Basic Science Aspects of Epilepsy
Core concepts
A seizure is an abnormal, excessive, synchronous discharge of neurons; epilepsy is a predisposition to recurrent unprovoked seizures. Distinguish ictal (seizure), postictal (after), and interictal states. Know the mechanisms of excitability: enhanced glutamatergic (NMDA, AMPA) transmission, impaired GABAergic inhibition, altered ion channel function (sodium, potassium, calcium), and changes in the neuronal microenvironment. Paroxysmal depolarizing shift (PDS) is the cellular correlate of interictal spikes; it reflects a sustained depolarization with burst firing. Synaptic and non-synaptic mechanisms (gap junctions, ephaptic transmission) both contribute to synchronization.
Channels and genetics
Understand the channelopathies: SCN1A (Dravet syndrome, loss of function in GABAergic interneurons), SCN2A, KCNQ2 (benign familial neonatal seizures), and GABRA1. Note that the same gene can produce gain- or loss-of-function phenotypes with different treatment implications.
Traps
- Confusing epileptogenesis (process by which normal brain becomes epileptic) with ictogenesis (mechanism of individual seizure generation).
- Assuming all channelopathies are treated with sodium channel blockers - in Dravet, sodium blockers often worsen seizures.
- Forgetting that status epilepticus produces excitotoxic injury through calcium influx and receptor trafficking (GABA-A receptors internalize, making benzodiazepines less effective over time).
Rule of thumb
When a question describes a genetic epilepsy with fever-sensitive seizures and developmental decline, think SCN1A/Dravet and avoid sodium channel blockers.