Neurology
Epileptic Seizure
Hypersynchronous neuronal firing, EEG spike-wave, and the 5-minute emergency rule
A seizure is a transient burst of excessive synchronous neuronal firing. EEG shows spike-wave complexes. Status epilepticus — a seizure over 5 minutes — is a medical emergency requiring intravenous benzodiazepine first-line.
- Status epilepticus cutoff>5 min or 2 seizures without recovery
- Lifetime seizure risk~10% (epilepsy in 1-3%)
- First-line emergencyBenzodiazepine (lorazepam 4 mg IV)
- EEG signatureSpike-wave / polyspike complexes
- Seizure-free on monotherapy~⅔ of patients
- Status mortality10-20% (worse with delay)
Interactive visualization
Press play, or step through manually. Watch a focal onset evolve into hypersynchronous firing across the cortex, with the EEG trace below.
Watch the 60-second explainer
A condensed visual walkthrough — narrated, captioned, under a minute.
How it works
The healthy cortex is a precisely tuned balance of glutamate (excitatory) and GABA (inhibitory) signaling. A handful of pyramidal neurons fire, a wave of GABA inhibition follows, and the local network resets. In a seizure, this homeostasis fails. Excitation outruns inhibition. Membrane currents synchronize across a population: thousands of pyramidal neurons depolarize together, generating a large paroxysmal depolarization shift visible on scalp EEG as a sharp spike. The spike is followed by a slow GABA-mediated wave that briefly suppresses firing. The repeating spike-wave pattern is the electrographic seizure.
The triggers are diverse: scarring after stroke or trauma builds an irritable focus; hippocampal sclerosis from prolonged febrile seizures creates a mesial temporal generator; channel mutations (SCN1A in Dravet, KCNQ2 in neonatal epilepsy) lower seizure threshold; tumors irritate adjacent cortex; metabolic stresses (hypoglycemia, hyponatremia, alcohol withdrawal) tip the balance acutely. Whatever the trigger, the final common pathway is the same: hypersynchronous, hyperexcitable firing.
Worked clinical example
A 22-year-old college student is brought to the emergency department after a witnessed convulsion at his desk. Roommates report he made odd lip-smacking movements and stared blankly for about thirty seconds before stiffening, falling, and shaking rhythmically for two minutes. He bit his tongue and was incontinent. On arrival he is somnolent and confused — the post-ictal state. He has no prior seizures but has been studying through the night for finals. Examination is non-focal. CT is normal. Labs show CK 1,400, lactate 6.2, anion gap closing on repeat draw. Urine tox is negative. Routine EEG the next morning shows left temporal spikes — this is a focal seizure with impaired awareness evolving to bilateral tonic-clonic. He starts levetiracetam 500 mg twice daily, is advised against driving for six months per state law, and a 3 T MRI shows mild left hippocampal asymmetry suggesting mesial temporal sclerosis as the irritable focus.
Status epilepticus — the 5-minute rule
A seizure lasting more than five minutes will rarely terminate on its own. The neurons are still firing, the patient is still apneic in tonic phase, lactate is climbing, and excitotoxic injury is beginning. The clock starts at minute zero:
- 0-5 min — stabilization. Airway, breathing, circulation. Fingerstick glucose. IV access. Time the seizure.
- 5-20 min — first-line. Lorazepam 4 mg IV (repeat once at 10 min if seizure persists); or midazolam 10 mg IM if no IV access; or diazepam 20 mg PR in the field.
- 20-40 min — second-line. Levetiracetam 60 mg/kg IV, or fosphenytoin 20 mg PE/kg IV, or valproate 40 mg/kg IV. The ESETT trial showed roughly equivalent efficacy across all three.
- 40+ min — refractory status. Intubate. Continuous EEG. Anesthetic infusion (propofol, midazolam, or pentobarbital) titrated to burst suppression for 24-48 hours.
Every minute of delay to first-line therapy increases the chance of refractory status and worsens neurological outcome.
Common pitfalls
- Calling all collapses 'seizures'. Convulsive syncope — brief jerks during vasovagal fainting — is not epilepsy. Tongue biting (especially lateral), incontinence, and a true post-ictal state argue for seizure; a clear prodrome (warm flush, dimming vision, sweating) and immediate orientation on the floor argue for syncope.
- Using sodium-channel blockers for absence or myoclonic seizures. Carbamazepine, oxcarbazepine, and phenytoin can worsen these generalized epilepsies. The right choice is ethosuximide (absence) or valproate / levetiracetam (myoclonic / JME).
- Stopping anti-seizure drugs cold. Abrupt discontinuation, especially of benzodiazepines or phenobarbital, is a textbook trigger for status epilepticus.
- Missing pseudostatus (PNES). Psychogenic non-epileptic spells often have asynchronous limb movement, pelvic thrusting, eye closure with resistance, and normal capnography. Video-EEG is diagnostic. Treating PNES with escalating anesthetics is harmful.
- Ignoring driving restrictions. Most jurisdictions require a seizure-free interval (commonly 6-12 months) before driving — a frequently missed medico-legal counseling point.
| Feature | Focal onset | Generalized onset |
|---|---|---|
| Origin | One cortical zone, one hemisphere | Bilateral, both hemispheres from onset |
| Typical aura | Yes (déjà vu, fear, smell, motor) | No aura (instant loss of awareness) |
| EEG | Focal interictal spikes, regional rhythmic activity | 3-Hz spike-wave (absence) or 4-6 Hz polyspike-wave (JME) |
| Awareness | Preserved (simple) or impaired (complex) | Always impaired (except myoclonic, brief) |
| Common etiology | Mesial temporal sclerosis, stroke, tumor, trauma | Genetic generalized epilepsies (JME, CAE, JAE) |
| First-line drug | Lamotrigine, levetiracetam, oxcarbazepine | Valproate (men), lamotrigine or levetiracetam (women) |
| Surgery candidate | Often (resect the focus) | Rarely (callosotomy, VNS, RNS only) |
Frequently asked questions
What is a seizure, biologically?
A seizure is a transient episode of signs or symptoms caused by hypersynchronous, hyperexcitable neuronal activity in the brain. Normally, networks balance glutamatergic excitation (Na⁺/Ca²⁺ inflow, depolarization) with GABAergic inhibition (Cl⁻ inflow, hyperpolarization). When inhibition fails — through channel mutations, scarring, electrolyte shifts, sleep deprivation, drugs, or fever — a population of neurons fires in lockstep at 3-50 Hz, producing the symptoms and the characteristic EEG signature.
What's the difference between focal and generalized seizures?
Focal seizures begin in one hemisphere — a discrete cortical zone (often mesial temporal lobe in adults). Symptoms reflect the function of that zone: déjà vu, fear, automatisms, lip-smacking. Awareness may be preserved (simple) or impaired (complex). They can spread to become bilateral (secondarily generalized). Generalized seizures involve both hemispheres from onset: absence (brief staring, 3 Hz spike-wave), myoclonic (jerks), tonic-clonic (the classic 'grand mal'), atonic (drop attacks). Classification drives drug choice — many sodium-channel blockers worsen absence and myoclonic seizures.
Why is status epilepticus a medical emergency?
Status epilepticus is a seizure lasting more than 5 minutes, or two or more seizures without recovery of consciousness between them. The 5-minute cutoff is operational: spontaneous termination becomes unlikely beyond that point and neuronal injury starts. Mortality is 10-20%. First-line: intravenous benzodiazepine (lorazepam 4 mg IV, or midazolam 10 mg IM if no access). Second-line: levetiracetam, fosphenytoin, or valproate. Third-line: anesthetic infusion (propofol, midazolam, pentobarbital). Hyperthermia, rhabdomyolysis, and excitotoxic neuronal death drive the worst outcomes.
How does EEG detect a seizure?
Scalp EEG records the summed postsynaptic potentials of cortical pyramidal neurons through electrodes placed by the 10-20 system. A normal awake recording shows alpha (8-13 Hz, occipital, eyes closed) and beta (>13 Hz, frontal). Seizures produce stereotyped abnormalities: focal spikes at the seizure onset zone, generalized 3-Hz spike-wave in absence, polyspike-and-wave in juvenile myoclonic epilepsy, and high-amplitude rhythmic theta or delta evolving over seconds. About 50% of patients with active epilepsy show interictal epileptiform discharges on a single 30-minute EEG; sleep deprivation and sleep recording roughly double the yield.
What drugs treat epilepsy?
Antiseizure medications act at four broad targets. Sodium channels: phenytoin, carbamazepine, oxcarbazepine, lacosamide. GABA enhancement: valproate, benzodiazepines, phenobarbital. Calcium channels: ethosuximide (T-type, for absence), gabapentin, pregabalin (α2δ). Synaptic vesicles: levetiracetam (SV2A). Broad-spectrum agents (valproate, levetiracetam, lamotrigine, topiramate) work across seizure types; narrow-spectrum drugs target one mechanism. Roughly two-thirds of patients become seizure-free on monotherapy; the remaining one-third has drug-resistant epilepsy and may need surgery, vagus nerve stimulation, responsive neurostimulation, or ketogenic diet.
What is the post-ictal state?
After a generalized tonic-clonic seizure, patients are confused, drowsy, and often have a headache for 10-60 minutes. Todd's paralysis — unilateral weakness lasting up to 48 hours — can follow focal motor seizures and is sometimes mistaken for stroke. Lactate is elevated in arterial blood gas. CK rises from muscle activity. The post-ictal state reflects neuronal exhaustion, ATP depletion, and inhibitory rebound. Memory of the event is usually absent.
Is an isolated first seizure 'epilepsy'?
No. Epilepsy is defined as two or more unprovoked seizures more than 24 hours apart, or one seizure with a high (>60%) risk of recurrence (e.g., MRI lesion, abnormal EEG, prior stroke). About 10% of people will have a seizure in their lifetime; only 1-3% develop epilepsy. Provoked seizures — from fever (febrile in children under 5), hypoglycemia, hyponatremia, alcohol withdrawal, or stimulant overdose — do not count toward an epilepsy diagnosis. Provoked seizures resolve when the trigger is corrected.