seizure(s)

**DEFINITION & PATHOPHYSIOLOGY** - Seizure = paroxysmal event from abnormal hypersynchronous cortical neuronal discharge. Epilepsy = a predisposition to recurrent unprovoked seizures. - Mechanism: imbalance of excitation (glutamate; NMDA/AMPA receptors; Na+/Ca2+ influx) and inhibition (GABA-A; Cl- influx). Loss of inhibition or enhanced excitation leads to a paroxysmal depolarizing shift and spread of discharge.

**ILAE CLASSIFICATION** 1. **Focal onset** (one hemisphere) - Aware (formerly simple partial) vs impaired awareness (formerly complex partial). - Motor vs non-motor onset; may evolve to focal-to-bilateral tonic-clonic. - Temporal lobe: aura (déjà vu, rising epigastric sensation, olfactory), automatisms (lip smacking), postictal confusion. Associated with mesial temporal sclerosis (hippocampal). - Frontal lobe: Jacksonian march (motor cortex), brief and hypermotor, often during sleep. 2. **Generalized onset** (bilateral networks, with loss of consciousness) - **Absence (petit mal):** children 4–10 y; 5–15 s staring spells, no postictal state, hyperventilation provokes; EEG shows **3-Hz spike-and-wave**. Mechanism: T-type Ca2+ channels in the thalamus. Treat with **ethosuximide** (first line for absence alone); valproate if mixed with other generalized types. - **Tonic-clonic (grand mal):** tonic stiffening, then clonic jerking, then postictal confusion/somnolence. Tongue biting (lateral), incontinence. Elevated serum lactate, prolactin (10–20 min post-event), and CK. - **Myoclonic:** brief jerks. Juvenile myoclonic epilepsy shows morning jerks after sleep deprivation; valproate (or levetiracetam) is used. Avoid valproate in women of childbearing potential if possible (teratogenic: neural tube defects). - **Atonic (drop attacks), tonic:** Lennox-Gastaut syndrome (multiple seizure types, intellectual disability, slow spike-and-wave at 1.5–2.5 Hz). 3. **Unknown onset**

**ETIOLOGY BY AGE (high-yield)** - Neonates: hypoxic-ischemic encephalopathy, intracranial hemorrhage, infection, metabolic (hypoglycemia, hypocalcemia), inborn errors, drug withdrawal. - Infants/children: **febrile seizures** (6 mo–5 y; simple = generalized, <15 min, once in 24 h; benign, no antiepileptic needed), infantile spasms (West syndrome: hypsarrhythmia; treat with ACTH/vigabatrin; associated with tuberous sclerosis), genetic epilepsies, CNS infection. - Adolescents/young adults: trauma, drugs/alcohol withdrawal, genetic epilepsy, tumors. - Adults: **alcohol withdrawal** (6–48 h after last drink), stroke, tumor, trauma, metabolic disturbances. - Elderly: stroke (most common), neurodegenerative disease (Alzheimer), tumor, metabolic. - Provoked (acute symptomatic) causes: hyponatremia, hypoglycemia, hypocalcemia, hypomagnesemia, uremia, hepatic encephalopathy, eclampsia (treat with **IV magnesium sulfate**), drugs (bupropion, tramadol, isoniazid [B6 deficiency, treat with pyridoxine], theophylline, cocaine, TCA overdose), CNS infection (HSV encephalitis, neurocysticercosis – a common cause worldwide), PRES, and withdrawal of benzodiazepines/barbiturates.

**WORKUP** - Glucose, electrolytes (Na, Ca, Mg), toxicology, pregnancy test, and LP if infection is suspected. - **EEG** (interictal epileptiform discharges); **MRI brain** (preferred) or CT head if acute/emergent (trauma, hemorrhage). - Differentiate from **syncope** (brief, rapid recovery, prodrome of lightheadedness, minimal postictal confusion; brief myoclonic jerks possible) and **psychogenic nonepileptic events** (eyes closed, side-to-side head movement, long duration, normal prolactin, no postictal state, normal EEG during the event).

**MANAGEMENT** - **Status epilepticus** (≥5 min of continuous seizure or ≥2 seizures without recovery): ABCs, check glucose (give thiamine then dextrose if appropriate), **IV lorazepam** (first line; IM midazolam or rectal/IV diazepam if no access), then second-line IV **fosphenytoin/phenytoin, valproate, or levetiracetam**; refractory: anesthetic infusion (midazolam, propofol, pentobarbital) with continuous EEG. - Chronic therapy, by type: - Focal: **carbamazepine/oxcarbazepine, lamotrigine, levetiracetam**. - Generalized tonic-clonic: valproate, lamotrigine, levetiracetam. - Absence: ethosuximide. - Pregnancy: lamotrigine or levetiracetam preferred; give folic acid. - Drug-resistant epilepsy: surgery (temporal lobectomy), vagus nerve stimulation, responsive neurostimulation, ketogenic diet.

**KEY ANTIEPILEPTIC DRUG ADVERSE EFFECTS (Step 1)** - **Phenytoin:** gingival hyperplasia, hirsutism, nystagmus/ataxia, megaloblastic anemia, SLE-like syndrome, fetal hydantoin syndrome, zero-order kinetics, CYP450 inducer; IV: arrhythmia/hypotension (fosphenytoin is safer). - **Carbamazepine:** SIADH/hyponatremia, agranulocytosis/aplastic anemia, SJS/TEN (HLA-B*1502 in Asian patients), CYP450 inducer; also first-line for trigeminal neuralgia. - **Valproate:** hepatotoxicity, pancreatitis, tremor, weight gain, neural tube defects, CYP inhibitor, hyperammonemia. - **Lamotrigine:** SJS (titrate slowly; risk increased with valproate co-administration). - **Levetiracetam:** irritability/mood changes (SV2A binding). - **Topiramate:** kidney stones, weight loss, cognitive slowing, paresthesias, angle-closure glaucoma. - **Phenobarbital:** sedation, respiratory depression, CYP450 induction. - **Ethosuximide:** GI upset, headache, urticaria/SJS. - **Gabapentin/pregabalin:** sedation, ataxia, peripheral edema.

**OTHER HIGH-YIELD POINTS** - Postictal **Todd paralysis**: transient focal weakness after a focal seizure. - Neurocutaneous disorders (tuberous sclerosis, Sturge-Weber) are associated with seizures. - Driving restrictions apply after a seizure (state-specific seizure-free interval). - Provoked seizures: treat the underlying cause rather than starting long-term antiepileptics. After a first unprovoked seizure, antiepileptics are generally started if there is an abnormal EEG/MRI or a high recurrence risk.