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 antiepileptic drugs (AEDs), and may be associated with significant morbidity and mortality. Despite their clinical importance, there is still no clear understanding of how seizures may affect the developing brain. Although both basic neuroscience and clinical research have addressed these issues, there are difficulties in the design and analysis of each type of investigation. Animal studies should reflect the human condition, the most relevant studies being those that consider neocortical rather than hippocampal seizures. Clinical investigations should be based on precise, age-specific definitions of seizures of epileptic origin and of SE. Treatment strategies should be standardized with defined rationale and end points. Outcome measures are best when defined and quantifiable. The relative effects of underlying CNS injuries that coexist with the onset of neonatal seizures may be difficult to differentiate from the effects of the seizures themselves or their treatment. Current clinical studies suggest that the overriding factors in determining the outcome of neonates with seizures are the cause, the degree, and the distribution of brain injury at the time of seizure occurrence. However, such studies have limitations and may not yet employ methodology sensitive enough to detect a full range of adverse effects of seizures themselves.