Early treatment prevents neuronal loss in experimental status epilepticus: A magnetic resonance spectroscopic imaging study.

OBJECTIVE: In status epilepticus there are concerns that the prolonged high-intensity electrographic seizure activity causes neuronal death and poorer outcomes. In animal models of status epilepticus, early treatment that stops the seizures prevents the later development of epilepsy. We wished to determine if that same treatment prevents the neuronal damage that is associated with the prolonged seizures and later epilepsy. METHODS: In adult male rats, status epilepticus was induced by continuous electrical stimulation of the hippocampus. Some rats received phenobarbital to stop the seizure activity. They were compared to rats that did not receive treatment. At set intervals after status epilepticus (1 week and 8 weeks) the rats were examined for N-acetyl aspartate (NAA) concentrations, a biochemical marker for neurons, in selected brain regions with magnetic resonance spectroscopic imaging. RESULTS: Rats treated with phenobarbital had no decrease in NAA levels compared to untreated controls, which had significant decreases in the examined limbic regions. The decreases corresponded with neuronal loss seen by histological evalutation of the ventral hippocampus, olfactory cortex, and amygdala but not in the neocortex. SIGNIFICANCE: This study shows that early intervention to stop the status epilepticus prevents the neuronal loss that is associated with the development of epilepsy. The findings reinforce the principle of early and aggressive treatment for status epilepticus to improve long-term outcomes. The findings support recent clinical reports that tie early, aggressive treatment to improved neurological outcomes.