How Early Can a Seizure Happen? Pathophysiological Considerations of Extremely Premature Infant Brain Development

Seizures in neonates represent a neurologic emergency requiring prompt recognition, determination of etiology, and treatment. Yet, the definition and identification of neonatal seizures remain challenging and controversial, in part due to the unique physiology of brain development at this life stage. These issues are compounded when considering seizures in premature infants, in whom the complexities of brain development may engender different clinical and electrographic seizure features at different points in neuronal maturation. In extremely premature infants (< 28 weeks gestational age), seizure pathophysiology has not been explored in detail. This review discusses the physiological and structural development of the brain in this developmental window, focusing on factors that may lead to seizures and their consequences at this early time point. We hypothesize that the clinical and electrographic phenomenology of seizures in extremely preterm infants reflects the specific pathophysiology of brain development in that age window.