Seizures and Epilepsy
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.
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Risk factors
- Provoked (acute symptomatic) seizures: hypoglycemia, hyponatremia, hypocalcemia, alcohol/benzodiazepine withdrawal, fever (children), drugs (cocaine, tramadol, bupropion), eclampsia, acute stroke, head trauma, CNS infection, hypoxia
- Unprovoked (epilepsy): prior stroke, traumatic brain injury, CNS infection, brain tumor, neurodegenerative disease, cortical malformations, genetic epilepsy syndromes, perinatal injury
- Family history of epilepsy
- 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.
Clinical presentation
Symptoms
- Focal (formerly partial) — aware: motor (clonic jerking), sensory (paresthesia), autonomic, psychic (déjà vu, fear)
- Focal — impaired awareness: behavioral arrest, automatisms (lip smacking, picking), postictal confusion
- Focal to bilateral tonic-clonic (formerly secondary generalization)
- Generalized tonic-clonic: sudden LOC, tonic stiffening 10-20 s, clonic jerking 1-2 min, postictal confusion, tongue bite (lateral), urinary incontinence
- Absence (typical childhood): brief staring spells with 3 Hz spike-wave on EEG, no postictal state
- Myoclonic: brief shock-like jerks (juvenile myoclonic epilepsy classically morning jerks)
- Atonic ('drop attacks'): sudden loss of tone, falls
Signs / physical exam
- During seizure: rhythmic movements, gaze deviation, automatisms, postictal Todd paralysis (focal weakness lasting minutes-hours)
- Postictal confusion, somnolence (after generalized seizure)
- Lateral tongue bite (highly specific for seizure vs syncope)
- Skin: incontinence, abrasions
Classic findings
Witnessed rhythmic convulsions + postictal confusion + lateral tongue bite + urinary incontinence.
Differential diagnosis
- Syncope — Brief LOC, pallor, diaphoresis, rapid recovery; convulsive syncope can mimic seizure but lacks prolonged postictal state
- Psychogenic non-epileptic seizures (PNES) — Asynchronous limb movements, eyes closed, pelvic thrusting, side-to-side head movement, lack of postictal confusion; video-EEG diagnostic
- TIA / stroke — Typically negative symptoms (weakness, sensory loss); seizures usually positive (movements, paresthesias)
- Migraine with aura — Slower march of symptoms over minutes; visual scintillations, headache follows
- Cataplexy / narcolepsy — Sudden loss of muscle tone with preserved consciousness, triggered by emotion
- Movement disorders (tics, tremor) — Stereotyped movements with retained awareness
- Sleep disorders (REM behavior disorder, parasomnias) — Occur during sleep, video-EEG distinguishes
Diagnostic workup
Diagnostic criteria
Clinical event + EEG abnormality (interictal spikes or ictal pattern) supports epilepsy. ILAE definition of epilepsy: ≥2 unprovoked seizures >24 h apart OR ≥1 with ≥60% recurrence risk.
Labs
- Fingerstick glucose, BMP (sodium, calcium, magnesium), CBC, LFTs
- Toxicology screen, ethanol level
- Pregnancy test in women of childbearing age
- 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 |
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)
- Focal seizures: levetiracetam, lacosamide, oxcarbazepine, carbamazepine, lamotrigine
- Generalized tonic-clonic: levetiracetam, valproate, lamotrigine, topiramate
- Absence seizures: ethosuximide (first-line), valproate, lamotrigine
- Myoclonic: valproate, levetiracetam, lamotrigine (can worsen myoclonus in some patients)
- Treat reversible cause if provoked seizure — typically no chronic AED needed
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
- Ketogenic diet (especially pediatric refractory epilepsy)
- Counseling: driving restrictions (state-specific; typically 3-12 months seizure-free), safety (no swimming alone, careful with heights/machinery), SUDEP awareness
Complications
- Status epilepticus (see separate entry)
- Injury: tongue bite, falls, fractures, burns
- Sudden Unexpected Death in Epilepsy (SUDEP) — risk ~1/1000 patient-years, higher in poorly controlled epilepsy and during sleep
- Cognitive impairment, depression, anxiety (epilepsy comorbidities)
- Driving restrictions, vocational impact
- 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 — recurrence risk after first seizure ~30-50% over 2 years.
- 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 and Epilepsies (Fisher, Cross, French et al., Epilepsia 2017)
- AAN 2018 — Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults (Krumholz et al., Neurology 2015) — reaffirmed
- AES 2016 — Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus (Glauser et al., Epilepsy Currents 2016)
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