Clinical meaning
Epilepsy is a chronic neurological disorder defined by the International League Against Epilepsy (ILAE) as: (1) at least two unprovoked seizures occurring more than 24 hours apart, OR (2) one unprovoked seizure PLUS a recurrence risk of ≥60% over the next 10 years (based on EEG findings, neuroimaging, or etiology), OR (3) an epilepsy syndrome diagnosis. This updated definition allows treatment initiation after a single seizure when recurrence risk is high, rather than waiting for a second event. The fundamental pathophysiology involves an imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission in cortical neurons. Normal neuronal activity depends on the precise balance of excitatory postsynaptic potentials (EPSPs, mediated by glutamate acting on NMDA and AMPA receptors) and inhibitory postsynaptic potentials (IPSPs, mediated by GABA acting on GABA-A chloride channels). Seizures occur when excitation overwhelms inhibition, producing hypersynchronous, excessive neuronal firing. The paroxysmal depolarization shift (PDS) is the intracellular hallmark of seizure activity: a large, sustained depolarization with rapid-fire action potentials, followed by a hyperpolarizing afterpotential. When enough neurons undergo PDS simultaneously, clinical seizure activity becomes manifest. Seizure classification (2017 ILAE):...