Epilepsy after brain insult: targeting epileptogenesis

Seizures and epilepsy are common sequelae of acute brain insults such as stroke, traumatic brain injury, and central nervous system infections. Early, or acute symptomatic, seizures occur at the time of the brain insult and may be a marker of severity of injury. A cascade of morphologic and biologic changes in the injured area over months to years leads to hyperexcitability and epileptogenesis. After a variable latency period, late unprovoked seizures and epilepsy occur. The latent period may offer a therapeutic window for the prevention of epileptogenesis and the development of unprovoked seizures and epilepsy. Administration of anticonvulsant drugs following acute brain insults has thus far failed to prevent late epilepsy. Proper choice of disease models and target populations will aid in the development of putative antiepileptogenic agents. The incidence, timing, and pathophysiology of common epileptogenic brain injuries, including head trauma, cerebrovascular disease, brain tumors, neurosurgical procedures, neurodegenerative conditions, status epilepticus, and febrile seizures, are reviewed.