[The effect of neonatal convulsions and antiepileptic drugs on the developing brain: controversial aspects and therapeutic implications]

Neonatal seizures are the clinical or subclinical manifestations of epileptic nature during the first 28 days of life. Their pathophysiological basis depends on the anatomic and biochemical characteristics of the developing brain. The question whether neonatal seizures cause brain damage, even today, has not a clear answer.

Data from clinical cases suggest that neonatal seizures may increase the cerebral blood flow and augment the energy requirements of the developing brain. Clinical research studies also suggest that neonatal seizures, even when they are only electrographic, may cause brain lesion independently from their cause. Multiple experimental investigations using mostly rat models of isolated or repeated induced seizures, have demonstrated that neonatal seizures may alter brain metabolic content, maturation of glutamatergic and GABAergic receptors, future cognitive development and epileptogenic risk, neuroneogenesis, intranuclear penetration of calcium, and neuronal apoptotic activation. On the other hand, some experimental studies suggest that phenobarbital, phenytoin and benzodiazepines may have a negative effect on brain development.

In my opinion, the ideal short-term goal of treating neonatal seizures should be stopping not only the clinical but also the subclinical epileptic activity. If prolonged treatment is necessary, one should consider to stop it as soon as the clinical and EEG course allows it. There is a need for future randomized, controlled trials of sufficient statistical power to assess the efficacy and tolerability of classic and new antiepileptic drugs in the treatment of neonatal seizures.