Progressive hippocampal and extrahippocampal atrophy in drug resistant epilepsy

This article reviews recent experimental and clinical evidence for seizure-related progressive brain damage and discusses possible mechanisms of ongoing brain atrophy in epilepsy.

Experimental data indicate that seizures induce brain plasticity that may result in either damage or protection. Brief seizures or status epilepticus may promote resistance to additional damage but also induce cumulative neuronal loss and increase susceptibility to network synchronization. Some experimental studies indicated that, following the initial damage caused by status epilepticus, further brief seizures may not produce significant continuing neuronal loss and hippocampal atrophy, whereas other studies showed the contrary. There is recent evidence that progressive damage and atrophy may occur after an acute insult but are not directly associated with recurrent seizures. Clinical research data continue to show discrepancies regarding whether ongoing seizures cause progressive atrophy. Some cross-sectional and longitudinal magnetic resonance imaging studies in patients with partial epilepsies have shown progressive hippocampal and extrahippocampal atrophy, the severity of which correlated with the duration of epilepsy, seizure frequency, or lifetime seizure number, whereas others have failed to show a clear association.

Experimental data indicate that epileptogenesis in developing brain may not require significant neuronal loss, which is in keeping with clinical observations that progressive cognitive and behavioural impairment may occur in patients with no detectable brain atrophy. A better understanding of why, when and how progressive brain atrophy occurs will lead to better clinical management, earlier surgical intervention when necessary and, ultimately, prevention of epileptogenesis.