Neonatal seizures: to treat or not to treat?

The immature brain is intrinsically hyperexcitable, a feature that, despite being crucial for learning, synaptogenesis and neuronal plasticity, predisposes the neonate to seizures. Seizures represent the most common neurologic manifestation of impaired brain function in this age group. Importantly, although seizure-induced neuronal injury is minimal in the "healthy" neonatal brain, the "metabolically-compromised" brain appears more vulnerable. Even in the "healthy" brain, however, seizures result in impaired learning, enhanced susceptibility to further seizures, and increased risk of brain injury with seizures later in life, as a result of altered hippocampal circuitry. Given these findings, an aggressive approach to neonatal seizures appears warranted. However, our current conventional therapies (including phenobarbital, phenytoin, and benzodiazepines), even when used in combination, are often ineffective in controlling seizures. Lidocaine may yield better efficacy but requires more study. Recent animal data suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonists such as topiramate may have a neuroprotective role. However, further work is needed to confirm the safety of excitatory amino acid antagonists in neonates because there remains a prevailing concern that such agents may impair normal neurodevelopmental processes.