Pathophysiology
Clinical meaning
Status epilepticus (SE) is defined as a seizure lasting >5 minutes OR two or more seizures without return to baseline consciousness between episodes. This represents a neurological emergency with a mortality rate of 15-22% in adults. The pathophysiology involves failure of normal seizure termination mechanisms: as seizures persist, inhibitory GABA-A receptors internalize (become less effective), while excitatory NMDA glutamate receptors are upregulated and traffic to the synaptic surface, creating a self-sustaining cycle of excitation. This explains why benzodiazepines (GABA-A agonists) become less effective the longer a seizure continues - the receptors they target are physically removed from the cell membrane. Excitotoxicity occurs as excessive glutamate release through NMDA receptors causes massive calcium influx into neurons, activating destructive enzymes (calpains, phospholipases, endonucleases) that damage cellular structures and trigger apoptotic pathways. Sustained seizure activity dramatically increases cerebral metabolic demand (up to 300% of normal): neurons consume oxygen and glucose at unsustainable rates, leading to energy failure, ATP depletion, and neuronal death. Systemically, prolonged convulsive SE causes: lactic acidosis from sustained muscle contraction, hyperthermia from excessive motor activity, rhabdomyolysis with myoglobinuria and acute...