nidus is a tangle of abnormal vessels, with no capillary bed, between feeding arteries and early-draining veins; the vessels appear as dark flow voids on T2, and catheter angiography is the reference test." }, { "type": "li", "text": "**Bleeding risk shapes lesional epilepsy care**: arteriovenous malformations bleed about 2% a year when unruptured and 4.5% a year after a rupture, whereas a cavernoma outside the brainstem that presented without a bleed or new focal deficit carries about a 4% risk over 5 years." }, { "type": "li", "text": "**Sturge–Weber syndrome** (somatic GNAQ): facial port-wine stain in the V1 area, leptomeningeal angioma, gyriform calcification and hemiatrophy; early focal seizures and stroke-like episodes. **Roach types**: I, facial and leptomeningeal angioma (the classic form, glaucoma possible); II, facial angioma without brain involvement (glaucoma possible); III, leptomeningeal angioma alone (usually no glaucoma). Brain risk concentrates in stains on any part of the forehead, including the upper eyelid. Of those with seizures, about three quarters start in the first year. The cortical calcification has a \"tram-track\" appearance. Contrast-enhanced MRI is the key test: leptomeningeal enhancement, an enlarged ipsilateral choroid plexus, and later atrophy and calcification; it can be falsely normal in early infancy. Glaucoma, usually on the side of the stain, affects about half, so every child with a high-risk stain needs an ophthalmologist as well as a neurologist." }, { "type": "h3", "text": "Neurocutaneous syndromes" }, { "type": "li", "text": "**Tuberous sclerosis complex (TSC)**: autosomal dominant, often de novo. TSC1 (chromosome 9q34) encodes hamartin and TSC2 (16p13.3) encodes tuberin; losing either switches on mTOR. TSC2 disease is usually more severe, with more seizures, intellectual disability, tubers and kidney disease." }, { "type": "li", "text": "**2021 diagnostic criteria**: a pathogenic TSC1 or TSC2 variant is diagnostic on its own. Clinically, definite TSC needs two major features, or one major plus two or more minor features (lymphangioleiomyomatosis with renal angiomyolipomas alone is not enough). The update renamed \"cortical dysplasias\" as multiple cortical tubers and/or radial migration lines and restored sclerotic bone lesions as a minor feature. A negative blood test does not exclude TSC: standard testing finds no variant in 10–15%, and deeper sequencing then finds one in most of them, usually mosaic or intronic." }, { "type": "table", "head": [ "Major features", "Minor features" ], "rows": [ [ "Hypomelanotic macules (3 or more, at least 5 mm); angiofibromas (3 or more) or fibrous cephalic plaque; shagreen patch; ungual fibromas (2 or more)", "Confetti skin lesions; dental enamel pits (more than 3); intraoral fibromas (2 or more)" ], [ "Multiple cortical tubers and/or radial migration lines; subependymal nodules (2 or more); subependymal giant cell astrocytoma", "Sclerotic bone lesions; retinal achromic patch" ], [ "Cardiac rhabdomyoma; renal angiomyolipomas (2 or more); lymphangioleiomyomatosis; multiple retinal hamartomas", "Multiple renal cysts; hamartomas outside the kidneys" ] ] }, { "type": "li", "text": "**Brain lesions**: cortical tubers are bright on T2 and fluid-attenuated inversion recovery (FLAIR) images and dark on T1 once myelination is complete (the reverse in newborns) and often calcify. Subependymal nodules line the ventricles and often calcify, best seen on CT. A **subependymal giant cell astrocytoma (SEGA)** is an enhancing, slowly growing lesion near the foramen of Monro in 10–20% that can block it and cause hydrocephalus; MRI every 1–3 years until age 25 screens for it." }, { "type": "li", "text": "**Epilepsy**: vigabatrin first for spasms, with EEG surveillance through infancy. Everolimus (an mTOR inhibitor) reduced drug-resistant focal seizures in EXIST-3, and the response rate rose with blood level (40% in the high trough range, 28% in the low range, 15% on placebo). It also shrinks SEGA: in EXIST-1 it at least halved the tumor in 35%, against none on placebo. Refer drug-resistant patients early for surgery." }, { "type": "li", "text": "**Incontinentia pigmenti**: X-linked dominant (IKBKG, also called NEMO) with presumed male lethality, so it is seen in girls. Skin lesions follow Blaschko's lines through stages: blistering streaks in the newborn, then warty plaques, then swirled brown pigmentation and pale, atrophic streaks. Infants can have focal seizures and hemorrhagic infarcts; retinal vasculopathy can cause blindness; teeth are missing or peg-shaped." }, { "type": "mcq", "id": "q-1luxttb", "stem": "A 12-year-old with tuberous sclerosis complex has a routine MRI. A 1.4-cm enhancing nodule at the left foramen of Monro has grown since a scan 2 years ago, and the lateral ventricles are mildly enlarged. He has no headache or vomiting. What is the lesion, and what is an appropriate treatment?", "options": [ "A calcified subependymal nodule; no action", "A subependymal giant cell astrocytoma; an mTOR inhibitor such as everolimus", "A cortical tuber; epilepsy surgery", "Periventricular nodular heterotopia; FLNA testing", "A choroid plexus papilloma; urgent resection" ], "answer": 1, "explain": "A growing, enhancing subependymal lesion near the foramen of Monro in tuberous sclerosis is a subependymal giant cell astrocytoma. For a growing tumor without acute symptoms, the international recommendations accept either an mTOR inhibitor or surgical resection, chosen case by case; in EXIST-1, everolimus at least halved tumor volume in 35% of patients. Acute hydrocephalus needs surgery. The other pairings name the wrong lesion." }, { "type": "h3", "text": "After stroke and head injury" }, { "type": "li", "text": "**Stroke** is the commonest identifiable cause of new epilepsy after 60. Seizures in the first week are acute symptomatic. A seizure after that carries a high recurrence risk, so one late seizure usually justifies treatment. Cortical involvement, hemorrhage, larger and more severe strokes, and early seizures raise the risk." }, { "type": "li", "text": "**Traumatic brain injury**: penetrating injury, depressed skull fracture, intracranial (especially subdural) hematoma, early seizures and greater severity raise the risk of post-traumatic epilepsy. A week of phenytoin or levetiracetam after severe injury reduces early seizures only." }, { "type": "mcq", "id": "q-muhcdv", "stem": "A 12-year-old has drug-resistant focal seizures. MRI shows blurring of the gray–white junction in the right frontal lobe with a T2 hyperintense band tapering from the cortex toward the lateral ventricle. What is the most likely pathology?", "options": [ "Focal cortical dysplasia type I", "Focal cortical dysplasia type IIb", "Dysembryoplastic neuroepithelial tumor", "Periventricular nodular heterotopia", "Hippocampal sclerosis" ], "answer": 1, "explain": "The transmantle sign is characteristic of FCD type IIb (dysmorphic neurons and balloon cells). Type I is often MRI-negative." }, { "type": "mcq", "id": "q-1d11upl", "stem": "A 42-year-old has a 7-mm cortical cavernous malformation found on MRI done for headaches. She has never had a seizure. What is the best management?", "options": [ "Start levetiracetam", "Resect the lesion with its hemosiderin rim", "No ASM or surgery; follow clinically and explain which symptoms to report", "Radiosurgery", "Routine EEG every six months" ], "answer": 2, "explain": "An incidental cavernoma without seizures does not warrant prophylactic ASMs or surgery. Resection with the hemosiderin rim is considered when the lesion causes epilepsy or bleeds." }, { "type": "cards", "items": [ { "id": "c-if3w0i", "front": "FCD type IIb", "back": "Dysmorphic neurons plus balloon cells; transmantle sign; often somatic mTOR variants." }, { "id": "c-bhdto7", "front": "FCD type III", "back": "Dysplasia adjacent to another lesion: IIIa hippocampal sclerosis, IIIb tumor, IIIc vascular, IIId other early injury." }, { "id": "c-1wdc4p9", "front": "MOGHE", "back": "Mild malformation with oligodendroglial hyperplasia in epilepsy; added in the 2022 FCD update." }, { "id": "c-1e0iyts", "front": "Most epileptogenic tumors", "back": "Low-grade: ganglioglioma and DNET." }, { "id": "c-wbhxed", "front": "Prophylactic ASM for a brain tumor without seizures", "back": "Not recommended." }, { "id": "c-1hhkmtg", "front": "Cavernoma surgery for epilepsy", "back": "Resect with the hemosiderin rim." }, { "id": "c-gyxxx4", "front": "Sturge–Weber gene", "back": "Somatic GNAQ." }, { "id": "c-5mi2mk", "front": "Seizure after the first week post-stroke", "back": "Unprovoked; high recurrence risk; usually treat." }, { "id": "c-qqk6gw", "front": "Phenytoin for a week after severe head injury", "back": "Reduces early seizures only." }, { "id": "c-16ax6wy", "front": "MOGHE gene", "back": "Brain-only (somatic) SLC35A2 variants in many cases." }, { "id": "c-1ifvs3f", "front": "Lissencephaly gradient", "back": "LIS1 worse posteriorly; DCX worse anteriorly (band heterotopia in girls)." }, { "id": "c-cqnbcy", "front": "Periventricular nodular heterotopia on MRI", "back": "Smooth nodules with gray-matter signal that do not enhance; tuberous sclerosis nodules often calcify." }, { "id": "c-1fmt9zv", "front": "Schizencephaly", "back": "Full-thickness cleft from cortex to ventricle lined by polymicrogyric gray matter; open-lip or closed-lip." }, { "id": "c-10ght8m", "front": "Acquired causes of polymicrogyria", "back": "Congenital cytomegalovirus infection and prenatal ischemia." }, { "id": "c-12nirm7", "front": "Hemimegalencephaly before hemispherotomy", "back": "Check the other hemisphere (often small and abnormal) and look for independent contralateral seizures." }, { "id": "c-rgftpb", "front": "Ganglioglioma versus dysembryoplastic neuroepithelial tumor (DNET) on MRI", "back": "Ganglioglioma: cystic, enhancing nodule, often calcified, mostly temporal. DNET: multicystic and bubbly, bright on T2, little mass effect, enhances less often." }, { "id": "c-qmkn8e", "front": "Hypothalamic hamartoma", "back": "Non-enhancing, gray-matter-like mass between pituitary stalk and mammillary bodies; pedunculated forms cause precocious puberty; gelastic seizures arise in the lesion itself." }, { "id": "c-1y4thi6", "front": "Cavernoma on MRI", "back": "Popcorn core with a dark hemosiderin rim that blooms on susceptibility-weighted imaging; about 20% have several, often familial." }, { "id": "c-q655zj", "front": "Arteriovenous malformation on MRI", "back": "Nidus of tangled vessels with flow voids on T2; catheter angiography is the reference test." }, { "id": "c-1gg3snv", "front": "Bleeding risk: arteriovenous malformation versus cavernoma", "back": "Arteriovenous malformation about 2% a year unruptured, 4.5% after rupture; cavernoma outside the brainstem presenting without a bleed or new deficit about 4% over 5 years." }, { "id": "c-1fdb8xd", "front": "Roach types of Sturge–Weber syndrome", "back": "I face and brain; II face only; III brain only." }, { "id": "c-1u41bwl", "front": "Sturge–Weber imaging", "back": "Tram-track cortical calcification; leptomeningeal enhancement and an enlarged choroid plexus on contrast MRI, which can be normal in early infancy." }, { "id": "c-zecigh", "front": "High-risk port-wine stain", "back": "Any part of the forehead, including the upper eyelid; needs neurology and eye review (glaucoma)." }, { "id": "c-1khoehv", "front": "TSC1 and TSC2", "back": "TSC1 (9q34) encodes hamartin; TSC2 (16p13.3) encodes tuberin; TSC2 disease is usually more severe." }, { "id": "c-1bvqtur", "front": "Tuberous sclerosis 2021 criteria", "back": "A pathogenic TSC1 or TSC2 variant alone, or two major features, or one major plus two or more minor features." }, { "id": "c-4s589g", "front": "Clinical TSC with a negative blood test", "back": "Still TSC; 10–15% have no variant on standard testing, mostly mosaic or intronic." }, { "id": "c-1olx37l", "front": "Subependymal giant cell astrocytoma", "back": "Enhancing, growing lesion near the foramen of Monro; can cause hydrocephalus; mTOR inhibitors shrink it." }, { "id": "c-5ipl8w", "front": "EXIST-3", "back": "Everolimus reduced drug-resistant focal seizures in tuberous sclerosis; response rose with trough level (40% high, 28% low, 15% placebo)." }, { "id": "c-v6hi5v", "front": "Incontinentia pigmenti", "back": "X-linked dominant (IKBKG); girls; staged skin lesions along Blaschko's lines; infant seizures and hemorrhagic infarcts." } ] } ], "sources": [ { "title": "ILAE FCD classification update (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35706131/" }, { "title": "Phenytoin after head injury (Temkin 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2115976/" }, { "title": "ILAE definition of acute symptomatic seizures (2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19732133/" }, { "title": "Systematic approach to epileptogenic lesions on imaging (2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41544245/" }, { "title": "SLC35A2 mosaicism in MOGHE (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33407896/" }, { "title": "LIS1 and DCX lissencephaly patterns (Pilz 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9817918/" }, { "title": "Gyral pattern in LIS1 and DCX lissencephaly (1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10430413/" }, { "title": "Doublecortin, band heterotopia and lissencephaly (1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9489699/" }, { "title": "Polymicrogyria review (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24888723/" }, { "title": "Hemimegalencephaly: imaging (2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12150586/" }, { "title": "Contralateral hemimicrencephaly in hemimegalencephaly (2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16291806/" }, { "title": "Hemispheric surgery for hemimegalencephaly (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37873610/" }, { "title": "Dysembryoplastic neuroepithelial tumors on MR and CT (1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/8881234/" }, { "title": "Hamartomas of the tuber cinereum on CT and MR (1991)", "url": "https://pubmed.ncbi.nlm.nih.gov/1902033/" }, { "title": "Syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "Intrinsic epileptogenesis of hypothalamic hamartomas (1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9225686/" }, { "title": "Laser ablation of hypothalamic hamartomas (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29631919/" }, { "title": "Cerebral cavernous malformation guidelines (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28387823/" }, { "title": "Untreated cavernous malformations, individual patient data meta-analysis (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26654287/" }, { "title": "Natural history of brain arteriovenous malformations, meta-analysis (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23198804/" }, { "title": "Vascular malformations of the brain (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/37502170/" }, { "title": "CNS vascular malformations: clinical review (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33434339/" }, { "title": "Sturge–Weber syndrome by Roach type (2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40604834/" }, { "title": "Port-wine stain distribution and Sturge–Weber risk (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24976116/" }, { "title": "Sturge–Weber syndrome: age at onset of seizures and glaucoma (1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7769179/" }, { "title": "Sturge–Weber syndrome consensus: neurology, neuroimaging, ophthalmology (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34153815/" }, { "title": "Updated TSC diagnostic criteria and recommendations (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34399110/" }, { "title": "Tuberous sclerosis complex, GeneReviews", "url": "https://www.ncbi.nlm.nih.gov/books/NBK1220/" }, { "title": "TSC1 gene on chromosome 9q34 (1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9242607/" }, { "title": "TSC2 gene on chromosome 16 (1993)", "url": "https://pubmed.ncbi.nlm.nih.gov/8269512/" }, { "title": "Greater severity of TSC2 disease (2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11112665/" }, { "title": "Mosaic and intronic variants in TSC (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26540169/" }, { "title": "Brain abnormalities in TSC (2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15563010/" }, { "title": "Tuberous sclerosis on CT and MR (1988)", "url": "https://pubmed.ncbi.nlm.nih.gov/3357966/" }, { "title": "Cerebral tuberous sclerosis on MR (1989)", "url": "https://pubmed.ncbi.nlm.nih.gov/2916045/" }, { "title": "SEGA recommendations (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24138953/" }, { "title": "EXIST-3, everolimus for TSC seizures (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27613521/" }, { "title": "EXIST-1, everolimus for SEGA (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23158522/" }, { "title": "TSC epilepsy recommendations (2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37669572/" }, { "title": "Incontinentia pigmenti (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26564087/" } ], "words": 2213, "bank": 12 }, { "id": "immune-infectious-metabolic", "n": "8", "title": "Immune, infectious and metabolic causes", "tags": [ "seizure-management", "ilae-classification" ], "updated": false, "goals": [ "Distinguish acute symptomatic seizures in autoimmune encephalitis from autoimmune-associated epilepsy", "manage neurocysticercosis", "recognize the treatable metabolic epilepsies" ], "blocks": [ { "type": "h3", "text": "Autoimmune" }, { "type": "p", "text": "The ILAE separates two situations:" }, { "type": "li", "text": "**Acute symptomatic seizures secondary to autoimmune encephalitis**: usually with antibodies to neuronal surface proteins (NMDA receptor, LGI1, CASPR2, GABA-B, AMPA receptor). They respond to immunotherapy, and seizures usually stop as the encephalitis settles." }, { "type": "li", "text": "**Autoimmune-associated epilepsy**: usually with antibodies to intracellular antigens (GAD65, onconeural antibodies such as Hu). T-cell mediated, less responsive to immunotherapy, and more likely to persist." }, { "type": "table", "head": [ "Antibody", "Clinical signature" ], "rows": [ [ "NMDA receptor", "Young women and children; psychiatric onset, seizures, dyskinesias, autonomic instability, hypoventilation; ovarian teratoma; extreme delta brush; can follow herpes simplex encephalitis" ], [ "LGI1", "Older adults; **faciobrachial dystonic seizures** (very brief, very frequent arm-and-face jerks); hyponatremia; memory decline" ], [ "CASPR2", "Neuromyotonia, Morvan syndrome, limbic encephalitis" ], [ "GABA-B receptor", "Severe refractory seizures or status; small-cell lung cancer" ], [ "GAD65", "Temporal lobe epilepsy, stiff-person spectrum, type 1 diabetes; poor response to immunotherapy" ] ] }, { "type": "p", "text": "Faciobrachial dystonic seizures respond far better to immunotherapy than to antiseizure medications (ASMs), and treating them early can prevent the cognitive decline that follows. First-line immunotherapy is corticosteroids, IVIG or plasma exchange; rituximab or cyclophosphamide is second-line. Always look for a tumor." }, { "type": "li", "text": "**Order the specific antibodies.** Test for LGI1 and CASPR2 antibodies directly. A positive \"voltage-gated potassium channel (VGKC) complex\" antibody without either is not a reliable marker of autoimmune inflammation and should not by itself drive immunotherapy." }, { "type": "li", "text": "**A diagnostic trial of immunotherapy** helps when autoimmune epilepsy is suspected, with or without an antibody (for example frequent drug-resistant seizures with other autoimmune disease): a time-limited course of IV methylprednisolone, IVIG or both, judged by objective seizure counts. In one series 62% responded (50% or greater reduction): most patients with surface antibodies, a third of those with GAD65 antibodies, and a third of those with no antibody. Earlier treatment predicted response." }, { "type": "li", "text": "**Systemic autoimmune disease** raises the risk of epilepsy (odds ratio 3.8 across 12 diseases, including type 1 diabetes, lupus and celiac disease, and higher in children). Celiac disease can cause epilepsy with parieto-occipital calcifications that resemble Sturge–Weber syndrome; a gluten-free diet helps only if started early. **Steroid-responsive encephalopathy with autoimmune thyroiditis** (SREAT, also called Hashimoto encephalopathy) presents with tremor, transient aphasia, myoclonus, ataxia and seizures (60% in one series) and is often first mistaken for viral encephalitis or Creutzfeldt–Jakob disease." }, { "type": "h3", "text": "Infectious" }, { "type": "p", "text": "**Neurocysticercosis** is a leading cause of acquired epilepsy worldwide. For viable parenchymal cysts, antiparasitic treatment (albendazole, adding praziquantel when there are more than two cysts) is given with corticosteroids and an ASM. Calcified cysts need no antiparasitic treatment. Examine the fundi before antiparasitic drugs. Other causes to remember: tuberculosis, cerebral malaria, HIV and its opportunistic infections, and the sequelae of viral encephalitis." }, { "type": "p", "text": "Parenchymal cysts pass through four imaging stages, and the stage decides whether antiparasitic drugs can help:" }, { "type": "table", "head": [ "Stage", "Imaging", "Antiparasitic drugs" ], "rows": [ [ "Vesicular (viable)", "Thin-walled cyst with fluid like CSF and an eccentric scolex (a bright \"dot\"); no enhancement or edema", "Effective, with corticosteroids" ], [ "Colloidal vesicular (degenerating)", "Thicker ring-enhancing wall, cloudy fluid, shrunken scolex, edema around the cyst", "Albendazole speeds resolution of a single enhancing lesion" ], [ "Granular nodular", "Small enhancing nodule with mild edema", "As for colloidal" ], [ "Nodular calcified", "Small calcified nodule, best seen on CT, no edema", "No effect" ] ] }, { "type": "p", "text": "Degenerating, enhancing cysts are what most patients in South Asia have when seizures begin; viable cysts are seen more often in Latin America. A calcified cyst is not always inert: it can release antigen and flare with edema, and it can be the cause of drug-resistant focal epilepsy. In a surgical series, removing the calcified lesion (especially with gliosis around it) stopped seizures, and calcifications often coexist with hippocampal sclerosis; when both were present, removing both did best. Evaluate the lesion and the mesial temporal structures together before [surgery](#surgical-options)." }, { "type": "h3", "text": "Metabolic and vitamin-responsive" }, { "type": "table", "head": [ "Disorder", "Clue", "Treatment" ], "rows": [ [ "Pyridoxine-dependent epilepsy (ALDH7A1)", "Refractory neonatal seizures; raised α-aminoadipic semialdehyde and pipecolic acid. \"Folinic acid-responsive seizures\" are the same ALDH7A1 disorder. Most have some intellectual disability despite good seizure control", "Pyridoxine for life, with lysine restriction (lysine reduction may also help cognition)" ], [ "PNPO deficiency", "As above, with poor response to pyridoxine; low pyridoxal 5′-phosphate in CSF", "Pyridoxal 5′-phosphate" ], [ "GLUT1 deficiency (SLC2A1)", "Absences before age 4 or drug-resistant absences; paroxysmal eye–head movements in infancy; later paroxysmal exercise-induced dyskinesia and ataxia; worse with fasting and in the morning. Low CSF glucose relative to blood, on a lumbar puncture after a 4–6-hour fast with blood glucose taken just before it", "Ketogenic diet, as early as possible and continued into adolescence and adulthood" ], [ "Biotinidase deficiency", "Seizures, alopecia, rash, hearing loss", "Biotin" ], [ "Creatine deficiency (GAMT)", "Absent creatine peak on MR spectroscopy", "Creatine (with ornithine)" ], [ "Cerebral folate deficiency", "Low CSF 5-MTHF; FOLR1 variants cause cerebral folate transport deficiency (regression, ataxia, hypomyelination)", "Folinic acid" ], [ "POLG disease", "Refractory focal (often occipital) seizures and epilepsia partialis continua with liver involvement", "Avoid valproate" ], [ "Nonketotic hyperglycinemia", "Neonatal encephalopathy, hiccups, burst-suppression; high CSF-to-plasma glycine", "Sodium benzoate and dextromethorphan (supportive)" ], [ "Nonketotic hyperglycemia (a different disorder)", "Focal motor seizures, often aware, or epilepsia partialis continua in an adult; the first sign of diabetes in 40%; very high glucose without ketones; subcortical T2 hypointensity under the involved cortex", "Correct the hyperglycemia; ASMs alone controlled seizures in under a fifth and can worsen them" ] ] }, { "type": "case", "id": "case-lgi1", "title": "Brief jerks and memory loss at 64", "intro": [ "A 64-year-old man has had dozens of daily episodes, each about two seconds long, in which his left arm stiffens and the left side of his face grimaces. Over two months his memory has declined. His sodium is 128 mmol/L. Routine EEG is normal." ], "steps": [ { "narrative": [], "stem": "What is the most likely diagnosis?", "options": [ "Functional movement disorder", "Focal motor seizures from a right frontal tumor", "LGI1 antibody encephalitis with faciobrachial dystonic seizures", "Creutzfeldt–Jakob disease", "Hemifacial spasm" ], "answer": 2, "explain": "Very brief, very frequent arm-and-face dystonic seizures (faciobrachial dystonic seizures), hyponatremia and subacute memory decline in an older man are characteristic of LGI1 antibody encephalitis. The EEG is often normal during them." }, { "narrative": [], "stem": "Levetiracetam and then lacosamide have had little effect. What is the most important treatment?", "options": [ "Add a third ASM", "Immunotherapy, starting with corticosteroids (or IVIG or plasma exchange)", "Epilepsy surgery", "Vagus nerve stimulation", "Ketogenic diet" ], "answer": 1, "explain": "Faciobrachial dystonic seizures respond much better to immunotherapy than to ASMs. Early immunotherapy can prevent progression to the full limbic encephalitis and permanent memory loss." } ], "outro": [ "This is the classic acute symptomatic pattern of antibody-mediated encephalitis: seizures that ASMs barely touch, and that stop with immunotherapy." ] }, { "type": "mcq", "id": "q-1mg6ts4", "stem": "Which antibody is most typical of autoimmune-associated epilepsy that responds poorly to immunotherapy?", "options": [ "NMDA receptor", "LGI1", "GAD65", "CASPR2", "AMPA receptor" ], "answer": 2, "explain": "Antibodies to intracellular antigens such as GAD65 indicate a T-cell-mediated process that responds poorly to immunotherapy. Surface-antibody encephalitides usually respond and seizures often resolve." }, { "type": "cards", "items": [ { "id": "c-146ssq0", "front": "Surface versus intracellular antibodies", "back": "Surface (NMDAR, LGI1, CASPR2, GABA-B, AMPA): immunotherapy-responsive, seizures usually acute symptomatic. Intracellular (GAD65, Hu): T-cell mediated, poorer response." }, { "id": "c-puy918", "front": "Faciobrachial dystonic seizures", "back": "LGI1 antibodies; respond to immunotherapy more than ASMs." }, { "id": "c-1tuzz9b", "front": "NMDA receptor encephalitis tumor", "back": "Ovarian teratoma." }, { "id": "c-hucijj", "front": "GABA-B receptor encephalitis tumor", "back": "Small-cell lung cancer." }, { "id": "c-qalai", "front": "Neurocysticercosis with viable cysts", "back": "Albendazole (plus praziquantel if more than two cysts) with corticosteroids and an ASM." }, { "id": "c-1hh4smp", "front": "Pyridoxine-dependent epilepsy gene and marker", "back": "ALDH7A1; raised α-aminoadipic semialdehyde." }, { "id": "c-6afhjz", "front": "GLUT1 deficiency", "back": "Low CSF glucose relative to blood; ketogenic diet." }, { "id": "c-v99hy2", "front": "GLUT1 deficiency: when to test", "back": "Absences before age 4 or drug-resistant absences, paroxysmal eye–head movements, exercise-induced dyskinesia, symptoms worse with fasting." }, { "id": "c-kowgmi", "front": "VGKC-complex antibody without LGI1 or CASPR2", "back": "Not a reliable sign of autoimmune disease; test LGI1 and CASPR2 specifically." }, { "id": "c-1p4sk42", "front": "Diagnostic immunotherapy trial", "back": "Time-limited IV methylprednisolone and/or IVIG in suspected autoimmune epilepsy, judged by objective seizure counts." }, { "id": "c-13aw5t9", "front": "Steroid-responsive encephalopathy with autoimmune thyroiditis", "back": "Encephalopathy with tremor, aphasia, myoclonus and seizures; thyroid antibodies; responds to steroids." }, { "id": "c-x8i0ne", "front": "Celiac disease and epilepsy", "back": "Parieto-occipital calcifications resembling Sturge–Weber syndrome." }, { "id": "c-1dflftq", "front": "Neurocysticercosis stages", "back": "Vesicular (cyst with scolex, no enhancement), colloidal (ring enhancement, edema), granular nodular (enhancing nodule), calcified." }, { "id": "c-9jc8p7", "front": "Calcified neurocysticercosis in drug-resistant epilepsy", "back": "Can be the epileptogenic lesion; often coexists with hippocampal sclerosis, so assess both." }, { "id": "c-12a35zp", "front": "Second biochemical marker of ALDH7A1 deficiency", "back": "Raised pipecolic acid (with α-aminoadipic semialdehyde); folinic acid-responsive seizures are the same disorder." }, { "id": "c-1isb4ev", "front": "PNPO deficiency marker", "back": "Low pyridoxal 5′-phosphate in CSF." }, { "id": "c-sfyx9y", "front": "Nonketotic hyperglycemia", "back": "Focal motor seizures or epilepsia partialis continua with very high glucose and no ketones; correct the glucose." } ] } ], "sources": [ { "title": "ILAE: autoimmune encephalitis seizures and autoimmune-associated epilepsy (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32544279/" }, { "title": "IDSA/ASTMH neurocysticercosis guideline (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29481580/" }, { "title": "NSGC guideline on genetic testing (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36281494/" }, { "title": "VGKC positivity without LGI1 or CASPR2 antibodies (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27037230/" }, { "title": "Immunotherapy trial in presumed autoimmune epilepsy (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24706013/" }, { "title": "Autoimmune disease and epilepsy risk (2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24687183/" }, { "title": "Coeliac disease, epilepsy and cerebral calcifications (1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1354781/" }, { "title": "Steroid-responsive encephalopathy with autoimmune thyroiditis (2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16476807/" }, { "title": "Pediatric neurocysticercosis review (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/29388588/" }, { "title": "Calcified neurocysticercosis and drug-resistant epilepsy (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24032594/" }, { "title": "Calcified neurocysticercosis and hippocampal sclerosis (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35153977/" }, { "title": "Syndromes with onset in neonates and infants (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35503712/" }, { "title": "Glut1 deficiency syndrome: international consensus (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32913944/" }, { "title": "Pyridoxine-dependent epilepsy consensus guidelines (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33200442/" }, { "title": "Folinic acid-responsive seizures are pyridoxine-dependent epilepsy (2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19142996/" }, { "title": "FOLR1 and cerebral folate transport deficiency (2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22586289/" }, { "title": "Nonketotic hyperglycemia seizures, meta-analysis (2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/36773573/" } ], "words": 1284, "bank": 13 } ], "intro": [ "A syndrome diagnosis predicts the course, points to the right drugs and away from the wrong ones, and tells the family what to expect. The ILAE 2022 papers organize syndromes by age at onset. For quick lookups, use the [syndrome lookup on the ILAE page](ilae_classification.html#syndromes-tab)." ] }, { "id": "treatment", "n": "7", "title": "Medical treatment", "short": "Treatment", "sections": [ { "id": "treatment-principles", "n": "1", "title": "Starting, choosing and stopping", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Choose a first ASM by seizure type, syndrome and person", "recognize drug resistance early", "counsel on withdrawal after remission" ], "blocks": [ { "type": "h3", "text": "How often the first drug works" }, { "type": "p", "text": "In a long-term cohort of newly treated epilepsy, about half of patients became seizure-free on the first ASM, roughly one in eight more on the second, and only a few percent on each regimen after that. The curve flattens fast. That is the reason to refer for specialist and surgical evaluation after two appropriate drugs have failed, rather than after five." }, { "type": "h3", "text": "Choosing the first drug" }, { "type": "li", "text": "**Match the drug to the seizure type and syndrome first.** Broad-spectrum drugs (valproate, lamotrigine, levetiracetam, and others) suit generalized or unclassified epilepsy. Sodium channel blockers suit focal epilepsy but can worsen absence and myoclonic seizures." }, { "type": "li", "text": "**Then match it to the person**: the possibility of pregnancy, age, psychiatric and cognitive comorbidity, weight, bone health, kidney and liver function, other medicines, and cost." }, { "type": "li", "text": "**Trial evidence (SANAD II)**: for focal epilepsy, lamotrigine remained the first choice; neither levetiracetam nor zonisamide did better. For generalized and unclassified epilepsy, valproate outperformed levetiracetam, so valproate remains the most effective option where it can be used safely." }, { "type": "li", "text": "**Ethosuximide** is first choice for childhood absence epilepsy without other seizure types." }, { "type": "h3", "text": "Dosing and combining" }, { "type": "li", "text": "Start low, increase slowly, and aim for the lowest effective dose." }, { "type": "li", "text": "If the first drug fails because of side effects or lack of effect, substituting a second monotherapy and adding a second drug are both reasonable. Combine drugs with different mechanisms; two sodium channel blockers together add side effects (dizziness, diplopia, ataxia)." }, { "type": "li", "text": "Valproate plus lamotrigine is an effective combination, but valproate roughly doubles lamotrigine levels, so lamotrigine is started lower and titrated more slowly." }, { "type": "li", "text": "Before calling a drug a failure, check adherence, the dose, and whether the events are epileptic at all." }, { "type": "li", "text": "**Generic substitution**: the US Food and Drug Administration (FDA) accepts a generic as bioequivalent when the 90% confidence intervals for the ratios of its area under the concentration curve and its peak concentration to the reference product both lie within 80–125%. Bioequivalence describes average exposure in a group. Therapeutic equivalence is the FDA's judgment that a pharmaceutically equivalent, bioequivalent product can be expected to have the same clinical effect and safety. Switchability is the patient's question: will my levels and seizures stay the same after a switch? In the EQUIGEN (Equivalence among Generic Antiepileptic Drugs) trials, people with epilepsy moved between the two most different generic lamotrigine products had near-identical exposure (90% intervals 98–103% for area under the curve, 99–105% for peak) with no change in seizures or side effects, and a single-dose study found no subject-by-formulation interaction. The American Epilepsy Society now regards FDA bioequivalence standards as appropriate in epilepsy. Generics can differ in shape, color and excipients, so tell patients when the tablet will look different, and do not swap an extended-release product for an immediate-release one." }, { "type": "h3", "text": "Stopping after remission" }, { "type": "p", "text": "Withdrawal can be considered after about two years seizure-free. Relapse is more likely with a longer epilepsy before remission, many seizures before control, adolescent onset (juvenile myoclonic epilepsy relapses in most), developmental delay, a structural cause, and epileptiform discharges on the EEG before withdrawal. Most relapses occur within the first year or two, and most patients regain control when the drug is restarted. Taper gradually, and discuss driving during and after the taper." }, { "type": "p", "text": "The **2021 American Academy of Neurology (AAN) practice advisory** on withdrawal found that adults seizure-free for 2 years who taper possibly have a higher long-term risk of recurrence than those who stay on treatment (15% against 7% over 2–5 years in the one Class I study), and that tapering possibly does not raise the risk of status epilepticus. In children, starting withdrawal after 2 rather than 4 seizure-free years probably makes no difference, and an epileptiform EEG raises the risk. **Age at onset** matters: epilepsy that began in childhood relapses less often than epilepsy that began in adolescence (relative risk about 1.8) or adulthood (about 1.3). An individual-participant meta-analysis of 1,769 patients (46% relapsed) found eight independent predictors of relapse: epilepsy duration before remission, the seizure-free interval, age at onset, a history of febrile seizures, the number of seizures before remission, the absence of a self-limited syndrome, developmental delay, and an epileptiform EEG before withdrawal. It turned them into published **nomograms** (and a web tool) for an individual estimate." }, { "type": "note", "label": "Try it", "text": "[ASM withdrawal](seizure_management.html#asm-withdrawal) on the Seizure Management page sets out the points to discuss before a taper." }, { "type": "note", "label": "Drug trial phases (FDA)", "text": "phase 1 tests safety and dosage in 20–100 healthy volunteers or patients; phase 2 looks for efficacy and side effects in up to several hundred patients; phase 3 confirms efficacy and monitors adverse reactions in 300–3,000 patients; phase 4 is post-marketing study and safety surveillance after approval." }, { "type": "mcq", "id": "q-1wxpjbw", "stem": "A 30-year-old man with focal epilepsy has seizures despite lamotrigine at a good dose. Levetiracetam was stopped after two weeks at 250 mg twice daily because of irritability. How many adequate trials has he failed?", "options": [ "One", "Two", "Three", "None", "It cannot be determined without drug levels" ], "answer": 0, "explain": "Only lamotrigine was an adequate, tolerated trial. Levetiracetam was stopped early at a low dose for side effects and does not count as a failed trial for defining drug resistance." }, { "type": "mcq", "id": "q-ihki5w", "stem": "According to SANAD II, which drug remains the most effective first choice for a man with newly diagnosed generalized epilepsy?", "options": [ "Levetiracetam", "Lamotrigine", "Valproate", "Zonisamide", "Carbamazepine" ], "answer": 2, "explain": "In SANAD II, levetiracetam was not non-inferior to valproate for generalized and unclassified epilepsy. Valproate remains first choice where teratogenicity is not a concern." }, { "type": "cards", "items": [ { "id": "c-1po5up4", "front": "Seizure freedom with the first, second and later ASMs", "back": "About half with the first, about one in eight more with the second, a few percent with each later regimen." }, { "id": "c-1c2oeun", "front": "When to refer for surgical evaluation", "back": "After two appropriate, adequate ASM trials have failed." }, { "id": "c-1b3kfck", "front": "SANAD II focal epilepsy", "back": "Lamotrigine remains first choice; levetiracetam and zonisamide did no better." }, { "id": "c-eew3n5", "front": "SANAD II generalized epilepsy", "back": "Valproate outperformed levetiracetam." }, { "id": "c-oeg19p", "front": "Valproate and lamotrigine", "back": "Valproate roughly doubles lamotrigine levels; start lamotrigine lower and titrate slowly." }, { "id": "c-au1qrc", "front": "When to consider withdrawal", "back": "After about two years seizure-free." }, { "id": "c-12n8838", "front": "Syndrome with a very high relapse rate after withdrawal", "back": "Juvenile myoclonic epilepsy." }, { "id": "c-1sgk8w9", "front": "AAN 2021 advisory on withdrawal in adults", "back": "Tapering after 2 seizure-free years possibly raises long-term recurrence (15% against 7%); no clear rise in status epilepticus." }, { "id": "c-1patt8u", "front": "Relapse after withdrawal by age at onset", "back": "Lowest for childhood onset; higher for adolescent and adult onset." }, { "id": "c-jw7i2a", "front": "Tool for an individual relapse estimate", "back": "Published nomograms (and web tool) from the individual-participant meta-analysis." }, { "id": "c-a5c4jr", "front": "FDA bioequivalence criterion", "back": "90% confidence intervals of the area-under-the-curve and peak concentration ratios within 80–125%." }, { "id": "c-1slpwgf", "front": "Therapeutic equivalence", "back": "Pharmaceutically equivalent and bioequivalent; expected to have the same clinical effect and safety." }, { "id": "c-1imttrp", "front": "Switchability", "back": "Whether an individual patient can move between products without change; tested in EQUIGEN." }, { "id": "c-gdoe3y", "front": "EQUIGEN trials", "back": "Generic lamotrigine products were bioequivalent in people with epilepsy, with no change in seizures or side effects." }, { "id": "c-kmtbmt", "front": "Drug trial phases", "back": "1 safety and dose; 2 efficacy and side effects; 3 confirm efficacy in hundreds to thousands; 4 post-marketing surveillance." } ] } ], "sources": [ { "title": "SANAD II, focal epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838757/" }, { "title": "SANAD II, generalized and unclassifiable epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838758/" }, { "title": "Treatment outcomes over 30 years (Chen 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29279892/" }, { "title": "Early identification of refractory epilepsy (Kwan and Brodie 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/10660394/" }, { "title": "AAN practice advisory on ASM withdrawal in seizure-free patients (Gloss 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34873018/" }, { "title": "Relapse after ASM withdrawal: a meta-analysis (Berg and Shinnar 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/8164811/" }, { "title": "Individualised prediction of relapse after withdrawal (Lamberink 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28483337/" }, { "title": "EQUIGEN generic-to-generic lamotrigine switches (Privitera 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26875743/" }, { "title": "EQUIGEN single-dose study (Berg 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28654954/" }, { "title": "AES position statement on generic substitution (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27330454/" }, { "title": "FDA Orange Book preface", "url": "https://www.fda.gov/drugs/development-approval-process-drugs/orange-book-preface" }, { "title": "FDA: clinical research phases", "url": "https://www.fda.gov/patients/drug-development-process/step-3-clinical-research" } ], "words": 1137, "bank": 8 }, { "id": "asm-pharmacology", "n": "2", "title": "How ASMs are handled by the body", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Predict interactions from enzyme induction and inhibition", "recognize the drugs with unusual kinetics", "decide when a level is useful" ], "blocks": [ { "type": "h3", "text": "Enzyme inducers" }, { "type": "p", "text": "Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers. They lower levels of many other drugs: hormonal contraceptives, warfarin and the direct oral anticoagulants, statins, some chemotherapy, antiretrovirals, and transplant immunosuppressants. Weaker or dose-dependent inducers include oxcarbazepine, eslicarbazepine, topiramate (above about 200 mg/day), perampanel (at 12 mg/day), rufinamide, felbamate, cenobamate and clobazam." }, { "type": "p", "text": "**Time course.** Induction needs new enzyme to be made, so it builds over days to weeks, and it wears off just as slowly when the inducer is stopped: levels of the other drugs keep climbing for weeks. After carbamazepine was stopped, perampanel's concentration-to-dose ratio had doubled by weeks 1–2 and was up 276% at 8 weeks, with dizziness, somnolence and ataxia; modeling put the return to uninduced levels at about 25 days after abrupt withdrawal and about 48 days after a weekly taper. Inhibition is competitive and starts at once; the inhibited drug settles at its new level about five of its own half-lives later, so within days for most drugs. Check levels 2–4 weeks after adding or removing an interacting drug, and for longer after removing an inducer." }, { "type": "h3", "text": "Enzyme inhibitors" }, { "type": "li", "text": "**Valproate** inhibits glucuronidation and CYP2C9: lamotrigine levels roughly double, phenobarbital rises, and phenytoin is displaced from albumin. It is a broad inhibitor: it also raises ethosuximide, rufinamide (by up to 70%, most in children) and the carbamazepine epoxide." }, { "type": "li", "text": "**Felbamate, stiripentol and cenobamate** raise levels of several other ASMs; cenobamate raises phenytoin and phenobarbital." }, { "type": "li", "text": "**Cannabidiol and stiripentol** raise N-desmethylclobazam, the active metabolite of clobazam, causing sedation. Cenobamate (a CYP2C19 inhibitor) and felbamate raise it too, so expect sleepiness when either is added to clobazam." }, { "type": "li", "text": "**Weak inducers that inhibit CYP2C19**: oxcarbazepine, eslicarbazepine and topiramate induce CYP3A4 weakly, enough to make hormonal contraception less reliable, yet inhibit CYP2C19 and so can raise phenytoin. Felbamate and cenobamate share the CYP2C19 effect; cenobamate can double phenytoin levels, so its label advises cutting phenytoin by up to half during titration." }, { "type": "li", "text": "**Carbamazepine-10,11-epoxide**, the active metabolite, is cleared by epoxide hydrolase. Valproate and brivaracetam both inhibit that enzyme (brivaracetam 100 mg twice daily raised the epoxide by up to 198%), and felbamate raises the epoxide (by 57%) while lowering carbamazepine itself (by 31%). Neurotoxicity can therefore appear without any rise in the carbamazepine level." }, { "type": "li", "text": "**Carbapenems** (meropenem, ertapenem, imipenem) cut valproate levels sharply, by about 60% on average within 24 hours (less with imipenem), and raising the valproate dose does not restore them; levels recover over about a week after the antibiotic stops. Use a non-carbapenem antibiotic, or cover with another ASM if a carbapenem is unavoidable." }, { "type": "table", "head": [ "ASM", "Induces", "Inhibits" ], "rows": [ [ "Carbamazepine, phenytoin, phenobarbital", "CYP3A4, CYP2C9, CYP1A2 and glucuronidation (UGT)", "—" ], [ "Oxcarbazepine", "CYP3A4 (weak), UGT1A4", "CYP2C19 (weak)" ], [ "Eslicarbazepine", "CYP3A4", "CYP2C19" ], [ "Topiramate", "CYP3A4 (weak, above 200 mg/day)", "CYP2C19 (weak)" ], [ "Cenobamate", "CYP3A4, CYP2B6", "CYP2C19" ], [ "Felbamate", "CYP3A4 (weak)", "CYP2C19" ], [ "Valproate", "—", "UGT, CYP2C9, epoxide hydrolase" ], [ "Stiripentol", "—", "CYP1A2, CYP3A4, CYP2C19" ] ] }, { "type": "h3", "text": "Drugs with unusual kinetics" }, { "type": "li", "text": "**Phenytoin** has saturable (Michaelis–Menten) kinetics: above the saturation point, small dose increases cause large rises in level. It is about 90% protein-bound, so check a free level in low albumin, uremia, late pregnancy, or with valproate." }, { "type": "li", "text": "**Carbamazepine** induces its own metabolism over the first weeks, so the level falls on a steady dose." }, { "type": "li", "text": "**Lamotrigine** clearance rises with estrogen and pregnancy and falls with valproate." }, { "type": "li", "text": "**What phenytoin's Vmax and Km mean**: Vmax is the most phenytoin the liver can metabolize in a day; Km is the level at which it works at half that rate. Near Vmax the apparent half-life lengthens (it averages 22 hours, range 7–42), so a toxic level falls slowly, over days, and a dose increase of 10% can raise the level out of proportion. A person with a low Km is already close to saturation at therapeutic levels, so each dose step moves the level further." }, { "type": "li", "text": "**Valproate** has saturable protein binding: the free fraction rises from about 10% at a total level of 40 mcg/mL to 18.5% at 130 mcg/mL, so total levels climb less than the dose while free drug rises in proportion. The free fraction is also higher with low albumin, kidney or liver disease, in older adults, and with aspirin. If a patient is toxic with a total level in range, measure free valproate." }, { "type": "li", "text": "**Gabapentin** absorption is saturable: its bioavailability falls from about 60% at 900 mg/day to 33% at 3,600 mg/day, so each dose increase adds less. **Pregabalin** is absorbed almost completely (90% or more) at every dose, and its levels rise in proportion." }, { "type": "figure", "html": "phenytoin-model", "caption": "Phenytoin steady-state level against daily dose, from the Michaelis–Menten relation: level = Km × dose ÷ (Vmax − dose). The starting values reproduce the case below, where 300 mg/day gives 12 mcg/mL and 400 mg/day gives 32. Vmax and Km vary widely between people, so real doses change in small steps with levels.", "n": 14 }, { "type": "h3", "text": "Pharmacokinetic principles" }, { "type": "li", "text": "**Steady state** comes about five half-lives after starting a drug, changing its dose, or adding or removing an interacting drug (for phenytoin, 7–10 days). A level taken sooner does not show where it will settle." }, { "type": "li", "text": "**Restarting after a gap**: once lamotrigine has been stopped for more than five half-lives, restart with the full initial titration, because rash risk rises with a high starting dose. Its half-life depends on co-medication (about 30 hours alone, about 60 with valproate), so the gap that resets titration is roughly a week alone and two weeks with valproate." }, { "type": "li", "text": "**Release forms**: extended-release forms spread release over time, allowing less frequent dosing and smaller swings between peak and trough. Delayed-release (enteric-coated) forms only postpone release until the tablet has left the stomach, after which they behave like immediate release. They are not interchangeable mg for mg: once-daily extended-release divalproex is about 89% as bioavailable as the delayed-release form, so the daily dose is raised by 8–20% when switching." }, { "type": "li", "text": "**Loading dose** = volume of distribution × target concentration. Phenobarbital's volume is about 0.6 L/kg, so reaching 20 mg/L takes about 12 mg/kg. For a top-up, use the gap: dose = volume × weight × (target − measured level); an 80-kg patient with a phenobarbital level of 10 mg/L needs about 0.6 × 80 × 10 = 480 mg to reach 20 mg/L. Phenytoin's volume is larger (about 0.95 L/kg in one adult study at an albumin of 3 g/dL) and depends on albumin. Volumes vary widely in critically ill patients (in one study of phenobarbital in refractory status, the between-patient coefficient of variation for volume was about 80%), so check a level after loading." }, { "type": "li", "text": "**Age**: neonates clear drugs slowly because glucuronidation and other enzymes are immature (valproate half-life 10–67 hours in the first 10 days against 7–13 hours after 2 months), and their lower protein binding raises the free fraction. Infants older than 2–3 months and children clear most ASMs faster per kilogram than adults (valproate clearance is about 50% higher between 3 months and 10 years) and need larger mg/kg doses; adult values return by about age 10. Older adults clear less, through slower metabolism and falling kidney function; in older people valproate's intrinsic clearance was 39% lower and its free fraction 44% higher." }, { "type": "h3", "text": "Kidney and liver" }, { "type": "li", "text": "**Mainly renal**: levetiracetam, gabapentin, pregabalin, vigabatrin, eslicarbazepine, and partly lacosamide and topiramate. Reduce doses in kidney failure, and give a supplement after hemodialysis for the dialysable drugs (levetiracetam, gabapentin, pregabalin, lacosamide, topiramate)." }, { "type": "li", "text": "**Mainly hepatic**: valproate, carbamazepine, phenytoin, phenobarbital, lamotrigine, perampanel, cenobamate, benzodiazepines. In liver failure favor renally cleared drugs and avoid valproate and felbamate." }, { "type": "h3", "text": "When to check a level" }, { "type": "p", "text": "Levels help to confirm adherence, investigate toxicity, guide phenytoin dosing, establish a baseline before pregnancy and follow changes during it, manage kidney or liver disease, and sort out interactions. In a stable patient who is seizure-free without side effects, a routine level changes nothing." }, { "type": "note", "label": "Try it", "text": "The [medication profiles](seizure_management.html#anti-seizure-medications) in the Seizure Management course give each drug's mechanism and key adverse effects." }, { "type": "mcq", "id": "q-199l6ax", "stem": "A woman on warfarin and atorvastatin is started on carbamazepine. Two weeks later her INR is 1.3 (previously 2.5) and her LDL has risen. What explains this?", "options": [ "Carbamazepine inhibits CYP2C9", "Carbamazepine induces hepatic enzymes, lowering warfarin and atorvastatin levels", "Carbamazepine displaces warfarin from albumin", "She has stopped taking warfarin", "Carbamazepine causes vitamin K deficiency" ], "answer": 1, "explain": "Carbamazepine is a strong inducer of CYP3A4 and other enzymes and lowers levels of warfarin, statins, hormonal contraceptives and many other drugs. A non-inducing ASM avoids the problem." }, { "type": "mcq", "id": "q-kuqgmv", "stem": "A man on phenytoin 300 mg daily has a level of 12 mcg/mL. His dose is raised to 400 mg daily. Two weeks later he has nystagmus and ataxia with a level of 32 mcg/mL. Why did the level rise so much?", "options": [ "Phenytoin induces its own metabolism", "Phenytoin is renally cleared", "Phenytoin metabolism is saturable, so small dose increases can cause large rises in level", "The laboratory measured the free level", "He has developed hypoalbuminemia" ], "answer": 2, "explain": "Phenytoin follows Michaelis–Menten kinetics. Once metabolism nears saturation, levels rise disproportionately with dose. Increase by small steps at higher doses." }, { "type": "cards", "items": [ { "id": "c-u1dxki", "front": "Strong enzyme-inducing ASMs", "back": "Carbamazepine, phenytoin, phenobarbital, primidone." }, { "id": "c-1ez8ryi", "front": "Valproate interactions", "back": "Doubles lamotrigine, raises phenobarbital, displaces phenytoin." }, { "id": "c-nkoz6d", "front": "Phenytoin kinetics", "back": "Saturable (Michaelis–Menten); about 90% protein-bound." }, { "id": "c-yn6oxk", "front": "When to measure free phenytoin", "back": "Low albumin, uremia, late pregnancy, co-therapy with valproate." }, { "id": "c-dm5vz3", "front": "Carbamazepine autoinduction", "back": "Levels fall over the first weeks on a steady dose." }, { "id": "c-10043k", "front": "Mainly renally cleared ASMs", "back": "Levetiracetam, gabapentin, pregabalin, vigabatrin, eslicarbazepine (partly lacosamide, topiramate)." }, { "id": "c-1sld877", "front": "Supplemental dose after hemodialysis", "back": "Levetiracetam, gabapentin, pregabalin, lacosamide, topiramate." }, { "id": "c-1gd7z1c", "front": "Drugs raising N-desmethylclobazam", "back": "Cannabidiol, stiripentol (and cenobamate)." }, { "id": "c-1c3t6t9", "front": "Carbapenems and valproate", "back": "Valproate falls by about 60% within a day; raising the dose does not help; change the antibiotic." }, { "id": "c-e5kbd", "front": "Time course of induction against inhibition", "back": "Induction builds and fades over weeks; inhibition acts within about five half-lives of the affected drug." }, { "id": "c-1e08bv1", "front": "Weak CYP3A4 inducers that inhibit CYP2C19", "back": "Oxcarbazepine, eslicarbazepine, topiramate (also felbamate, cenobamate); can raise phenytoin." }, { "id": "c-1uhvak6", "front": "Carbamazepine epoxide raised by", "back": "Valproate (epoxide hydrolase inhibition), felbamate, brivaracetam." }, { "id": "c-1h993up", "front": "Valproate free fraction", "back": "Rises with total level (about 10% at 40, 18.5% at 130 mcg/mL), low albumin, kidney or liver disease, old age." }, { "id": "c-zvki9t", "front": "Gabapentin against pregabalin absorption", "back": "Gabapentin saturable (60% falling to 33%); pregabalin linear, 90% or more." }, { "id": "c-27m39", "front": "Phenytoin Km", "back": "The level at which metabolism runs at half its maximum rate; a low Km means big swings with small dose changes." }, { "id": "c-gg8v4c", "front": "Time to steady state", "back": "About five half-lives." }, { "id": "c-gjadk9", "front": "Restarting lamotrigine", "back": "Full initial titration if stopped for more than five half-lives." }, { "id": "c-1htlvmc", "front": "Extended against delayed release", "back": "Extended release spreads absorption; delayed (enteric-coated) release only postpones it." }, { "id": "c-1dnyz3k", "front": "Loading dose", "back": "Volume of distribution × target concentration (phenobarbital about 0.6 L/kg)." }, { "id": "c-1jra4jl", "front": "Children's ASM clearance", "back": "Higher per kg than adults from about 2–3 months to 10 years; neonates and older adults clear less." } ] } ], "sources": [ { "title": "SANAD II, focal epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838757/" }, { "title": "Cenobamate in focal epilepsy (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31734103/" }, { "title": "Antiepileptic drug interactions: principles and clinical implications (Johannessen and Landmark 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/21358975/" }, { "title": "Clinically important drug interactions in epilepsy (Patsalos and Perucca 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12849151/" }, { "title": "Perampanel after carbamazepine discontinuation (Murugesu 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32782230/" }, { "title": "Perampanel de-induction simulations (Schuck 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32430908/" }, { "title": "Carbapenems and valproate levels (Wu 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27322166/" }, { "title": "Meropenem prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b0075b72-c3cc-f844-e053-2a95a90a417f" }, { "title": "Xcopri (cenobamate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=565c2126-57ae-4e29-b443-723bbe7e2072" }, { "title": "Aptiom (eslicarbazepine) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d0c9554-eaeb-4694-8089-00133fcadce3" }, { "title": "Briviact (brivaracetam) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3cf2f439-0e97-443e-8e33-25ecef616f6c" }, { "title": "Felbatol (felbamate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2f522701-397a-11de-8a39-0800200c9a66" }, { "title": "Depakote prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08a65cf4-7749-4ceb-6895-8f4805e2b01f" }, { "title": "Depakote ER prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dc024ce-efc8-4690-7cb5-639c728fccac" }, { "title": "Dilantin prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86dd27d1-9cee-48ae-b55d-e2d2f7dbc593" }, { "title": "Lamictal prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7e3572d-56fe-4727-2bb4-013ccca22678" }, { "title": "Pregabalin and gabapentin pharmacokinetics (Bockbrader 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20818832/" }, { "title": "FDA guidance: bioavailability studies, including extended- and delayed-release products", "url": "https://www.fda.gov/media/121311/download" }, { "title": "Phenobarbital pharmacokinetics in adults (Nelson 1982)", "url": "https://pubmed.ncbi.nlm.nih.gov/7068937/" }, { "title": "Population kinetics of intravenous phenytoin (Frame 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9712466/" }, { "title": "Phenobarbital pharmacokinetics in refractory status (Stoschus 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40569218/" }, { "title": "New ASMs at the extremes of age (Italiano and Perucca 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23640503/" }, { "title": "Pediatric pharmacokinetics of older ASMs (Battino 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/8549027/" } ], "words": 1738, "bank": 12 }, { "id": "asm-profiles", "n": "3", "title": "ASM profiles and choosing for a patient", "tags": [ "seizure-management" ], "updated": true, "goals": [ "Recall the spectrum and signature adverse effects of each common ASM", "choose a drug for a specific patient" ], "blocks": [ { "type": "table", "head": [ "Drug", "Main action", "Spectrum", "Know it for" ], "rows": [ [ "Carbamazepine", "Sodium channel", "Focal", "Strong inducer; hyponatremia; HLA-B*15:02 and SJS; worsens absence and myoclonus" ], [ "Oxcarbazepine", "Sodium channel", "Focal", "More hyponatremia than carbamazepine; weaker inducer" ], [ "Eslicarbazepine", "Sodium channel", "Focal", "Once daily; hyponatremia" ], [ "Phenytoin", "Sodium channel", "Focal, status", "Saturable kinetics; gum hypertrophy, coarse features, neuropathy, cerebellar atrophy" ], [ "Lamotrigine", "Sodium channel and more", "Broad", "Rash with fast titration or valproate; lowered by estrogen; can worsen myoclonus" ], [ "Lacosamide", "Slow sodium inactivation", "Focal", "PR prolongation; IV available; few interactions" ], [ "Valproate", "Several", "Broad", "Most effective for generalized epilepsy; teratogenic; liver, pancreas, platelets (dose-related), ammonia, weight, tremor" ], [ "Levetiracetam", "SV2A", "Broad", "Few interactions; IV; irritability, depression" ], [ "Brivaracetam", "SV2A", "Focal", "Fewer behavioral effects than levetiracetam; switch directly, no titration" ], [ "Topiramate", "Several", "Broad", "Word-finding difficulty, stones, acidosis, acute myopia with angle-closure glaucoma, oligohidrosis, weight loss; teratogenic" ], [ "Zonisamide", "Several", "Broad", "Sulfonamide; stones, oligohidrosis, weight loss" ], [ "Ethosuximide", "T-type calcium", "Absence only", "First choice in childhood absence epilepsy; gastrointestinal upset, hiccups, behavior change, blood dyscrasias, lupus" ], [ "Clobazam", "GABA-A", "Broad", "Lennox–Gastaut; tolerance; raised by cannabidiol and stiripentol" ], [ "Phenobarbital", "GABA-A", "Broad", "Neonatal first-line; sedation; strong inducer; connective tissue effects" ], [ "Gabapentin, pregabalin", "α2δ", "Focal (weak)", "Renal; weight gain; can worsen myoclonus" ], [ "Vigabatrin", "GABA transaminase", "Spasms, focal", "Permanent peripheral visual field loss" ], [ "Perampanel", "AMPA", "Broad", "Boxed warning for aggression and other psychiatric effects; long half-life" ], [ "Cenobamate", "Sodium current and GABA-A", "Focal", "High seizure-freedom rates; slow titration to prevent DRESS; shortens QT; contraindicated in familial short QT" ], [ "Rufinamide", "Sodium channel", "Lennox–Gastaut", "Shortens QT; avoid in familial short QT" ], [ "Felbamate", "NMDA and GABA-A", "Broad (refractory)", "Aplastic anemia and liver failure" ], [ "Cannabidiol", "Several (not cannabinoid receptors)", "Dravet, Lennox–Gastaut, TSC", "Raised liver enzymes (especially with valproate); raises clobazam metabolite; absorption rises sharply with fatty food" ], [ "Fenfluramine", "Serotonergic, sigma-1", "Dravet, Lennox–Gastaut", "Restricted distribution program; echocardiographic monitoring for valve disease and pulmonary hypertension" ], [ "Stiripentol", "GABA-A, enzyme inhibition", "Dravet", "Used with clobazam; raises clobazam metabolite" ], [ "Everolimus", "mTOR inhibitor", "TSC focal seizures", "Targets the cause in tuberous sclerosis" ], [ "Ganaxolone", "Neurosteroid GABA-A", "CDKL5 deficiency", "Approved for CDKL5 deficiency disorder" ] ] }, { "type": "note", "label": "Try it", "text": "Search the drugs, or filter them by mechanism and spectrum, in the [medication profiles](seizure_management.html#anti-seizure-medications)." }, { "type": "li", "text": "**Ethosuximide** is well absorbed, minimally protein-bound and slowly eliminated; children under 10 need more per kilogram. Expect gastrointestinal upset (nausea, abdominal pain, weight loss) and hiccups; sleep disturbance, night terrors and aggression, rarely psychosis; and, rarely, blood dyscrasias (check counts periodically), drug-induced lupus and Stevens–Johnson syndrome. It treats absence seizures only." }, { "type": "li", "text": "**Valproate's dose- and age-related effects**: tremor is common; thrombocytopenia is dose-related, likelier at trough levels above 110 mcg/mL in women and 135 mcg/mL in men. Long-term use can cause an insidious syndrome of parkinsonism and cognitive decline (sometimes with apparent brain atrophy on imaging) that improves after stopping. Older adults are more prone to somnolence and tremor." }, { "type": "li", "text": "**Brivaracetam against levetiracetam**: both bind SV2A, brivaracetam with about 20-fold higher affinity. It needs no titration, so a patient with behavioral side effects on levetiracetam can switch in one step (27 of 29 improved in a small open study). Adding it to levetiracetam brings no benefit. It is partly metabolized by CYP2C19: rifampin lowers it (double the dose), carbamazepine, phenytoin and phenobarbital lower it by about a fifth to a quarter, and it can raise phenytoin by up to about 20% and the carbamazepine epoxide." }, { "type": "li", "text": "**Topiramate**: oligohidrosis with overheating occurs as with zonisamide, mostly in children and in hot weather. Its eye reaction is acute myopia with secondary angle-closure glaucoma, usually within the first month. Cognitive effects are more frequent with fast titration and high starting doses, so titrate slowly." }, { "type": "li", "text": "**Cannabidiol** does not appear to act through cannabinoid receptors. A high-fat meal raises exposure 4- to 5-fold, so dose it consistently with respect to meals. Check transaminases and bilirubin before starting and at 1, 3 and 6 months. It is licensed for Lennox–Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex from age 1." }, { "type": "li", "text": "**Fenfluramine** is available only through a restricted distribution program (a Risk Evaluation and Mitigation Strategy, REMS): echocardiogram before treatment, every 6 months during it, and 3–6 months after the last dose. The valve and pulmonary risk comes from serotonin 5-HT2B agonism by fenfluramine and its metabolite norfenfluramine." }, { "type": "li", "text": "**Cognitive effects of ASMs** are mainly slowed psychomotor speed and reduced attention and vigilance, worse with fast titration, high doses and polytherapy. Phenobarbital and topiramate carry the most burden: topiramate worsened cognitive speed, verbal fluency and short-term memory where levetiracetam changed nothing, and healthy volunteers did better on lamotrigine than on topiramate on 80% of measures. Levetiracetam's problems are mainly mood and behavior rather than cognition." }, { "type": "figure", "html": "asm-targets", "caption": "Where the drugs in the table act, in an original schematic that is not to scale. Each target and drug lists the sources for what it says; the same model sits beside the medication table in Seizure Management.", "n": 15 }, { "type": "calc", "name": "asm-chooser" }, { "type": "p", "updated": true, "label": "Ezogabine", "text": "Ezogabine (retigabine), a potassium channel (Kv7) opener, was withdrawn worldwide in 2017 because of retinal pigment changes and blue skin discoloration. Newer Kv7 openers are in trials. One of them, azetukalner (XEN1101), is a selective Kv7 opener; after two positive trials in focal seizures, its maker submitted a US new drug application in September 2026. It was not approved as of October 2026." }, { "type": "mcq", "id": "q-1m9shrg", "stem": "A 68-year-old man with new focal epilepsy after a stroke takes apixaban, atorvastatin and sertraline. Which ASM is the most appropriate first choice?", "options": [ "Carbamazepine", "Phenytoin", "Phenobarbital", "Levetiracetam or lamotrigine", "Valproate" ], "answer": 3, "explain": "In older adults, lamotrigine and levetiracetam are well tolerated and lack enzyme induction. Carbamazepine, phenytoin and phenobarbital lower apixaban and statin levels and harm bone health; phenytoin also has difficult kinetics." }, { "type": "mcq", "id": "q-18lyrvs", "stem": "Which ASM requires baseline and periodic perimetry because of permanent peripheral visual field loss?", "options": [ "Topiramate", "Ethosuximide", "Vigabatrin", "Lacosamide", "Zonisamide" ], "answer": 2, "explain": "Vigabatrin causes irreversible concentric peripheral visual field constriction related to dose and duration. Topiramate's eye risk is acute angle-closure glaucoma, which is reversible if treated promptly." }, { "type": "match", "id": "match-asm-effects", "prompt": "Match each ASM to its signature adverse effect", "pairs": [ [ "Vigabatrin", "Permanent peripheral visual field loss" ], [ "Felbamate", "Aplastic anemia and liver failure" ], [ "Topiramate", "Acute angle-closure glaucoma and kidney stones" ], [ "Lacosamide", "PR interval prolongation" ], [ "Rufinamide", "QT shortening" ], [ "Perampanel", "Aggression and psychiatric effects" ], [ "Oxcarbazepine", "Hyponatremia" ] ] }, { "type": "cards", "items": [ { "id": "c-1vybybi", "front": "Ethosuximide spectrum", "back": "Absence seizures only." }, { "id": "c-319orr", "front": "Lamotrigine rash risk factors", "back": "Fast titration, valproate co-therapy, children." }, { "id": "c-1mdnx1f", "front": "Cenobamate DRESS prevention", "back": "Slow titration from a low starting dose." }, { "id": "c-1zjlwx", "front": "Drugs contraindicated in familial short QT", "back": "Rufinamide and cenobamate." }, { "id": "c-a1gdbl", "front": "Fenfluramine monitoring", "back": "Echocardiography for valve disease and pulmonary hypertension." }, { "id": "c-d6fwrc", "front": "Perampanel boxed warning", "back": "Serious psychiatric and behavioral reactions, including aggression." }, { "id": "c-1ct9v58", "front": "Everolimus in epilepsy", "back": "Refractory focal seizures in tuberous sclerosis." }, { "id": "c-i2t8ab", "front": "Ezogabine", "back": "Kv7 opener withdrawn in 2017 (retinal pigment changes, blue skin discoloration)." }, { "id": "c-16pxjpb", "front": "Azetukalner", "back": "Investigational Kv7 opener for focal seizures; US application submitted September 2026, not yet approved." }, { "id": "c-1nfvqrr", "front": "Ethosuximide adverse effects", "back": "Gastrointestinal upset, hiccups, sleep and behavior problems (rarely psychosis), blood dyscrasias, lupus, rare Stevens–Johnson syndrome." }, { "id": "c-wj38x", "front": "Ethosuximide kinetics", "back": "Minimally protein-bound and slowly eliminated; children under 10 need more per kilogram." }, { "id": "c-1tbv1di", "front": "Valproate thrombocytopenia", "back": "Dose-related; likelier above trough 110 mcg/mL (women) or 135 mcg/mL (men)." }, { "id": "c-1skj5c4", "front": "Valproate in long-term use", "back": "Reversible parkinsonism and cognitive decline." }, { "id": "c-ep0k29", "front": "Brivaracetam and levetiracetam", "back": "About 20-fold higher SV2A affinity; direct switch without titration; no benefit in combination." }, { "id": "c-17n3be3", "front": "Brivaracetam metabolism", "back": "Partly CYP2C19; rifampin lowers it (double the dose); can raise phenytoin and carbamazepine epoxide." }, { "id": "c-1vfmv8s", "front": "Topiramate oligohidrosis", "back": "Decreased sweating and hyperthermia, mostly children in hot weather (also zonisamide)." }, { "id": "c-1t9vmrt", "front": "Topiramate eye reaction", "back": "Acute myopia with secondary angle-closure glaucoma, usually within a month." }, { "id": "c-1nuibdx", "front": "Cannabidiol pharmacology", "back": "No cannabinoid-receptor action; high-fat meal raises exposure 4–5-fold; liver tests at baseline, 1, 3 and 6 months." }, { "id": "c-yho8k5", "front": "Fenfluramine safety program", "back": "REMS; echocardiogram before, every 6 months during, and 3–6 months after treatment; 5-HT2B agonism." }, { "id": "c-1l3ga5d", "front": "Main cognitive effects of ASMs", "back": "Slowed psychomotor speed and reduced attention; worse with fast titration, high doses, polytherapy." }, { "id": "c-8j5xgh", "front": "ASMs with the greatest cognitive burden", "back": "Phenobarbital and topiramate." } ] } ], "sources": [ { "title": "Cenobamate in focal epilepsy (2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31734103/" }, { "title": "Fenfluramine in Dravet syndrome (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31862249/" }, { "title": "SANAD II, focal epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838757/" }, { "title": "Zarontin (ethosuximide) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e008f33-70a1-4bc6-b3a0-d45214418ab6" }, { "title": "Pediatric pharmacokinetics of older ASMs (Battino 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/8549027/" }, { "title": "Depakote prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08a65cf4-7749-4ceb-6895-8f4805e2b01f" }, { "title": "Reversible parkinsonism and cognitive impairment with valproate (Armon 1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/8797455/" }, { "title": "Brivaracetam binding to SV2A (Gillard 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21575627/" }, { "title": "Switching from levetiracetam to brivaracetam (Yates 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26432008/" }, { "title": "Briviact (brivaracetam) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3cf2f439-0e97-443e-8e33-25ecef616f6c" }, { "title": "Topamax (topiramate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21628112-0c47-11df-95b3-498d55d89593" }, { "title": "Epidiolex (cannabidiol) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec" }, { "title": "Fintepla (fenfluramine) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e88f360e-33ad-4cd6-b2de-5ef885857c5d" }, { "title": "Xcopri (cenobamate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=565c2126-57ae-4e29-b443-723bbe7e2072" }, { "title": "Cognitive outcomes and predictive factors in epilepsy (Meador 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11971129/" }, { "title": "Levetiracetam against topiramate on cognition (Gomer 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17409025/" }, { "title": "Lamotrigine against topiramate in healthy volunteers (Meador 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15985582/" }, { "title": "Xenon: azetukalner new drug application (September 2026)", "url": "https://www.globenewswire.com/news-release/2026/09/17/3364364/33485/en/xenon-announces-azetukalner-nda-submission-to-fda-for-focal-seizures-and-provides-update-on-psychiatry-clinical-program.html" } ], "words": 1262, "bank": 12 }, { "id": "asm-safety", "n": "4", "title": "Serious adverse effects and pharmacogenomics", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Screen for HLA risk alleles before aromatic ASMs", "recognize the idiosyncratic reactions that need the drug stopped", "know which ASMs can aggravate seizures" ], "blocks": [ { "type": "h3", "text": "Pharmacogenomics" }, { "type": "li", "text": "**HLA-B*15:02** (common in people of Han Chinese and Southeast Asian ancestry) greatly increases the risk of Stevens–Johnson syndrome and toxic epidermal necrolysis with carbamazepine; test before starting it in at-risk ancestry. Phenytoin, fosphenytoin and oxcarbazepine carry a smaller association." }, { "type": "li", "text": "**HLA-A*31:01** (found in European, Japanese and Korean populations) is associated with carbamazepine hypersensitivity, including DRESS and milder rashes." }, { "type": "li", "text": "**CYP2C9 poor metabolizers** accumulate phenytoin and have more toxicity and severe skin reactions." }, { "type": "h3", "text": "Reactions that mean stopping the drug" }, { "type": "li", "text": "**Severe cutaneous reactions** (SJS/TEN, DRESS): mostly in the first two months, most often with aromatic drugs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital, lamotrigine). Cross-reactivity among aromatic drugs is common." }, { "type": "li", "text": "**Valproate**: hepatotoxicity (highest risk in children under two on several drugs, and in mitochondrial disease such as POLG), pancreatitis, and hyperammonemic encephalopathy, even with normal liver tests." }, { "type": "li", "text": "**Felbamate**: aplastic anemia and liver failure. Aplastic anemia may occur at more than 100 times the background rate; in reported cases it began 5–30 weeks after starting, the marrow injury may precede it by weeks to months, and the risk does not end when the drug stops. Reserve felbamate for epilepsy severe enough to justify the risk, and obtain the patient's or guardian's written acknowledgment before starting. Routine blood counts cannot reliably prevent aplastic anemia, though they sometimes catch it early." }, { "type": "li", "text": "**Carbamazepine**: agranulocytosis and aplastic anemia (rare); mild leukopenia is common and usually harmless." }, { "type": "li", "text": "**Topiramate**: acute myopia with secondary angle-closure glaucoma, usually in the first month; stop the drug as quickly as possible." }, { "type": "h3", "text": "Seizure aggravation" }, { "type": "li", "text": "Sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin, sometimes lamotrigine) can worsen absence and myoclonic seizures and Dravet syndrome." }, { "type": "li", "text": "Vigabatrin and tiagabine can worsen absence seizures." }, { "type": "li", "text": "Gabapentin and pregabalin can worsen myoclonus." }, { "type": "li", "text": "Benzodiazepines can trigger tonic status in Lennox–Gastaut syndrome." }, { "type": "li", "text": "Toxic levels of phenytoin or carbamazepine can themselves cause seizures." }, { "type": "h3", "text": "Mood, suicidality and bone" }, { "type": "p", "text": "All ASMs carry an FDA warning about suicidal thoughts and behavior, based on pooled trial data. Screen for depression and ask about suicidal thinking. Levetiracetam, perampanel, topiramate and phenobarbital are the drugs most often linked to mood problems; lamotrigine can stabilize mood. Enzyme inducers and valproate reduce bone density; supplement vitamin D and calcium in long-term treatment." }, { "type": "mcq", "id": "q-hjuwkz", "stem": "A 29-year-old man of Han Chinese ancestry has trigeminal neuralgia and focal seizures. Before starting carbamazepine, which test is recommended?", "options": [ "HLA-A*31:01", "HLA-B*15:02", "CYP2D6 genotyping", "TPMT activity", "G6PD level" ], "answer": 1, "explain": "HLA-B*15:02, common in Han Chinese and Southeast Asian populations, strongly predicts carbamazepine-induced SJS/TEN. Screening is recommended before starting carbamazepine in at-risk ancestry." }, { "type": "mcq", "id": "q-vukae0", "stem": "A 23-year-old on valproate and topiramate becomes confused and lethargic. Liver tests are normal. What test is most likely to reveal the cause?", "options": [ "Serum sodium", "Plasma ammonia", "Serum amylase", "Platelet count", "Creatine kinase" ], "answer": 1, "explain": "Valproate can cause hyperammonemic encephalopathy with normal liver tests, and topiramate increases the risk. Check ammonia; carnitine supplementation is sometimes used." }, { "type": "cards", "items": [ { "id": "c-10pswc7", "front": "HLA-B*15:02", "back": "Carbamazepine SJS/TEN risk; Han Chinese and Southeast Asian ancestry; test before starting." }, { "id": "c-18gosgh", "front": "HLA-A*31:01", "back": "Carbamazepine hypersensitivity (DRESS, rash) in European, Japanese and Korean populations." }, { "id": "c-15yyxac", "front": "CYP2C9 poor metabolizers", "back": "Phenytoin accumulation and toxicity." }, { "id": "c-wcb129", "front": "When severe skin reactions appear", "back": "Mostly within the first two months." }, { "id": "c-r84akx", "front": "Valproate hyperammonemia", "back": "Encephalopathy even with normal liver tests; more likely with topiramate." }, { "id": "c-1otd22f", "front": "Highest risk of valproate hepatotoxicity", "back": "Children under two on polytherapy; mitochondrial disease (POLG)." }, { "id": "c-vc36ne", "front": "Benzodiazepines in Lennox–Gastaut", "back": "Can provoke tonic status." }, { "id": "c-erpabh", "front": "FDA ASM class warning", "back": "Suicidal thoughts and behavior." }, { "id": "c-12hbohk", "front": "Felbamate aplastic anemia", "back": "Possibly over 100 times background; onset 5–30 weeks in reported cases; written acknowledgment before starting; blood counts do not reliably prevent it." } ] } ], "sources": [ { "title": "SANAD II, focal epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838757/" }, { "title": "NSGC guideline on genetic testing (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36281494/" }, { "title": "Screening for depression in epilepsy, NDDI-E (2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16632310/" }, { "title": "Felbatol (felbamate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2f522701-397a-11de-8a39-0800200c9a66" }, { "title": "Felbamate: consensus of current clinical experience (Pellock 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16889941/" }, { "title": "Topamax (topiramate) prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=21628112-0c47-11df-95b3-498d55d89593" } ], "words": 566, "bank": 12 }, { "id": "women", "n": "5", "title": "Women with epilepsy", "tags": [ "seizure-management" ], "updated": true, "goals": [ "Plan contraception around enzyme induction", "choose ASMs before and during pregnancy", "manage levels, delivery, breastfeeding and catamenial seizures" ], "blocks": [ { "type": "h3", "text": "Contraception" }, { "type": "li", "text": "Enzyme-inducing ASMs make combined pills, progestogen-only pills, implants and patches less reliable. Intrauterine devices (copper or levonorgestrel) are unaffected and are usually the best option." }, { "type": "li", "text": "Emergency contraception follows the same rule: both emergency pills (levonorgestrel and ulipristal) may fail with an inducer, so a copper IUD is the method of choice." }, { "type": "li", "text": "Lamotrigine is the two-way exception. It does not weaken contraception, but estrogen roughly halves lamotrigine levels. Seizures can break through during active-pill weeks, and toxicity can appear in the pill-free week." }, { "type": "note", "label": "Try it", "text": "The [contraception chart](seizure_management.html#wh-contraception) on the Seizure Management page gives each method's US eligibility category with an enzyme inducer and with lamotrigine." }, { "type": "h3", "text": "Pregnancy" }, { "type": "p", "updated": true, "label": "AAN/AES/SMFM 2024", "text": "The guideline says to consider lamotrigine, levetiracetam or oxcarbazepine for people with epilepsy who could become pregnant, to avoid valproate because of malformations, neural tube defects and effects on neurodevelopment (including autism and lower IQ), and to avoid valproate and topiramate to reduce the risk of babies born small for gestational age." }, { "type": "p", "text": "Major malformation rates on monotherapy at conception in the EURAP registry (2024 analysis of 9,840 pregnancies, 1999–2022):" }, { "type": "table", "head": [ "ASM", "Major malformations" ], "rows": [ [ "Valproate", "9.9% (dose-dependent)" ], [ "Phenytoin", "6.3% (few exposures)" ], [ "Phenobarbital", "6.2% (dose-dependent)" ], [ "Carbamazepine", "5.4% (dose-dependent)" ], [ "Topiramate", "4.9% (few exposures)" ], [ "Lamotrigine", "3.1%" ], [ "Oxcarbazepine", "2.9%" ], [ "Levetiracetam", "2.5%" ] ] }, { "type": "p", "text": "The order of the drugs is the point, not the decimals: valproate highest, then the old enzyme inducers, with levetiracetam, oxcarbazepine and lamotrigine lowest. As prescribing moved from valproate and carbamazepine to lamotrigine and levetiracetam, the registry's overall malformation rate fell from 6.1% (1998–2004) to 3.7% (2015–2022). The 2018 report had also found a dose effect for lamotrigine; the 2024 analysis confirms it only for valproate, phenobarbital and carbamazepine. For comparison, the 2024 AAN/AES/SMFM guideline puts the rate of major malformations in babies of people without epilepsy at about 2.4–2.9%." }, { "type": "figure", "html": "mcm-risk", "caption": "The EURAP 2024 rates with 95% intervals computed from the counts (for example, 153 malformations in 1,549 pregnancies on valproate and 33 in 1,325 on levetiracetam).", "n": 16 }, { "type": "li", "text": "**Which malformation goes with which drug** (2024 guideline): neural tube defects are commonest with valproate (about 1.4% of exposed births) and less common with carbamazepine (about 0.6%); cardiac malformations with phenobarbital (4.4%); oral clefts with phenobarbital (2.2%) and topiramate (1.4%); urogenital and renal malformations with valproate." }, { "type": "li", "text": "**The NEAD study** (Neurodevelopmental Effects of Antiepileptic Drugs) followed children of women on one ASM. IQ at age 6 was lower after valproate (mean 97) than after carbamazepine (105), lamotrigine (108) or phenytoin (108), and only valproate showed a dose effect. Children whose mothers took folic acid around conception had higher IQs (108 against 101)." }, { "type": "li", "text": "**The neurodevelopmental ranking is not the malformation ranking.** Valproate stands apart, with lower IQ and more autism. Phenobarbital lowered verbal intelligence by about half a standard deviation in men exposed before birth, though the Nordic SCAN-AED registry found no consistent excess of autism or intellectual disability with it. Topiramate is unsettled: the same registry found more autism and intellectual disability after exposure (adjusted hazard ratios 2.8 and 3.5), but a large US cohort found no excess autism once confounding was accounted for. Lamotrigine and levetiracetam show no consistent signal." }, { "type": "li", "text": "**The MONEAD study** (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs) followed US women enrolled by 20 weeks of pregnancy. Seizures that impair awareness became more frequent during pregnancy in 23%, no more often than in nonpregnant women with epilepsy followed over the same months (25%), yet ASM doses were changed in 74% of pregnancies. Drug levels in breastfed infants were far below their mothers', and about half were too low to measure. The children, mostly exposed to lamotrigine or levetiracetam, did as well as children of women without epilepsy at ages 2 and 3." }, { "type": "li", "text": "**Folic acid**: at least 0.4 mg daily before conception and through pregnancy for anyone on an ASM, to reduce neural tube defects and possibly improve neurodevelopment. More is not clearly better: in 27,784 children of mothers with epilepsy, periconceptional folic acid above about 1 mg a day was linked to a 0.9% absolute rise in childhood cancer before age 20. The 2024 guideline sets no dose beyond \"at least 0.4 mg\" and asks clinicians to weigh benefit against the possible harms of high doses." }, { "type": "li", "text": "**Levels**: clearance rises in pregnancy, most of all for lamotrigine and levetiracetam. Take a baseline level before conception, monitor through pregnancy, and reduce the dose again over the first weeks after delivery to avoid toxicity." }, { "type": "li", "text": "**Seizure control before pregnancy** predicts control during it. Convulsive seizures are the main danger to mother and baby; do not stop an effective ASM abruptly because of pregnancy." }, { "type": "li", "text": "**Epilepsy raises the mother's own risk.** In US delivery admissions, women with epilepsy died at 80 per 100,000 against 6 per 100,000 without epilepsy (adjusted odds more than tenfold), with more preeclampsia, preterm labor and stillbirth. In UK maternal death reports for 2013–2015, most epilepsy-related deaths were from sudden unexpected death in epilepsy (SUDEP); all the women with prepregnancy data had uncontrolled seizures, and five had stopped their ASMs during pregnancy. This is the reason not to stop an effective drug." }, { "type": "li", "text": "**Breastfeeding** is encouraged. Watch babies exposed to phenobarbital, primidone or benzodiazepines for sedation and poor feeding." }, { "type": "note", "label": "Try it", "text": "[Pregnancy](seizure_management.html#wh-pregnancy) on the Seizure Management page plots lamotrigine levels through pregnancy with three ways of adjusting the dose." }, { "type": "p", "updated": true, "label": "Valproate precautions", "text": "European regulators run a pregnancy prevention program for valproate and, since 2023, for topiramate. In 2024 the EMA also advised precautions for men taking valproate around conception because of a possible neurodevelopmental risk to their children. In the UK, from January 2024, valproate must not be started in anyone, male or female, under 55 unless two specialists independently document that no other treatment is effective or tolerated, or that the reproductive risks do not apply; in 2025 the Medicines and Healthcare products Regulatory Agency (MHRA) confirmed that men already taking valproate do not need the second specialist review." }, { "type": "h3", "text": "Catamenial epilepsy" }, { "type": "p", "text": "Seizures that at least double in a particular phase of the cycle:" }, { "type": "li", "text": "**C1, perimenstrual**: falling progesterone and its neurosteroid metabolite allopregnanolone (a GABA-A modulator). The commonest pattern." }, { "type": "li", "text": "**C2, periovulatory**: the estrogen surge, unopposed." }, { "type": "li", "text": "**C3, luteal**: an inadequate luteal phase in anovulatory cycles." }, { "type": "p", "text": "Cyclic clobazam or acetazolamide around the vulnerable days are used. A large trial of progesterone was negative overall, with benefit only in women with a marked perimenstrual increase." }, { "type": "note", "label": "Try it", "text": "Enter seizure counts across one cycle in the [catamenial calculator](seizure_management.html#wh-catamenial) to see whether a pattern meets the doubling rule." }, { "type": "h3", "text": "Men with epilepsy" }, { "type": "p", "text": "Sexual dysfunction affects about half of men and women with epilepsy and is rarely volunteered, so ask. Men mostly report erectile problems; women, low desire. Uncontrolled seizures and enzyme-inducing ASMs make it more likely. Enzyme inducers raise sex hormone-binding globulin and lower bioactive testosterone: men on carbamazepine or phenytoin had lower sexual function scores and bioactive testosterone than controls, while men on lamotrigine matched controls. Carbamazepine, oxcarbazepine and valproate were linked to abnormal sperm, and valproate to smaller testes in men with abnormal sperm. Switching to a drug without enzyme induction is a reasonable step when sexual function suffers." }, { "type": "case", "id": "case-pregnancy", "title": "Planning a pregnancy on valproate", "intro": [ "A 27-year-old with juvenile myoclonic epilepsy has been seizure-free for three years on valproate 1,500 mg daily. She tells you she would like to become pregnant next year." ], "steps": [ { "narrative": [], "stem": "What is the most important message about her current medication?", "options": [ "Valproate is safe at this dose", "Valproate carries the highest risk of malformations and neurodevelopmental harm, and switching should be planned before conception", "She should stop valproate immediately", "All ASMs carry the same risk", "High-dose folic acid removes valproate's risk" ], "answer": 1, "explain": "Valproate has the highest rate of major malformations (about 10% overall, higher at larger doses) and lowers IQ and increases autism risk in exposed children. Folic acid does not neutralize this. Stopping abruptly risks convulsive seizures; the switch should be planned." }, { "narrative": [], "stem": "Which drug is the most reasonable replacement for her syndrome?", "options": [ "Carbamazepine", "Topiramate", "Levetiracetam (or lamotrigine)", "Phenytoin", "Gabapentin" ], "answer": 2, "explain": "Levetiracetam and lamotrigine have the lowest malformation rates and work in juvenile myoclonic epilepsy (lamotrigine can sometimes worsen myoclonus). Carbamazepine and phenytoin worsen myoclonus; topiramate has a higher risk of small-for-gestational-age babies and malformations." }, { "narrative": [ "She switches to levetiracetam and remains seizure-free. She becomes pregnant six months later." ], "stem": "What should happen with her levetiracetam during pregnancy?", "options": [ "Nothing; levels do not change in pregnancy", "Monitor levels against her pre-pregnancy baseline and increase the dose as clearance rises", "Stop it in the first trimester to protect the fetus", "Switch back to valproate after the first trimester", "Halve the dose in the third trimester" ], "answer": 1, "explain": "Levetiracetam clearance rises substantially in pregnancy, as lamotrigine's does. Compare levels with the preconception baseline, adjust the dose, and reduce it again after delivery." } ], "outro": [ "Every person with epilepsy who could become pregnant needs a plan: effective contraception, the lowest-risk effective drug before conception, folic acid, and a monitoring schedule." ] }, { "type": "mcq", "id": "q-4h2ois", "stem": "A woman stable for years on lamotrigine has breakthrough seizures during the active weeks of a newly started combined oral contraceptive. Why?", "options": [ "Lamotrigine induces metabolism of the contraceptive", "Ethinylestradiol induces lamotrigine glucuronidation, roughly halving levels", "Progestogens lower seizure threshold", "The contraceptive displaces lamotrigine from albumin", "Lamotrigine interacts only with progestogen-only pills" ], "answer": 1, "explain": "Estrogen roughly halves lamotrigine levels. Levels recover in the pill-free week, sometimes causing toxicity. An intrauterine device avoids the interaction." }, { "type": "cards", "items": [ { "id": "c-1w6odfm", "front": "Best contraception with enzyme-inducing ASMs", "back": "Intrauterine device (copper or levonorgestrel)." }, { "id": "c-rn3n3r", "front": "Emergency contraception with an enzyme-inducing ASM", "back": "Copper IUD; both emergency pills may fail." }, { "id": "c-lgk4ai", "front": "Estrogen and lamotrigine", "back": "Estrogen roughly halves lamotrigine levels." }, { "id": "c-plsg62", "front": "Lowest malformation rates in EURAP (2024)", "back": "Levetiracetam 2.5%, oxcarbazepine 2.9%, lamotrigine 3.1%." }, { "id": "c-mh7qvp", "front": "Valproate major malformation rate (EURAP 2024)", "back": "9.9%, dose-dependent; about 10%, against 2–3% for levetiracetam." }, { "id": "c-1cwdcmo", "front": "ASMs with dose-dependent malformation risk in EURAP", "back": "Valproate, phenobarbital and carbamazepine." }, { "id": "c-17pgjx0", "front": "Folic acid on an ASM", "back": "At least 0.4 mg daily before conception and through pregnancy." }, { "id": "c-1qbqacs", "front": "ASMs whose clearance rises most in pregnancy", "back": "Lamotrigine and levetiracetam." }, { "id": "c-3gx2yr", "front": "After delivery", "back": "Reduce doses back toward pre-pregnancy levels over the first weeks." }, { "id": "c-1y7qgfo", "front": "C1 catamenial pattern", "back": "Perimenstrual; withdrawal of progesterone and allopregnanolone." }, { "id": "c-1duj5t6", "front": "Background major malformation rate without epilepsy", "back": "About 2.4–2.9%." }, { "id": "c-sz26vo", "front": "Malformations by drug", "back": "Neural tube: valproate (less often carbamazepine); cardiac: phenobarbital; oral clefts: phenobarbital and topiramate; urogenital and renal: valproate." }, { "id": "c-19g4gk4", "front": "NEAD study", "back": "Valproate in pregnancy: lower IQ at age 6 (mean 97 against 105–108), dose-dependent; periconceptional folic acid linked to higher IQ." }, { "id": "c-110s1zj", "front": "Neurodevelopmental risk by ASM", "back": "Valproate clearly; phenobarbital (lower verbal IQ); topiramate unsettled; lamotrigine and levetiracetam reassuring." }, { "id": "c-1m0qzr8", "front": "MONEAD study", "back": "Seizures no likelier to worsen in pregnancy than outside it; doses changed in most pregnancies; low infant levels with breastfeeding; normal child outcomes at 2 and 3." }, { "id": "c-12axj5l", "front": "High-dose folic acid", "back": "Above about 1 mg a day linked to childhood cancer in one cohort; give at least 0.4 mg." }, { "id": "c-u8t9nq", "front": "Maternal death with epilepsy", "back": "More than ten times higher at delivery; most epilepsy-related deaths are SUDEP, often after stopping ASMs." }, { "id": "c-rdklko", "front": "UK rule for starting valproate", "back": "Under 55, either sex: two specialists must agree; not needed for men already taking it." }, { "id": "c-1ybt68s", "front": "Enzyme-inducing ASMs in men", "back": "Higher sex hormone-binding globulin, lower bioactive testosterone and sexual function; lamotrigine neutral." }, { "id": "c-1jvo5bi", "front": "ASMs linked to abnormal sperm", "back": "Carbamazepine, oxcarbazepine and valproate." } ] } ], "sources": [ { "title": "AAN/AES/SMFM guideline on ASMs in pregnancy (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38748979/" }, { "title": "EURAP registry, major malformations with eight ASM monotherapies, 9,840 pregnancies (Battino 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38497990/" }, { "title": "EURAP registry, eight ASMs by dose (Tomson 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29680205/" }, { "title": "NEAD: IQ at age 6 after fetal ASM exposure (Meador 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23352199/" }, { "title": "Prenatal phenobarbital and adult intelligence (Reinisch 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7474220/" }, { "title": "SCAN-AED: prenatal ASMs and autism or intellectual disability (Bjørk 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35639399/" }, { "title": "Topiramate in pregnancy and autism (Hernández-Díaz 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38507750/" }, { "title": "MONEAD: seizure frequency and dosing in pregnancy (Pennell 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/33369356/" }, { "title": "MONEAD: ASM exposure through breastfeeding (Birnbaum 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31886825/" }, { "title": "MONEAD: outcomes at age 2 (Meador 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34096986/" }, { "title": "MONEAD: outcomes at age 3 (Meador 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37479375/" }, { "title": "Maternal death and morbidity at delivery with epilepsy (MacDonald 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26147878/" }, { "title": "MHRA Drug Safety Update on valproate (February 2025)", "url": "https://assets.publishing.service.gov.uk/media/67ae07036e6c8d18118acd83/Valproate_DSU_February_2025_-_FINAL_PDF.pdf" }, { "title": "ASMs, sexual function and hormones in men (Herzog 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16217052/" }, { "title": "Epilepsy, ASMs and male reproductive health (Isojärvi 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/14745062/" }, { "title": "Sexual dysfunction in people with epilepsy (Rathore 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31577987/" } ], "words": 1728, "bank": 15 }, { "id": "special-populations", "n": "6", "title": "Older adults and other special groups", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Adjust ASM choice for older adults, organ failure and psychiatric comorbidity", "avoid the interactions that matter most" ], "blocks": [ { "type": "h3", "text": "Older adults" }, { "type": "p", "text": "New-onset epilepsy is commonest after 60, most often from cerebrovascular disease; neurodegeneration and tumors follow. Seizures may present as confusion or falls. Start low and go slow. Lamotrigine and levetiracetam are well tolerated. Avoid strong inducers (bone loss, lipids, and interactions with anticoagulants and statins) and phenytoin. Watch for hyponatremia with oxcarbazepine and carbamazepine, and for cognitive effects with topiramate and phenobarbital." }, { "type": "h3", "text": "Anticoagulants, transplant and HIV medicines" }, { "type": "p", "text": "Strong inducers (carbamazepine, phenytoin, phenobarbital) substantially lower direct oral anticoagulant, tacrolimus, cyclosporine and many antiretroviral levels. Prefer drugs without induction." }, { "type": "h3", "text": "Kidney and liver failure" }, { "type": "p", "text": "Reduce renally cleared drugs as filtration falls and supplement after dialysis. In liver failure, prefer renally cleared drugs; avoid valproate and felbamate." }, { "type": "h3", "text": "Psychiatric comorbidity" }, { "type": "p", "text": "Depression affects about a third of people with epilepsy and is the strongest driver of poor quality of life. Screen with a validated tool such as the NDDI-E. SSRIs (sertraline, escitalopram) are safe at usual doses. Bupropion lowers seizure threshold in a dose-dependent way, as do clomipramine and maprotiline; avoid them. Choose ASMs with mood in mind." }, { "type": "mcq", "id": "q-178np7j", "stem": "A 45-year-old kidney transplant recipient on tacrolimus develops focal seizures. Which ASM is most likely to cause rejection by lowering tacrolimus levels?", "options": [ "Levetiracetam", "Lacosamide", "Carbamazepine", "Gabapentin", "Brivaracetam" ], "answer": 2, "explain": "Carbamazepine induces CYP3A4 and lowers tacrolimus levels. Levetiracetam and lacosamide have few interactions and are usually preferred after transplantation, with dosing adjusted to kidney function." }, { "type": "mcq", "id": "q-xmssrp", "stem": "Which antidepressant should be avoided in a patient with poorly controlled epilepsy because of dose-dependent seizure risk?", "options": [ "Sertraline", "Escitalopram", "Bupropion", "Mirtazapine", "Fluoxetine" ], "answer": 2, "explain": "Bupropion lowers seizure threshold in a dose-dependent way. SSRIs are safe at therapeutic doses and are first-line for depression in epilepsy." }, { "type": "cards", "items": [ { "id": "c-hg6ozh", "front": "Commonest cause of new epilepsy after 60", "back": "Cerebrovascular disease." }, { "id": "c-1xm1058", "front": "Preferred ASMs in older adults", "back": "Lamotrigine and levetiracetam." }, { "id": "c-8pvyxy", "front": "Strong inducers and DOACs", "back": "Carbamazepine, phenytoin and phenobarbital lower DOAC levels; avoid the combination." }, { "id": "c-1db6b2v", "front": "ASM choice after organ transplant", "back": "A non-inducing drug such as levetiracetam or lacosamide." }, { "id": "c-oiwg31", "front": "Depression screening tool in epilepsy", "back": "NDDI-E." }, { "id": "c-bsud8l", "front": "Antidepressants to avoid", "back": "Bupropion, clomipramine, maprotiline." } ] } ], "sources": [ { "title": "Screening for depression in epilepsy, NDDI-E (2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16632310/" }, { "title": "SANAD II, focal epilepsy (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33838757/" } ], "words": 325, "bank": 8 }, { "id": "status-epilepticus", "n": "7", "title": "Status epilepticus", "tags": [ "seizure-management", "acns-terminology" ], "updated": false, "goals": [ "Apply the ILAE 2015 time points", "run the staged treatment on time and at full dose", "manage refractory and super-refractory status and recognize NORSE" ], "blocks": [ { "type": "h3", "text": "Definitions (ILAE 2015)" }, { "type": "p", "text": "Status epilepticus is a seizure that fails to stop by itself or seizures that recur without recovery. Two time points guide action: **t1**, when treatment should start, and **t2**, after which long-term consequences become likely." }, { "type": "table", "head": [ "Type", "t1 (treat)", "t2 (lasting harm likely)" ], "rows": [ [ "Tonic–clonic", "5 minutes", "30 minutes" ], [ "Focal with impaired consciousness", "10 minutes", "Over 60 minutes" ], [ "Absence", "10–15 minutes", "Unknown" ] ] }, { "type": "p", "text": "The classification has four axes: semiology, etiology, EEG correlates and age." }, { "type": "h3", "text": "Staged treatment" }, { "type": "li", "text": "**Stabilize** (first 5 minutes): airway, breathing, circulation, oxygen, ECG, glucose, IV access, blood tests. If glucose is low, give thiamine and glucose. In the American Epilepsy Society (AES) algorithm the trigger is a glucose below 60 mg/dL: adults get thiamine 100 mg IV and then 50 mL of 50% dextrose; children aged 2 or more get 2 mL/kg of 25% dextrose, and children under 2 get 4 mL/kg of 12.5% dextrose." }, { "type": "li", "text": "**First line** (about 5–20 minutes): a benzodiazepine at full dose. IM midazolam 10 mg (for over 40 kg; 5 mg for 13–40 kg), IV lorazepam 0.1 mg/kg (maximum 4 mg, may repeat once), or IV diazepam 0.15–0.2 mg/kg (maximum 10 mg, may repeat once). Under-dosing is the commonest error. In RAMPART, IM midazolam before hospital was at least as effective as IV lorazepam." }, { "type": "li", "text": "**Why midazolam won RAMPART**: speed of delivery, not speed of action. Among patients whose convulsions stopped before arrival, the median time to active treatment was 1.2 minutes for IM midazolam and 4.8 minutes for IV lorazepam, even though lorazepam stopped convulsions faster once it was in (1.6 against 3.3 minutes); some patients in the lorazepam group never got the drug because no vein could be found. Fewer patients given midazolam were admitted to hospital (58% against 66%) or intensive care (29% against 36%). The lesson for any protocol: a full dose early, by the fastest route available." }, { "type": "li", "text": "**Do not hold back for fear of breathing problems.** In the Prehospital Treatment of Status Epilepticus (PHTSE) trial, paramedics gave adults IV lorazepam, IV diazepam or placebo. Status had stopped on arrival in 59%, 43% and 21%. Respiratory or circulatory complications followed in about 10% after either benzodiazepine and in 22.5% after placebo, a difference that was not statistically significant (P = 0.08); the AES guideline concludes (Level A) that breathing problems are an important consequence of untreated status." }, { "type": "li", "text": "**If none of the three first-line options is available**, the AES algorithm lists IV phenobarbital 15 mg/kg (Level A evidence, but slower to give), rectal diazepam 0.2–0.5 mg/kg (maximum 20 mg; Level B), or intranasal or buccal midazolam (Level B). In children arriving at hospital still seizing without IV access, buccal midazolam stopped seizures more often than rectal diazepam (56% against 27%), with no more respiratory depression." }, { "type": "li", "text": "**Why diazepam wears off**: after an IV dose diazepam moves quickly out of the brain into fat, so seizures often recur even though the body eliminates it slowly. In children treated for status, its plasma level fell with a half-life of about 30 minutes, while its terminal elimination half-life was 18–25 hours. Lorazepam's smaller volume of distribution gives it a longer effect against status." }, { "type": "li", "text": "**Second line** (about 20–40 minutes): levetiracetam 60 mg/kg (max 4,500 mg), fosphenytoin 20 mg PE/kg (max 1,500 mg PE), or valproate 40 mg/kg (max 3,000 mg). In ESETT the three stopped seizures with improved responsiveness in a similar proportion (about half), so choose on patient factors. Phenobarbital is an alternative." }, { "type": "li", "text": "**Third line** (about 40–60 minutes): anesthetic infusion with continuous EEG: midazolam, propofol, or pentobarbital, and ketamine in some centers." }, { "type": "figure", "html": "se-timeline", "caption": "The ILAE time points and the treatment stages on one clock. Treatment should start at t1; after t2, lasting harm becomes likely.", "n": 17 }, { "type": "h3", "text": "Refractory and beyond" }, { "type": "li", "text": "**Established** status continues despite an adequate dose of benzodiazepine. This is the stage the second-line drugs treat, and the one ESETT (the Established Status Epilepticus Treatment Trial) studied." }, { "type": "li", "text": "**Refractory** status continues despite a benzodiazepine and one second-line drug." }, { "type": "li", "text": "**Super-refractory** status continues or recurs 24 hours or more after anesthesia is started, including on weaning." }, { "type": "li", "text": "**NORSE** is refractory status in someone without active epilepsy and without a clear acute cause; **FIRES** is NORSE after a febrile illness. Search for autoimmune, infectious and genetic causes, and start immunotherapy early when no other cause is found. The ketogenic diet and anakinra are options." }, { "type": "li", "text": "**Anticytokine drugs**: in cryptogenic NORSE or FIRES without features of antibody-mediated encephalitis, the 2022 international consensus advises second-line immunotherapy with either anakinra (an interleukin-1 receptor antagonist) or tocilizumab (an antibody against the interleukin-6 receptor). Pediatric experts put anakinra first; adult experts more often chose rituximab, then tocilizumab, because antibody-mediated encephalitis is commoner in adults. If a pathogenic antibody is found or strongly suspected, rituximab is the second-line choice." }, { "type": "li", "text": "**Long coma alone does not mean a hopeless outcome.** In 63 patients whose status persisted through at least a week of induced coma, two thirds survived to discharge and 22% had a good functional outcome (modified Rankin score 0–3) at six months or later, after up to 79 days of status. Normal imaging and a reactive EEG favored recovery. The Neurocritical Care Society guideline notes that the total duration of anesthetic infusion does not predict long-term prognosis; the cause, the brain imaging and the patient's prior health matter more when deciding whether to continue." }, { "type": "p", "text": "**Prognosis.** Mortality climbs with each stage. In a registry of 804 adult episodes it was 9.8% for status that responded to first- or second-line drugs, 24.5% for refractory and 37.9% for super-refractory status. Cause and age are the strongest predictors: status from an acute brain or systemic illness does far worse than status from missed doses in known epilepsy, and in a population study 3% of children died against 26% of adults. In nonconvulsive status, mortality was 39% with severe impairment of consciousness against 7% with mild impairment, and 27% with an acute medical cause against 3% in known epilepsy. In 130 patients with NORSE, half stayed cryptogenic; autoimmune (19%) and paraneoplastic (18%) encephalitis were the commonest causes found; 22% died and 62% had a poor outcome at discharge, though over half of those followed up improved in the following months, and over a third developed epilepsy. In FIRES, about one child in nine died in the acute phase, and 93% of survivors were left with drug-resistant epilepsy." }, { "type": "h3", "text": "Anesthetic infusions" }, { "type": "p", "text": "No trial shows that one infusion is best, so the choice rests on side effects. Titrate to continuous EEG, not to drug levels." }, { "type": "table", "head": [ "Drug", "In its favor", "Against it" ], "rows": [ [ "Midazolam", "Usual first choice; less hypotension than pentobarbital", "Tachyphylaxis within 24–48 hours, so doses climb; half-life lengthens to 6–50 hours with long infusion" ], [ "Propofol", "Short half-life: fast titration, and the patient can be examined soon after weaning", "Propofol infusion syndrome (acidosis, rhabdomyolysis, arrhythmia, heart and kidney failure): use caution above 80 mcg/kg/min (about 5 mg/kg/h) for more than 48 hours, and avoid in young children; a relative contraindication with the ketogenic diet" ], [ "Pentobarbital", "Fewest breakthrough seizures", "Hypotension and cardiac depression, ileus, longer ventilation; stores in fat (half-life up to about 36 hours after infusion); at high doses abolishes all neurological function, so a brain-death evaluation must wait until it has cleared" ], [ "Ketamine", "N-methyl-D-aspartate (NMDA) receptor antagonist, a different target once GABA-A receptors have been internalized in prolonged status; keeps blood pressure stable", "Observational evidence only" ] ] }, { "type": "li", "text": "**Pentobarbital against midazolam and propofol (Claassen 2002)**: in a systematic review of 193 patients, pentobarbital had fewer breakthrough seizures (12% against 42%) but more hypotension (77% against 34%), and mortality was the same. That trade-off is why midazolam or propofol usually comes first and barbiturates are kept for failures." }, { "type": "li", "text": "**Ketamine**: starting it in 68 patients with super-refractory status, most already on midazolam, was followed by at least a halving of seizure burden within 24 hours in 81%, with stable blood pressure and falling vasopressor needs." }, { "type": "li", "text": "**Depth**: the Neurocritical Care Society guideline accepts either seizure suppression or burst suppression as the target. Neither has been tested against the other prospectively; deeper suppression gave fewer breakthrough seizures but more hypotension in the systematic review." }, { "type": "li", "text": "**Duration and weaning**: hold electrographic control for 24–48 hours, then withdraw the infusion slowly under continuous EEG, with maintenance ASMs at full doses. If seizures return, go back to the previous or a higher dose for a further period, with or without another drug, before trying again. This is a weak recommendation based on very low-quality evidence." }, { "type": "note", "label": "Try it", "text": "The sedation scenario in the [Persyst trend lab](natus_instructions.html#pq-lab-section) shows burst suppression on the trends giving way to a continuous background as an infusion is weaned." }, { "type": "h3", "text": "Nonconvulsive and focal status" }, { "type": "p", "text": "Treat the patient, not the EEG. Generalized convulsive status justifies early anesthesia once second-line drugs fail. Focal status with preserved awareness, and nonconvulsive status (NCSE) in a patient who is awake enough to protect the airway, can usually be treated more conservatively: further non-anesthetic IV ASMs, continuous EEG and treatment of the cause. In critically ill patients with nonconvulsive seizures, IV lacosamide was noninferior to fosphenytoin (TRENdS trial). Anesthetic coma carries its own harm: in one cohort, patients given anesthetic infusions had more infections and about three times the risk of death, though some of that reflects how refractory their status was. The balance shifts toward anesthesia as consciousness falls, because injury and death are commoner in stupor and coma." }, { "type": "li", "text": "**Absence status epilepticus**: hours or days of confusion or slowed thinking, often with eyelid or perioral myoclonus, with continuous or repeated generalized spike-and-wave on EEG (see [generalized patterns](#generalized-eeg)). It occurs in idiopathic generalized epilepsy, often provoked by the wrong drug (carbamazepine, phenytoin, vigabatrin or gabapentin) or by stopping an ASM. **De novo absence status of late onset** affects middle-aged and older adults without epilepsy, mostly women on psychotropic drugs, and most often follows benzodiazepine withdrawal. An IV benzodiazepine often ends it, with the EEG and the patient improving together; valproate is the usual next drug, and the intensive care unit is rarely needed. De novo cases often need no long-term ASM once the trigger is corrected." }, { "type": "li", "text": "**Epilepsia partialis continua (EPC)**: continuous repetitive jerking of one body part, often a distal limb, with awareness kept, lasting at least an hour and sometimes years. Rasmussen syndrome is the commonest cause in children; stroke is a common acute cause in adults; mitochondrial disease (including POLG disease), nonketotic hyperglycemia, tumors and encephalitis are others. The scalp EEG often shows no clear correlate (focal epileptiform discharges in only 22% of a UK series). EPC is usually drug-resistant: treat the cause, use non-sedating ASMs, and do not escalate to anesthetic coma for the jerks alone. **Aura continua** is the sensory (non-motor) equivalent." }, { "type": "mcq", "id": "q-1kl8w20", "stem": "A 71-year-old woman with no history of epilepsy has been confused and slow for two days after stopping long-term lorazepam. She is awake, follows simple commands slowly, and has eyelid fluttering. EEG shows nearly continuous generalized spike-and-wave. What is the best next step?", "options": [ "Intubate and start a propofol infusion", "Give an IV benzodiazepine while recording the EEG", "Start carbamazepine", "Observe; this is a benzodiazepine withdrawal delirium", "Load phenytoin" ], "answer": 1, "explain": "This is de novo absence status of late onset, classically after benzodiazepine withdrawal in an older woman on psychotropic drugs. An IV benzodiazepine often stops it, and clinical and EEG improvement together support the diagnosis. Carbamazepine and phenytoin can provoke or worsen absence status, and anesthesia is out of proportion for an awake patient." }, { "type": "case", "id": "case-status", "title": "Convulsions that do not stop", "intro": [ "A 44-year-old with known epilepsy is brought to the emergency department still convulsing, 12 minutes after onset. Paramedics gave no medication. Weight 80 kg; IV access is in place." ], "steps": [ { "narrative": [], "stem": "What is the first treatment?", "options": [ "Levetiracetam 60 mg/kg IV", "Lorazepam 4 mg IV, repeated once if needed", "Lorazepam 1 mg IV", "Propofol infusion", "Wait for the glucose result" ], "answer": 1, "explain": "Give a full dose of benzodiazepine: lorazepam 0.1 mg/kg, maximum 4 mg per dose, which can be repeated once. Under-dosing is the commonest error. Check glucose, but do not delay the benzodiazepine for it." }, { "narrative": [ "The convulsions continue five minutes after the second lorazepam dose. His last ECG showed second-degree atrioventricular block, and he has chronic hepatitis." ], "stem": "Which second-line drug fits best?", "options": [ "Levetiracetam 60 mg/kg (maximum 4,500 mg)", "Valproate 40 mg/kg", "Fosphenytoin 20 mg PE/kg infused rapidly", "A third lorazepam dose", "Oral lacosamide" ], "answer": 0, "explain": "ESETT found levetiracetam, fosphenytoin and valproate similarly effective, so choose on patient factors. Valproate is unsuitable in liver disease, and fosphenytoin is contraindicated in second- or third-degree atrioventricular block and can also cause arrhythmia and hypotension." }, { "narrative": [ "Twenty minutes later he is no longer convulsing but remains unresponsive, with subtle eyelid twitching." ], "stem": "What is the next step?", "options": [ "Assume postictal state and observe for several hours", "Obtain EEG urgently to look for nonconvulsive status", "Discharge once he wakes", "Give flumazenil", "Obtain an MRI first" ], "answer": 1, "explain": "After convulsive status, persistent unresponsiveness should prompt urgent EEG, since nonconvulsive seizures commonly continue and need treatment." }, { "narrative": [ "EEG shows ongoing right hemispheric seizures. A second second-line drug fails, and he is intubated." ], "stem": "How is this treated?", "options": [ "Add oral clobazam and wait 24 hours", "Anesthetic infusion (midazolam or propofol) titrated to stop seizures, with continuous EEG", "Stop all sedation to allow neurological examination", "Give a fourth benzodiazepine bolus", "Ketogenic diet only" ], "answer": 1, "explain": "Refractory status needs anesthetic infusion titrated to seizure suppression on continuous EEG, while the cause is sought and maintenance ASMs are optimized." } ], "outro": [ "Time and dose: full-dose benzodiazepine by 5 minutes, a second-line drug by about 20, and EEG whenever consciousness does not return." ] }, { "type": "mcq", "id": "q-jkge1s", "stem": "In the ESETT trial of benzodiazepine-refractory status epilepticus, what was the main finding?", "options": [ "Fosphenytoin was superior to levetiracetam", "Valproate was superior to both other drugs", "Levetiracetam, fosphenytoin and valproate had similar efficacy, each stopping seizures in about half of patients", "Levetiracetam caused more hypotension", "None of the drugs was better than placebo" ], "answer": 2, "explain": "The three drugs were equally effective (success in about 45–47%), with similar adverse event rates. Choose among them on patient factors." }, { "type": "cards", "items": [ { "id": "c-1n2gwcq", "front": "t1 and t2 for tonic–clonic status", "back": "5 and 30 minutes." }, { "id": "c-xu7e0y", "front": "t1 and t2 for focal impaired-consciousness status", "back": "10 minutes and over 60 minutes." }, { "id": "c-tlx02", "front": "IM midazolam dose in status (over 40 kg)", "back": "10 mg." }, { "id": "c-145jarn", "front": "IV lorazepam dose in status", "back": "0.1 mg/kg, maximum 4 mg, may repeat once." }, { "id": "c-giu1ju", "front": "Second-line doses (ESETT)", "back": "Levetiracetam 60 mg/kg (max 4,500 mg); fosphenytoin 20 mg PE/kg (max 1,500 mg PE); valproate 40 mg/kg (max 3,000 mg)." }, { "id": "c-lhf95m", "front": "Refractory status", "back": "Continues after a benzodiazepine and one second-line drug." }, { "id": "c-1azcd5w", "front": "Super-refractory status", "back": "Continues or recurs 24 hours or more after starting anesthesia." }, { "id": "c-1fovjdo", "front": "NORSE", "back": "New refractory status without active epilepsy or a clear acute cause; FIRES is the post-febrile form." }, { "id": "c-ru49ca", "front": "Established status epilepticus", "back": "Continues after an adequate benzodiazepine dose; the stage second-line drugs treat (studied in ESETT)." }, { "id": "c-36fxe0", "front": "IM midazolam dose for 13–40 kg", "back": "5 mg." }, { "id": "c-1gaitdg", "front": "Why IM midazolam won RAMPART", "back": "It was given sooner (1.2 against 4.8 minutes), although IV lorazepam acted faster once given." }, { "id": "c-gma5ob", "front": "PHTSE trial", "back": "Paramedic IV lorazepam or diazepam stopped status more often than placebo (59% and 43% against 21%); respiratory or circulatory complications were no commoner than with placebo (about 10% against 22.5%)." }, { "id": "c-fnpuec", "front": "First-line alternatives in the AES algorithm", "back": "IV phenobarbital 15 mg/kg; rectal diazepam; intranasal or buccal midazolam." }, { "id": "c-cs2csk", "front": "Buccal midazolam against rectal diazepam in children", "back": "Buccal midazolam stopped seizures more often (56% against 27%)." }, { "id": "c-dmr0pt", "front": "Why diazepam's effect is brief", "back": "It redistributes out of the brain into fat, despite a long elimination half-life." }, { "id": "c-a2kid1", "front": "Midazolam infusion problem", "back": "Tachyphylaxis within 24–48 hours." }, { "id": "c-1qh7rns", "front": "Pentobarbital against midazolam or propofol (Claassen 2002)", "back": "Fewer breakthrough seizures, more hypotension, no difference in mortality." }, { "id": "c-1hywuu7", "front": "EEG target and duration for anesthetic infusions", "back": "Seizure or burst suppression; hold 24–48 hours, then wean slowly on continuous EEG." }, { "id": "c-ncze5l", "front": "Ketamine in refractory status", "back": "NMDA antagonist that keeps blood pressure stable." }, { "id": "c-fvxr60", "front": "Anakinra and tocilizumab", "back": "Interleukin-1 receptor antagonist and interleukin-6 receptor antibody; second-line options in cryptogenic NORSE or FIRES." }, { "id": "c-1le6zgy", "front": "Mortality by stage of status (one adult registry)", "back": "About 10% non-refractory, 25% refractory, 38% super-refractory." }, { "id": "c-xwkv7c", "front": "Nonconvulsive status with the worst outcome", "back": "Status with severe impairment of consciousness or an acute medical cause." }, { "id": "c-o97xrp", "front": "De novo absence status of late onset", "back": "Middle-aged or older adults, often women on psychotropic drugs, usually after benzodiazepine withdrawal." }, { "id": "c-awd4uz", "front": "Epilepsia partialis continua", "back": "Continuous focal jerking with awareness kept; Rasmussen syndrome in children, stroke in adults; scalp EEG often unrevealing." }, { "id": "c-136i0en", "front": "Aura continua", "back": "The sensory (non-motor) equivalent of epilepsia partialis continua." } ] }, { "type": "note", "label": "Try it", "text": "The [status epilepticus lessons](seizure_management.html#status-epilepticus) in the Seizure Management course set these steps against the clock." } ], "sources": [ { "title": "ILAE definition and classification of status epilepticus (2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26336950/" }, { "title": "AES guideline on convulsive status epilepticus (2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26900382/" }, { "title": "ESETT trial (2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31774955/" }, { "title": "RAMPART trial (2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22335736/" }, { "title": "NORSE and FIRES consensus definitions (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29399791/" }, { "title": "PHTSE trial: lorazepam, diazepam and placebo before hospital (Alldredge 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11547716/" }, { "title": "Buccal midazolam against rectal diazepam in children (McIntyre 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16023510/" }, { "title": "Benzodiazepines in status epilepticus (Treiman 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2159132/" }, { "title": "Diazepam injection prescribing information (Pfizer)", "url": "https://labeling.pfizer.com/ShowLabeling.aspx?id=4460" }, { "title": "Neurocritical Care Society guideline on status epilepticus (Brophy 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22528274/" }, { "title": "Management of refractory status epilepticus in adults (Rossetti 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21939901/" }, { "title": "Pentobarbital, propofol or midazolam for refractory status: systematic review (Claassen 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11903460/" }, { "title": "Ketamine for super-refractory status epilepticus (Alkhachroum 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32873691/" }, { "title": "Brain death/death by neurologic criteria guideline (Greer 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37821233/" }, { "title": "TRENdS: lacosamide against fosphenytoin for nonconvulsive seizures (Husain 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29733464/" }, { "title": "Anesthetic drugs in status epilepticus (Sutter 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24319039/" }, { "title": "Typical absence status in adults (Agathonikou 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9860061/" }, { "title": "Absence and myoclonic status precipitated by ASMs (Thomas 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16513683/" }, { "title": "De novo absence status of late onset (Thomas 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1734289/" }, { "title": "Absence status review (Thomas 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10637922/" }, { "title": "Epilepsia partialis continua: a review (Mameniškienė and Wolf 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28029552/" }, { "title": "Epilepsia partialis continua in the UK (Cockerell 1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/8800935/" }, { "title": "Management of epilepsia partialis continua: systematic review (Tan 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39813748/" }, { "title": "International NORSE/FIRES management consensus (Wickstrom 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35997591/" }, { "title": "Outcomes after prolonged refractory status (Kilbride 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23479069/" }, { "title": "Refractory and super-refractory status in adults (Delaj 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27080243/" }, { "title": "Status epilepticus in Richmond, Virginia (DeLorenzo 1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/8780085/" }, { "title": "Morbidity and mortality in nonconvulsive status (Shneker and Fountain 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/14581666/" }, { "title": "NORSE: etiology, clinical features and outcome (Gaspard 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26296517/" }, { "title": "FIRES outcome in 77 children (Kramer 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21883180/" }, { "title": "ESETT registration (ClinicalTrials.gov NCT01960075)", "url": "https://clinicaltrials.gov/study/NCT01960075" } ], "words": 2588, "bank": 14 }, { "id": "diet-and-other", "n": "8", "title": "Dietary therapy and other treatments", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Know the dietary options, their indications and contraindications", "use rescue medicines and immunotherapy appropriately" ], "blocks": [ { "type": "h3", "text": "The diets" }, { "type": "table", "head": [ "Diet", "Composition", "Notes" ], "rows": [ [ "Classic ketogenic", "4:1 or 3:1 fat to protein-plus-carbohydrate by weight", "Most restrictive; weighed meals" ], [ "Modified Atkins", "Carbohydrate limited to about 10–20 g/day, fat encouraged", "No weighing; suits adolescents and adults" ], [ "Medium-chain triglyceride", "MCT oil produces ketones efficiently, allowing more carbohydrate", "Gastrointestinal side effects" ], [ "Low glycemic index treatment", "Carbohydrates limited and restricted to a low glycemic index", "Least restrictive" ] ] }, { "type": "h3", "text": "When to use it" }, { "type": "li", "text": "**The treatment of choice** for [GLUT1 deficiency](ilae_classification.html#syndrome-12) and pyruvate dehydrogenase deficiency, where ketones supply the brain with fuel around the block." }, { "type": "li", "text": "**Strong evidence** in infantile epileptic spasms syndrome, Dravet syndrome, epilepsy with myoclonic–atonic seizures, tuberous sclerosis, FIRES and super-refractory status. Consider it after two ASMs have failed." }, { "type": "li", "text": "**Also high response rates** in Angelman syndrome, complex I mitochondrial disorders, Ohtahara syndrome, and children or infants fed only by formula, including those fed by gastrostomy. The diet is used alongside ASMs, not instead of them." }, { "type": "li", "text": "**Contraindications**: disorders of fat oxidation and ketone use: primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency, β-oxidation defects, pyruvate carboxylase deficiency and porphyria. Screen before starting." }, { "type": "li", "text": "**Relative contraindications**: inability to maintain adequate nutrition, a surgical focus identified on imaging and video-EEG, parents or caregivers who cannot follow the diet, and concurrent propofol." }, { "type": "li", "text": "Give it about three months before judging it. Watch for acidosis, hypoglycemia, kidney stones (citrate helps), constipation, dyslipidemia, poor growth and reduced bone density." }, { "type": "h3", "text": "Running the diet" }, { "type": "li", "text": "**Starting**: fasting is optional and admission is not required. Fasting does not improve ketosis or seizure control at 3 months and causes more hypoglycemia, acidosis and weight loss, though it may speed the response when time matters, as in status epilepticus. For children under 2 the consensus recommends a nonfasting start. Children under 2 start the classic diet, often as formula; modified Atkins and the low glycemic index diet are recommended for adolescents and usually start as outpatients." }, { "type": "li", "text": "**Measuring ketosis**: β-hydroxybutyrate is measured in blood (more accurate, and better linked to seizure control in some studies; preferred in infants), acetoacetate in urine with dipsticks (checked at home several times a week; lower in the morning), and acetone in breath (tracks blood ketones in research studies)." }, { "type": "li", "text": "**Supplements for everyone**: a carbohydrate-free multivitamin with minerals, including selenium (levels fall on the diet, and deficiency has been linked to cardiomyopathy), plus calcium and vitamin D. **Secondary carnitine deficiency** can develop on the diet, more often with valproate; give carnitine if levels are low or symptoms appear. It is distinct from primary carnitine deficiency, which forbids the diet." }, { "type": "li", "text": "**Monitoring**: blood count, liver and kidney tests, fasting lipids, calcium, vitamin D and magnesium every 3 months in the first year; height and weight at every visit. After 2 years on the diet the risks are slowed growth, fractures and kidney stones; about half of centers check bone density." }, { "type": "li", "text": "**In intensive care**: give the classic diet as enteral formula and check glucose often in the first days. Strip out hidden carbohydrate: dextrose in IV fluids and drug diluents, and the propylene glycol in IV lorazepam, phenobarbital and pentobarbital; use saline or balanced crystalloids. Replace propofol with another anesthetic, because the combination may raise the risk of propofol infusion syndrome (fatal in a child started on the diet during propofol). In 15 adults with super-refractory status given the diet, all reached ketosis in a median of 2 days, and status resolved in 11 of the 14 who completed treatment." }, { "type": "li", "text": "**How long**: about 3 months is a fair trial (most children who respond do so within two weeks); stop sooner if seizures clearly worsen. After success, reconsider at about 2 years and wean over 1–3 months; about 80% of children seizure-free on the diet stay seizure-free after it. Infantile spasms and status epilepticus may need shorter courses. GLUT1 deficiency and pyruvate dehydrogenase deficiency need it much longer: in GLUT1 deficiency at least until puberty and often into adulthood, because the diet supplies the fuel the brain lacks rather than only suppressing seizures." }, { "type": "h3", "text": "Rescue medicines" }, { "type": "p", "text": "For clusters or prolonged seizures at home: intranasal midazolam, intranasal or rectal diazepam, or buccal midazolam, with a written seizure action plan." }, { "type": "h3", "text": "Immunotherapy and hormones" }, { "type": "p", "text": "Corticosteroids, IVIG, plasma exchange, rituximab and cyclophosphamide for autoimmune epilepsy and encephalitis; ACTH or high-dose prednisolone for infantile spasms; steroids in spike-wave activation in sleep." }, { "type": "mcq", "id": "q-1n80j4g", "stem": "A child is being considered for the ketogenic diet. Which condition must be excluded first because the diet could be fatal?", "options": [ "GLUT1 deficiency", "Pyruvate dehydrogenase deficiency", "Carnitine palmitoyltransferase II deficiency", "Tuberous sclerosis", "Dravet syndrome" ], "answer": 2, "explain": "Fat oxidation defects, including CPT I and II deficiency, carnitine deficiency and translocase deficiency, make the diet dangerous. GLUT1 and pyruvate dehydrogenase deficiency are its strongest indications." }, { "type": "cards", "items": [ { "id": "c-wvuc6g", "front": "Ketogenic diet treatment of choice", "back": "GLUT1 deficiency and pyruvate dehydrogenase deficiency." }, { "id": "c-6y3xa4", "front": "Ketogenic diet contraindications", "back": "Fat oxidation defects (carnitine deficiency, CPT I/II, translocase, β-oxidation), pyruvate carboxylase deficiency, porphyria." }, { "id": "c-1ku18j5", "front": "Classic ketogenic ratio", "back": "4:1 or 3:1 fat to protein plus carbohydrate." }, { "id": "c-6tebrf", "front": "Modified Atkins carbohydrate limit", "back": "About 10–20 g per day." }, { "id": "c-rmx5p2", "front": "How long to try the diet", "back": "About three months." }, { "id": "c-1y7mnet", "front": "Home rescue options", "back": "Intranasal midazolam, intranasal or rectal diazepam, buccal midazolam." }, { "id": "c-184olof", "front": "Other conditions with high diet response rates", "back": "Angelman syndrome, complex I mitochondrial disorders, Ohtahara syndrome, formula-fed children." }, { "id": "c-b8cn9y", "front": "Relative contraindications to the ketogenic diet", "back": "Poor nutrition, a surgical focus, caregivers unable to comply, concurrent propofol." }, { "id": "c-16t6v4a", "front": "Fasting at diet initiation", "back": "Optional; no better ketosis or seizure control at 3 months, more hypoglycemia; not in children under 2." }, { "id": "c-8xkmov", "front": "Diet for children under 2", "back": "The classic ketogenic diet, often as formula." }, { "id": "c-75es2e", "front": "Ketone bodies and where each is measured", "back": "β-hydroxybutyrate in blood, acetoacetate in urine, acetone in breath." }, { "id": "c-quha0m", "front": "Universal supplements on the diet", "back": "Carbohydrate-free multivitamin with minerals (including selenium), calcium and vitamin D." }, { "id": "c-1sv78b2", "front": "Selenium deficiency on the diet", "back": "Linked to cardiomyopathy." }, { "id": "c-1wrt0lp", "front": "Secondary carnitine deficiency on the diet", "back": "More likely with valproate; supplement if low or symptomatic." }, { "id": "c-1usutv1", "front": "Ketogenic diet in intensive care", "back": "Enteral formula, no dextrose in fluids or drug diluents, frequent glucose checks, avoid propofol." }, { "id": "c-mgz7rt", "front": "When to stop the diet", "back": "After about 3 months if it fails; reconsider at about 2 years if it works." }, { "id": "c-1r7tqwi", "front": "Diet duration in GLUT1 deficiency", "back": "At least until puberty, often into adulthood." } ] } ], "sources": [ { "title": "International Ketogenic Diet Study Group consensus (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29881797/" }, { "title": "NORSE and FIRES consensus definitions (2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29399791/" }, { "title": "Ketogenic diet in adult status epilepticus: a guide for the intensivist (Katz 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33671485/" }, { "title": "Ketogenic diet for adult super-refractory status epilepticus (Cervenka 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28179470/" }, { "title": "Fatal propofol infusion syndrome with the ketogenic diet (Baumeister 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15328567/" }, { "title": "Breath acetone as an indicator of ketosis (Musa-Veloso 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12081817/" }, { "title": "GLUT1 deficiency syndrome consensus (Klepper 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32913944/" } ], "words": 1009, "bank": 6 } ], "intro": [ "Choosing, dosing, combining and stopping antiseizure medications (ASMs), treating women and other special groups, and stopping status epilepticus. For bedside dosing tables, see the [Seizure Management guide](seizure_management.html)." ] }, { "id": "surgery", "n": "8", "title": "Epilepsy surgery and devices", "short": "Surgery", "sections": [ { "id": "presurgical-evaluation", "n": "1", "title": "Who to refer, and the presurgical zones", "tags": [ "epilepsy-surgery" ], "updated": false, "goals": [ "Recognize who should be referred for surgical evaluation, and when", "name the six cortical zones and the test that defines each", "explain why agreement between tests matters more than any single test" ], "blocks": [ { "type": "h3", "text": "Refer early" }, { "type": "p", "text": "Once two appropriate, tolerated ASMs have failed, the chance that the next drug will stop the seizures is small. That is the point to refer to a comprehensive epilepsy center, not after five or six drugs. Earlier referral also makes sense when the diagnosis is in doubt, when MRI shows a lesion that fits the seizures, or when a child's development is being harmed by frequent seizures." }, { "type": "p", "text": "Two randomized trials settled the question for temporal lobe epilepsy:" }, { "type": "li", "text": "**Surgery versus continued medication (Wiebe 2001)**: at one year, 58% of the surgical group were free of seizures that impair awareness, against 8% of the medical group." }, { "type": "li", "text": "**Early surgery (ERSET 2012)**: in patients within two years of failing a second drug, 11 of 15 treated surgically were seizure-free in the second year, against none of 23 treated medically." }, { "type": "li", "text": "**Children (Dwivedi 2017)**: in a trial of 116 children and adolescents, 77% were seizure-free at one year after surgery against 7% on medication alone." }, { "type": "p", "text": "Despite this, adults often reach surgery after about two decades of epilepsy, by which time psychosocial and cognitive harm is harder to undo." }, { "type": "p", "text": "The **ILAE expert consensus on referral (2022)** puts it plainly. Offer referral (up to age 70) as soon as drug resistance is established, whatever the duration of epilepsy, the seizure or epilepsy type (developmental and epileptic encephalopathies included), the localization, the chance that a resection will prove possible, or comorbidity, including severe psychiatric illness or coexisting psychogenic nonepileptic seizures, provided the patient cooperates with care. Consider referral for adults over 70 with no surgical contraindication, and for anyone seizure-free on one or two ASMs who has a lesion in noneloquent cortex. The only situation in which the experts advised against referral was active substance misuse in a patient not cooperating with management." }, { "type": "li", "text": "**Older adults**: in a meta-analysis of 1111 patients aged 50 or more, about 70% became seizure-free after resection, no different from younger adults, but any complication was almost three times as likely." }, { "type": "li", "text": "**Low IQ**: in a national surgery register, 61% of patients with an IQ of 70 or more were seizure-free at 2 years, against 37% with IQ 50–69 and 22% below 50. Low IQ lowers the odds but does not exclude surgery, especially when there is a lesion." }, { "type": "li", "text": "**A normal MRI or a long history** is no reason to wait either. The specialist evaluation may find a lesion that was missed, or a palliative option." }, { "type": "h3", "text": "The six zones" }, { "type": "p", "text": "Surgery aims to remove or disconnect the **epileptogenic zone**: the cortex whose removal stops the seizures. No test measures it directly. It is inferred from six other zones, each defined by a different test, and it is only proven when the patient is seizure-free after surgery." }, { "type": "table", "head": [ "Zone", "What it is", "Main test" ], "rows": [ [ "Symptomatogenic zone", "Cortex that produces the signs of the seizure", "Semiology on video" ], [ "Irritative zone", "Cortex that produces interictal spikes", "Interictal EEG, MEG" ], [ "Seizure-onset zone", "Where recorded seizures begin", "Ictal EEG (scalp or intracranial), ictal SPECT" ], [ "Epileptogenic lesion", "The structural abnormality responsible", "MRI" ], [ "Functional deficit zone", "Cortex that works abnormally between seizures", "Examination, neuropsychology, FDG-PET, focal slowing" ], [ "Eloquent cortex", "Cortex needed for language, movement or vision", "Stimulation mapping, fMRI, Wada test, MEG" ] ] }, { "type": "figure", "html": "presurgical-zones", "caption": "The six zones in a left temporal example, each drawn on its own against the epileptogenic zone (dashed). They overlap it, but rarely match it in size or position.", "n": 18 }, { "type": "h3", "text": "Concordance decides the plan" }, { "type": "p", "text": "When semiology, EEG, MRI and the functional tests all point to the same region, the chance of seizure freedom is high, and the team may operate without intracranial EEG. Discordant results are the main reason to record intracranially, or to choose a palliative option instead. These decisions are made together at a multidisciplinary conference." }, { "type": "figure", "html": "presurg-workup", "caption": "From the noninvasive workup to a treatment decision: everyone has phase I, the team weighs concordance, and the decision branches to surgery, intracranial EEG or a palliative option.", "n": 19 }, { "type": "p", "text": "**When the lesion and the EEG disagree**, remember that noninvasive tests can show where a seizure spreads rather than where it starts. In one series, scalp EEG falsely localized or lateralized 28% of occipital and 16% of parietal seizures; occipital seizures often reach the scalp record only after spreading to the temporal lobe. After severe early damage to one hemisphere, the first clear scalp rhythm may appear over the healthy side: depth electrodes then showed onset in the damaged hemisphere, and surgery on that side stopped the seizures. PET misleads too if a seizure occurred during tracer uptake. Give the lesion due weight, and let intracranial EEG settle the side rather than operating on the scalp EEG alone. See also [Seizures on the EEG](#ictal-scalp)." }, { "type": "p", "text": "**The person, not only the tests**: in a series of 100 patients, a lifetime psychiatric history predicted a worse seizure outcome after anterior temporal lobectomy. The expectations of the patient and family before surgery shape how well they adjust afterward. Even when surgery succeeds, two-thirds of patients in one series reported a \"burden of normality\" within 2 years: difficulty giving up the role of being ill and adjusting to life without seizures. Psychiatric treatment, realistic goals and family support belong in the workup." }, { "type": "note", "label": "Board pearl", "text": "A seizure can be silent until it spreads. The first sign then comes from the symptomatogenic zone, which can be some distance from where the seizure begins." }, { "type": "mcq", "id": "q-3g1zeo", "stem": "Which zone can be confirmed only by the result of surgery?", "options": [ "Irritative zone", "Seizure-onset zone", "Epileptogenic zone", "Functional deficit zone", "Symptomatogenic zone" ], "answer": 2, "explain": "The epileptogenic zone is defined by what happens after it is removed: if the patient is seizure-free, it was included in the resection. Every other zone has a test that defines it before surgery." }, { "type": "mcq", "id": "q-s6gs3z", "stem": "A 26-year-old's seizures begin with clonic jerking of the right hand. Intracranial EEG shows that onset is in the left premotor cortex, and the hand jerking appears only when the discharge reaches primary motor cortex. What does the primary motor cortex represent here?", "options": [ "Seizure-onset zone", "Symptomatogenic zone", "Irritative zone", "Epileptogenic lesion", "Functional deficit zone" ], "answer": 1, "explain": "The motor cortex produces the first sign but is reached by spread. Resecting it would cause a deficit without stopping the seizures, which start in premotor cortex." }, { "type": "mcq", "id": "q-143qobi", "stem": "A 38-year-old has had focal seizures with impaired consciousness for 20 years. They have tried levetiracetam, lamotrigine and lacosamide at adequate doses. MRI shows left hippocampal sclerosis. What is the best next step?", "options": [ "Add a fourth ASM and review in six months", "Refer to a comprehensive epilepsy center for presurgical evaluation", "Refer only if seizures become more frequent", "Implant a vagus nerve stimulator", "Start the ketogenic diet" ], "answer": 1, "explain": "After two adequate ASM trials, this is drug-resistant epilepsy, and hippocampal sclerosis responds well to surgery. Waiting for more drug trials only delays the most effective treatment." }, { "type": "match", "id": "match-zones", "prompt": "Match each zone to the test that best defines it", "pairs": [ [ "Symptomatogenic zone", "Video analysis of the seizure" ], [ "Irritative zone", "Interictal EEG or MEG" ], [ "Seizure-onset zone", "Ictal EEG" ], [ "Epileptogenic lesion", "MRI" ], [ "Functional deficit zone", "FDG-PET and neuropsychology" ], [ "Eloquent cortex", "Electrical stimulation mapping" ] ] }, { "type": "cards", "items": [ { "id": "c-1kekcdt", "front": "Epileptogenic zone", "back": "The cortex whose removal or disconnection stops the seizures. Inferred from the other zones, proven only by outcome." }, { "id": "c-1j83d02", "front": "Symptomatogenic zone", "back": "Cortex that produces the ictal signs; can be distant from the onset when a seizure is silent until it spreads." }, { "id": "c-1n0q5u4", "front": "Irritative zone", "back": "Cortex that produces interictal spikes; usually larger than the epileptogenic zone." }, { "id": "c-v6dk2w", "front": "Functional deficit zone", "back": "Cortex working abnormally between seizures; shown by FDG-PET, neuropsychology and focal slowing." }, { "id": "c-1yr272m", "front": "Wiebe 2001 trial", "back": "Temporal lobe epilepsy: 58% free of seizures impairing awareness after surgery versus 8% on medication at one year." }, { "id": "c-264v93", "front": "ERSET 2012 trial", "back": "Early surgery: 11 of 15 seizure-free in year two, against none of 23 on medication." }, { "id": "c-ywffdq", "front": "When to refer for presurgical evaluation", "back": "After two appropriate, tolerated ASMs have failed." }, { "id": "c-xrbv8h", "front": "ILAE referral consensus (2022)", "back": "Refer as soon as drug resistance is established, whatever the duration, epilepsy type, localization, likely resectability or comorbidity, if the patient cooperates; consider referral over age 70, and for a noneloquent lesion even when seizure-free." }, { "id": "c-grlv03", "front": "Epilepsy surgery after age 50", "back": "Seizure freedom about 70%, as in younger adults; complications about three times as likely." }, { "id": "c-29909e", "front": "Low IQ and epilepsy surgery", "back": "Lower chance of seizure freedom (22–37% against 61% at 2 years) but not a reason to refuse surgery." }, { "id": "c-ezvl8y", "front": "False lateralization after early hemispheric damage", "back": "The first scalp rhythm can appear over the healthy hemisphere; depth recording shows onset on the damaged side." }, { "id": "c-b8stel", "front": "Occipital and parietal seizures on scalp EEG", "back": "Often seen only after spread; falsely localized or lateralized in 28% and 16% in one series." }, { "id": "c-1d6fotn", "front": "Burden of normality", "back": "Difficulty adjusting to life without seizures after successful surgery; prepare the patient and family before surgery." } ] } ], "sources": [ { "title": "Presurgical evaluation of epilepsy (Rosenow and Lüders 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11522572/" }, { "title": "Randomized trial of surgery for temporal lobe epilepsy (Wiebe 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11484687/" }, { "title": "Early surgical therapy for drug-resistant temporal lobe epilepsy (ERSET, 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22396514/" }, { "title": "Surgery for drug-resistant epilepsy in children (Dwivedi 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29069568/" }, { "title": "Definition of drug-resistant epilepsy (ILAE 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19889013/" }, { "title": "Timing of referral to evaluate for epilepsy surgery: ILAE expert consensus recommendations (Jehi 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35842919/" }, { "title": "Epilepsy surgery in adults older than 50 years: meta-analysis (Vary O'Neal 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38581402/" }, { "title": "Seizure outcome after resective surgery in patients with low IQ (Malmgren 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18063587/" }, { "title": "The localizing value of ictal EEG in focal epilepsy (Foldvary 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11739820/" }, { "title": "Occipital lobe epilepsy: seizure spread patterns and results of surgery (Williamson 1992)", "url": "https://pubmed.ncbi.nlm.nih.gov/1543348/" }, { "title": "False lateralization by surface EEG with gross focal cerebral lesions (Sammaritano 1987)", "url": "https://pubmed.ncbi.nlm.nih.gov/3579221/" }, { "title": "A lifetime psychiatric history predicts a worse seizure outcome after temporal lobectomy (Kanner 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19255406/" }, { "title": "Paradoxical results in the cure of chronic illness: the burden of normality (Wilson 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/14751201/" }, { "title": "The longitudinal course of adjustment after seizure surgery (Wilson 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11437614/" } ], "words": 1421, "bank": 9 }, { "id": "epilepsy-imaging", "n": "2", "title": "Imaging and functional testing", "tags": [ "epilepsy-surgery" ], "updated": false, "goals": [ "Order an epilepsy-protocol MRI and know what it looks for", "recognize hippocampal sclerosis and focal cortical dysplasia", "know what PET, SPECT, MEG, fMRI, the Wada test and neuropsychology each add" ], "blocks": [ { "type": "h3", "text": "MRI: the most important test" }, { "type": "p", "text": "A routine brain MRI misses many epileptogenic lesions. The ILAE's recommended protocol (HARNESS-MRI) has three core sequences:" }, { "type": "li", "text": "A 3D T1-weighted volume with 1 mm isotropic voxels" }, { "type": "li", "text": "A 3D FLAIR volume" }, { "type": "li", "text": "High-resolution coronal T2, cut perpendicular to the long axis of the hippocampus" }, { "type": "p", "text": "Have the scan read, or re-read, by someone experienced in epilepsy imaging, with the clinical and EEG findings in hand. A dedicated protocol reviewed by an expert finds lesions that routine scans and reports miss. Add susceptibility-weighted imaging to look for cavernomas and calcification." }, { "type": "li", "text": "**Higher field strength**: at 1.5 and 3 tesla, only about 60–85% of scans show the epileptogenic lesion. A 7-tesla task force has set out when to use 7 tesla clinically. In one center using its protocol, 7 tesla showed a new potential lesion in 19% of patients whose 3-tesla scan was negative." }, { "type": "li", "text": "**Infants**: myelination changes how dysplasia looks. Some type II dysplasias are clearest on scans in the first year and later fade to subtle blurring; others become visible only as myelination proceeds. Image early, and repeat the MRI as the brain matures if the first scan is normal." }, { "type": "li", "text": "**Post-processing**: software compares the patient's 3D T1 volume with a normal database (voxel-based morphometry), or applies a trained classifier such as the Multi-centre Epilepsy Lesion Detection (MELD) algorithm, to flag subtle gray–white blurring for a targeted second look. In 150 MRI-negative candidates, morphometric analysis flagged a region in 43% (2% of controls). Resected flagged regions contained mostly dysplasia without balloon cells; complete removal gave the best outcome and partial removal the worst. MELD found 85% of type IIB dysplasias in seizure-free patients but only 59% of all lesions, with low specificity. A flag is a lead to check against the electroclinical data, not proof of the onset zone." }, { "type": "li", "text": "**Peri-ictal changes**: after prolonged seizures or status epilepticus, MRI can show T2/FLAIR and diffusion changes in cortex, hippocampus and the pulvinar of the thalamus. They reflect the seizure, not its cause. Pulvinar diffusion restriction occurred in 20% of patients with status epilepticus and in none of 150 controls with other causes. In 26 patients, the changes resolved in 15 and left gliosis or focal atrophy in 11, over about 2 months on average. Repeat the scan after some weeks before calling such a change an infarct, a tumor or a surgical target." }, { "type": "h3", "text": "Hippocampal sclerosis" }, { "type": "li", "text": "**On MRI**: a small hippocampus with high T2 and FLAIR signal and loss of its internal structure. Supporting signs include a shrunken fornix and mammillary body on the same side, a larger temporal horn, and blurring of the temporal pole." }, { "type": "li", "text": "**ILAE types**: type 1 (neuron loss in CA1 and CA4) is the commonest and has the best seizure outcome after surgery. Type 2 affects mainly CA1 and type 3 mainly CA4. \"Gliosis only, no hippocampal sclerosis\" is a separate category." }, { "type": "h3", "text": "Focal cortical dysplasia" }, { "type": "p", "text": "The 2022 ILAE classification keeps the three main types and adds genetic findings to an integrated diagnosis." }, { "type": "li", "text": "**Type I**: abnormal layering of the cortex. It is often invisible on MRI." }, { "type": "li", "text": "**Type II**: dysmorphic neurons, without (IIa) or with (IIb) balloon cells. On MRI it shows thick cortex, a blurred gray–white junction and, in IIb, a **transmantle sign**: a funnel of FLAIR signal tapering from the cortex toward the ventricle. Type II lesions are often small and sit at the **bottom of a sulcus**. Somatic variants in the mTOR pathway are a common cause." }, { "type": "li", "text": "**Type III**: dysplasia next to another main lesion: hippocampal sclerosis (IIIa), a tumor (IIIb), a vascular malformation (IIIc), or another lesion acquired early in life (IIId)." }, { "type": "li", "text": "**Dual pathology is not type IIIa**: dual pathology means hippocampal sclerosis plus a separate principal lesion elsewhere, such as a tumor, a vascular malformation or a type II dysplasia. Two independent lesions without hippocampal sclerosis are called double pathology." }, { "type": "li", "text": "**Added in 2022**: mild malformation of cortical development (mMCD), and MOGHE (mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy)." }, { "type": "h3", "text": "Functional tests" }, { "type": "li", "text": "**FDG-PET**: interictal hypometabolism helps lateralize temporal lobe epilepsy, especially when the MRI is normal. The hypometabolic area is wider than the epileptogenic zone. Sensitivity is highest in temporal lobe epilepsy (79–95%) and lower in extratemporal epilepsy (about 55%), especially without an MRI lesion. Thalamic hypometabolism on the same side is usual in mesial temporal epilepsy; on the opposite side it goes with a poorer surgical outcome (for its value in nonlesional epilepsy, see [Resection, ablation and disconnection](#surgical-options))." }, { "type": "li", "text": "**PET in children**: PET showed unilateral hypometabolism in 5 of 13 infants with spasms of unknown cause; the 4 whose abnormal region was removed had dysplasia on pathology and became seizure-free. PET also checks the function of the hemisphere that will remain before hemispherotomy." }, { "type": "li", "text": "**PET must be truly interictal**: FDG is trapped in proportion to glucose use during uptake. A seizure in that window makes the active cortex hypermetabolic, and the normal side can then be misread as hypometabolic, reversing the lateralization. Where possible, scan at least 24 hours after focal aware seizures and 48 hours after focal impaired awareness or tonic–clonic seizures, record the time of the last seizure, and supervise the patient during uptake." }, { "type": "li", "text": "**PET–MRI fusion**: fusing PET with MRI and taking a second look finds lesions missed at first reading, notably focal cortical dysplasia. Heterotopia, and dysplasia in some young children, can be hypermetabolic rather than hypometabolic." }, { "type": "li", "text": "**Other PET tracers**: carbon-11 flumazenil shows reduced binding at the benzodiazepine site of gamma-aminobutyric acid type A (GABA-A) receptors, often over a smaller area than the FDG defect. Alpha-[11C]methyl-L-tryptophan uptake rises between seizures in the epileptogenic tubers of tuberous sclerosis complex, whereas FDG shows every tuber as hypometabolic. Carbon-11 has a half-life of about 20 minutes (fluorine-18, about 110), so these tracers need a cyclotron on site and few centers offer them." }, { "type": "li", "text": "**Ictal SPECT**: tracer injected within seconds of seizure onset shows hyperperfusion at the onset. Subtracting an interictal scan and fusing the result with MRI (SISCOM) sharpens the picture. A late injection shows where the seizure spread, not where it began." }, { "type": "li", "text": "**How SPECT tracers work**: the technetium-99m perfusion tracers are fixed in the brain within 1–2 minutes of injection. The image, acquired 30–90 minutes later, therefore shows blood flow at the moment of injection: the injection time, not the scan time, decides what is shown. Inject within 20 seconds of onset if possible, from a syringe kept ready on the monitoring unit, under continuous video-EEG. Interictal SPECT alone localizes poorly (sensitivity about 50%, against 73% for ictal SPECT) and serves mainly as the subtraction baseline. In MRI-negative epilepsy, statistical comparison with a normal database (STATISCOM) placed the hyperperfusion at the resection site more often than SISCOM." }, { "type": "li", "text": "**MEG**: localizes the sources of interictal spikes. It is most useful in neocortical and MRI-negative epilepsy, and it can also map eloquent cortex." }, { "type": "li", "text": "**fMRI**: lateralizes language. It can replace the Wada test in many patients with temporal lobe epilepsy, and fMRI of verbal memory or language helps predict memory decline after surgery." }, { "type": "li", "text": "**What fMRI measures**: active neurons trigger a rise in blood flow far larger than the rise in oxygen use (29% against 5% in one PET study). Deoxyhemoglobin, a natural magnetic contrast agent, therefore falls and the blood oxygen level–dependent (BOLD) signal rises. fMRI maps this blood-flow response, not neuronal firing." }, { "type": "li", "text": "**Limits of fMRI mapping**: activation shows cortex that takes part in a task, not cortex that is essential, and absent activation does not prove cortex can be removed. Tumors, vascular malformations and inflammation can uncouple blood flow from neural activity, silencing working cortex beside the lesion while the healthy opposite side activates normally (\"pseudo-dominance\"). Against direct cortical stimulation, language fMRI sensitivity ranged from 59% to 100% and specificity from 0% to 97%. The American Academy of Neurology (AAN) guideline found too little evidence to use fMRI in place of the Wada test in temporal neocortical epilepsy or temporal tumors. When a resection approaches language cortex, map it with electrical stimulation; a Wada test can settle doubtful lateralization." }, { "type": "li", "text": "**Task and language matter**: maps differ by task, so centers combine paradigms, for example sentence completion for receptive and word generation for expressive language. A bilingual patient may need mapping in each language." }, { "type": "li", "text": "**Language dominance**: right-hemisphere language rises with left-handedness in healthy people, from 4% in strong right-handers to 27% in strong left-handers. Atypical (bilateral or right) language is commoner in epilepsy: 22% of right-handed patients against 6% of right-handed controls in one fMRI study, linked to earlier brain injury and weaker right-hand preference." }, { "type": "li", "text": "**EEG–fMRI**: EEG recorded in the scanner lets BOLD changes be mapped against interictal spikes. It needs spikes during the scan; when they occurred, a response was found in about two-thirds of patients, mostly concordant with the presumed onset. It remains an adjunct, mainly to suggest targets for intracranial electrodes." }, { "type": "li", "text": "**MR spectroscopy**: reduced N-acetylaspartate and a lactate peak on one side help lateralize mesial temporal epilepsy (86% accuracy in one small series). N-acetylaspartate ratios also fall transiently after a seizure." }, { "type": "li", "text": "**Diffusion tensor imaging and tractography**: water diffuses more freely along axons than across them, and anisotropy measures such as fractional anisotropy express this directionality. Loss of myelin raises diffusion across fibers (radial diffusivity) while diffusion along them is unchanged. Tractography of the optic radiation (Meyer's loop) explained 65% of the variance in field loss after temporal resection; displayed during surgery, it reduced field defects, and no patient failed the driving standard, against 13% without it." }, { "type": "li", "text": "**Wada test**: an intracarotid barbiturate (or similar drug) briefly anesthetizes one hemisphere while language and memory are tested. It is now reserved mainly for patients whose fMRI is atypical or unreliable." }, { "type": "li", "text": "**Neuropsychology**: sets a baseline and helps lateralize. Poor verbal memory suggests dominant (usually left) temporal dysfunction; the nondominant pattern is less reliable. European centers agree on the domains: verbal and visual memory, attention, executive function, language, visuospatial skills and intelligence, with mood and quality of life; the tests themselves vary widely." }, { "type": "li", "text": "**Performance validity**: scores are interpreted only after stand-alone or embedded validity measures, such as the Test of Memory Malingering, show that the patient engaged with testing. Failure means the profile cannot be trusted, not that the patient is malingering; in epilepsy it is linked with low IQ, memory impairment, a left-sided focus and recent seizures." }, { "type": "h3", "text": "Magnetoencephalography (MEG)" }, { "type": "p", "text": "MEG records the magnetic fields of the same neuronal currents that generate the EEG, using cryogenic superconducting quantum interference device (SQUID) sensors in a helmet inside a magnetically shielded room. Coils on the head and digitized landmarks register the recording to the MRI. MEG is most sensitive to tangential sources in the walls of sulci, and EEG to radial sources on the crowns of gyri, so the two complement each other." }, { "type": "li", "text": "**What it shows**: spikes are modeled as single equivalent current dipoles, so MEG marks the irritative zone, not the seizure-onset zone. A standard recording lasts about an hour: seizures are caught by chance (11% in one series), and some studies contain no spikes (about a fifth of operated patients in one cohort). Metal implants and movement degrade the signal, and the equipment is costly." }, { "type": "li", "text": "**Clinical role**: localization in drug-resistant focal epilepsy, especially MRI-negative or extratemporal epilepsy or when the scalp EEG does not localize, and guidance for placing intracranial electrodes or for a targeted second look at the MRI. In 132 operated patients, 85% of those whose MEG findings lay within the resection became seizure-free, against 37% when they did not. In a series of 1000 patients, MEG was most accurate in extratemporal and nonlesional epilepsy." }, { "type": "li", "text": "**Temporal dipoles**: in one series, anterior temporal dipoles oriented front to back (horizontal) pointed to the anterior inferolateral temporal tip, anterior vertical dipoles went with mesial onsets, and lateral vertical dipoles with neocortical onsets." }, { "type": "li", "text": "**Mapping**: magnetic evoked fields localize somatosensory cortex and the central sulcus (median nerve stimulation), primary auditory cortex and primary visual cortex before resection. Language-evoked fields lateralize language, agreeing with the Wada test or intracranial mapping in 80–95% of patients." }, { "type": "mcq", "id": "q-v14e9b", "stem": "A 27-year-old with MRI-negative frontal lobe epilepsy has MEG showing a tight cluster of spike dipoles in the right superior frontal sulcus, concordant with the semiology. What does the cluster most directly mark?", "options": [ "The seizure-onset zone", "The irritative zone", "The symptomatogenic zone", "Eloquent motor cortex", "The functional deficit zone" ], "answer": 1, "explain": "MEG models interictal spikes, which define the irritative zone. A tight, concordant cluster is a strong guide for implanting electrodes and predicts a good outcome if it is resected, but intracranial EEG defines where seizures begin." }, { "type": "h3", "text": "Who is most at risk of memory decline" }, { "type": "p", "text": "Verbal memory is most likely to fall after surgery on the dominant temporal lobe in someone whose memory is still good before surgery. The risk is higher still when the hippocampus looks normal on MRI, the epilepsy began later in life, or fMRI shows memory activation on the side of surgery. Tissue that still works has more to lose." }, { "type": "p", "text": "Two models are named. **Functional adequacy**: the better the tissue to be removed still works (good baseline memory, a normal-looking hippocampus, fMRI or Wada memory on the operated side), the more memory is lost; most evidence supports this model as the predictor of decline. **Functional reserve**: the capacity of the opposite hippocampus to sustain memory alone decides whether a global amnesia could follow. The Wada memory test was originally designed to check reserve, by anesthetizing the side to be operated on and testing the other alone." }, { "type": "p", "text": "**Naming** is tested with the Boston Naming Test. In a prospective multicenter cohort, naming declined in 56% after left anterior temporal lobectomy. Decline was more likely with later onset of epilepsy, a hippocampus without sclerosis, and stronger left-sided language on fMRI, the best single predictor. Laser ablation of the amygdala and hippocampus largely spares naming." }, { "type": "mcq", "id": "q-10kgs41", "stem": "In a patient with MRI-negative temporal lobe epilepsy, ictal SPECT was injected 70 seconds after clinical onset. It shows hyperperfusion in the right frontal lobe. How should this be interpreted?", "options": [ "The right frontal lobe is the seizure-onset zone", "The finding may show spread rather than onset because the injection was late", "Ictal SPECT cannot be used in temporal lobe epilepsy", "The scan should be read as interictal", "Hyperperfusion always marks the functional deficit zone" ], "answer": 1, "explain": "Blood flow follows the seizure as it spreads. The earlier the injection after onset, the more likely the hyperperfusion marks where the seizure began." }, { "type": "mcq", "id": "q-1466gjl", "stem": "Which candidate for anterior temporal lobectomy is at highest risk of verbal memory decline?", "options": [ "Right-sided resection, severe hippocampal sclerosis, poor visual memory", "Left-sided resection, severe hippocampal sclerosis, poor verbal memory", "Left-sided resection, normal-looking hippocampus, strong verbal memory", "Right-sided resection, normal MRI, strong verbal memory", "Left-sided resection in a right-hemisphere-dominant patient with poor memory" ], "answer": 2, "explain": "The risk is highest when the dominant hippocampus still works well: normal on MRI and with good baseline verbal memory. Removing an already sclerotic hippocampus costs less." }, { "type": "mcq", "id": "q-o0rqaa", "stem": "A 19-year-old has drug-resistant focal motor seizures. MRI shows a small area of FLAIR signal tapering from the depth of a frontal sulcus toward the lateral ventricle. What is the most likely diagnosis?", "options": [ "Hippocampal sclerosis", "Cavernous malformation", "Focal cortical dysplasia type IIb", "Dysembryoplastic neuroepithelial tumor", "Polymicrogyria" ], "answer": 2, "explain": "The transmantle sign is typical of type IIb dysplasia, which often sits at the bottom of a sulcus. Complete resection gives a good chance of seizure freedom." }, { "type": "cards", "items": [ { "id": "c-wtb839", "front": "HARNESS-MRI core sequences", "back": "3D T1 (1 mm isotropic), 3D FLAIR, and high-resolution coronal T2 perpendicular to the hippocampus." }, { "id": "c-s9pmcb", "front": "Hippocampal sclerosis on MRI", "back": "Small hippocampus, high T2 and FLAIR signal, loss of internal structure." }, { "id": "c-u7gvjj", "front": "Hippocampal sclerosis type with the best surgical outcome", "back": "ILAE type 1 (CA1 and CA4 neuron loss), also the commonest." }, { "id": "c-88u2ob", "front": "Transmantle sign", "back": "A funnel of FLAIR signal from cortex toward the ventricle; focal cortical dysplasia type IIb." }, { "id": "c-kgfqew", "front": "Bottom-of-sulcus dysplasia", "back": "A small type II focal cortical dysplasia at the depth of a sulcus; easy to miss on a routine MRI." }, { "id": "c-vqgkic", "front": "FDG-PET in epilepsy", "back": "Interictal hypometabolism; lateralizes but overestimates the epileptogenic zone." }, { "id": "c-1br3bgn", "front": "Why ictal SPECT timing matters", "back": "Late injection shows spread, not onset." }, { "id": "c-1jaiv4y", "front": "Highest risk of verbal memory decline", "back": "Dominant temporal resection with good baseline memory and a normal-looking hippocampus." }, { "id": "c-1h8bt6m", "front": "Dual pathology", "back": "Hippocampal sclerosis plus a separate principal lesion elsewhere; dysplasia beside hippocampal sclerosis is focal cortical dysplasia type IIIa, not dual pathology." }, { "id": "c-c423c0", "front": "Functional adequacy model", "back": "The better the tissue to be removed still works, the greater the memory loss after surgery." }, { "id": "c-18ie849", "front": "Functional reserve model", "back": "Whether the opposite hippocampus can sustain memory alone; poor reserve risks global amnesia." }, { "id": "c-3p36oc", "front": "fMRI pseudo-dominance", "back": "A lesion uncouples blood flow from neural activity, so working cortex beside it looks silent and the healthy side looks dominant." }, { "id": "c-fjanm", "front": "BOLD signal", "back": "Blood flow rises more than oxygen use, so deoxyhemoglobin falls and the signal rises; an indirect measure of neural activity." }, { "id": "c-1bygo2g", "front": "SPECT injection time", "back": "The tracer is fixed within 1–2 minutes, so the injection time, not the scan time, decides what the image shows." }, { "id": "c-1mn202c", "front": "Seizure during FDG uptake", "back": "The active side becomes hypermetabolic and the normal side looks hypometabolic, reversing the lateralization." }, { "id": "c-1fst0gc", "front": "Alpha-methyl-tryptophan PET", "back": "Uptake rises in the epileptogenic tuber in tuberous sclerosis complex, unlike FDG." }, { "id": "c-1lw0lnk", "front": "Peri-ictal MRI changes", "back": "T2 and diffusion changes in cortex, hippocampus and pulvinar after prolonged seizures; repeat the scan after weeks." }, { "id": "c-zozru7", "front": "MELD", "back": "Machine-learning detector of focal cortical dysplasia on MRI; a flag prompts a second look, not surgery by itself." }, { "id": "c-np7o8c", "front": "MEG spike dipoles", "back": "Mark the irritative zone; a tight concordant cluster guides electrodes and predicts seizure freedom after resection." }, { "id": "c-j3l9bo", "front": "Boston Naming Test", "back": "The standard naming test; decline is common after dominant anterior temporal lobectomy." }, { "id": "c-1jshyv9", "front": "Performance validity testing", "back": "Checks engagement before scores are interpreted; failure invalidates the profile but does not prove malingering." }, { "id": "c-d7v832", "front": "Radial diffusivity", "back": "Water diffusion across fibers on diffusion tensor imaging; rises with loss of myelin." } ] } ], "sources": [ { "title": "HARNESS-MRI protocol (ILAE Neuroimaging Task Force 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31135062/" }, { "title": "ILAE classification of hippocampal sclerosis (2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23692496/" }, { "title": "ILAE classification of focal cortical dysplasia, 2022 update", "url": "https://pubmed.ncbi.nlm.nih.gov/35706131/" }, { "title": "AAN guideline: fMRI in presurgical evaluation (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28077494/" }, { "title": "Presurgical evaluation of epilepsy (Rosenow and Lüders 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11522572/" }, { "title": "ILAE consensus classification of focal cortical dysplasias (Blümcke 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21219302/" }, { "title": "7T Epilepsy Task Force recommendations on 7T MRI in clinical practice (Opheim 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33361257/" }, { "title": "A 7T task force protocol in routine presurgical work-up (Hangel 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/37805665/" }, { "title": "Taylor-type dysplasia in infants: lesions that fade with myelination (Eltze 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16393166/" }, { "title": "Longitudinal MRI and PET in West syndrome with subtle dysplasia (Sakaguchi 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30213810/" }, { "title": "Voxel-based morphometric MRI post-processing in MRI-negative epilepsies (Wang 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25807928/" }, { "title": "Interpretable surface-based detection of focal cortical dysplasias: the MELD study (Spitzer 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35953082/" }, { "title": "Seizure-induced brain lesions on MRI (Cianfoni 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23787273/" }, { "title": "MRI fingerprints of status epilepticus (Bosque Varela 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38507291/" }, { "title": "EANM practice guidelines for PET and SPECT in epilepsy (Traub-Weidinger 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38393374/" }, { "title": "PET identifies focal cortical dysgenesis in cryptogenic infantile spasms (Chugani 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2353794/" }, { "title": "Alpha-methyl-tryptophan PET of epileptogenic tubers (Chugani 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9851429/" }, { "title": "Physics of positron emitters for PET (Conti 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27271304/" }, { "title": "Statistical SPECT processing in MRI-negative epilepsy surgery (Sulc 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24532274/" }, { "title": "Brain MRI with contrast dependent on blood oxygenation (Ogawa 1990)", "url": "https://pubmed.ncbi.nlm.nih.gov/2124706/" }, { "title": "Uncoupling of cerebral blood flow and oxidative metabolism during stimulation (Fox 1986)", "url": "https://pubmed.ncbi.nlm.nih.gov/3485282/" }, { "title": "Language fMRI compared with direct cortical stimulation (Giussani 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/19935438/" }, { "title": "Lesion-induced pseudo-dominance at fMRI (Ulmer 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15335424/" }, { "title": "Canadian recommendations on fMRI to lateralize language (Falby 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38572544/" }, { "title": "Language fMRI in a bilingual patient with epilepsy (O'Grady 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27653991/" }, { "title": "Handedness and hemispheric language dominance in healthy humans (Knecht 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/11099452/" }, { "title": "Language dominance in normal and epilepsy subjects (Springer 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10545389/" }, { "title": "Hemodynamic correlates of epileptiform discharges: EEG–fMRI in 63 patients (Salek-Haddadi 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16678803/" }, { "title": "Proton MR spectroscopy in mesial temporal lobe epilepsy (Chernov 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19647269/" }, { "title": "MR spectroscopy after temporal lobe seizures (Fadaie 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27838503/" }, { "title": "Quantitative diffusion tensor MRI (Basser 1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/8661285/" }, { "title": "Dysmyelination seen as increased radial diffusion (Song 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12414282/" }, { "title": "Optic radiation tractography in anterior temporal lobe resection (Winston 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22451201/" }, { "title": "Preventing visual field deficits from neurosurgery (Winston 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/25015363/" }, { "title": "Neuropsychological assessment in European epilepsy surgery centers (Vogt 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28067423/" }, { "title": "Performance validity in a presurgical epilepsy population (Lesica 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39138860/" }, { "title": "Performance validity tests in people with epilepsy: review (Roberts-West 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/39754938/" }, { "title": "Evidence for magnetic source imaging in presurgical evaluation (Carrette 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31551904/" }, { "title": "Cerebellar signal detectability in MEG and EEG (Matsubara 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41990896/" }, { "title": "MEG localization predicts seizure freedom after surgery (Englot 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25921215/" }, { "title": "MEG for focus localization in 1000 cases (Rampp 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31373622/" }, { "title": "MEG source localization and outcome in temporal lobe epilepsy (Assaf 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15294209/" }, { "title": "ACMEGS guideline 2: presurgical mapping with magnetic evoked fields (Burgess 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21811122/" }, { "title": "Hippocampal adequacy versus functional reserve (Chelune 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/14588901/" }, { "title": "Wada memory asymmetries predict verbal memory decline after temporal lobectomy (Loring 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7617192/" }, { "title": "Use of the intracarotid amobarbital procedure in the evaluation of memory (Acharya 1997)", "url": "https://pubmed.ncbi.nlm.nih.gov/9337141/" }, { "title": "fMRI language lateralization predicts naming outcome after left temporal surgery (Gross 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35410903/" }, { "title": "Naming decline after left temporal lobectomy and hippocampal pathology (Davies 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9578031/" }, { "title": "Naming after tailored left temporal resection: later onset raises risk (Davies 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/16040279/" }, { "title": "Object recognition and naming after laser amygdalohippocampotomy (Drane 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25489630/" } ], "words": 2914, "bank": 12 }, { "id": "invasive-eeg", "n": "3", "title": "Intracranial EEG", "tags": [ "epilepsy-surgery", "eeg-fundamentals" ], "updated": false, "goals": [ "Decide when intracranial EEG is needed", "compare stereo-EEG with subdural grids", "interpret intracranial onsets and stimulation mapping with their limits in mind" ], "blocks": [ { "type": "h3", "text": "When to record intracranially" }, { "type": "li", "text": "The noninvasive tests disagree, or the MRI is normal." }, { "type": "li", "text": "The likely onset lies next to eloquent cortex that needs mapping." }, { "type": "li", "text": "Seizures may start independently in both temporal lobes." }, { "type": "li", "text": "Two possible sources exist, such as a lesion plus hippocampal sclerosis (dual pathology)." }, { "type": "li", "text": "Seizures return after a technically complete temporal resection. The zone may extend beyond the temporal lobe to the insula, operculum or orbitofrontal cortex (\"temporal plus\" epilepsy), regions that stereo-EEG can sample. In one surgical cohort, only 15% of patients with temporal plus epilepsy were free of disabling seizures at 10 years, against 75% with unilateral temporal lobe epilepsy." }, { "type": "p", "text": "Intracranial electrodes record only the tissue they touch. The plan must start from a clear hypothesis about where seizures begin and spread, built from the noninvasive data. Otherwise the recording shows the seizure arriving from somewhere unsampled." }, { "type": "h3", "text": "Stereo-EEG or subdural electrodes" }, { "type": "table", "head": [ "", "Stereo-EEG (depth electrodes)", "Subdural grids and strips" ], "rows": [ [ "Placement", "Through small drill holes", "Through a craniotomy" ], [ "Reaches", "Deep structures, sulcal depths, insula, both hemispheres", "The surface of the convexity" ], [ "Mapping", "Samples points in 3D", "Continuous surface coverage for functional mapping" ], [ "Risk", "Lower: small risk of bleeding and infection", "Higher: bleeding, infection, CSF leak, brain swelling" ], [ "Leading complication", "Hemorrhage, usually small and silent along a track", "Infection; also hemorrhage and raised intracranial pressure" ], [ "Best fit", "Deep or bilateral hypotheses; insula; failed earlier resection", "A hypothesis confined to one convexity region that needs continuous mapping" ], [ "After the study", "Resection follows less often", "Resection follows more often" ] ] }, { "type": "figure", "html": "seeg-implant", "caption": "A stereo-EEG implant in a coronal slice through the hippocampal bodies, seen from the front with the patient's left on the right. Point at a lead to see what it samples. An original schematic, not a patient implant.", "n": 20 }, { "type": "p", "text": "**The electrodes.** A typical depth electrode (DIXI Microdeep) is 0.8 mm across and carries 5 to 18 platinum–iridium contacts in a row, each 2 mm long and 3.5 mm apart center to center, so 1.5 mm of insulation separates neighbors. Contacts are numbered from the deepest." }, { "type": "p", "text": "Stereo-EEG has become the preferred method in many centers. Through the same electrodes, radiofrequency thermocoagulation can treat a small onset zone." }, { "type": "p", "text": "**Complications by method**: with grids, complications occurred in 26% of 198 monitoring sessions in one series (infection 12%, transient deficits 11%), and the risk rose with more than about 60 contacts, more than 10 days of monitoring and older age. A meta-analysis put intracranial hemorrhage at 4% and neurological infection at 2.3% with grids. With stereo-EEG, blinded review of every postimplant CT found bleeding after 19% of implantations. Most bleeds were small and silent (17% of implantations); 2.2% were symptomatic; 0.4% (2 of 549) left a permanent deficit, and 0.2% (1 of 549) died. More electrodes, older age and male sex raised the bleeding risk. Pooled surgical complications of stereo-EEG are about 1.3%." }, { "type": "p", "text": "**Outcome after each method**: in a 2025 meta-analysis, seizure freedom after resection was similar whichever method guided it (63% for both), but resection followed grid studies more often and infection was more frequent with grids (1.8% against 0.3%)." }, { "type": "p", "text": "**Placement**: depth electrodes are placed with a stereotactic frame, frameless image guidance or a robot. Robots are said to be more accurate, but a meta-analysis found the studies too heterogeneous to compare techniques, and one series found no difference in accuracy between frame-based and robot-assisted insular implantation." }, { "type": "h3", "text": "Reading the onset" }, { "type": "li", "text": "**Low-voltage fast activity** (beta or gamma range) is the commonest intracranial onset pattern, and it points to a nearby onset." }, { "type": "li", "text": "**A focal series of rhythmic spikes** before the fast activity is typical of mesial temporal onset." }, { "type": "li", "text": "**If the first change on intracranial EEG is already a well-formed, slower rhythm**, or it appears on the edge contacts, suspect that the true onset lies outside the sampled area." }, { "type": "li", "text": "**High-frequency oscillations** (ripples at 80–250 Hz and fast ripples above 250 Hz) are markers of epileptogenic tissue. Using them to guide the extent of resection has not yet been shown to improve outcome." }, { "type": "li", "text": "**The full repertoire of onset patterns** also includes low-frequency high-amplitude periodic spikes, sharp activity at 13 Hz or slower, spike-and-wave activity, a burst of polyspikes, burst-suppression and delta brush. In one depth-electrode series, periodic spikes occurred only with mesial temporal sclerosis and delta brush only with focal cortical dysplasia. A burst of polyspikes followed by low-voltage fast activity points to dysplasia and a focal zone, and near-continuous rhythmic spiking on electrocorticography is another dysplasia signature. Onsets that include low-voltage fast activity predict a better surgical outcome. See also [Seizures on the EEG](#ictal-scalp)." }, { "type": "li", "text": "**Normal background differs by region**: in an atlas of healthy intracranial contacts, frontal cortex showed beta peaks (20–24 Hz, most consistently over the precentral gyrus), occipital cortex a clear alpha peak at about 9–10 Hz, and the hippocampus slow activity around 1 Hz. Rhythm alone therefore does not mark a contact as abnormal." }, { "type": "p", "text": "**Intraoperative electrocorticography** records from the cortex during surgery, and resections are tailored by removing cortex that shows frequent interictal spikes. In the randomized HFO trial (78 patients), tailoring by high-frequency oscillations (HFOs) instead of spikes was not non-inferior: 67% against 90% were seizure-free at 1 year. HFOs remain a research tool for this purpose." }, { "type": "h3", "text": "Stimulation mapping" }, { "type": "p", "text": "Brief trains of electrical stimulation between adjacent contacts identify motor, sensory, visual and language cortex. Speech arrest or naming failure marks cortex to spare. Stimulation can also trigger afterdischarges or a habitual seizure; a habitual seizure supports the proposed onset zone." }, { "type": "li", "text": "**Methods**: stereo-EEG centers use both high-frequency (50 Hz) and low-frequency (1 Hz) stimulation, for functional mapping and to provoke seizures." }, { "type": "li", "text": "**Current**: thresholds vary widely, even between adjacent electrodes (from 2 to more than 15 mA in one subdural series). Too low a current makes eloquent cortex look silent; too high a current provokes afterdischarges. Current is therefore raised at each site until a response, an afterdischarge or the maximum is reached, and a site counts as negative only after that." }, { "type": "li", "text": "**Habitual seizures**: a stimulated seizure counts only if it reproduces the patient's own seizure. Stimulation-induced typical seizures were more frequent in patients with a good surgical outcome, and resecting more of the contacts that induced them went with better results." }, { "type": "li", "text": "**Afterdischarges** are epileptiform discharges provoked by stimulation, usually at the stimulated contacts. They followed 19% of stimulation trials in one series and arise outside as well as inside the seizure-onset zone, so on their own they do not mark it. They sometimes lead into a seizure; afterdischarges just before stimulated seizures appeared at lower currents than others." }, { "type": "li", "text": "**Basal temporal language area**: stimulating the dominant fusiform gyrus, 3–7 cm behind the temporal tip, interfered with language in 8 of 22 patients, causing a receptive and expressive aphasia. Language cortex therefore extends beyond the perisylvian areas. In that series, resection of this area left no lasting language deficit." }, { "type": "note", "label": "Board pearl", "text": "A normal intracranial EEG in the sampled area does not exclude an onset elsewhere. Coverage is always the limit." }, { "type": "mcq", "id": "q-8q9nxq", "stem": "A patient with MRI-negative epilepsy has seizures that suggest either insular or bilateral mesial temporal onset. Which invasive approach samples these areas best?", "options": [ "Stereo-EEG with depth electrodes", "A large left frontotemporal subdural grid", "Bilateral foramen ovale electrodes alone", "Repeated scalp video-EEG", "Intraoperative electrocorticography during resection" ], "answer": 0, "explain": "Depth electrodes reach deep structures such as the insula and both hippocampi through small drill holes, which a surface grid cannot do." }, { "type": "mcq", "id": "q-msbvzc", "stem": "On stereo-EEG, a patient's seizures begin with well-formed 6 Hz rhythmic activity that appears first on the deepest contact of an electrode aimed at the edge of the hypothesized zone. What is the most important concern?", "options": [ "The electrode has failed", "The true onset may lie outside the sampled region", "This confirms a mesial temporal onset", "The seizure is nonepileptic", "The patient needs an extra dose of their ASM" ], "answer": 1, "explain": "A well-formed slower rhythm at the start, especially on edge contacts, suggests the seizure began elsewhere and spread to the electrode. Low-voltage fast activity at a contact points to a nearby onset." }, { "type": "cards", "items": [ { "id": "c-1l3p9pp", "front": "Why record intracranially", "back": "Discordant or MRI-negative workup, onset near eloquent cortex, possible bitemporal onset, or dual pathology." }, { "id": "c-1wzqo38", "front": "Stereo-EEG strength", "back": "Samples deep structures, sulcal depths, insula and both hemispheres through small drill holes." }, { "id": "c-1ussgic", "front": "Subdural grid strength", "back": "Continuous surface coverage for mapping eloquent cortex on the convexity." }, { "id": "c-1f1h1e1", "front": "Commonest intracranial onset pattern", "back": "Low-voltage fast activity." }, { "id": "c-10d9bnq", "front": "Clue that the onset is outside the sampled area", "back": "Well-formed, slower rhythm at onset, or first changes on edge contacts." }, { "id": "c-13dpj66", "front": "High-frequency oscillations", "back": "Ripples 80–250 Hz, fast ripples above 250 Hz; markers of epileptogenic tissue, not yet proven to guide resection." }, { "id": "c-1yf55yy", "front": "Temporal plus epilepsy", "back": "A temporal epileptogenic zone extending to insula, operculum or orbitofrontal cortex; a major cause of failed temporal lobectomy." }, { "id": "c-2m9l7t", "front": "Stereo-EEG bleeding", "back": "Some bleeding on 19% of postimplant CTs, mostly silent; permanent deficit or death about 0.6%." }, { "id": "c-9e4fcg", "front": "Subdural grid complications", "back": "Infection, hemorrhage, raised intracranial pressure; risk rises with more than about 60 contacts and more than 10 days." }, { "id": "c-cs1vsc", "front": "Periodic spikes at intracranial seizure onset", "back": "Low-frequency, high-amplitude periodic spikes; seen with mesial temporal sclerosis." }, { "id": "c-12oh40q", "front": "Delta brush or polyspike burst at onset", "back": "Point to focal cortical dysplasia." }, { "id": "c-5ntt40", "front": "HFO trial", "back": "Tailoring by high-frequency oscillations was not non-inferior to spike-guided tailoring (67% vs 90% seizure-free at 1 year)." }, { "id": "c-cnqyzv", "front": "Afterdischarge", "back": "Epileptiform discharge provoked by stimulation; occurs outside the onset zone too, so it does not mark it." }, { "id": "c-15m675i", "front": "Negative stimulation site", "back": "Counts only after the current was raised to a response, an afterdischarge or the maximum." }, { "id": "c-15dmta9", "front": "Basal temporal language area", "back": "Dominant fusiform gyrus 3–7 cm behind the temporal tip; stimulation causes aphasia." } ] }, { "type": "note", "label": "Try it", "text": "Explore standard, mesial temporal, frontal and insular stereo-EEG implants, and the structures each contact samples, in 3D in the [Epilepsy Brain Atlas](eeg_atlas.html). [Stereo EEG](seizure_management.html#seeg) on the Seizure Management page explains how the leads are named." } ], "sources": [ { "title": "French guidelines on stereo-EEG (Isnard 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29277357/" }, { "title": "Presurgical evaluation of epilepsy (Rosenow and Lüders 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11522572/" }, { "title": "Temporal plus epilepsy and temporal lobe surgery failures (Barba 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26700686/" }, { "title": "Complications of invasive monitoring with subdural grids (Hamer 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/11781412/" }, { "title": "Adverse events with subdural grid monitoring: meta-analysis (Arya 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23294329/" }, { "title": "Risk analysis of hemorrhage in stereo-EEG (McGovern 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30746685/" }, { "title": "Is SEEG safe? Meta-analysis of complications (Mullin 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26899389/" }, { "title": "Stereo-EEG versus subdural electrodes: outcomes and complications (Muthiah 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/41142150/" }, { "title": "Stereo-EEG versus subdural electrodes: individual patient data meta-analysis (Remick 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/31770717/" }, { "title": "Accuracy of stereo-EEG electrode placement: meta-analysis (Vakharia 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28261785/" }, { "title": "Frame-based and robot-assisted insular stereo-EEG (Machetanz 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33930861/" }, { "title": "Intracranial seizure-onset patterns and pathology (Perucca 2014)", "url": "https://pubmed.ncbi.nlm.nih.gov/24176980/" }, { "title": "The repertoire of seizure onset patterns in focal epilepsies (Lagarde 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30426477/" }, { "title": "Intrinsic epileptogenicity of dysplastic cortex on corticography (Palmini 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7717684/" }, { "title": "Atlas of the normal intracranial EEG (Frauscher 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29506200/" }, { "title": "The HFO trial: HFO- versus spike-guided tailoring (Zweiphenning 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/36270309/" }, { "title": "Stimulation-induced seizures in children undergoing stereo-EEG (Chiarello 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/41973515/" }, { "title": "Cortical afterdischarge and functional response thresholds (Lesser 1984)", "url": "https://pubmed.ncbi.nlm.nih.gov/6479112/" }, { "title": "Stimulation-induced seizures and surgical outcome (Cuello Oderiz 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31180505/" }, { "title": "Afterdischarge properties in stimulation mapping (Kons 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38241911/" }, { "title": "Basal temporal language area (Lüders 1991)", "url": "https://pubmed.ncbi.nlm.nih.gov/2043946/" }, { "title": "DIXI Microdeep depth electrode, FDA 510(k) K170959 (2017)", "url": "https://www.accessdata.fda.gov/cdrh_docs/pdf17/K170959.pdf" }, { "title": "Microdeep 18-contact electrode, FDA Global Unique Device Identification Database", "url": "https://accessgudid.nlm.nih.gov/devices/03664539000176" } ], "words": 1594, "bank": 8 }, { "id": "surgical-options", "n": "4", "title": "Resection, ablation and disconnection", "tags": [ "epilepsy-surgery" ], "updated": false, "goals": [ "Match the procedure to the cause", "quote expected outcomes and complications", "score outcome with the Engel and ILAE scales" ], "blocks": [ { "type": "h3", "text": "Procedures" }, { "type": "li", "text": "**Anterior temporal lobectomy**: the standard operation for mesial temporal lobe epilepsy with hippocampal sclerosis. In reviews, about two-thirds of patients become free of disabling seizures." }, { "type": "li", "text": "**Selective amygdalohippocampectomy**: removes the mesial structures and spares the lateral temporal cortex. Seizure outcome is similar, with small differences in cognitive outcome." }, { "type": "li", "text": "**Laser interstitial thermal therapy (LITT)**: MRI-guided ablation through a single burr hole. Seizure freedom after mesial temporal ablation is somewhat lower than after open surgery, but naming and recognition are better preserved and recovery is quicker. It suits small deep targets such as a **hypothalamic hamartoma**." }, { "type": "li", "text": "**How LITT works and what it achieves**: near-infrared laser light delivered through a fiber heats the target, while MR thermometry shows the heating in real time. In 268 patients treated for mesial temporal lobe epilepsy at 11 centers, 56% were in Engel class I at 1 year and 49% at a median follow-up of about 4 years; two-thirds of those who relapsed and then had a lobectomy became seizure-free. Verbal memory is also better preserved: after language-dominant procedures it declined in 2 of 19 patients after ablation, against 9 of 19 after open resection. Other targets include focal cortical dysplasia (insular dysplasia among them), periventricular nodular heterotopia, cavernous malformations, tubers in tuberous sclerosis complex and small tumors." }, { "type": "li", "text": "**LITT for hypothalamic hamartoma**: in 71 patients, 93% were free of [gelastic seizures](#semiology) at 1 year, and about a quarter needed more than one ablation. Complications include short-term memory loss and endocrine and hypothalamic effects: in one series of 18, delayed memory loss and weight gain each affected 22%, and hypothyroidism 11%. Across surgical techniques, a systematic review found hyperphagia with weight gain the commonest complication; others included electrolyte disturbance, diabetes insipidus and hypothyroidism." }, { "type": "li", "text": "**Stereotactic radiosurgery**: a noninvasive option for mesial temporal lobe epilepsy. In the randomized ROSE trial (58 patients), remission in months 25–36 occurred in 52% after radiosurgery and 78% after anterior temporal lobectomy, so non-inferiority was not shown. The effect builds slowly (seizures fell significantly only by about a year in the pilot study), cerebral edema can need steroids, and formal perimetry found a visual field defect in about 90% after either treatment." }, { "type": "li", "text": "**Lesionectomy**: for tumors that cause epilepsy (ganglioglioma, dysembryoplastic neuroepithelial tumor) and cavernomas. Complete removal predicts success; for a cavernoma, include the hemosiderin rim." }, { "type": "li", "text": "**Dual pathology**: when hippocampal sclerosis coexists with a separate lesion, removing both gave seizure freedom in 73% of patients, against 20% after hippocampal resection alone and 12.5% after lesionectomy alone. Remove both when it is safe, or record intracranially if their roles are unclear." }, { "type": "li", "text": "**Multiple subpial transection**: cuts the horizontal fibers within the cortex while sparing its vertical columns and vessels, to treat a focus in speech, motor or sensory cortex that cannot be removed. Benefit often fades: in a series of 54 patients followed for about 5 years, half were seizure-free or nearly so, but 19% had more seizures again years after an initial improvement. Responsive neurostimulation now offers another way to treat a focus in eloquent cortex." }, { "type": "li", "text": "**Hemispherotomy**: disconnects one hemisphere. Used for Rasmussen encephalitis, hemimegalencephaly, large perinatal stroke and Sturge–Weber syndrome. Seizure freedom rates are high. It causes, or completes, a contralateral hemiparesis and hemianopia, so it suits those who already have them." }, { "type": "li", "text": "**Corpus callosotomy**: a palliative operation for drop attacks, as in Lennox–Gastaut syndrome." }, { "type": "note", "label": "Try it", "text": "The [Epilepsy Brain Atlas](eeg_atlas.html) includes an illustrative laser ablation path through the left mesial temporal lobe among its examples." }, { "type": "h3", "text": "What predicts a good result" }, { "type": "p", "text": "Good predictors are a clear lesion on MRI (especially hippocampal sclerosis or a low-grade tumor), agreement between tests, complete removal, and a shorter duration of epilepsy. Results are poorer when the MRI is normal, the onset is outside the temporal lobe, or both hemispheres are involved. Outcomes in children are similar to those in adults." }, { "type": "li", "text": "**Imaging status**: the odds of seizure freedom are about 2.5 times higher when a lesion is seen on MRI or histopathology. Without a lesion, concordant functional tests still help: in nonlesional temporal lobe epilepsy, localized PET hypometabolism and concordant presurgical findings predicted a better outcome." }, { "type": "li", "text": "**Completeness**: after gross-total removal of a glioneuronal tumor the odds of seizure freedom were about five times those after subtotal removal, and leaving behind a flagged post-processing abnormality or a field of continuous dysplastic discharges predicts failure." }, { "type": "li", "text": "**Pathology**: in the European Epilepsy Brain Bank series of 9523 specimens, hippocampal sclerosis was the commonest diagnosis (36%, mostly in adults), followed by tumors (24%, mainly ganglioglioma) and malformations of cortical development (20%; focal cortical dysplasia was the commonest diagnosis in children). In 9147 patients from the same consortium, freedom from disabling seizures at 2 years was highest with low-grade epilepsy-associated tumors (78%), vascular malformations (74%) and hippocampal sclerosis (72%). It was lowest with focal cortical dysplasia type I or mild malformations (50%), other malformations (52%) and no histopathological lesion (54%). A longer duration of epilepsy lowered the chance of a good outcome for every pathology except hippocampal sclerosis." }, { "type": "h3", "text": "Complications" }, { "type": "p", "text": "**Defining a complication**: reviews separate minor complications, which resolve completely (within 3 months in one systematic review), from major ones that persist, and medical complications from neurological ones. A deficit that is the expected and accepted price of the operation, such as hemianopia after hemispherotomy, is an expected adverse effect rather than a complication. The general surgical Clavien–Dindo system grades a complication mainly by the treatment needed to manage it, and reports life-threatening and permanently disabling complications separately." }, { "type": "p", "text": "**How often**: in a systematic review of resections, minor and major medical complications occurred in 5.1% and 1.5% of patients, cerebrospinal fluid leak being the commonest. Minor neurological complications occurred in 10.9% and were about twice as frequent in children; major neurological complications occurred in 4.7%, most often a lasting visual field defect (2.1%). Invasive monitoring carried minor complications in 7.7% and major ones in 0.6%. Older age raises the risk (see [Refer early](#presurgical-evaluation))." }, { "type": "li", "text": "**Death**: perioperative mortality is rare, about 0.4% after temporal and about 1% after extratemporal resection in a systematic review." }, { "type": "li", "text": "**Vision**: the commonest neurological complication of temporal resection is a contralateral superior quadrantanopia (\"pie in the sky\"), from damage to Meyer's loop." }, { "type": "li", "text": "**Language and memory**: naming difficulty and verbal memory decline, after surgery on the dominant temporal lobe (for who is at risk, see [Imaging and functional testing](#epilepsy-imaging))." }, { "type": "li", "text": "**Mood**: new or worse depression or anxiety, most often in the first months." }, { "type": "li", "text": "**Rarer**: hemiparesis (anterior choroidal artery territory) and diplopia (fourth cranial nerve). Diplopia is commoner than once thought: in a prospective series it followed 9 of 47 anterior temporal lobectomies, always from a fourth nerve palsy, and resolved within 3–6 months." }, { "type": "h3", "text": "Scoring the outcome" }, { "type": "table", "head": [ "Engel class", "Meaning" ], "rows": [ [ "I", "Free of disabling seizures (IA: completely seizure-free since surgery; IB: auras only)" ], [ "II", "Rare disabling seizures" ], [ "III", "Worthwhile improvement" ], [ "IV", "No worthwhile improvement" ] ] }, { "type": "table", "head": [ "ILAE class", "Meaning" ], "rows": [ [ "1", "Completely seizure-free, no auras" ], [ "2", "Auras only" ], [ "3", "1 to 3 seizure days a year" ], [ "4", "4 seizure days a year, up to a 50% reduction from baseline" ], [ "5", "Less than 50% reduction, up to a 100% increase" ], [ "6", "More than a 100% increase" ] ] }, { "type": "note", "label": "Board pearl", "text": "The ILAE scale separates \"auras only\" (class 2) from complete freedom (class 1). Engel groups both under class I." }, { "type": "case", "id": "case-mtle", "title": "Mesial temporal lobe epilepsy", "intro": [ "A 32-year-old right-handed accountant has had seizures since age 14 that begin with a rising epigastric feeling. Then comes staring with lip-smacking and fumbling of the left hand, while the right arm stiffens in a twisted posture. She has tried three ASMs at adequate doses and still has two seizures a month." ], "steps": [ { "narrative": [], "stem": "Which side does the semiology point to?", "options": [ "Left temporal", "Right temporal", "Left frontal", "It cannot be lateralized", "Bilateral" ], "answer": 0, "explain": "Dystonic posturing of one arm is contralateral to the onset (the right arm here, so a left-sided onset). Hand automatisms usually occur on the same side as the onset (the left hand here)." }, { "narrative": [ "MRI shows left hippocampal sclerosis. Video-EEG records five typical seizures with left temporal rhythmic theta, and interictal spikes are seen only over the left anterior temporal region. Neuropsychology shows impaired verbal memory, and fMRI shows left language dominance." ], "stem": "What is the best next step?", "options": [ "Stereo-EEG of both temporal lobes before any decision", "Present at the surgical conference and offer left temporal surgery", "Add a fourth ASM", "Vagus nerve stimulation", "Repeat MRI in a year" ], "answer": 1, "explain": "Semiology, EEG, MRI and neuropsychology agree. With this concordance, intracranial EEG adds little, and surgery gives the best chance of seizure freedom." }, { "narrative": [ "She chooses an open anterior temporal lobectomy rather than laser ablation." ], "stem": "Which new deficit is she most likely to have after surgery?", "options": [ "Right hemiparesis", "A right upper quadrant visual field defect", "Left upper quadrant visual field defect", "Dense global amnesia", "Right facial numbness" ], "answer": 1, "explain": "Temporal resection interrupts Meyer's loop, causing a contralateral superior quadrantanopia. It is often not noticed by the patient but matters for driving assessments." }, { "narrative": [ "Two years later she has had only three brief episodes of her old rising epigastric feeling, with no loss of awareness." ], "stem": "How is her outcome scored?", "options": [ "Engel IA, ILAE class 1", "Engel IB, ILAE class 2", "Engel II, ILAE class 3", "Engel III, ILAE class 4", "Engel IV, ILAE class 5" ], "answer": 1, "explain": "Auras only since surgery is Engel IB and ILAE class 2. It counts as a good outcome and is common after temporal lobectomy." } ], "outro": [ "Concordant semiology, EEG, MRI and neuropsychology mean a high chance of seizure freedom without invasive monitoring. Discuss vision, memory and mood before surgery, not after." ] }, { "type": "match", "id": "match-procedures", "prompt": "Match each procedure to a classic indication", "pairs": [ [ "Anterior temporal lobectomy", "Hippocampal sclerosis" ], [ "Laser interstitial thermal therapy", "Hypothalamic hamartoma with gelastic seizures" ], [ "Hemispherotomy", "Rasmussen encephalitis" ], [ "Corpus callosotomy", "Drop attacks in Lennox–Gastaut syndrome" ], [ "Lesionectomy including the hemosiderin rim", "Cavernous malformation" ] ] }, { "type": "cards", "items": [ { "id": "c-1tag5tb", "front": "Anterior temporal lobectomy outcome", "back": "About two-thirds free of disabling seizures." }, { "id": "c-1bigex5", "front": "LITT versus open temporal surgery", "back": "Somewhat lower seizure freedom, but better naming and recognition and quicker recovery." }, { "id": "c-1pgoswn", "front": "Hemispherotomy indications", "back": "Rasmussen encephalitis, hemimegalencephaly, large perinatal stroke, Sturge–Weber syndrome." }, { "id": "c-3cykyh", "front": "Corpus callosotomy", "back": "Palliative surgery for drop attacks." }, { "id": "c-13vfzpa", "front": "Pie in the sky", "back": "Contralateral superior quadrantanopia from Meyer's loop damage in temporal resection." }, { "id": "c-1iz8loh", "front": "Engel IB", "back": "Auras only since surgery." }, { "id": "c-1jbdk5k", "front": "ILAE class 2", "back": "Auras only." }, { "id": "c-1jld5uj", "front": "ILAE class 3", "back": "1 to 3 seizure days a year." }, { "id": "c-16xi70c", "front": "Perioperative mortality of epilepsy surgery", "back": "Rare: about 0.4% after temporal and about 1% after extratemporal resection." }, { "id": "c-2f92j0", "front": "Poorer surgical outcome", "back": "Normal MRI, extratemporal onset, bilateral involvement, incomplete resection." }, { "id": "c-14gdh06", "front": "ROSE trial", "back": "Radiosurgery versus lobectomy for mesial temporal lobe epilepsy: remission 52% vs 78%; non-inferiority not shown; field defects in about 90% with either." }, { "id": "c-1cy6gkl", "front": "Dual pathology surgery", "back": "Remove both the lesion and the sclerotic hippocampus (73% seizure-free, against 20% or 12.5% with one alone)." }, { "id": "c-hwd1gh", "front": "Multiple subpial transection", "back": "Cuts horizontal intracortical fibers, sparing vertical columns, for a focus in eloquent cortex; late relapse after initial benefit is common." }, { "id": "c-fzbnlo", "front": "LITT for hypothalamic hamartoma", "back": "About 93% free of gelastic seizures at 1 year; risks include short-term memory loss, weight gain and hypothyroidism." }, { "id": "c-1iv7a29", "front": "Commonest pathology in surgical specimens", "back": "Hippocampal sclerosis in adults, focal cortical dysplasia in children; tumors second in both." }, { "id": "c-152yzhf", "front": "Best and worst pathologies for outcome", "back": "Best: low-grade epilepsy-associated tumors, vascular malformations, hippocampal sclerosis. Worst: focal cortical dysplasia type I or mild malformations, no lesion." }, { "id": "c-1rkr7l", "front": "Minor versus major complication", "back": "Minor resolves completely (within 3 months in one review); major persists." }, { "id": "c-1shl3o4", "front": "Commonest medical complication of resection", "back": "Cerebrospinal fluid leak." }, { "id": "c-1xn0vyn", "front": "Diplopia after temporal lobectomy", "back": "Usually a transient fourth nerve palsy." } ] } ], "sources": [ { "title": "Resective epilepsy surgery for drug-resistant focal epilepsy (Jobst and Cascino 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25602999/" }, { "title": "ILAE classification of outcome after epilepsy surgery (Wieser 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11240604/" }, { "title": "Randomized trial of surgery for temporal lobe epilepsy (Wiebe 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11484687/" }, { "title": "Surgery for drug-resistant epilepsy in children (Dwivedi 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29069568/" }, { "title": "Complications of epilepsy surgery: a systematic review (Hader 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23551133/" }, { "title": "MR-guided laser interstitial thermal therapy in brain tumors and epilepsy (Nielsen 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39167226/" }, { "title": "Long-term outcomes of mesial temporal laser ablation: multicentre cohort (Youngerman 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37336643/" }, { "title": "Superior verbal memory outcome after laser amygdalohippocampotomy (Drane 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34956059/" }, { "title": "Robot-assisted MRI-guided laser ablation in children (Lee 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37209074/" }, { "title": "MR-guided laser ablation of hypothalamic hamartomas (Curry 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29631919/" }, { "title": "Laser thermal therapy for hypothalamic hamartomas (Xu 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29346599/" }, { "title": "Outcome after surgery for hypothalamic hamartoma: systematic review (Luisi 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38820683/" }, { "title": "Radiosurgery versus open surgery: the ROSE trial (Barbaro 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/29600809/" }, { "title": "Visual field defects in the ROSE trial (Quigg 2018)", "url": "https://pubmed.ncbi.nlm.nih.gov/30408713/" }, { "title": "Pilot study of radiosurgery for mesial temporal lobe epilepsy (Barbaro 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19243009/" }, { "title": "Surgical outcome with dual pathology (Li 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10355666/" }, { "title": "Multiple subpial transection (Morrell 1989)", "url": "https://pubmed.ncbi.nlm.nih.gov/2492335/" }, { "title": "Late seizure recurrence after multiple subpial transections (Orbach 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11580759/" }, { "title": "Long-term seizure outcomes after epilepsy surgery: meta-analysis (Téllez-Zenteno 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15758038/" }, { "title": "Surgical outcomes in lesional and non-lesional epilepsy: meta-analysis (Téllez-Zenteno 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20227852/" }, { "title": "Surgical treatment of nonlesional temporal lobe epilepsy (Kim 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33611174/" }, { "title": "Seizure freedom after resection of glioneuronal tumors (Englot 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/21933181/" }, { "title": "Voxel-based morphometric post-processing in MRI-negative epilepsies (Wang 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25807928/" }, { "title": "Intrinsic epileptogenicity of dysplastic cortex (Palmini 1995)", "url": "https://pubmed.ncbi.nlm.nih.gov/7717684/" }, { "title": "Histopathological findings in brain tissue from epilepsy surgery (Blümcke 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/29069555/" }, { "title": "Seizure outcome after epilepsy surgery by histopathology (Lamberink 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32822635/" }, { "title": "Classification of complications of epilepsy surgery: a proposed protocol (Bjellvi 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34405890/" }, { "title": "Classification of surgical complications (Dindo 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15273542/" }, { "title": "Diplopia after anterior temporal lobectomy: prospective analysis (Cohen-Gadol 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12959436/" } ], "words": 1782, "bank": 10 }, { "id": "neuromodulation", "n": "5", "title": "Neuromodulation", "tags": [ "epilepsy-surgery" ], "updated": false, "goals": [ "Choose between vagus nerve, responsive and deep brain stimulation", "know the pivotal trial results and side effects", "set realistic expectations" ], "blocks": [ { "type": "h3", "text": "What devices do" }, { "type": "p", "text": "Devices are for people who are not candidates for resection, or who prefer not to have it. They rarely make anyone seizure-free, but the benefit tends to grow over years of stimulation." }, { "type": "figure", "html": "neuromod-devices", "caption": "Where each device sits, from the front: the patient's left is on the right of the drawing. Choose a device for its parts, its target and when it stimulates.", "n": 21 }, { "type": "table", "head": [ "", "Vagus nerve stimulation (VNS)", "Responsive neurostimulation (RNS)", "Deep brain stimulation (DBS)" ], "rows": [ [ "Target", "Left cervical vagus nerve", "One or two seizure foci", "Anterior nucleus of the thalamus" ], [ "How", "Scheduled stimulation, plus a magnet to trigger extra stimulation", "Detects seizure patterns and stimulates in response", "Scheduled stimulation" ], [ "Loop", "Open loop; heart rate–triggered models add a closed loop driven by a cardiac signal", "Closed loop, stimulating at the onset zone", "Open loop, stimulating a remote network node" ], [ "Mechanism", "Mostly afferent fibers (about 4 to 1) to the nucleus tractus solitarius, then the locus coeruleus (noradrenaline) and raphe nuclei (serotonin)", "Stimulates the onset zone whenever its seizure pattern is detected", "The anterior nucleus relays the limbic (Papez) circuit from the mammillary bodies to the cingulate gyrus" ], [ "Pivotal trial", "28% vs 15% seizure reduction at 3 months", "38% vs 17% reduction in the blinded phase", "40% vs 15% reduction in the blinded phase" ], [ "Trial and control", "E05 (1998), after E03 (1994); control was low-level stimulation, not sham", "Pivotal trial (2011); sham control", "SANTE (2010); sham control" ], [ "Suits", "Focal seizures; also used for generalized epilepsies such as Lennox–Gastaut syndrome; no intracranial surgery", "One or two well-defined foci that cannot be removed, such as both hippocampi or eloquent cortex", "Focal epilepsy, often with no single resectable focus" ], [ "US label", "Age 4 or more; adjunctive therapy for focal seizures refractory to ASMs", "Age 18 or more; focal seizures from no more than 2 foci; 2 or more failed ASMs; frequent disabling seizures (tested with 3 or more a month)", "Age 18 or more; focal seizures refractory to 3 or more ASMs (tested with 6 or more a month)" ], [ "Side effects", "Hoarseness, cough, throat discomfort, breathlessness during stimulation; can worsen sleep apnea", "Implant-site infection, bleeding", "Paresthesias, implant-site infection; depression and memory complaints were more common in the trial" ], [ "More on safety", "Implant-site infection is more likely in children", "Over 9 years, serious implant-site infection in 12% (4% per procedure), nonseizure hemorrhage in 3%; no serious stimulation-related events; no decline in mood or cognition", "Stimulation can trigger arousals and disrupt sleep, more so at higher voltage; in a small series, lowering the night-time voltage helped without loss of efficacy" ], [ "US approval for epilepsy", "1997", "2013", "2018" ], [ "MRI", "MR Conditional; conditions depend on the model and generator position (see Practical points)", "RNS-320 model MR Conditional for full-body 1.5 tesla scans (2020)", "Follow the device's MRI labeling" ] ] }, { "type": "figure", "html": "neuromod-hardware", "caption": "What each device looks like, and how it shows on a plain film: the hardware drawn to scale from published dimensions, beside a frontal or lateral radiograph of a typical placement. The numbers match the list under each picture.", "n": 22 }, { "type": "h3", "text": "Practical points" }, { "type": "li", "text": "**VNS is placed on the left** because the right vagus nerve carries more fibers to the sinoatrial node, so right-sided stimulation risks bradycardia." }, { "type": "li", "text": "**Some VNS models detect a sudden rise in heart rate** (ictal tachycardia) and stimulate automatically. The detection threshold is set between a 20% and a 70% rise. Exercise and other normal heart-rate changes cause false triggers; if automatic stimulation is too frequent, move the threshold toward 70%. Day–night programming runs two parameter schedules at different times of day." }, { "type": "li", "text": "**VNS and MRI**: VNS systems are MR Conditional, not MR safe. Before a scan, program the normal, magnet and automatic output currents to 0 mA, and on models that sense heart rate turn detection off. The generator model and its position decide whether body-coil imaging is allowed or only head and limb scans with a transmit–receive coil." }, { "type": "li", "text": "**American Academy of Neurology (AAN) guideline update (2013)**: VNS may be considered for seizures in children (at least a 50% reduction in 55% of 470), for seizures in Lennox–Gastaut syndrome (55% of 113) and for mood in adults, and its effect may improve over time (responder rate up about 7% from 1 to 5 years). Children have more implant-site infections (odds ratio 3.4)." }, { "type": "li", "text": "**Why the anterior thalamus**: besides relaying the limbic (Papez) circuit (see the table), the anterior nucleus receives hippocampal output and connects widely with association cortex. In guinea pigs, cutting the mammillothalamic tract prevented pentylenetetrazol seizures. In SANTE, focal impaired awareness (\"complex partial\") and \"most severe\" seizures fell significantly with stimulation." }, { "type": "li", "text": "**RNS monitors the brain continuously** and stores detection counts and short electrocorticography clips. These show how often seizures happen and at what time of day, and whether bilateral temporal seizures really come from both sides." }, { "type": "li", "text": "**In all three trials, benefit kept rising** in the open-label years that followed: a median 75% reduction at 9 years with RNS, and 75% at 7 years with DBS." }, { "type": "figure", "html": "neuromod-trials", "caption": "Seizure reduction in the blinded phases of the pivotal trials, and in long-term open-label follow-up. Open-label results have no control arm and include medication changes.", "n": 23 }, { "type": "li", "text": "**Stimulation of the centromedian thalamus** is being studied for generalized epilepsies such as Lennox–Gastaut syndrome. The centromedian nucleus is targeted to engage the thalamocortical circuits of generalized epilepsy. In the ESTEL trial in Lennox–Gastaut syndrome (19 randomized), the diary-based primary outcome was not met (50% vs 22% responders), but electrographic seizures halved in 59% of stimulated patients against none of the controls. Responsive centromedian stimulation for idiopathic generalized epilepsy with tonic–clonic seizures (the NAUTILUS trial, 87 patients) met its safety endpoint but missed its primary effectiveness endpoint, time to a second tonic–clonic seizure. Anterior thalamic DBS is labeled only for focal-onset seizures, so its use in generalized epilepsy is off-label." }, { "type": "note", "label": "Try it", "text": "The neuromodulation example in the [Epilepsy Brain Atlas](eeg_atlas.html) shows the anterior thalamic and pulvinar targets, centromedian landmarks and hippocampal responsive neurostimulation leads in 3D." }, { "type": "mcq", "id": "q-14qa3wq", "stem": "A 35-year-old has drug-resistant focal seizures with impaired consciousness. Intracranial EEG shows independent onsets from both hippocampi, and memory testing shows that each side still supports memory. What is the best option?", "options": [ "Left anterior temporal lobectomy", "Bilateral anterior temporal lobectomy", "Responsive neurostimulation with a lead in each hippocampus", "Corpus callosotomy", "Hemispherotomy" ], "answer": 2, "explain": "Removing both hippocampi would cause severe amnesia. Responsive neurostimulation treats both foci without removing tissue, and its recordings show which side seizures come from over time." }, { "type": "mcq", "id": "q-1pzhy3x", "stem": "Why is the vagus nerve stimulator placed on the left?", "options": [ "The left vagus nerve is larger", "The right vagus nerve carries more fibers to the sinoatrial node, so right-sided stimulation risks bradycardia", "The left side is closer to the brainstem", "The right vagus nerve does not project to the nucleus tractus solitarius", "The left vagus nerve does not supply the larynx" ], "answer": 1, "explain": "The right vagus nerve provides most of the parasympathetic supply to the sinoatrial node. Left-sided stimulation avoids most cardiac effects; hoarseness still occurs because fibers of the left recurrent laryngeal nerve run in the vagus trunk under the electrode." }, { "type": "mcq", "id": "q-1jnqwpt", "stem": "A 42-year-old with drug-resistant focal epilepsy and a history of severe depression is considering a device. Which trial finding is most relevant to this patient's counseling?", "options": [ "VNS worsened depression in its pivotal trial", "Anterior thalamic DBS was associated with more reports of depression and memory problems", "RNS was associated with a high rate of suicide", "All three devices improve depression", "Devices have no psychiatric effects" ], "answer": 1, "explain": "In the SANTE trial, depression and memory complaints were more common with active stimulation. VNS, by contrast, is also approved for treatment-resistant depression." }, { "type": "cards", "items": [ { "id": "c-19oo3rl", "front": "VNS target and side", "back": "Left cervical vagus nerve." }, { "id": "c-2l52ff", "front": "VNS side effects", "back": "Hoarseness, cough, throat discomfort and breathlessness during stimulation; can worsen sleep apnea." }, { "id": "c-27cx1k", "front": "VNS magnet", "back": "Triggers an extra stimulation train to shorten or abort a seizure." }, { "id": "c-1dn5fg6", "front": "RNS", "back": "Detects seizure patterns at one or two foci and stimulates in response; also records long-term ECoG." }, { "id": "c-rqxq9r", "front": "RNS best fit", "back": "Two independent mesial temporal onsets, or a focus in eloquent cortex." }, { "id": "c-19rkq69", "front": "DBS target in epilepsy", "back": "Anterior nucleus of the thalamus (SANTE trial)." }, { "id": "c-162wzew", "front": "SANTE side effects to counsel on", "back": "Depression and memory complaints." }, { "id": "c-134i9av", "front": "Devices over time", "back": "Benefit grows over years of stimulation; seizure freedom is uncommon." }, { "id": "c-ysr7z6", "front": "Control arm in the VNS pivotal trials (E03, E05)", "back": "Low-level stimulation, not sham; the RNS and SANTE trials used sham stimulation." }, { "id": "c-1fk63po", "front": "Closed-loop versus open-loop stimulation", "back": "Closed loop (RNS) stimulates in response to a detected pattern; open loop (VNS, anterior thalamic DBS) stimulates on a schedule." }, { "id": "c-8ezjxs", "front": "How VNS reaches the brain", "back": "Mostly afferent vagal fibers to the nucleus tractus solitarius, then the locus coeruleus and raphe nuclei." }, { "id": "c-k8xl08", "front": "RNS label", "back": "Age 18 or more, focal seizures from no more than 2 foci, 2 or more failed ASMs, frequent disabling seizures." }, { "id": "c-i11hqr", "front": "VNS before MRI", "back": "Program normal, magnet and automatic output currents to 0 mA and turn heart-rate detection off; follow the model-specific labeling." }, { "id": "c-1n2ud9w", "front": "Heart rate–triggered VNS", "back": "Threshold set between a 20% and a 70% rise in heart rate; exercise causes false triggers, so move the threshold toward 70%." }, { "id": "c-55cqc", "front": "AAN 2013 VNS guideline", "back": "Possibly effective in children, Lennox–Gastaut syndrome and for mood in adults; benefit may grow; more infections in children." }, { "id": "c-1yranqz", "front": "Why target the anterior thalamic nucleus", "back": "It relays the limbic (Papez) circuit; mammillothalamic tract lesions blocked seizures in animals." }, { "id": "c-vh2nny", "front": "ESTEL trial", "back": "Centromedian DBS in Lennox–Gastaut syndrome: diary endpoint not met, but electrographic seizures fell." }, { "id": "c-6cirh7", "front": "US approval order for epilepsy devices", "back": "VNS 1997, RNS 2013, anterior thalamic DBS 2018." } ] } ], "sources": [ { "title": "VNS pivotal trial (Handforth 1998)", "url": "https://pubmed.ncbi.nlm.nih.gov/9674777/" }, { "title": "Responsive neurostimulation at 9 years (Nair 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/32690786/" }, { "title": "SANTE at 7 and 10 years (Salanova 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33830503/" }, { "title": "Responsive cortical stimulation pivotal trial (Morrell 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21917777/" }, { "title": "Anterior thalamic stimulation: SANTE (Fisher 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20331461/" }, { "title": "VNS for partial seizures: the first controlled study, E03 (Ben-Menachem 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/8026408/" }, { "title": "Vagus nerve stimulation: central mechanisms (Krahl 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/23230530/" }, { "title": "Neuromodulation in pediatric epilepsy: open- and closed-loop devices (Ali 2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/34215387/" }, { "title": "Temporal patterns of neurostimulation efficacy, including closed-loop VNS (Tian 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42303163/" }, { "title": "FDA premarket approval: NeuroPace RNS System (P100026)", "url": "https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026" }, { "title": "FDA premarket approval: VNS Therapy System (P970003)", "url": "https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P970003" }, { "title": "FDA premarket approval: Medtronic DBS Therapy for Epilepsy (P960009/S219)", "url": "https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P960009S219" }, { "title": "NeuroPace RNS System receives FDA approval for MRI labeling (2020)", "url": "https://www.businesswire.com/news/home/20200309005306/en/" }, { "title": "Differential neuropsychological outcomes after responsive neurostimulation (Loring 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26385758/" }, { "title": "ANT DBS disrupts sleep in epilepsy (Voges 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26041007/" }, { "title": "MRI guidelines for VNS Therapy (LivaNova 2024)", "url": "https://www.livanova.com/getcontentasset/190ef4f5-c55d-40f2-90cb-68cfd6d10042/dfc3d011-8f63-43f6-9ed8-4b444333a1d0/mri-guidelines-for_vns-therapy-2024.pdf" }, { "title": "VNS Therapy technical guide (LivaNova 2020)", "url": "https://www.livanova.com/getcontentasset/2c75dc2a-113a-4dc1-b329-ace3ee78e7b2/dfc3d011-8f63-43f6-9ed8-4b444333a1d0/sentecgd19u1-rev-3-sentiva-technical-guide-final.pdf" }, { "title": "VNS physician's labeling (FDA P970003/S207)", "url": "https://www.accessdata.fda.gov/cdrh_docs/pdf/P970003S207C.pdf" }, { "title": "AAN guideline update: VNS for epilepsy (Morris 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23986299/" }, { "title": "Interruption of the mammillothalamic tract prevents seizures (Mirski 1984)", "url": "https://pubmed.ncbi.nlm.nih.gov/6433485/" }, { "title": "Neuromodulation of the anterior thalamic nucleus (Moreira-Holguín 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35725219/" }, { "title": "Anterior thalamic stimulation evoked potentials and connectivity (Wu 2023)", "url": "https://pubmed.ncbi.nlm.nih.gov/37353098/" }, { "title": "Centromedian DBS for Lennox–Gastaut syndrome: the ESTEL trial (Dalic 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/34877694/" }, { "title": "Responsive thalamic stimulation for idiopathic generalized epilepsy: the NAUTILUS trial (Uysal 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42233958/" }, { "title": "From Velasco to NAUTILUS: centromedian targeting in epilepsy (Neudorfer 2026)", "url": "https://pubmed.ncbi.nlm.nih.gov/42139739/" } ], "words": 1547, "bank": 9 } ], "intro": [ "About a third of people with epilepsy keep having seizures despite medication. For many with focal epilepsy, surgery gives the best chance of seizure freedom, yet it is underused and usually comes late. This part follows a patient from referral, through the presurgical workup, to resection, ablation or a device." ] }, { "id": "living", "n": "9", "title": "Living with epilepsy", "short": "Living with epilepsy", "sections": [ { "id": "sudep-mortality", "n": "1", "title": "SUDEP and mortality", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Define SUDEP and give its incidence", "name the strongest risk factor and what lowers risk", "counsel patients and families in plain numbers" ], "blocks": [ { "type": "h3", "text": "Why people with epilepsy die early" }, { "type": "p", "text": "Mortality in epilepsy is about two to three times that of the general population. In a Finnish cohort of children followed for 40 years, a quarter had died. Over half of those deaths were related to epilepsy: sudden unexpected death, seizures and drowning. Causes of excess death:" }, { "type": "li", "text": "The underlying disease (tumor, stroke, neurodegenerative disease)" }, { "type": "li", "text": "Sudden unexpected death in epilepsy (SUDEP)" }, { "type": "li", "text": "Status epilepticus" }, { "type": "li", "text": "Accidents, especially drowning" }, { "type": "li", "text": "Suicide" }, { "type": "li", "text": "Aspiration pneumonia" }, { "type": "p", "text": "The global picture: the World Health Organization (WHO) estimates that about 50 million people have epilepsy, nearly 80% of them in low- and middle-income countries. Up to 70% could live seizure-free if properly diagnosed and treated, yet three-quarters of people with epilepsy in low-income countries do not get the treatment they need (the treatment gap). About a quarter of cases are potentially preventable." }, { "type": "h3", "text": "Definition" }, { "type": "p", "text": "SUDEP is a sudden, unexpected death in a person with epilepsy, witnessed or not, that is not caused by trauma, drowning or documented status epilepticus. It occurs with or without evidence of a seizure. Autopsy finds no toxic or structural cause of death." }, { "type": "li", "text": "**Definite SUDEP**: an autopsy was done." }, { "type": "li", "text": "**Probable SUDEP**: no autopsy was done." }, { "type": "li", "text": "**SUDEP plus**: another condition, such as long QT syndrome, could have contributed." }, { "type": "li", "text": "**Near-SUDEP**: resuscitation succeeded and the person survived more than an hour." }, { "type": "li", "text": "**Not SUDEP**: any evidence of submersion in water excludes it, and so does status epilepticus lasting 30 minutes or more." }, { "type": "h3", "text": "How common, and who is at risk" }, { "type": "li", "text": "**Incidence**: about 1 in 4,500 children with epilepsy each year, and about 1 in 1,000 adults." }, { "type": "li", "text": "**The major risk factor is generalized tonic–clonic seizures**, and risk rises with their frequency. Three or more a year carries a risk many times higher than none." }, { "type": "li", "text": "**Other risk factors**: seizures during sleep, sleeping alone or unsupervised, young age at onset, long duration, a structural cause, and male sex. Polytherapy is linked to risk, largely because it marks severe epilepsy; the priority is fewer tonic–clonic seizures, not fewer drugs." }, { "type": "figure", "html": "sudep-counsel", "caption": "The AAN and AES counseling numbers, as a picture a patient can keep: about 1 in 1,000 adults and 1 in 4,500 children with epilepsy each year.", "n": 24 }, { "type": "h3", "text": "What happens" }, { "type": "p", "text": "Most SUDEP happens at night, often with the person found face down. Monitoring-unit cases (MORTEMUS) showed a consistent sequence after a generalized tonic–clonic seizure: rapid breathing, then, within minutes, failure of breathing and heart function. The terminal apnea came before the final cardiac arrest." }, { "type": "p", "text": "The EEG sign of this postictal shutdown is **postictal generalized EEG suppression (PGES)**: after a tonic–clonic seizure, activity over the whole scalp goes flat for a time. In a case-control study of monitored patients who later died of SUDEP, the odds of SUDEP rose with PGES longer than 50 seconds and roughly quadrupled beyond 80 seconds. PGES goes with longer postictal immobility and worse breathing after the seizure (lower oxygen saturation, more carbon dioxide retention). It is not a reliable predictor in one person, though: in people with several recorded convulsions it came and went from seizure to seizure, and it was more frequent after seizures arising from sleep and during ASM tapering." }, { "type": "h3", "text": "What lowers risk" }, { "type": "li", "text": "**Seizure freedom, above all freedom from tonic–clonic seizures.** Treat actively and refer for surgery when appropriate." }, { "type": "li", "text": "**Successful epilepsy surgery brings mortality down.** In a surgical cohort, none of the 199 patients who stayed seizure-free died, and their mortality did not differ from that of the matched general population; those whose seizures continued had a standardized mortality ratio of about 4.7. In a later cohort of over 1,000 patients, mortality was lower in those who had surgery than in those evaluated but not operated on, and more than two tonic–clonic seizures a year after surgery went with higher mortality." }, { "type": "li", "text": "Take medicines reliably and avoid sleep deprivation and alcohol excess." }, { "type": "li", "text": "**Nighttime supervision or a listening device** may help. Someone who can reposition the person and stimulate breathing may interrupt the sequence." }, { "type": "li", "text": "**Wearable seizure detectors**: the ILAE and IFCN recommend clinically validated devices to detect tonic–clonic seizures, especially in people who sleep unsupervised, where an alarm can bring rapid help." }, { "type": "note", "label": "Board pearl", "text": "Tell every patient, early and in plain numbers. The AAN and AES guideline advises telling adults that SUDEP affects about 1 in 1,000 adults with epilepsy each year, and that seizure freedom, especially from tonic–clonic seizures, strongly lowers the risk." }, { "type": "mcq", "id": "q-10znrbq", "stem": "Which factor is most strongly associated with SUDEP?", "options": [ "Number of ASMs taken", "Frequency of generalized tonic–clonic seizures", "Frequency of focal seizures with preserved consciousness", "Female sex", "Interictal spike frequency on EEG" ], "answer": 1, "explain": "Generalized (including focal to bilateral) tonic–clonic seizures are the major risk factor, and risk rises with how often they occur. The link with polytherapy largely reflects more severe epilepsy." }, { "type": "mcq", "id": "q-1llneil", "stem": "The parents of a 7-year-old recently diagnosed with epilepsy ask about the risk of sudden death. What is the best answer?", "options": [ "\"It is too rare to be worth discussing.\"", "\"About 1 in 100 children with epilepsy die suddenly each year.\"", "\"About 1 in 4,500 children with epilepsy each year; controlling seizures, especially convulsive ones, lowers the risk.\"", "\"The risk is the same as for any child.\"", "\"It only happens in people who do not take their medicine.\"" ], "answer": 2, "explain": "The AAN and AES guideline advises giving the actual figure (1 in 4,500 children a year) and linking it to what families can do. Most families want to be told." }, { "type": "mcq", "id": "q-1184gcz", "stem": "A 45-year-old is found dead in bed, face down, with a bitten tongue. Autopsy shows no anatomic or toxicologic cause. There is a history of drug-resistant focal epilepsy with nocturnal tonic–clonic seizures. How is this classified?", "options": [ "Definite SUDEP", "Probable SUDEP", "Possible SUDEP", "Near-SUDEP", "Death from status epilepticus" ], "answer": 0, "explain": "A sudden, unexpected death in someone with epilepsy, with an autopsy showing no other cause, is definite SUDEP. Without an autopsy it would be probable SUDEP." }, { "type": "h3", "text": "Seizure-related cardiac and breathing events" }, { "type": "p", "text": "Heart rhythm changes during a seizure and after it mean different things." }, { "type": "li", "text": "**Ictal bradycardia and ictal asystole** occur during focal seizures with impaired awareness, mostly of temporal onset (91% in a systematic review of reported cases), with no consistent side. They stop on their own. Ictal asystole was found in about 0.3% of people with drug-resistant epilepsy undergoing video-EEG monitoring." }, { "type": "li", "text": "**Ictal syncope**: in one monitoring-unit series, almost every pause longer than 6 seconds made the patient go limp and fall, and no shorter pause did. Syncope shows on the EEG as sudden diffuse slowing and then flattening. A permanent pacemaker prevented further syncope in every patient who received one; consider it when epilepsy surgery is not an option." }, { "type": "li", "text": "**Postictal arrhythmias** (asystole, atrioventricular block, ventricular fibrillation) mostly follow convulsive seizures and are often linked to SUDEP or near-SUDEP; postictal asystole is usually preceded by PGES and apnea. They matter more for SUDEP than ictal arrhythmias do." }, { "type": "mcq", "id": "q-15dds4c", "stem": "A 52-year-old with drug-resistant temporal lobe epilepsy falls and injures his face during some focal seizures. Video-EEG with ECG shows that in those seizures the heart stops for 10 seconds about 30 seconds after seizure onset, the EEG then flattens, and he recovers within seconds once the rhythm returns. He is not a surgical candidate. What is the best way to prevent the falls?", "options": [ "A beta-blocker", "Fludrocortisone and extra salt", "A permanent cardiac pacemaker, alongside continued ASM treatment", "Higher ASM doses alone", "Reassurance, because ictal asystole always ends on its own" ], "answer": 2, "explain": "This is ictal asystole with ictal syncope. The pause is self-limited, but pauses longer than about 6 seconds cause falls, and a pacemaker prevents the syncope. ASM changes should continue but cannot be relied on in drug-resistant epilepsy. Fludrocortisone and salt are for reflex syncope, and a beta-blocker could slow the heart further." }, { "type": "cards", "items": [ { "id": "c-137c9ni", "front": "SUDEP incidence in children", "back": "About 1 in 4,500 a year (0.22 per 1,000 patient-years)." }, { "id": "c-1lxkb00", "front": "SUDEP incidence in adults", "back": "About 1 in 1,000 a year (1.2 per 1,000 patient-years)." }, { "id": "c-1rop1v1", "front": "Major SUDEP risk factor", "back": "Frequency of generalized tonic–clonic seizures." }, { "id": "c-enmkid", "front": "Definite versus probable SUDEP", "back": "Definite has an autopsy that finds no other cause; probable has no autopsy." }, { "id": "c-aae5k3", "front": "Near-SUDEP", "back": "Cardiorespiratory arrest reversed by resuscitation, with survival for more than an hour." }, { "id": "c-4c3p7m", "front": "MORTEMUS sequence", "back": "Tonic–clonic seizure, rapid breathing, then within minutes failure of breathing and heart function; terminal apnea before cardiac arrest." }, { "id": "c-2q088e", "front": "Wearable seizure detectors", "back": "Recommended for tonic–clonic seizures, especially in people who sleep unsupervised." }, { "id": "c-1an29qe", "front": "Postictal generalized EEG suppression (PGES)", "back": "Flat EEG over the whole scalp after a tonic–clonic seizure; longer PGES (over 50 seconds) went with higher odds of SUDEP, but it varies from seizure to seizure in one person." }, { "id": "c-1nf6dru", "front": "Mortality after seizure-free epilepsy surgery", "back": "Falls to that of the matched general population; continued seizures after surgery keep it high." }, { "id": "c-ggt2a7", "front": "Ictal versus postictal asystole", "back": "Ictal: during focal (usually temporal) seizures, self-limited, causes falls, treated with a pacemaker. Postictal: after convulsions, usually preceded by PGES and apnea, linked to SUDEP." }, { "id": "c-yv8c50", "front": "Asystole length that causes ictal syncope", "back": "Longer than about 6 seconds." }, { "id": "c-clxz5j", "front": "WHO global figures", "back": "About 50 million people with epilepsy, nearly 80% in low- and middle-income countries; up to 70% could be seizure-free with treatment; about 25% of cases preventable." } ] } ], "sources": [ { "title": "AAN and AES guideline: SUDEP incidence and risk factors (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28438841/" }, { "title": "Unified SUDEP definitions (Nashef 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22191982/" }, { "title": "Combined analysis of SUDEP risk factors (Hesdorffer 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21671925/" }, { "title": "MORTEMUS (Ryvlin 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/24012372/" }, { "title": "Long-term mortality in childhood-onset epilepsy (Sillanpää and Shinnar 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/21175314/" }, { "title": "ILAE and IFCN guideline on wearable seizure detection (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33666944/" }, { "title": "WHO fact sheet: epilepsy (2024)", "url": "https://www.who.int/news-room/fact-sheets/detail/epilepsy" }, { "title": "Electroclinical case-control study of SUDEP and PGES (Lhatoo 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20882604/" }, { "title": "Postictal immobility and PGES with respiratory dysfunction (Kuo 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26763069/" }, { "title": "PGES: an inconsistent finding in people with multiple seizures (Lamberts 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23966251/" }, { "title": "Seizure control and mortality after epilepsy surgery (Sperling 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10401779/" }, { "title": "A reappraisal of mortality after epilepsy surgery (Sperling 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27164679/" }, { "title": "Cardiac arrhythmias during or after epileptic seizures (van der Lende 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26038597/" }, { "title": "Ictal asystole and ictal syncope (Bestawros 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25391254/" } ], "words": 1485, "bank": 7 }, { "id": "comorbidities", "n": "2", "title": "Mood, behavior and cognition", "tags": [ "seizure-management" ], "updated": false, "goals": [ "Screen for depression, anxiety and suicidal thoughts", "treat depression safely alongside ASMs", "recognize peri-ictal psychiatric syndromes and the psychiatric effects of ASMs" ], "blocks": [ { "type": "h3", "text": "How common" }, { "type": "p", "text": "Depression and anxiety are the commonest psychiatric conditions in epilepsy, each affecting roughly one in four to one in three people. The relationship runs both ways: depression before the first seizure raises the risk of later epilepsy, and epilepsy raises the risk of depression. Depression predicts a worse quality of life more strongly than seizure frequency does, and suicide is more common than in the general population." }, { "type": "p", "text": "Depression and other psychiatric illness also predict how the epilepsy will behave. In a 20-year cohort of newly diagnosed patients, prior or current psychiatric illness, especially depression, predicted drug resistance. A lifetime psychiatric history predicted a worse seizure outcome after temporal lobectomy. A personal or family psychiatric history raises the risk of psychiatric side effects from ASMs. In a Swedish total-population study, three-quarters of people with epilepsy who died of external causes such as suicide and accidents had a psychiatric disorder, and the odds were highest with depression or substance misuse." }, { "type": "h3", "text": "Screen" }, { "type": "li", "text": "**In adults**: the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a six-item questionnaire designed so that ASM side effects are not mistaken for depression. A score above 15 suggests major depression." }, { "type": "li", "text": "**In children and adolescents**: the ILAE recommends screening everyone for anxiety and depression, with closer watch from age 12." }, { "type": "li", "text": "**Suicidal thoughts**: the FDA warning applies to all ASMs. It is a reason to ask about suicidal thoughts at every visit, not a reason to withhold treatment." }, { "type": "h3", "text": "Treat" }, { "type": "li", "text": "**Mild depression**: psychological treatment, such as cognitive behavioral therapy, comes first." }, { "type": "li", "text": "**Moderate or severe depression**: SSRIs are the first-choice drugs, and at usual doses they do not meaningfully worsen seizures. Venlafaxine is a reasonable switch if an SSRI fails." }, { "type": "li", "text": "**Duration**: continue for at least six months after remission, or nine months if there have been earlier episodes." }, { "type": "li", "text": "**Avoid**: bupropion (especially immediate-release or at high doses), clomipramine, maprotiline and amoxapine lower the seizure threshold. Tricyclics are dangerous in overdose." }, { "type": "li", "text": "**Check interactions**: enzyme-inducing ASMs lower levels of many antidepressants and antipsychotics. Fluoxetine and fluvoxamine can raise phenytoin levels." }, { "type": "li", "text": "**Psychosis**: most antipsychotics are safe at usual doses. Risperidone is a reasonable first choice: its seizure rate did not differ from placebo in drug-approval trials, and it has few interactions with ASMs. Clozapine carries the highest seizure risk and a boxed warning; the risk is dose-related (in a US series, 1% below 300 mg a day and 4.4% at 600 mg or more), so start at 12.5 mg, titrate slowly and keep it for selected cases. Olanzapine and quetiapine carry a smaller excess risk, and with enzyme-inducing ASMs such as carbamazepine, quetiapine levels can be undetectable." }, { "type": "li", "text": "**Stopping a mood-stabilizing ASM** (carbamazepine, oxcarbazepine, valproate or lamotrigine) can bring back a mood or anxiety disorder that it had been keeping in remission; restart it or switch to an ASM with similar psychotropic effects. ASM withdrawal can also cause anxiety and depression in its own right: when inpatients were withdrawn from all ASMs, 38% developed moderate to severe psychiatric symptoms, which settled within 2 weeks of restarting." }, { "type": "h3", "text": "Psychiatric effects of ASMs" }, { "type": "li", "text": "**Can worsen mood or behavior**: levetiracetam (irritability, low mood, rarely psychosis), perampanel (aggression; boxed warning), topiramate (low mood, slowed thinking), zonisamide, and phenobarbital (depression in adults, hyperactivity in children)." }, { "type": "li", "text": "**Can help mood**: lamotrigine, valproate and carbamazepine." }, { "type": "li", "text": "**Personal risk matters**: a history of psychiatric illness raises the chance of behavioral side effects from levetiracetam and perampanel." }, { "type": "li", "text": "**GABA-enhancing ASMs**: in add-on trials, vigabatrin raised the rate of depression (12% versus 3.5% on placebo) and, less often, psychosis. Tiagabine is also among the ASMs with negative psychotropic effects." }, { "type": "li", "text": "**Topiramate depends on how it is started**: about 1 in 4 patients in a large series had psychiatric side effects, and a high starting dose, rapid titration, and a personal or family psychiatric history all raised the risk. Rapid titration raised the risk of depression about fivefold, and far more in people with a history of depression." }, { "type": "h3", "text": "Psychiatric syndromes tied to seizures" }, { "type": "li", "text": "**Postictal psychosis**: follows a cluster of seizures after a clear interval of hours to a few days. It lasts days, often recurs, and is more common with seizures arising from both hemispheres. Treat with short-term antipsychotics and prevent the clusters." }, { "type": "li", "text": "**Alternative psychosis (\"forced normalization\")**: psychosis or mood change that appears when seizures stop abruptly and the EEG improves, for example after a new, effective ASM." }, { "type": "li", "text": "**Interictal psychosis**: a chronic, schizophrenia-like illness in long-standing epilepsy." }, { "type": "li", "text": "**Peri-ictal mood and anxiety symptoms** are distinct from interictal depression and are easily missed. Mood can sink over the day or days before a seizure (preictal dysphoria). Fear, anxiety or panic can be the seizure itself: a focal emotional seizure, often from mesial temporal networks, especially the amygdala. Postictal symptoms are common in drug-resistant focal epilepsy: of 100 consecutive patients, 43 had habitual postictal depressive symptoms, 45 postictal anxiety and 13 postictal suicidal thoughts (8 passive, 5 active). Postictal depressive symptoms last about a day (median 24 hours); antidepressants do not seem to prevent them, and seizure control does. Ask about suicidal thoughts after seizures, not only between them." }, { "type": "li", "text": "**Psychosis or mania after epilepsy surgery**: new (de novo) psychosis is uncommon (1.1% in a prospective study) and usually occurs when seizures continue or surgery is complicated. When it follows successful surgery, forced normalization is suspected. New mania after temporal lobectomy is more common after a right-sided resection and when the preoperative EEG showed abnormalities over both hemispheres; it is usually transient, and in one series all but one episode remitted within a year. Unlike postictal psychosis, neither needs a seizure cluster. Mood or anxiety symptoms are more common: up to a third of patients need treatment for them in the first 3 months after surgery." }, { "type": "li", "text": "**Functional seizures**: these can coexist with epilepsy, so recording the typical event is essential before changing treatment." }, { "type": "h3", "text": "Children and cognition" }, { "type": "p", "text": "ADHD, autism and learning disability are common in childhood epilepsy. Methylphenidate is effective for ADHD in children with epilepsy and does not meaningfully worsen well-controlled seizures. Memory and word-finding complaints in adults have several causes: the epilepsy itself, ASMs (topiramate especially), depression and poor sleep. Treat each one." }, { "type": "p", "text": "What drives cognitive impairment: poor cognitive outcome goes with early onset, long duration and poor seizure control, and in children epilepsy can disturb the development of cognitive skills. In adolescents and adults followed over time, the mild decline linked to seizures follows tonic–clonic seizures rather than focal ones. In a community cohort of children followed from diagnosis, about 1 in 4 had subnormal global cognition; onset before age 5, a known (symptomatic) cause, an epileptic encephalopathy and continuing ASM treatment each predicted it. The link runs the other way too: about a fifth of people with intellectual disability have epilepsy, more as the disability is more severe." }, { "type": "p", "text": "The pattern of deficits points to where the epilepsy is, although the profiles overlap and temporal lobe epilepsy can impair executive function as well:" }, { "type": "table", "head": [ "Epilepsy", "Typical cognitive profile" ], "rows": [ [ "Temporal lobe", "Memory loss that depends on the side (verbal with left, visual with right); with left temporal epilepsy, also naming and semantic memory (knowledge of words and objects)" ], [ "Frontal lobe", "Executive problems: poor planning and response inhibition, reduced attention span, poor motor coordination; memory suffers mainly from inefficient learning (shallow encoding through poor attention)" ], [ "Parietal or occipital", "Broader deficits: visuoconstruction, verbal and executive functions" ] ] }, { "type": "p", "text": "Bedside screening: the Montreal Cognitive Assessment (MoCA) usually counts a score below 26 as impaired. It was built to detect mild cognitive impairment, which the Mini-Mental State Examination (MMSE) misses: at the same cut-off of 26, the MMSE detected 18% of people with mild cognitive impairment and the MoCA 90%. In older adults with focal epilepsy, a MoCA below 26 was sensitive (88%) but not specific (64%) against full neuropsychological testing, and below 24 balanced the two better. A screen picks out who needs formal neuropsychological testing; it does not replace it." }, { "type": "mcq", "id": "q-1oxoyag", "stem": "A 34-year-old with focal epilepsy scores 18 on the NDDI-E. The patient denies suicidal intent and has moderate depressive symptoms. Seizures are controlled on lamotrigine. What is the best treatment?", "options": [ "Avoid all antidepressants because they provoke seizures", "Start an SSRI such as sertraline, and offer cognitive behavioral therapy", "Start bupropion", "Switch lamotrigine to levetiracetam", "Start clomipramine" ], "answer": 1, "explain": "SSRIs are first-choice drugs for moderate depression in epilepsy and do not meaningfully worsen seizures at usual doses. Cognitive behavioral therapy adds benefit. Bupropion and clomipramine lower the seizure threshold, and levetiracetam may worsen mood." }, { "type": "mcq", "id": "q-p2jd6l", "stem": "Two days after a cluster of four focal to bilateral tonic–clonic seizures, a 40-year-old who had recovered to normal becomes agitated, paranoid and hears voices. What is the most likely diagnosis?", "options": [ "Postictal psychosis", "Nonconvulsive status epilepticus", "New schizophrenia", "Alternative psychosis", "Levetiracetam toxicity" ], "answer": 0, "explain": "Postictal psychosis follows a seizure cluster after a clear interval of hours to days, then lasts days. EEG helps to exclude nonconvulsive status when the picture is unclear." }, { "type": "match", "id": "match-psych-asm", "prompt": "Match each ASM to its psychiatric profile", "pairs": [ [ "Levetiracetam", "Irritability and low mood, especially with a psychiatric history" ], [ "Perampanel", "Aggression and hostility; boxed warning" ], [ "Lamotrigine", "Mood-stabilizing; used in bipolar depression" ], [ "Topiramate", "Low mood and slowed thinking and word-finding" ], [ "Phenobarbital", "Depression in adults, hyperactivity in children" ] ] }, { "type": "h3", "text": "Sleep and medical comorbidity" }, { "type": "li", "text": "**Seizures by sleep stage**: in video-EEG monitoring, 43% of focal seizures began in sleep, mostly in non-rapid eye movement (non-REM) stage N1 (23%) or N2 (68%); they were rare in slow-wave sleep and none began in REM sleep. Frontal lobe seizures are the most likely to arise from sleep, and temporal lobe seizures that start in sleep become bilateral tonic–clonic more often than those that start awake." }, { "type": "li", "text": "**Obstructive sleep apnea**: a third of drug-resistant surgical candidates had undiagnosed apnea on polysomnography, more often men, older patients and those with seizures in sleep. In older adults, worsening or late-onset seizures went with a higher apnea–hypopnea index and more daytime sleepiness. Treat it with continuous positive airway pressure (CPAP): in a retrospective series, seizures fell in patients who used CPAP but not in those who did not, although randomized evidence is limited to a pilot trial." }, { "type": "li", "text": "**Insomnia**: clinically significant in 43% of clinic patients, and linked to continuing seizures and worse quality of life even after allowing for depression. Lamotrigine can cause dose-related insomnia (6% of patients in one clinic needed a dose change)." }, { "type": "li", "text": "**Migraine**: people with epilepsy are about 2.4 times as likely to have migraine as relatives without epilepsy, across seizure types and causes, and highest when the epilepsy followed head trauma. When both need treatment, choose one drug for both: topiramate or valproate, which have established efficacy for migraine prevention. Lamotrigine is ineffective for migraine prevention." }, { "type": "li", "text": "**Multiple sclerosis (MS)**: seizures affect about 3% of people with MS (pooled population-based prevalence), several times the general-population rate. They go with cortical lesions rather than with the white matter lesion load." }, { "type": "cards", "items": [ { "id": "c-12emn0u", "front": "NDDI-E", "back": "Six-item depression screen for epilepsy; above 15 suggests major depression." }, { "id": "c-tc1yqx", "front": "First-line drug for depression in epilepsy", "back": "An SSRI." }, { "id": "c-tdxn3q", "front": "Antidepressants that lower the seizure threshold", "back": "Bupropion, clomipramine, maprotiline, amoxapine." }, { "id": "c-609yrl", "front": "Duration of antidepressant treatment", "back": "At least six months after remission; nine if there were earlier episodes." }, { "id": "c-1y47v4t", "front": "Postictal psychosis", "back": "After a seizure cluster and a clear interval of hours to days; lasts days; often recurs." }, { "id": "c-10zt9pp", "front": "Alternative psychosis", "back": "Psychosis when seizures stop abruptly and the EEG improves (\"forced normalization\")." }, { "id": "c-1gvt5tb", "front": "ADHD in children with epilepsy", "back": "Methylphenidate is effective and does not meaningfully worsen controlled seizures." }, { "id": "c-1iva5pn", "front": "Postictal depression, anxiety and suicidal thoughts", "back": "Common in drug-resistant focal epilepsy (43, 45 and 13 of 100 patients); last about a day; prevented by seizure control, not antidepressants." }, { "id": "c-1otbf0c", "front": "Ictal fear", "back": "A focal emotional seizure, often from mesial temporal networks (amygdala); a seizure, not a panic attack." }, { "id": "c-slpt9u", "front": "Antipsychotic choice in epilepsy", "back": "Risperidone is a reasonable first choice; clozapine has the highest, dose-related seizure risk and a boxed warning." }, { "id": "c-1ufz8p1", "front": "Stopping carbamazepine, valproate or lamotrigine", "back": "Can bring back a mood or anxiety disorder it had been controlling; restart it or switch to a similar ASM." }, { "id": "c-13webnc", "front": "Vigabatrin and mood", "back": "Depression in 12% versus 3.5% on placebo; psychosis less often." }, { "id": "c-13lz92j", "front": "Topiramate psychiatric risk factors", "back": "High starting dose, rapid titration, personal or family psychiatric history." }, { "id": "c-zirv6a", "front": "Depression as a prognostic marker", "back": "Predicts drug resistance, worse seizure outcome after temporal lobectomy, ASM psychiatric side effects and death from external causes." }, { "id": "c-1h9mu2d", "front": "De novo psychosis after epilepsy surgery", "back": "About 1%; usually with continued seizures or complications; after successful surgery, think of forced normalization." }, { "id": "c-iinxp1", "front": "Mania after temporal lobectomy", "back": "More after right-sided resection and with bilateral preoperative EEG abnormalities; usually remits within a year." }, { "id": "c-1w17rmw", "front": "Frontal versus temporal lobe epilepsy cognition", "back": "Frontal: executive, attention, response inhibition and motor coordination deficits. Temporal: side-specific memory loss; naming and semantic deficits with left temporal epilepsy." }, { "id": "c-1xcv2zr", "front": "Predictors of poor cognition in childhood epilepsy", "back": "Onset before age 5, known cause, epileptic encephalopathy, continued ASM treatment." }, { "id": "c-1huf0a9", "front": "MoCA cut-off", "back": "Below 26 counts as impaired; much more sensitive than the MMSE for mild impairment; a screen, not a substitute for neuropsychological testing." }, { "id": "c-1tmx0vn", "front": "Seizures by sleep stage", "back": "Mostly non-REM stage N2, some N1, rare in slow-wave sleep, almost never in REM sleep." }, { "id": "c-1v12sn7", "front": "Sleep apnea in drug-resistant epilepsy", "back": "Found in about a third of surgical candidates; treat with CPAP, which may improve seizure control." }, { "id": "c-1xj1075", "front": "Migraine and epilepsy", "back": "Migraine about 2.4 times as common; treat both with topiramate or valproate, not lamotrigine." }, { "id": "c-1x2jidn", "front": "Seizures in multiple sclerosis", "back": "About 3%; linked to cortical lesions." } ] } ], "sources": [ { "title": "NDDI-E validation (Gilliam 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16632310/" }, { "title": "ILAE recommendations: treating depression in adults with epilepsy (2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/34866176/" }, { "title": "ILAE recommendations: anxiety and depression in children with epilepsy (2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/39320421/" }, { "title": "Predictors of pharmacoresistant epilepsy (Hitiris 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17628429/" }, { "title": "Lifetime psychiatric history and seizure outcome after temporal lobectomy (Kanner 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19255406/" }, { "title": "Premature mortality in epilepsy and psychiatric comorbidity (Fazel 2013)", "url": "https://pubmed.ncbi.nlm.nih.gov/23883699/" }, { "title": "Treatment of psychoses in patients with epilepsy (Agrawal and Mula 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/31316747/" }, { "title": "Seizure incidence in psychopharmacological trials (Alper 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17223086/" }, { "title": "Clozaril prescribing information (DailyMed)", "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90876802-0e3a-44c9-9ff7-1754dfbe736a" }, { "title": "Clozapine-related seizures (Devinsky 1991)", "url": "https://pubmed.ncbi.nlm.nih.gov/2006003/" }, { "title": "Suicidality in patients with epilepsy (Kanner 2022)", "url": "https://pubmed.ncbi.nlm.nih.gov/35712347/" }, { "title": "Anticonvulsant withdrawal-emergent psychopathology (Ketter 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/8290092/" }, { "title": "Psychiatric adverse events during vigabatrin therapy (Levinson and Devinsky 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10534259/" }, { "title": "Topiramate and psychiatric adverse events (Mula 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12752464/" }, { "title": "Can ASMs unmask a susceptibility to psychiatric disorders? (Kanner 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/19262587/" }, { "title": "Mood change preceding epileptic seizures (Blanchet and Frommer 1986)", "url": "https://pubmed.ncbi.nlm.nih.gov/3734769/" }, { "title": "ILAE: focal emotional seizures", "url": "https://epilepsydiagnosis.org/seizure/emotional-overview.html" }, { "title": "Postictal psychiatric symptoms in partial epilepsy (Kanner 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15007118/" }, { "title": "Postictal affective episodes (Kanner 2010)", "url": "https://pubmed.ncbi.nlm.nih.gov/20817613/" }, { "title": "Mania following temporal lobectomy (Carran 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/14504319/" }, { "title": "Chronic epilepsy and cognition (Elger 2004)", "url": "https://pubmed.ncbi.nlm.nih.gov/15488459/" }, { "title": "Progressive cognitive decline in adolescents and adults with epilepsy (Dodrill 2002)", "url": "https://pubmed.ncbi.nlm.nih.gov/12143358/" }, { "title": "Global cognitive function in children with epilepsy (Berg 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18070088/" }, { "title": "Epilepsy in people with intellectual disabilities (Robertson 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/26076844/" }, { "title": "Neuropsychological aspects of frontal lobe epilepsy (Helmstaedter 1996)", "url": "https://pubmed.ncbi.nlm.nih.gov/9148196/" }, { "title": "Neurocognitive functioning in frontal lobe epilepsy (Patrikelis 2009)", "url": "https://pubmed.ncbi.nlm.nih.gov/18926928/" }, { "title": "List-learning profiles in childhood epilepsy syndromes (Schraegle 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27484747/" }, { "title": "Material-specific memory in temporal lobe epilepsy (Yoo 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16720797/" }, { "title": "Semantic memory in partial epilepsy (Giovagnoli 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15989938/" }, { "title": "Frontal lobe function in temporal lobe epilepsy (Stretton and Thompson 2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22100147/" }, { "title": "Neuropsychological profile of parietal and occipital lobe epilepsy (Traianou 2019)", "url": "https://pubmed.ncbi.nlm.nih.gov/30909077/" }, { "title": "The Montreal Cognitive Assessment (Nasreddine 2005)", "url": "https://pubmed.ncbi.nlm.nih.gov/15817019/" }, { "title": "Validity of the MoCA in epilepsy (Reyes 2024)", "url": "https://pubmed.ncbi.nlm.nih.gov/38874380/" }, { "title": "Distribution of partial seizures during the sleep–wake cycle (Herman 2001)", "url": "https://pubmed.ncbi.nlm.nih.gov/11402100/" }, { "title": "Obstructive sleep apnea in medically refractory epilepsy (Malow 2000)", "url": "https://pubmed.ncbi.nlm.nih.gov/11061259/" }, { "title": "Sleep apnea and seizures in older adults (Chihorek 2007)", "url": "https://pubmed.ncbi.nlm.nih.gov/17984449/" }, { "title": "CPAP and seizure control (Vendrame 2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21849000/" }, { "title": "Treating sleep apnea in epilepsy: randomized pilot trial (Malow 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18711110/" }, { "title": "Insomnia in epilepsy (Quigg 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26994361/" }, { "title": "Lamotrigine associated with insomnia (Sadler 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10080513/" }, { "title": "Comorbidity of migraine and epilepsy (Ottman and Lipton 1994)", "url": "https://pubmed.ncbi.nlm.nih.gov/7969967/" }, { "title": "AAN and AHS guideline: episodic migraine prevention (2012)", "url": "https://pubmed.ncbi.nlm.nih.gov/22529202/" }, { "title": "Seizure disorders in multiple sclerosis: systematic review (Marrie 2015)", "url": "https://pubmed.ncbi.nlm.nih.gov/25533301/" }, { "title": "Cortical inflammation and epilepsy in multiple sclerosis (Calabrese 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18227989/" } ], "words": 2187, "bank": 11 }, { "id": "safety-driving-law", "n": "3", "title": "Driving, safety, work and school", "tags": [ "seizure-management" ], "updated": true, "goals": [ "Counsel on driving using the seizure-free interval and local law", "give practical safety and first-aid advice", "know the protections available at work and school" ], "blocks": [ { "type": "h3", "text": "Driving" }, { "type": "p", "text": "In the United States, each state sets its own rules. Most require a seizure-free interval of three to twelve months before driving, and many allow exceptions:" }, { "type": "li", "text": "Seizures only during sleep, in an established pattern" }, { "type": "li", "text": "Auras that never impair awareness or control" }, { "type": "li", "text": "A seizure after a doctor-directed medication change, once the previous regimen is restored" }, { "type": "li", "text": "Provoked seizures whose cause has resolved" }, { "type": "p", "text": "Most states rely on the driver to report. A few require physicians to report: a 1999 legal review named six (California, Delaware, Nevada, New Jersey, Oregon and Pennsylvania), and a survey of state licensing agencies in 1999 to 2000 also found six with mandatory reporting, about half permitting physician reports and the rest with no law on it. Laws change, so check the current rule. Commercial driving across state lines has much stricter federal standards (see Occupations and the law, below)." }, { "type": "p", "updated": true, "label": "2025 position statement", "text": "The American Academy of Neurology (AAN), the American Epilepsy Society and the Epilepsy Foundation updated their 1994 and 2007 statements on driving. A minimum seizure-free interval of 3 months should ordinarily be required before driving, lengthened in individual cases after review of favorable and unfavorable features." }, { "type": "li", "text": "**Provoked seizures**: when the provoking factor is unlikely to recur, no seizure-free interval may be needed." }, { "type": "li", "text": "**Short medication interruptions**: a person with previously well-controlled epilepsy who has a seizure after a brief interruption of ASMs in hospital, or during a practitioner-directed titration, may not need an interval once effective levels are restored." }, { "type": "li", "text": "**Tapering**: pause driving during an ASM taper and after stopping it, unless another ASM replaces it." }, { "type": "li", "text": "**Side effects**: do not drive if ASMs impair cognition or coordination." }, { "type": "li", "text": "**Reporting**: practitioners should be allowed but not required to report drivers at elevated risk, with no legal liability for reporting or for declining to report." }, { "type": "p", "text": "The evidence behind the seizure-free interval: in a case-control study, a seizure-free interval of 12 months or more lowered the odds of a seizure-related crash by 93%. A reliable warning aura also lowered the odds. Over half of the drivers who crashed were driving illegally, before their required seizure-free interval had passed, and a fifth had missed an ASM dose just before. When Arizona shortened its interval from 12 to 3 months, seizure-related crashes did not increase." }, { "type": "p", "text": "When a patient keeps driving against advice, the physician weighs the patient's autonomy and confidentiality against public safety. The American Medical Association (AMA) Code of Medical Ethics asks physicians to assess and counsel, to explain in advance when they may have to report, and, if they do report, to disclose only the minimum necessary information; the licensing authority, not the physician, decides fitness to drive. Where the law permits but does not require reporting, a good-faith report is reasonable once counseling has failed and the risk to others is clear; tell the patient first. Confidentiality with adolescents has similar limits: offer time alone and explain its limits beforehand. Parents may be involved without the adolescent's agreement when that is needed to avert life-threatening harm, such as suicidal thoughts with a plan." }, { "type": "note", "label": "Board pearl", "text": "Counsel every patient about driving, record that you did so, and check your own state's rules. The law is not the same everywhere." }, { "type": "h3", "text": "Everyday safety" }, { "type": "li", "text": "**Water**: take showers rather than baths, and never swim alone. Drowning is a leading cause of accidental death in epilepsy, often in a bathtub." }, { "type": "li", "text": "**Heights, fire and tools**: avoid unprotected heights. Use the back burners of the stove and a microwave where possible. Use power tools with guards and cutoffs." }, { "type": "li", "text": "**Common triggers**: missed doses, sleep deprivation and alcohol excess are the commonest causes of breakthrough seizures." }, { "type": "li", "text": "**Photosensitive epilepsy**: sit farther from the screen, play in a well-lit room, avoid playing when tired, and cover one eye if flashing starts." }, { "type": "li", "text": "**Sports and exercise**: encourage them. Exercise may help seizure control, and seizures are unlikely during exertion itself. The International League Against Epilepsy (ILAE) groups sports by the danger if a seizure happens. Group 1, no significant added risk: athletics (other than pole vault), golf, dancing, racquet sports, cross-country skiing and team ground sports such as basketball, football and volleyball. Group 2, moderate risk to the person but not to bystanders: swimming, cycling, alpine skiing, horse riding, gymnastics, boxing and karate. Group 3, major risk: scuba diving, climbing, aviation, parachuting, motor sports, surfing and solitary sailing. Advice depends on the sport, the chance of a seizure, its type and timing, its triggers, and how much risk the person accepts." }, { "type": "li", "text": "**Alcohol**: small amounts are usually tolerated. In a double-blind study, one to three drinks twice a week did not change seizure frequency, the EEG or ASM levels. Heavy drinking is different: withdrawal seizures come within about 48 hours of stopping, and alcohol misuse precipitates 9% to 25% of status epilepticus." }, { "type": "li", "text": "**Adherence**: in a large Medicaid cohort, about a quarter of treatment periods were nonadherent, and those periods carried over three times the risk of death, along with more emergency visits, hospital admissions, motor vehicle injuries and fractures. Ask about missed doses at every visit. Reminders (phone alarms, pill organizers) and combined education-and-behavior programs improve adherence." }, { "type": "h3", "text": "Seizure first aid" }, { "type": "li", "text": "Stay with the person, time the seizure, and move hard objects away." }, { "type": "li", "text": "After the convulsion, turn the person onto one side." }, { "type": "li", "text": "Put nothing in the mouth, and do not hold the person down." }, { "type": "li", "text": "**Give rescue medication**, as the seizure action plan directs, for a prolonged seizure or a cluster. Options include intranasal midazolam or diazepam, buccal midazolam and rectal diazepam." }, { "type": "li", "text": "**Call emergency services** if a convulsion lasts 5 minutes or longer, or seizures repeat without recovery in between. Also call if the person is injured, pregnant or having trouble breathing, if the seizure happened in water, or if it is a first seizure." }, { "type": "h3", "text": "Work and school" }, { "type": "p", "text": "Under the Americans with Disabilities Act (ADA), epilepsy counts as a disability. Employers with 15 or more employees must provide reasonable accommodations unless they cause undue hardship, and cannot ask about health conditions before a job offer. At school, a written seizure action plan, and a 504 plan or individualized education program, secure rescue medication, supervision and learning support." }, { "type": "li", "text": "**Why controlled epilepsy still counts (ADA Amendments Act of 2008)**: disability is judged without regard to mitigating measures such as medication or surgery. An impairment that is episodic or in remission is a disability if it would substantially limit a major life activity when active, and the regulations name epilepsy as substantially limiting neurological function. A person treated adversely because of actual or perceived epilepsy is also covered (\"regarded as\")." }, { "type": "li", "text": "**The hiring sequence**: before a job offer, no questions about epilepsy or medicines. After a conditional offer, health questions or a medical examination are allowed only if every entering employee in the same job category gets them. Once employed, questions and examinations must be job-related and consistent with business necessity." }, { "type": "li", "text": "**Asking for accommodation**: the employee, or someone on their behalf, must tell the employer that a change is needed because of epilepsy. The employer may ask only for documentation enough to establish the epilepsy and explain the need. Examples include breaks to take medicines, a place to rest after a seizure, and a consistent start time or a move from night to day shifts." }, { "type": "li", "text": "**Direct threat**: excluding someone for safety needs an individualized finding of a significant risk of substantial harm that accommodation cannot remove. The employer must weigh the duration, severity, likelihood and imminence of harm, using current medical evidence; a diagnosis is not enough. Complaints go to the Equal Employment Opportunity Commission (EEOC), generally within 180 days (300 days where a state or local agency also enforces such laws)." }, { "type": "li", "text": "**Individualized education program (IEP) or Section 504 plan**: an IEP, under the Individuals with Disabilities Education Act (IDEA), provides special education with measurable annual goals. It requires that the child need special education (epilepsy is listed under \"other health impairment\"), and from the IEP in force at age 16 at the latest it must include transition goals and services. A 504 plan, under the Rehabilitation Act, gives the accommodations and related services a student needs for equal access, such as trained staff for rescue medication, rest after seizures and supervision. IDEA's school services cover ages 3 to 21 and end with a regular high school diploma; in college, students rely on Section 504 and the ADA." }, { "type": "li", "text": "**Transition to adult care**: the Child Neurology Foundation consensus asks the child neurology team to discuss transition by age 13, assess self-management yearly from age 12, and raise the youth's expected legal competency with caregivers by age 14. For a youth who may lack capacity, guardianship or a less restrictive alternative takes time to arrange and should be in place before adulthood." }, { "type": "case", "id": "case-driving", "title": "Back behind the wheel", "intro": [ "A 24-year-old delivery driver has juvenile myoclonic epilepsy. The last generalized tonic–clonic seizure was 14 months ago, after a night without sleep. The patient has occasional morning myoclonic jerks, usually after a late night, and takes levetiracetam, occasionally missing evening doses." ], "steps": [ { "narrative": [], "stem": "What is the most important first step in advising about driving?", "options": [ "Say that nobody with epilepsy may drive", "Check the state's rules, discuss the seizure-free interval and triggers, and record the discussion", "Say that driving is fine because the last seizure was more than a year ago", "Report the patient to the licensing authority in every case", "Order an EEG and base the advice only on that" ], "answer": 1, "explain": "Driving rules vary by state and by the kind of license. Advice should cover the interval, the risk factors (sleep loss, missed doses) and how to reduce them, and the discussion should be documented." }, { "narrative": [ "The patient asks about driving a delivery truck across state lines." ], "stem": "What should the patient be told?", "options": [ "The same rules apply as for a private car", "Interstate commercial driving has much stricter federal standards", "Commercial driving is allowed once seizure-free for three months", "Only the employer decides", "Epilepsy has no effect on commercial licensing" ], "answer": 1, "explain": "Interstate commercial vehicles fall under federal medical standards that are much stricter than state rules for private cars. The patient needs to check them before planning a career around interstate driving." }, { "narrative": [ "The patient wants to know how to lower the chance of another seizure." ], "stem": "Which advice matters most?", "options": [ "Stop levetiracetam once two years seizure-free", "Regular sleep, taking every dose (a pill organizer or phone alarm), and limiting alcohol", "Avoid all screens", "Take an extra dose before driving", "Switch to carbamazepine" ], "answer": 1, "explain": "Sleep deprivation, missed doses and alcohol are the main triggers in juvenile myoclonic epilepsy, which usually needs lifelong treatment. Carbamazepine can worsen myoclonus." } ], "outro": [ "Driving advice has three parts: the local law, the person's own risk and how to lower it, and a written record of the discussion." ] }, { "type": "mcq", "id": "q-1t2b4wa", "stem": "Which situation most often permits driving before the usual seizure-free interval in many US states?", "options": [ "Any focal seizure with impaired consciousness", "A seizure caused by a doctor-directed medication change, once the previous regimen is restored", "Seizures that happen only while driving", "A patient who has stopped taking medication", "Seizures with a short postictal phase" ], "answer": 1, "explain": "Many states allow exceptions for seizures after a supervised medication change, seizures only during sleep, auras that never impair awareness, and provoked seizures whose cause has resolved." }, { "type": "mcq", "id": "q-1ittl34", "stem": "A person has a convulsive seizure in a shopping center. It has lasted 3 minutes when you arrive. What should you do?", "options": [ "Put something between the teeth to protect the tongue", "Hold the arms and legs still", "Time it, protect the head, move hard objects away, and call emergency services if it reaches 5 minutes", "Pour water on the face", "Leave to find a doctor" ], "answer": 2, "explain": "Time the seizure and keep the person safe. Nothing goes in the mouth, and restraint causes injury. Call emergency services at 5 minutes or if seizures repeat." }, { "type": "h3", "text": "Occupations and the law" }, { "type": "p", "text": "Some jobs fall under federal medical standards that override state driving rules." }, { "type": "li", "text": "**Interstate commercial drivers**: the federal standard disqualifies anyone with an established history or diagnosis of epilepsy. A medical examiner may certify a driver with a history of epilepsy only if seizure-free and off ASMs for 10 years. Otherwise the Federal Motor Carrier Safety Administration (FMCSA) can grant an exemption after 8 seizure-free years, on or off medication, with a treatment plan unchanged for 2 years and yearly recertification (4 seizure-free years after a single unprovoked seizure)." }, { "type": "li", "text": "**Pilots**: epilepsy is disqualifying under Federal Aviation Administration (FAA) medical standards. The aviation medical examiner cannot certify it; the FAA may consider a special issuance after 10 seizure-free years with the last 3 off medication (after a single unprovoked seizure, 4 years with the last 2 off medication). A pilot who knows of a disqualifying condition must stop flying at once, whatever the certificate's expiry date, and BasicMed is not an option until a special issuance has been granted." }, { "type": "li", "text": "**Disability benefits**: Social Security Disability Insurance (SSDI) pays people insured through past work, and Supplemental Security Income (SSI) pays people with limited income and resources. Both require inability to do any substantial gainful activity because of an impairment expected to last at least 12 months or to cause death. The epilepsy listing (11.02) is met, for example, by tonic–clonic seizures at least once a month, or focal impaired awareness (dyscognitive) seizures at least once a week, for at least 3 consecutive months despite adherence to prescribed treatment. These programs pay benefits; the ADA, by contrast, forbids discrimination." }, { "type": "mcq", "id": "q-wpnz77", "stem": "A 40-year-old has focal epilepsy and has been seizure-free for 5 years on an unchanged dose of lamotrigine. He drives a car legally and asks about driving trucks across state lines and about keeping his private pilot certificate. What is the correct advice?", "options": [ "Both are allowed now, because he meets his state's driving rules", "A medical examiner can certify him for commercial driving now, because his seizures are controlled", "He is not yet eligible for either; an FMCSA exemption needs 8 seizure-free years, and the FAA considers special issuance only after 10 years with the last 3 off medication", "He may fly under BasicMed without further review", "Neither is ever possible with a diagnosis of epilepsy" ], "answer": 2, "explain": "State rules for private cars do not govern interstate commercial driving or flying. The FMCSA exemption needs 8 seizure-free years on a plan stable for 2 years (an examiner alone can certify only after 10 years seizure-free off ASMs). The FAA defers epilepsy to its own review and considers special issuance after 10 seizure-free years with the last 3 off medication; BasicMed requires that special issuance first. Both routes exist, so a lifetime bar is wrong." }, { "type": "cards", "items": [ { "id": "c-1sy5sw4", "front": "Typical US seizure-free interval for driving", "back": "Three to twelve months, depending on the state." }, { "id": "c-3rxvsf", "front": "Common driving exceptions", "back": "Sleep-only seizures, auras that do not impair consciousness, a seizure after a doctor-directed medication change, provoked seizures." }, { "id": "c-b4lkft", "front": "Seizure-free for at least 12 months and crash risk", "back": "93% lower odds of a seizure-related crash in one case-control study." }, { "id": "c-1lv6rrh", "front": "Bath or shower", "back": "Shower; drowning is a leading accidental death in epilepsy." }, { "id": "c-k7os5d", "front": "When to call emergency services", "back": "Convulsion lasting 5 minutes or more, repeated seizures without recovery, injury, pregnancy, breathing trouble, a seizure in water, or a first seizure." }, { "id": "c-ilax2d", "front": "Commonest causes of breakthrough seizures", "back": "Missed doses, sleep deprivation, alcohol." }, { "id": "c-i2dvyr", "front": "ADA and epilepsy", "back": "Epilepsy counts as a disability; employers with 15 or more employees must provide reasonable accommodations unless they cause undue hardship." }, { "id": "c-1qtlurs", "front": "Minimum seizure-free interval for driving, 2025 joint statement", "back": "3 months, lengthened for individual unfavorable features; none may be needed for provoked seizures unlikely to recur or a seizure after a brief, supervised ASM interruption once levels are restored." }, { "id": "c-19aydee", "front": "States with mandatory physician reporting (around 1999)", "back": "California, Delaware, Nevada, New Jersey, Oregon, Pennsylvania." }, { "id": "c-n4u239", "front": "Reporting a driver against advice (AMA)", "back": "Counsel first, tell the patient before reporting, disclose the minimum necessary; the licensing authority decides fitness to drive." }, { "id": "c-1fbf2o9", "front": "FMCSA epilepsy exemption", "back": "8 seizure-free years, on or off medication, plan stable for 2 years, yearly recertification; examiner alone only if 10 years seizure-free off ASMs." }, { "id": "c-1ihi8f7", "front": "FAA and epilepsy", "back": "Disqualifying; special issuance considered after 10 seizure-free years with the last 3 off medication; BasicMed needs that special issuance first." }, { "id": "c-xj1h6g", "front": "ADA Amendments Act of 2008", "back": "Disability judged without mitigating measures such as medication; episodic conditions count if limiting when active; \"regarded as\" coverage." }, { "id": "c-fljpaz", "front": "Direct threat (ADA)", "back": "Individualized finding of significant risk of substantial harm that accommodation cannot remove; weigh duration, severity, likelihood, imminence." }, { "id": "c-16aqf0p", "front": "IEP versus 504 plan", "back": "IEP (IDEA): special education with measurable goals and transition planning by age 16. 504 plan: accommodations for equal access, no special education needed." }, { "id": "c-1f6gzl4", "front": "Social Security epilepsy listing (11.02)", "back": "For example, tonic–clonic seizures at least monthly, or focal impaired awareness seizures at least weekly, for 3 consecutive months despite adherence." }, { "id": "c-1sxyq5f", "front": "ILAE sports groups", "back": "1, no added risk (most team sports); 2, risk to the person only (swimming, cycling, alpine skiing); 3, major risk (scuba diving, climbing, aviation, motor sports)." }, { "id": "c-ik23ov", "front": "Social drinking and seizures", "back": "One to three drinks did not change seizure frequency; heavy drinking and withdrawal (within about 48 hours of stopping) provoke seizures." }, { "id": "c-inctir", "front": "Nonadherence and mortality", "back": "Periods of nonadherence carried over three times the risk of death." }, { "id": "c-1jiolc7", "front": "Transition and legal competency", "back": "Raise the youth's expected legal competency with caregivers by age 14, so guardianship or an alternative is ready before adulthood." } ] } ], "sources": [ { "title": "Risk factors for seizure-related motor vehicle crashes (Krauss 1999)", "url": "https://pubmed.ncbi.nlm.nih.gov/10227613/" }, { "title": "AAN and AES guideline: SUDEP incidence and risk factors (2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28438841/" }, { "title": "ILAE and IFCN guideline on wearable seizure detection (2021)", "url": "https://pubmed.ncbi.nlm.nih.gov/33666944/" }, { "title": "Seizures, driver licensure, and medical reporting: AAN position statement (Tolchin 2025)", "url": "https://pubmed.ncbi.nlm.nih.gov/40073306/" }, { "title": "Seizure-related crashes in Arizona after reducing the interval from 12 to 3 months (Drazkowski 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/12839076/" }, { "title": "Epilepsy, driving and the law (Finucane 1999)", "url": "https://www.aafp.org/afp/1999/0101/p199" }, { "title": "Physician reporting of medically impaired drivers (Aschkenasy 2006)", "url": "https://pubmed.ncbi.nlm.nih.gov/16434332/" }, { "title": "AMA Code of Medical Ethics opinion 8.2: impaired drivers", "url": "https://code-medical-ethics.ama-assn.org/ethics-opinions/impaired-drivers-their-physicians" }, { "title": "AMA Code of Medical Ethics opinion 2.2.2: confidential care for minors", "url": "https://code-medical-ethics.ama-assn.org/ethics-opinions/confidential-health-care-minors" }, { "title": "ILAE Task Force on Sports and Epilepsy (Capovilla 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/26662920/" }, { "title": "Epilepsy and social alcohol intake (Höppener 1983)", "url": "https://pubmed.ncbi.nlm.nih.gov/6873004/" }, { "title": "Seizures in alcohol-dependent patients (Hillbom 2003)", "url": "https://pubmed.ncbi.nlm.nih.gov/14594442/" }, { "title": "Nonadherence to ASMs and mortality (Faught 2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18565827/" }, { "title": "Strategies for improving ASM adherence (Cochrane 2020)", "url": "https://pubmed.ncbi.nlm.nih.gov/33089492/" }, { "title": "Epilepsy in the workplace and the ADA (EEOC)", "url": "https://www.eeoc.gov/laws/guidance/epilepsy-workplace-and-ada" }, { "title": "29 CFR 1630.2, definitions under the ADA (eCFR)", "url": "https://www.ecfr.gov/current/title-29/subtitle-B/chapter-XIV/part-1630/section-1630.2" }, { "title": "29 CFR 1630.14, medical examinations and inquiries (eCFR)", "url": "https://www.ecfr.gov/current/title-29/subtitle-B/chapter-XIV/part-1630/section-1630.14" }, { "title": "34 CFR 104.33, free appropriate public education under Section 504 (eCFR)", "url": "https://www.ecfr.gov/current/title-34/subtitle-B/chapter-I/part-104/subpart-D/section-104.33" }, { "title": "34 CFR 300.8, child with a disability under IDEA (eCFR)", "url": "https://www.ecfr.gov/current/title-34/subtitle-B/chapter-III/part-300/subpart-A/subject-group-ECFR2ce1b3bd1a8a1d7/section-300.8" }, { "title": "34 CFR 300.320, content of the IEP (eCFR)", "url": "https://www.ecfr.gov/current/title-34/subtitle-B/chapter-III/part-300/subpart-D/subject-group-ECFR1e9e1bc7f2a1b3a/section-300.320" }, { "title": "34 CFR 300.101 and 300.102, ages for a free appropriate public education (eCFR)", "url": "https://www.ecfr.gov/current/title-34/subtitle-B/chapter-III/part-300/subpart-B/subject-group-ECFR0f8fdf3e2cd7fd1/section-300.102" }, { "title": "The neurologist's role in transition to adult care (Brown 2016)", "url": "https://pubmed.ncbi.nlm.nih.gov/27466477/" }, { "title": "Child Neurology Foundation: eight principles of transition", "url": "https://www.childneurologyfoundation.org/wp-content/uploads/2017/08/CNF_8_Principles_Inforgraphic_v5a.pdf" }, { "title": "49 CFR 391.41, physical qualifications for drivers (eCFR)", "url": "https://www.ecfr.gov/current/title-49/subtitle-B/chapter-III/subchapter-B/part-391/subpart-E/section-391.41" }, { "title": "Appendix A to part 391, medical advisory criteria (eCFR)", "url": "https://www.ecfr.gov/current/title-49/subtitle-B/chapter-III/subchapter-B/part-391/appendix-Appendix%20A%20to%20Part%20391" }, { "title": "FMCSA seizure exemption criteria", "url": "https://www.fmcsa.dot.gov/medical/driver-medical-requirements/new-seizure-applicant-doc-email-version" }, { "title": "FAA Guide for Aviation Medical Examiners: seizures and epilepsy", "url": "https://www.faa.gov/ame_guide/media/Seizures_Epilepsy.pdf" }, { "title": "14 CFR 61.53, operations during medical deficiency (eCFR)", "url": "https://www.ecfr.gov/current/title-14/chapter-I/subchapter-D/part-61/subpart-A/section-61.53" }, { "title": "14 CFR 68.9, special issuance and BasicMed (eCFR)", "url": "https://www.ecfr.gov/current/title-14/chapter-I/subchapter-D/part-68/section-68.9" }, { "title": "SSA listing 11.00, neurological disorders (adult)", "url": "https://www.ssa.gov/disability/professionals/bluebook/11.00-Neurological-Adult.htm" }, { "title": "SSA: disability programs and definition of disability", "url": "https://www.ssa.gov/disability/professionals/bluebook/general-info.htm" } ], "words": 2713, "bank": 11 } ], "intro": [ "Epilepsy care does not end with seizure control. This part covers what kills people with epilepsy, the psychiatric and cognitive conditions that travel with it, and the practical questions raised at almost every clinic visit: driving, safety, work and school." ] } ] }