Neonatal Epilepsy: Beyond Seizures in a Developing Brain-A Narrative Review

Area of Science:

• Neonatal neurology
• Developmental neurobiology
• Pediatric epilepsy

Background:

• Neonatal seizures are the most frequent neurological emergency in newborns, occurring in a uniquely immature brain.
• Electroclinical dissociation is common, making seizures difficult to recognize without continuous electroencephalogram (cEEG) monitoring.
• The immature brain's unique neurobiology, including excitation-inhibition imbalance, contributes to distinct seizure characteristics.

Purpose of the Study:

• To provide an integrated overview of neonatal seizures, covering neurobiology, diagnosis, etiology, and treatment.
• To highlight the critical role of cEEG in accurate diagnosis and quantifying seizure burden.
• To discuss the impact of etiology and seizure burden on prognosis and the potential for precision medicine.

Main Methods:

• This narrative review synthesizes current evidence on neonatal seizures.
• It integrates findings from developmental neurobiology, clinical diagnostics, and therapeutic strategies.
• Key findings are identified and discussed based on the existing evidence base.

Main Results:

• The neonatal brain's immature state shapes a unique seizure phenotype, often electrographic only.
• cEEG is essential for detecting and quantifying seizure burden, which clinical observation misses.
• Etiology (HIE, stroke, genetic disorders) is the primary prognostic factor, with seizure burden as a modifiable factor.

Conclusions:

• Accurate diagnosis and quantification of neonatal seizures rely on cEEG due to frequent electrographic-only events.
• Etiology dictates prognosis, but seizure burden is a critical, potentially modifiable factor.
• Advances in diagnostics and AI are paving the way for precision neonatology, aiming to optimize neurodevelopmental outcomes beyond seizure control.