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Seizures — A Comprehensive Overview

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1. Definition

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2. ILAE 2017 Classification of Seizure Types

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2A. Focal (Partial) Onset Seizures

• Consciousness is fully preserved throughout
• Purely subjective manifestations are often called auras
• Semiology reflects the origin: tonic/clonic activity is contralateral to the hemisphere; somatosensory/visual/auditory auras have strong localizing value
• Auras typically last seconds to minutes; prolonged auras = aura continua (a form of focal nonconvulsive status epilepticus)

• Altered awareness — may range from subtle confusion to complete amnesia for the event
• Often begin with an aura or abrupt loss of awareness
• Automatisms (repetitive purposeless movements — lip smacking, picking) are characteristic
• Most commonly arise from the temporal lobe

• A focal seizure spreads to involve both hemispheres
• Preceded by an aura; key distinction from primary generalized tonic-clonic

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2B. Generalized Onset Seizures

• Most dramatic seizure type
• Tonic phase (10–20 sec): sustained muscle contraction, extension of trunk and extremities, apnea, cyanosis
• Clonic phase: rhythmic synchronous muscle contractions
• Autonomic changes: ↑ BP & HR, mydriasis, piloerection, urinary/fecal incontinence, diaphoresis
• Injuries from fall: shoulder dislocation, tongue biting
• Typical duration: 60–90 seconds (bystanders typically overestimate)
• Postictal period: slow return of consciousness, lethargy, confusion, myalgias, fatigue — may last hours; pathologically brisk reflexes may be present

• Onset: 5–15 years (childhood absence epilepsy typically 4–10 years, usually remits by age 12)
• Brief (usually 10–15 seconds, never >40 seconds), abrupt onset and offset
• Behavioral arrest, staring, eyelid fluttering — no postictal symptoms
• May occur >100 times/day, often mistaken for daydreaming
• Complex absence has additional clonic/tonic/autonomic or automatism components
• Provoked in clinic by hyperventilation for 3–4 minutes
• EEG: classic 3 Hz spike-and-wave discharges

• Sudden, brief (<100 ms) involuntary muscle contractions, often bilateral
• Characteristic of juvenile myoclonic epilepsy (JME), Dravet syndrome
• Less rhythmic and less sustained than clonus

• Sudden loss of postural muscle tone → forward fall
• Seen in Lennox-Gastaut syndrome

• Sustained increase in muscle tone; brief impairment of consciousness

• Sudden flexion, extension, or mixed truncal/proximal limb movements
• Classic in infantile spasms (West syndrome)

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3. Etiology and Classification of Epilepsy

• Lennox-Gastaut syndrome (multiple etiologies)
• Dravet syndrome (SCN1A mutation ~85%)
• CDKL5 deficiency disorder
• West syndrome (infantile spasms)
• PCDH19 clustering epilepsy, GLUT1 deficiency syndrome

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4. Pathophysiology

1. Failure of GABAergic inhibition — reduced inhibitory tone allows unchecked excitation
2. Enhanced glutamatergic excitation — excessive NMDA and AMPA receptor activation
3. Voltage-gated sodium channel dysregulation — during normal firing, sodium channels cycle through resting → open → inactivated states. In seizure discharges, repetitive high-frequency depolarization leads to channel accumulation in the inactivated state, but intrinsic channel defects or ion imbalances can impair this regulation
4. Abnormal calcium influx via T-type calcium channels (especially relevant in absence seizures — thalamocortical circuits)
5. Loss of surround inhibition in the perifocal area that normally contains a discharge

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5. Precipitants and Risk Factors

• Prior febrile seizures
• Family history of seizures
• Prior head trauma, stroke, CNS tumor, CNS infection
• Developmental abnormalities

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6. Epidemiology

• Incidence in North America: 16–51 per 100,000/year (higher in developing countries, up to 111/100,000)
• Prevalence: 2.7–7.1 per 1,000 (higher in males, lower socioeconomic status)
• Bimodal distribution: highest incidence in first decade and after age 65
• Cumulative lifetime risk of epilepsy: ~4% by age 80
• 2-year recurrence risk after first unprovoked seizure: ~40%
• Risk doubles after second seizure (61% at 2 years, 73% at 5 years)
• Factors predicting recurrence: abnormal EEG, abnormal neurological examination

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7. Clinical Evaluation

Harrison's Evaluation Flowchart

• Was this truly a seizure? (exclude syncope, TIA, migraine, acute psychosis, panic attack)
• What was before/during/after: aura, ictal semiology, postictal state
• Witness account is critical (patient often has no recollection of ictal and immediate postictal phases)
• Risk factors: prior febrile seizures, family history, head trauma, stroke, CNS infection, drugs/alcohol
• In known epilepsy: assess medication adherence and current drug levels

• Signs of systemic illness, infection, trauma
• Skin: tuberous sclerosis, neurofibromatosis, chronic liver/renal disease
• Cardiovascular: auscultation for causes of cerebrovascular disease
• Neurological: cranial nerve examination, motor/sensory exam, mental status (memory, language, abstract thinking), visual fields

• Absence: 3 Hz bilateral spike-and-wave
• Focal seizure: unilateral sharp waves or spike discharges
• GTC: high-amplitude polyspike and wave
• Interictal epileptiform discharges confirm epileptogenic tendency; normal interictal EEG does not exclude epilepsy

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8. Differential Diagnosis

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9. Antiseizure Medications (ASMs) — Mechanisms and Indications

Mechanism Classes

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Drug Selection by Seizure/Syndrome Type

• Enzyme inducers (carbamazepine, phenytoin, phenobarbital, rufinamide) → reduce levels of oral contraceptives, warfarin, many other drugs
• Enzyme inhibitors (valproate) → increase levels of other ASMs
• Low-interaction drugs (gabapentin, levetiracetam, brivaracetam, lacosamide) → preferred in elderly, polypharmacy, or women on OCP

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10. Status Epilepticus (SE)

• Convulsive SE (CSE): GTC activity; medical emergency with significant mortality
• Nonconvulsive SE (NCSE): Ongoing electrical seizures without obvious motor manifestations; requires continuous EEG for diagnosis; commonly missed; mortality increases with delayed recognition especially in age >60

Management Protocol

• IV lorazepam has onset in 3 min, duration 12–24 h; preferred over diazepam (15–60 min duration)
• IM midazolam is as safe and effective as IV lorazepam when no IV access; decreased seizure time and fewer ICU admissions in prehospital trials
• Do not attempt LP during SE; if meningitis/encephalitis suspected, start empiric antibiotics/antivirals immediately
• Paralytic agents mask convulsive activity → continuous EEG monitoring mandatory after neuromuscular blockade

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11. Special Situations

Febrile Seizures

• Most common seizure type in children (3 months–5 years)
• Simple febrile seizure: generalized, <15 min, single in 24 h — benign prognosis
• Complex febrile seizure: focal, >15 min, or recurs within 24 h — higher risk of epilepsy

Pregnancy and Seizures

• Volume of distribution and plasma clearance of ASMs increase → drug levels may fall
• Most ASMs are teratogenic; valproate, carbamazepine, phenytoin carry highest risk
• Preferred ASMs in pregnancy: levetiracetam or lamotrigine monotherapy
• Fetal bradycardia lasting up to 20 min can follow a single brief maternal seizure
• Status epilepticus in pregnancy carries significant maternal and fetal mortality → aggressive management including early intubation

Catamenial Epilepsy

• ~55% of women with epilepsy have seizure clustering related to menstruation
• Most common pattern: perimenstrual (3 days before to 3 days after onset of menses)
• Mechanism: estradiol (proconvulsant) vs. progesterone (anticonvulsant)
• Treatment: progesterone therapy as adjunct when standard ASMs fail

Post-Surgical Seizure Prophylaxis

• Routine prophylaxis is not indicated for most neurosurgical procedures unless seizure risk is high (traumatic brain injury, supratentorial surgery near cortex)

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12. Surgical Treatment

• Temporal lobectomy (most evidence): 60–70% seizure freedom in temporal lobe epilepsy with hippocampal sclerosis
• Lesionectomy: removal of epileptogenic lesion (cortical dysplasia, tumor, vascular malformation)
• Corpus callosotomy: palliative for drop attacks in Lennox-Gastaut
• Responsive neurostimulation (RNS): closed-loop device that detects and terminates ictal activity
• Vagal nerve stimulation (VNS): palliative, reduces seizure frequency by ~50% in ~50% of patients

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13. Prognosis

• ~65% of newly diagnosed epilepsy patients achieve complete remission on ASMs
• ~45–50% remit on the first drug; ~10–15% on the second; ~35% are drug-resistant
• Remission more likely: vascular malformations, stroke, tumors (63–78%)
• Remission less likely: hippocampal sclerosis, cortical malformations (40–50%)
• SUDEP (Sudden Unexpected Death in Epilepsy): rare but real risk (~1/1,000 patient-years in general epilepsy; higher in drug-resistant); mechanism unclear but involves cardiorespiratory dysfunction during/after GTC seizures
• Patients with epilepsy have significantly higher rates of psychiatric comorbidity (depression, anxiety — doubled risk), accidents, and some neurodegenerative conditions

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• Bradley and Daroff's Neurology in Clinical Practice — Seizure Classification, Types, Precipitants, Epidemiology
• Harrison's Principles of Internal Medicine 22e — Seizure evaluation, history, examination
• Tintinalli's Emergency Medicine — Seizure classification, status epilepticus management
• Katzung's Basic and Clinical Pharmacology 16e — Antiseizure medication mechanisms and pharmacology
• Goldman-Cecil Medicine — Choice of antiseizure medications, drug-resistant epilepsy, surgical therapyThe answer above draws directly from five major textbooks and covers every major domain. Here is a quick orientation to the sections:

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