Epilepsy & Seizures
Medicine · Neurology · lean revision notes
Epilepsy & Seizures
A perennial NEET PG favourite that cuts across Medicine, Pharmacology and Paediatrics. Mastery of the ILAE classification, age-specific EEG signatures, drug-of-choice by seizure type, and the status epilepticus protocol will reliably fetch you 2–4 questions every exam cycle.
Definitions & key concepts
A seizure is a transient occurrence of signs/symptoms due to abnormal, excessive or synchronous neuronal discharge in the brain. Epilepsy is a disease of the brain defined by ANY of the following (ILAE 2014 operational definition):
- At least two unprovoked (or reflex) seizures occurring >24 hours apart, OR
- One unprovoked seizure with a probability of recurrence ≥60% over the next 10 years (e.g. a remote symptomatic seizure with an old stroke + epileptiform EEG), OR
- Diagnosis of an epilepsy syndrome.
High-yield: A single provoked seizure (hyponatraemia, hypoglycaemia, alcohol withdrawal, fever, eclampsia, drug toxicity) is NOT epilepsy. Correct the trigger — do not commit to long-term antiepileptic drugs (AEDs).
Epileptogenesis involves an imbalance favouring excitation (glutamate, NMDA/AMPA) over inhibition (GABA-A, GABA-B). Common substrates: hippocampal sclerosis (mesial temporal lobe epilepsy — the commonest cause of refractory focal epilepsy in adults), cortical dysplasia, tumours, gliosis post-trauma/stroke/infection (neurocysticercosis is the leading cause of acquired epilepsy in India).
Classification (ILAE 2017)
The 2017 framework classifies by onset:
| Onset type | Subtypes | Awareness | Old terminology |
|---|---|---|---|
| Focal | Focal aware / Focal impaired awareness; motor vs non-motor onset; focal-to-bilateral tonic-clonic | Preserved or impaired | Simple partial / Complex partial / Secondarily generalised |
| Generalised | Tonic-clonic, absence (typical/atypical), myoclonic, tonic, atonic, clonic | Always impaired | Grand mal / Petit mal etc. |
| Unknown onset | Tonic-clonic, epileptic spasms, behaviour arrest | — | — |
High-yield: The terms "simple partial", "complex partial" and "secondarily generalised" are obsolete. Use focal aware, focal impaired awareness, and focal-to-bilateral tonic-clonic respectively.
Aura = focal aware seizure. It localises the focus: epigastric rising sensation / déjà vu / fear → mesial temporal lobe; visual flashes → occipital; tingling marching up a limb (Jacksonian march) → frontal/motor cortex; forced head/eye deviation → frontal eye field.
Focal vs generalised — distinguishing features
| Feature | Focal | Generalised |
|---|---|---|
| Onset | One hemisphere/region | Bilateral networks from start |
| Aura | Often present | Absent |
| Post-ictal confusion / Todd's palsy | Common | Variable (absent in absence) |
| Consciousness | May be preserved | Lost (except myoclonic where brief) |
| EEG | Focal spikes | Generalised spike-wave |
| Imaging yield | High (look for structural lesion) | Usually normal |
Important epilepsy syndromes (paediatric high-yield)
| Syndrome | Age | Seizure type | EEG | DOC / note |
|---|---|---|---|---|
| West syndrome | 3–8 months | Epileptic (infantile) spasms — flexor "salaam" | Hypsarrhythmia | ACTH / vigabatrin (vigabatrin first if tuberous sclerosis) |
| Lennox-Gastaut | 1–8 yrs | Mixed: tonic, atonic, atypical absence | Slow (<2.5 Hz) spike-wave | Valproate, lamotrigine, rufinamide; refractory |
| Childhood absence epilepsy | 4–10 yrs | Typical absence | 3 Hz generalised spike-wave (provoked by hyperventilation) | Ethosuximide (or valproate) |
| Juvenile myoclonic epilepsy (Janz) | Teens | Early-morning myoclonic jerks ± GTCS | 4–6 Hz polyspike-wave | Valproate (lifelong); avoid carbamazepine |
| Benign rolandic (BECTS) | 3–13 yrs | Nocturnal focal, face/oropharynx | Centrotemporal spikes | Often no treatment; excellent prognosis |
| Dravet syndrome | <1 yr | Prolonged febrile, hemiclonic | — | SCN1A mutation; avoid sodium-channel blockers |
High-yield (EEG triad to memorise): 3 Hz spike-wave = absence; hypsarrhythmia = West; slow spike-wave <2.5 Hz = Lennox-Gastaut.
High-yield: In West syndrome, look for tuberous sclerosis (ash-leaf macules, cardiac rhabdomyoma) — vigabatrin is the drug of choice in that setting.
Etiology
Mnemonic "VITAMINS" for seizure causes: Vascular (stroke), Infection (meningitis, NCC, encephalitis), Trauma/tumour, Autoimmune (anti-NMDA-R encephalitis, anti-LGI1), Metabolic (↓Na⁺, ↓glucose, ↓Ca²⁺, ↓Mg²⁺, uraemia), Idiopathic/genetic, Neurodegenerative/congenital malformations, Substance (alcohol/benzodiazepine withdrawal, cocaine, tramadol, isoniazid → give pyridoxine).
Age clue: neonate → HIE, hypoglycaemia, hypocalcaemia, sepsis; child → febrile seizure, genetic; young adult → trauma, NCC; elderly → stroke (commonest), tumour.
Clinical features
- Generalised tonic-clonic (GTCS): sudden loss of consciousness → tonic stiffening (often a cry from forced expiration) → clonic jerking → flaccid post-ictal phase with confusion, tongue-biting (lateral), urinary incontinence, and post-ictal headache/myalgia. Lasts 1–3 min.
- Absence: abrupt 5–10 s behavioural arrest with staring/eyelid flutter, no aura, no post-ictal confusion, immediate resumption of activity; provoked by hyperventilation.
- Myoclonic: brief shock-like jerks, consciousness retained.
- Atonic ("drop attacks"): sudden loss of tone → falls/injury.
- Focal impaired awareness: automatisms (lip-smacking, fumbling), staring, post-ictal confusion.
Seizure vs syncope vs pseudoseizure (PNES)
| Feature | Epileptic seizure | Syncope | Psychogenic (PNES) |
|---|---|---|---|
| Trigger | Often none | Posture, pain, micturition | Emotional/stress |
| Onset | Sudden | Pre-syncope (lightheaded) | Gradual, situational |
| Movements | Rhythmic, synchronous | Few myoclonic jerks | Asynchronous, pelvic thrust, side-to-side head, eyes closed |
| Tongue bite | Lateral | Rare/tip | Rare |
| Post-ictal | Confusion, ↑prolactin (early) | Rapid recovery | No confusion, normal prolactin |
| EEG (ictal) | Epileptiform | Normal | Normal during event |
High-yield: Serum prolactin rises within 10–20 min after GTCS/focal-impaired-awareness seizures and helps differentiate true seizure from PNES — but a normal level does not exclude a seizure, and it is unreliable for absence/myoclonic types.
Diagnosis & investigation of choice
A first-seizure workup answers two questions: Was it a seizure? and Why?
Stepwise approach: History (eye-witness account is key) → rule out provoked causes (glucose, Na⁺, Ca²⁺, Mg²⁺, toxicology, pregnancy test) → EEG (best test to characterise seizure type / epileptiform discharges) → MRI brain (investigation of choice for structural cause; far superior to CT for hippocampal sclerosis, dysplasia, low-grade tumours) → LP if infection suspected.
- EEG is the investigation of choice to classify the epilepsy and detect epileptiform activity; sensitivity rises with sleep deprivation, hyperventilation, photic stimulation and repeat/prolonged video-EEG. A normal interictal EEG does not exclude epilepsy.
- MRI brain is the imaging investigation of choice for aetiology (epilepsy protocol). CT is reserved for the acute/emergency setting (bleed, gross lesion) and where MRI is unavailable.
- Video-EEG monitoring is the gold standard to confirm PNES and for pre-surgical localisation.
High-yield: First single unprovoked seizure with a normal EEG, normal MRI and normal neuro exam → recurrence risk is low; AEDs are generally NOT started after one such seizure. Treat after a second seizure or when recurrence risk is high.
Management / drug of choice
Drug-of-choice by seizure type
| Seizure type | First-line / DOC | Alternatives | Avoid (worsen seizures) |
|---|---|---|---|
| Focal (± to bilateral) | Lamotrigine / levetiracetam (carbamazepine, oxcarbazepine) | Lacosamide, valproate | — |
| Generalised tonic-clonic | Valproate (lamotrigine, levetiracetam) | Topiramate | — |
| Absence | Ethosuximide (valproate) | Lamotrigine | Carbamazepine, phenytoin, vigabatrin, gabapentin |
| Myoclonic / JME | Valproate (levetiracetam) | Topiramate, clonazepam | Carbamazepine, phenytoin, gabapentin |
| Atonic / Lennox-Gastaut | Valproate | Lamotrigine, rufinamide | — |
| Infantile spasms (West) | ACTH / vigabatrin | Prednisolone | — |
High-yield: Sodium-channel blockers (carbamazepine, oxcarbazepine, phenytoin) and GABAergic agents (vigabatrin, gabapentin, pregabalin, tiagabine) can WORSEN absence and myoclonic seizures. A classic NEET PG trap: giving carbamazepine in JME aggravates myoclonus.
High-yield: Ethosuximide acts on T-type calcium channels in thalamic neurons → drug of choice for absence only (no effect on GTCS; if both coexist, use valproate).
Principle of monotherapy: Start one drug at low dose, titrate up; ~50% are controlled on the first drug. If it fails at maximal dose, substitute a second monotherapy before resorting to polytherapy. Drug-resistant (refractory) epilepsy = failure of 2 appropriately chosen, tolerated AEDs → refer for surgery (e.g. anterior temporal lobectomy for mesial temporal sclerosis), vagus nerve stimulation, or ketogenic diet.
Mechanisms (commonly asked)
- Phenytoin, carbamazepine, lamotrigine, lacosamide → block voltage-gated Na⁺ channels.
- Ethosuximide → blocks T-type Ca²⁺ channels.
- Valproate → broad: Na⁺ channel + ↑GABA + T-type Ca²⁺ (broadest spectrum AED).
- Benzodiazepines, barbiturates → enhance GABA-A (BZD ↑frequency of Cl⁻ channel opening; barbiturates ↑duration).
- Vigabatrin → irreversibly inhibits GABA transaminase.
- Levetiracetam → binds SV2A synaptic vesicle protein.
- Topiramate → multiple (Na⁺ block, GABA, AMPA/kainate antagonism, carbonic anhydrase inhibition).
- Perampanel → AMPA receptor antagonist.
Status epilepticus (SE)
Definition (operational, ILAE 2015): a seizure lasting ≥5 minutes (t1 — time to start treatment) or ≥2 seizures without recovery of consciousness between them. The older "30-minute" cut-off (t2 — risk of permanent injury) is for prognostic damage, not for when to treat. Convulsive SE is a medical emergency with mortality up to 20%.
Stepwise protocol (memorise the timeline):
- 0–5 min — Stabilise: ABC, oxygen, IV access, finger-stick glucose; if hypoglycaemic give dextrose (+ thiamine in alcoholics); check Na⁺/Ca²⁺/toxicology.
- 5–20 min — First-line (benzodiazepine): IV lorazepam 0.1 mg/kg (max 4 mg/dose, may repeat once). If no IV access → IM midazolam 10 mg or PR/buccal diazepam.
- 20–40 min — Second-line (load an AED): IV fosphenytoin (20 mg PE/kg) OR IV valproate (40 mg/kg) OR IV levetiracetam (60 mg/kg). The ESETT trial showed these three are equally effective (~half respond to any one).
- 40–60 min — Refractory SE: continuous infusion midazolam / propofol / thiopental under EEG monitoring + intubation/ICU.
Stepwise (one-line flow): Lorazepam → fosphenytoin/valproate/levetiracetam → anaesthetic infusion (midazolam/propofol) → EEG-guided burst-suppression.
High-yield: IV lorazepam is the preferred first-line benzodiazepine (longer anticonvulsant duration than diazepam, which redistributes quickly). When no IV access, IM midazolam is at least as good (RAMPART trial). Don't give phenytoin first — it is second-line.
High-yield: Fosphenytoin is preferred over phenytoin: water-soluble prodrug, less tissue injury, no propylene glycol, can be given IM. Phenytoin must be given slowly (<50 mg/min) with cardiac monitoring; extravasation causes purple glove syndrome.
AED toxicity & teratogenicity (very high-yield)
| Drug | Hallmark adverse effects |
|---|---|
| Phenytoin | Gum hyperplasia, hirsutism, coarse facies, cerebellar (nystagmus/ataxia), megaloblastic anaemia (↓folate), zero-order kinetics, DRESS, osteomalacia, fetal hydantoin syndrome |
| Carbamazepine | SIADH/hyponatraemia, aplastic anaemia/agranulocytosis, SJS/TEN in HLA-B*1502 (test Asians), diplopia, auto-induction; teratogenic — neural tube defects |
| Valproate | Hepatotoxicity, pancreatitis, hyperammonaemia, weight gain, tremor, alopecia, thrombocytopenia; MOST teratogenic — NTD, ↓IQ, autism |
| Lamotrigine | SJS/TEN (esp. with rapid titration or valproate co-use — titrate slowly) |
| Levetiracetam | Behavioural/mood changes, irritability, depression (give pyridoxine) |
| Topiramate | Weight loss, word-finding difficulty, renal stones, glaucoma, oligohidrosis, metabolic acidosis |
| Vigabatrin | Irreversible visual field constriction (peripheral) |
| Ethosuximide | GI upset, SJS, hiccups |
| Phenobarbitone | Sedation, hyperactivity in children, osteomalacia |
High-yield (teratogenicity ladder): Valproate is the most teratogenic AED (neural-tube defects, reduced IQ, autism spectrum). AVOID valproate in women of childbearing potential. Preferred AEDs in pregnancy: lamotrigine and levetiracetam. All women on AEDs should take folic acid 5 mg/day pre-conception.
High-yield: Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbitone, topiramate at high dose) reduce efficacy of oral contraceptives — counsel accordingly. Valproate, levetiracetam, lamotrigine are non-inducers.
Complications
- SUDEP (Sudden Unexpected Death in Epilepsy) — main risk factor is frequent uncontrolled GTCS, especially nocturnal.
- Status epilepticus — cerebral oedema, rhabdomyolysis, lactic acidosis, hyperthermia, aspiration.
- Injuries — fractures, burns, drowning (advise against unsupervised swimming/heights).
- Psychiatric — depression, anxiety, increased suicide risk (esp. with some AEDs).
- Driving / occupational restrictions until a seizure-free interval is met.
- Memory & cognitive decline in poorly controlled mesial temporal lobe epilepsy.
Key differentials
- Syncope (convulsive syncope can mimic seizure — short, no post-ictal confusion).
- Psychogenic non-epileptic seizures (PNES) — confirm with video-EEG.
- Transient ischaemic attack (usually "negative" deficits vs "positive" seizure phenomena).
- Migraine with aura (slower march, visual scintillations, headache).
- Panic attack, hypoglycaemia, breath-holding spells (children), parasomnias, transient global amnesia, paroxysmal movement disorders.
Recently asked / exam angle
- EEG image MCQs: identify 3 Hz spike-and-wave (absence) and hypsarrhythmia (West syndrome) — repeatedly asked with clinical vignettes.
- Drug-of-choice grids: ethosuximide for absence; valproate for JME; avoid carbamazepine in absence/myoclonic — the carbamazepine-aggravation trap.
- Status epilepticus sequence: "first-line drug" = lorazepam; "no IV access" = IM midazolam; second-line = fosphenytoin / valproate / levetiracetam (ESETT).
- Teratogenicity: valproate as the most teratogenic AED; preferred agents in pregnancy; folic acid dose.
- Pharmacology one-liners: ethosuximide = T-type Ca²⁺ channel; levetiracetam = SV2A; vigabatrin = GABA-transaminase inhibitor + visual field defect; lamotrigine + valproate combination → SJS risk.
- Phenytoin pharmacokinetics: zero-order (saturation) kinetics, gum hypertrophy, fosphenytoin advantages, purple glove syndrome.
- NCC as the commonest cause of acquired epilepsy / new-onset focal seizures in Indian adults (ring-enhancing lesion on contrast imaging).
- HLA-B*1502 and carbamazepine-induced SJS/TEN screening in Asians.
- Refractory epilepsy definition = failure of 2 appropriate AEDs → surgical referral.
Rapid revision
- Epilepsy = ≥2 unprovoked seizures >24 h apart, OR 1 seizure with ≥60% recurrence risk, OR a syndrome.
- 3 Hz spike-wave = absence; hypsarrhythmia = West; slow (<2.5 Hz) spike-wave = Lennox-Gastaut.
- DOC absence = ethosuximide; JME/myoclonic & generalised = valproate; focal = lamotrigine/levetiracetam.
- Carbamazepine, phenytoin, vigabatrin, gabapentin WORSEN absence & myoclonic seizures.
- Status epilepticus ≥5 min → lorazepam first, then fosphenytoin/valproate/levetiracetam (equal — ESETT), then anaesthetic infusion.
- No IV access in SE → IM midazolam (RAMPART).
- Valproate = most teratogenic AED (NTD, ↓IQ) — avoid in childbearing women; prefer lamotrigine/levetiracetam + folic acid 5 mg.
- MRI brain is the imaging investigation of choice for aetiology; EEG is best to classify; normal EEG does NOT exclude epilepsy.
- Ethosuximide → T-type Ca²⁺ channels; levetiracetam → SV2A; vigabatrin → GABA-transaminase (visual field loss).
- Mesial temporal sclerosis = commonest cause of refractory focal epilepsy; NCC = commonest acquired cause of epilepsy in India; stroke = commonest in the elderly.
- Vigabatrin is DOC for infantile spasms in tuberous sclerosis; otherwise ACTH/vigabatrin for West syndrome.
- Refractory epilepsy = failure of 2 appropriate AEDs → consider surgery, VNS, or ketogenic diet.