tonic-clonic seizure

**Definition:** Generalized seizure involving both hemispheres at onset (primary generalized) or evolving from a focal seizure (focal to bilateral tonic-clonic, formerly "secondary generalization"). Consciousness is lost from the start.

**Phases:** 1. Prodrome/aura (aura only if focal onset): epigastric rising sensation, déjà vu, odd smells. 2. Tonic phase (~10-20 s): sudden loss of consciousness, muscle stiffening/extension, "epileptic cry" from forced air through the glottis, apnea, cyanosis, possible tongue biting. 3. Clonic phase (~30-60 s): rhythmic flexor/extensor jerking, with frequency slowing toward the end. 4. Postictal phase (minutes to hours): confusion, lethargy, headache, myalgias. Incontinence is common. Focal weakness afterward (Todd paralysis) suggests a focal onset.

**Pathophysiology:** An imbalance of excitation (glutamate) and inhibition (GABA) causes hypersynchronous neuronal firing. Mechanisms include channelopathies (Na+, K+, Ca2+ channels), reduced GABAergic inhibition, and structural lesions. Thalamocortical circuits are important in primary generalized epilepsies.

**Causes (age/context-based):** - Children: febrile seizures, genetic epilepsies, infection, congenital disorders. - Young adults: trauma, alcohol or drug withdrawal, genetic epilepsy (e.g., juvenile myoclonic epilepsy), illicit drugs (cocaine). - Older adults: stroke, tumor, neurodegeneration, metabolic derangements. - Provoked causes: hypoglycemia, hyponatremia, hypocalcemia, uremia, eclampsia (treat with magnesium sulfate), CNS infection, drug toxicity (bupropion, tramadol, isoniazid, theophylline), and withdrawal from alcohol or benzodiazepines.

**Diagnosis:** - Clinical history with witness accounts. - EEG: generalized spike-and-wave or polyspike discharges. Interictal EEG can be normal. - Labs: glucose, electrolytes (Na, Ca, Mg), toxicology, pregnancy test, and prolactin or lactate shortly after the event (supportive, not definitive). - Neuroimaging: MRI preferred for new-onset seizure. Emergent CT if trauma, focal deficit, or concern for hemorrhage. - Lumbar puncture if infection is suspected. - Differential: syncope (brief jerks, rapid recovery), psychogenic nonepileptic seizures (eyes closed, side-to-side head movement, pelvic thrusting, prolonged duration, normal EEG, no postictal state).

**Management:** - Acute: protect the airway, place the patient in a lateral position, and check glucose. - Status epilepticus (≥5 min continuous or recurrent seizures without recovery): IV benzodiazepine (lorazepam; IM midazolam or rectal/intranasal diazepam if no IV access), then IV fosphenytoin/phenytoin, valproate, or levetiracetam. If refractory: intubation with propofol, midazolam, or barbiturates. - Chronic therapy for generalized tonic-clonic seizures: valproate (first-line, but avoid in pregnancy because of neural tube defects), lamotrigine, levetiracetam, topiramate. Carbamazepine and phenytoin can worsen absence and myoclonic seizures. - Treat the underlying cause in provoked seizures. Antiepileptic drugs are usually not needed for a single provoked seizure.

**Drug high-yield:** - Phenytoin: zero-order kinetics, gingival hyperplasia, hirsutism, cerebellar toxicity, fetal hydantoin syndrome, CYP450 inducer, and Stevens-Johnson syndrome risk (especially with HLA-B*1502 for carbamazepine). - Carbamazepine: SIADH, agranulocytosis, aplastic anemia, hepatotoxicity. - Valproate: hepatotoxicity, pancreatitis, tremor, weight gain, teratogenicity (neural tube defects). - Lamotrigine: Stevens-Johnson syndrome (slow titration needed). - Phenobarbital: first-line in neonates.

**Complications:** Injury, aspiration, rhabdomyolysis, lactic acidosis, posterior shoulder dislocation, vertebral compression fracture, SUDEP (sudden unexpected death in epilepsy), and status epilepticus.

**Driving/safety:** Driving restrictions after a seizure vary by state.

**Board pearls:** - Tonic = stiffening, clonic = jerking. - Lactate and CK may be elevated after the seizure. Prolactin is elevated for 10-20 min after a generalized tonic-clonic seizure. - Alcohol withdrawal seizures occur 6-48 hours after the last drink, and delirium tremens occurs later (48-96 hours). - Eclampsia = seizure in a preeclamptic patient. - Todd paralysis suggests a focal onset.