Acute and chronic effects of seizures in the developing brain: Lessons from clinical experience

Seizures in the neonate are often considered a form of status epilepticus ( SE) because they are relatively prolonged, difficult to control with antiep ileptic drugs (AEDs), and may be associated with significant morbidity and mortality. Despite their clinical importance, there is still no clear under standing of how seizures may affect the developing brain. Although both bas ic neuroscience and clinical research have addressed these issues, there ar e difficulties in the design and analysis of each type of investigation. An imal studies should reflect the human condition, the most relevant studies being those that consider neocortical rather than hippocampal seizures. Cli nical investigations should be based on precise, age-specific definitions o f seizures of epileptic origin and of SE. Treatment strategies should be st andardized with defined rationale and end points. Outcome measures are best when defined and quantifiable. The relative effects of underlying CNS inju ries that coexist with the onset of neonatal seizures may be difficult to d ifferentiate from the effects of the seizures themselves or their treatment . Current clinical studies suggest that the overriding factors in determini ng the outcome of neonates with seizures are the cause, the degree, and the distribution of brain injury at the time of seizure occurrence. However, s uch studies have limitations and may not yet employ methodology sensitive e nough to detect a full range of adverse effects of seizures themselves.