Excessive synchronous neuronal discharge from an imbalance of excitation and inhibition
Expansion
A seizure is excessive, hypersynchronous neuronal discharge, arising when excitation outweighs inhibition:
- Increased glutamate activity
- Reduced GABA inhibition
- Altered ion channel function
- Loss of the normal surround inhibition that confines activity
Precipitants in a susceptible brain: sleep deprivation, alcohol withdrawal, drugs lowering the threshold, hyponatraemia, hypoglycaemia, hypocalcaemia, fever in children, and photic stimulation.
Drug mechanisms
- Sodium channel blockade: phenytoin, carbamazepine, lamotrigine
- GABA enhancement: benzodiazepines, barbiturates, sodium valproate (multiple actions)
- Calcium channel blockade: ethosuximide, acting on thalamic T-type channels in absence seizures
- SV2A binding: levetiracetam
Status epilepticus is defined as a seizure lasting more than 5 minutes or repeated seizures without recovery. Prolonged activity causes neuronal injury through excitotoxicity, and GABA receptors are internalised over time, which is why benzodiazepines lose efficacy and treatment must escalate promptly.
Systemic effects include lactic acidosis, hyperthermia, rhabdomyolysis and hypoxia.