Paroxysmal neurologic events from abnormal hypersynchronous cortical discharge.
Also known as: seizure, epilepsy, focal seizure, generalized seizure, tonic-clonic, grand mal, absence
Overview
A seizure is a transient occurrence of signs and/or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain. Epilepsy is a disease characterized by an enduring predisposition to seizures, defined by ILAE 2014 as: (1) ≥2 unprovoked seizures >24 h apart, OR (2) one unprovoked seizure plus ≥60% recurrence risk over next 10 years, OR (3) diagnosis of an epilepsy syndrome.
Epidemiology
Lifetime risk of a seizure ~10%; epilepsy prevalence ~1%. Bimodal age distribution — peaks in childhood and after age 65.
Try two board-style Seizures and Epilepsy questions
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Question 1NeurologyEasy
A 19-year-old man is evaluated after his first unprovoked generalized tonic-clonic seizure, which lasted 3 minutes and was followed by return to baseline mental status. MRI of the brain and electroencephalogram (EEG) are normal, and there are no provoking factors. Which of the following is the most appropriate next step in management?
APrescribe as-needed rescue benzodiazepine
BAdmit for continuous video EEG monitoring
CDiscuss the risks and benefits of treatment
DReassure that no further workup is needed
EStart scheduled antiseizure medication now
Reveal answer & full explanation
Correct answer: C — Discuss the risks and benefits of treatment
APrescribe as-needed rescue benzodiazepine
BAdmit for continuous video EEG monitoring
CDiscuss the risks and benefits of treatment✓
DReassure that no further workup is needed
EStart scheduled antiseizure medication now
Why discussing the risks and benefits of treatment is correct
Epilepsy is defined as two unprovoked seizures, or one unprovoked seizure with a high recurrence risk (at least 60% over 10 years), which is suggested by risk factors such as an epileptiform electroencephalogram (EEG), a structural brain lesion, or a prior brain insult.
Two-year recurrence after a first unprovoked seizure is 21-45%, higher with an epileptiform EEG, a brain-imaging abnormality, a prior brain insult, or a nocturnal seizure; this patient has none of these, so his risk sits at the low end of that range and he does not meet the definition of epilepsy.
After a first unprovoked seizure, an antiseizure medication roughly halves short-term recurrence but does not improve long-term seizure freedom, so the decision is individualized through shared decision-making (per current American Academy of Neurology guidance).
The discussion should weigh driving restrictions, occupation, and patient preference.
Why the others are wrong
Start scheduled antiseizure medication now — Reflexively starting a drug ignores the low recurrence risk after a single seizure with a normal workup; premature-treatment trap.
Admit for continuous video EEG monitoring — The patient returned to baseline and the routine EEG is already normal; inpatient video EEG is for diagnostic uncertainty or status epilepticus, not a resolved first seizure; over-investigation trap.
Reassure that no further workup is needed — Dismisses the real recurrence risk and the need to counsel on driving and safety; under-management trap.
Prescribe as-needed rescue benzodiazepine — as-needed rescue therapy can look like a middle path between daily treatment and none, but rescue benzodiazepines are meant for patients with epilepsy who have seizure clusters or prolonged seizures, and this single seizure stopped on its own after 3 minutes; it also skips the counseling on recurrence risk and driving that the decision requires; wrong-indication trap.
Teaching point
After a first unprovoked seizure with a normal MRI and EEG, treatment is not mandatory; individualize the decision through shared decision-making.
Question 2NeurologyMedium
A 24-year-old female has had two unprovoked seizures 3 months apart. EEG shows generalized epileptiform discharges and MRI of the brain is normal. She uses no contraception and may want to become pregnant. Which of the following is the most appropriate first-line antiepileptic drug?
AValproate
BTopiramate
CCarbamazepine
DPhenytoin
ELamotrigine
Reveal answer & full explanation
Correct answer: E — Lamotrigine
AValproate
BTopiramate
CCarbamazepine
DPhenytoin
ELamotrigine✓
Why Lamotrigine is correct
Epilepsy diagnosis per International League Against Epilepsy (ILAE) 2014: two unprovoked seizures more than 24 hours apart, OR one unprovoked seizure with a high recurrence risk (abnormal EEG, structural lesion, prior brain injury, nocturnal seizure); treatment is therefore indicated here
For generalized epilepsy in a woman of childbearing age, lamotrigine (broad spectrum, favorable pregnancy profile with folic acid supplementation) and levetiracetam are preferred
Why the others are wrong
Valproate — the most effective generalized antiepileptic drug but highly teratogenic (neural tube defects, neurocognitive impairment) and avoided in this population unless no alternative exists (confused-with best-efficacy choice)
Phenytoin — not a preferred agent for generalized epilepsy in a woman of childbearing age due to teratogenicity and its narrow-spectrum profile (right-concept-wrong-drug)
Carbamazepine — also teratogenic and not preferred for generalized epilepsy in women who may become pregnant (anchoring on a familiar AED)
Topiramate — a broad-spectrum agent that covers generalized tonic-clonic seizures, but in utero exposure carries an increased risk of oral clefts and small-for-gestational-age infants, so it is not a preferred first-line choice for a woman who may become pregnant (confused-with broad-spectrum equivalence)
Additional high-yield points
Ethosuximide is indicated for absence seizures only and would not be appropriate here
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Sleep deprivation, photic stimulation (triggers in susceptible patients)
Pathophysiology
Excessive excitation (glutamate-driven) and/or insufficient inhibition (GABA-driven) at the cortical level produces hypersynchronous neuronal firing. Focal seizures begin in a discrete area and may remain focal or evolve to bilateral involvement. Generalized seizures involve both hemispheres from the outset, often via thalamocortical circuits.
Absence (typical childhood): brief staring spells with 3 Hz spike-wave on EEG, no postictal state
Myoclonic: brief shock-like jerks (juvenile myoclonic epilepsy: teen onset, jerks within an hour of waking ± GTC or absence, provoked by sleep deprivation and alcohol, 4-6 Hz polyspike-wave on EEG; usually needs lifelong AED because relapse after withdrawal is high)
Atonic ('drop attacks'): sudden loss of tone, falls
Prolactin elevated 10-20 min after generalized seizure (not absence or PNES) — limited utility now
Lumbar puncture if fever or meningitis suspected (after imaging)
Imaging
Non-contrast head CT in ED (acute structural lesion: hemorrhage, mass, stroke)
MRI brain with epilepsy protocol (thin coronal cuts through hippocampus) — for new-onset unprovoked seizures, focal features, or refractory epilepsy
EEG — standard initial (within 24-48 h boosts yield); sleep-deprived or prolonged EEG, video-EEG monitoring for diagnostic uncertainty or surgical workup
Diagnostic algorithm
Seizure Type
Awareness
Classic Features
First-Line AED
Focal aware
Preserved
Motor, sensory, autonomic, psychic symptoms
Levetiracetam, lamotrigine
Focal impaired awareness
Impaired
Automatisms, behavioral arrest
Levetiracetam, oxcarbazepine
Generalized tonic-clonic
Lost
Tonic stiffen → clonic jerks → postictal
Valproate, levetiracetam, lamotrigine
Absence
Brief loss
3 Hz spike-wave EEG, staring, no postictal
Ethosuximide, valproate
Myoclonic
Preserved
Brief shock-like jerks (JME morning jerks)
Valproate, levetiracetam
Atonic
May be impaired
Sudden tone loss, falls
Valproate, lamotrigine
ILAE 2017 seizure classification and first-line treatment.
Treatment
First-line
Acute single seizure: ensure airway, position on side, do NOT restrain or place objects in mouth; time the seizure
Antiepileptic — levetiracetam (1500-3000 mg/day) is broad-spectrum first-line for focal and generalized, lamotrigine (titrate slowly), valproate (avoid in women of childbearing potential — neural tube defects, reduced offspring IQ, autism risk)
Absence seizures: ethosuximide (first-line), valproate, lamotrigine; carbamazepine, oxcarbazepine, phenytoin, gabapentin/pregabalin and vigabatrin can worsen absence and myoclonic seizures — stop them (do not up-titrate) in generalized epilepsies such as childhood absence epilepsy and JME
Myoclonic: valproate, levetiracetam, lamotrigine (can worsen myoclonus in some patients)
Treat reversible cause if provoked seizure — typically no chronic AED needed
Febrile seizures (age 6 mo-5 yr, fever without CNS infection): simple = generalized, <15 min, no recurrence within 24 h — no routine EEG, neuroimaging or labs, find the fever source, LP if meningeal signs (an option at 6-12 mo if Hib/pneumococcal vaccination is incomplete, or at any age if pretreated with antibiotics), no prophylactic AED; complex = focal, >15 min or recurs within 24 h — warrants further evaluation
Infant seizures: neonatal seizures are often subtle (eye deviation, lip smacking, apnea) and need EEG confirmation — phenobarbital first-line (ILAE 2023) plus treat the cause (HIE most common, hypoglycemia, hypocalcemia, infection); infantile spasms/West syndrome (3-12 mo, clustered flexor spasms on waking, hypsarrhythmia, developmental regression; causes include HIE, Down syndrome, brain malformations and tuberous sclerosis) — ACTH, high-dose prednisolone or vigabatrin (preferred in tuberous sclerosis)
Second-line / adjunct
If breakthrough seizures: optimize first AED dose, then switch or add second agent
Refractory epilepsy (failure of 2 appropriate AEDs at adequate dose): refer to epilepsy center
Surgical options: temporal lobectomy (for mesial temporal sclerosis), focal cortical resection, laser ablation, corpus callosotomy for drop attacks
Neuromodulation: vagus nerve stimulator, responsive neurostimulation (RNS), deep brain stimulation
Medication side effects: valproate (weight gain, alopecia, hepatotoxicity, teratogenicity), lamotrigine (Stevens-Johnson syndrome), phenytoin (gingival hyperplasia, ataxia)
Pregnancy: valproate is the most teratogenic; lamotrigine and levetiracetam preferred
PANCE pearls
First unprovoked seizure does not automatically equal epilepsy — 2-yr recurrence risk is 21-45%, higher with an epileptiform EEG, structural brain lesion, prior brain insult or nocturnal seizure. Immediate AED lowers early recurrence but does not improve long-term remission, so whether to treat is an individualized, shared decision (AAN/AES 2015).
Lateral tongue bite is highly specific for generalized tonic-clonic seizure (tip-of-tongue bite occurs in syncope).
Postictal Todd paralysis can mimic stroke — resolves over minutes to hours; check old records and consider imaging if first event.
Ethosuximide treats absence ONLY (not generalized tonic-clonic). Valproate covers both.
Avoid valproate in women of childbearing potential when possible — neural tube defects, autism, IQ reduction. Folic acid 1-5 mg/day for women on any AED.
References
ILAE 2014 — ILAE Official Report: A Practical Clinical Definition of Epilepsy (Fisher et al., Epilepsia 2014)
ILAE 2017 — Operational Classification of Seizure Types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology (Fisher, Cross, French et al., Epilepsia 2017;58:522-530)
AAN/AES 2015 — Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults (Krumholz et al., Neurology 2015;84:1705-1713) — reaffirmed 2024
AES 2016 — Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus (Glauser et al., Epilepsy Currents 2016)
AAP 2011 — Neurodiagnostic Evaluation of the Child With a Simple Febrile Seizure (AAP Subcommittee on Febrile Seizures, Pediatrics 2011;127:389-394)
ILAE 2023 — Treatment of Seizures in the Neonate: Guidelines and Consensus-Based Recommendations — Special Report from the ILAE Task Force on Neonatal Seizures (Pressler et al., Epilepsia 2023;64:2550-2570)
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