Clinical meaning
Seizures result from abnormal, excessive, synchronous neuronal discharge in the cerebral cortex. The balance between excitatory (glutamate, NMDA/AMPA receptors) and inhibitory (GABA, chloride channel) neurotransmission is disrupted. In focal seizures, a discrete cortical focus generates paroxysmal depolarization shifts (PDS) — sustained depolarization driven by calcium influx through NMDA receptors, followed by GABA-mediated hyperpolarization. When inhibitory surround fails, the seizure propagates. Generalized seizures involve bilateral hemispheric networks from onset, often through thalamocortical circuits. Status epilepticus (SE) occurs when seizure-terminating mechanisms fail: GABA-A receptor internalization begins within 5 minutes of continuous seizure activity, while NMDA receptor expression increases on the cell surface — this explains why benzodiazepines become less effective and why treatment urgency is paramount. After 30 minutes of SE, excitotoxic neuronal death begins, with hippocampal neurons being most vulnerable.
Diagnosis & workup
Diagnostics & workup: - EEG (routine and prolonged): identifies epileptiform discharges, seizure focus lateralization, and subclinical seizures; continuous EEG (cEEG) monitoring for status epilepticus - MRI brain with epilepsy protocol: 3T with thin coronal cuts through temporal lobes to identify mesial temporal sclerosis, cortical dysplasia, tumors, vascular malformations - Basic metabolic panel: sodium, glucose, calcium, magnesium, BUN — rule out metabolic seizure causes - Antiepileptic drug levels: carbamazepine, phenytoin, valproic acid, lamotrigine (if on these medications) - Urine drug screen and blood alcohol level in new-onset seizures - LP if CNS infection suspected: cell count, protein, glucose, cultures, HSV PCR, autoimmune encephalitis panel - CT head (emergent): rule out hemorrhage, mass effect, hydrocephalus in acute presentation - Genetic testing: SCN1A, KCNQ2, CDKL5 in pediatric onset or refractory cases