Neonatal seizures represent one of the most common and challenging neurologic conditions encountered in the neonatal intensive care unit. The unique characteristics of the developing nervous system and their often subtle clinical manifestations complicate recognition and management, according to Lester M. “Max” Gallivan, M.D., a resident in pediatric neurology at the UofL School of Medicine and Samir R. Karia, M.D., a pediatric epileptologist with Norton Children’s Neuroscience Institute and an associate professor at the UofL School of Medicine.

Dr. Gallivan presented “Neonatal Seizures” at the 22^nd annual Pediatric Neurology Update continuing medical education opportunity, which was offered by Norton Children’s Neuroscience Institute.

A clinical assessment alone is only about 50% accurate in identifying neonatal seizures. Electroencephalogram (EEG) confirmation is important whenever possible.

Most commonly, seizures present as electroclinical events, with both EEG changes and clinical symptoms. A significant proportion, however, shows up as electrographic or subclinical seizures that are detectable only through EEG monitoring. It’s rarer for there to be clinical-only seizures without corresponding EEG changes.

“The evolving understanding of neonatal seizures continues to shape clinical practice, emphasizing the importance of prompt recognition, accurate diagnosis through EEG confirmation when possible and targeted treatment based on underlying etiology,” Dr. Gallivan said.

Success in managing these vulnerable patients requires a delicate balance of clinical acumen, technological support and evidence-based therapeutic intervention, according to Dr. Gallivan.

Clinical manifestations and seizure types

In a preterm infant, a subtle seizure is more common, characterized by sustained eye opening, abnormal eye movements, chewing motions and pedaling movements, according to Dr. Gallivan. Tonic seizures, manifesting as sustained posturing, usually have clear EEG correlations, while generalized tonic seizures are relatively rare and may signal underlying conditions such as hypoxic ischemic encephalopathy (HIE) or stroke.

Clinicians must be particularly adept at distinguishing true seizures from nonepileptic spasms. Jitteriness can be differentiated by several key features: the absence of associated eye movements, sensitivity to external stimuli and suppressibility with gentle restraint. Another common nonepileptic phenomenon, benign neonatal sleep myoclonus, occurs exclusively during sleep and resolves when awoken. Unlike seizure activity, these movements never involve the face and often can be induced by gentle rocking.

Causes of neonatal seizures

The etiology of neonatal seizures spans a broad spectrum, with HIE remaining the most common cause. In HIE cases, seizure burden peaks either in the first 24 hours of life or during the rewarming period following therapeutic hypothermia. Stroke presents another significant cause, often manifesting in the first 12 hours of life and sometimes serving as the only initial sign of injury. The presentation can vary significantly between arterial and venous strokes, with arterial strokes often presenting with more subtle clinical findings.

Various forms of intracranial hemorrhage can trigger seizures, with intracerebral hemorrhage carrying the highest seizure risk at approximately 60%. Metabolic disturbances, while becoming less common with improved neonatal intensive care unit (NICU) care, remain important considerations. Hypoglycemia typically presents around day two of life, with outcomes closely tied to the duration of the metabolic derangement. Early-onset hypocalcemia generally carries a better prognosis than its late-onset counterpart.

Neonatal seizure treatments

Treatment protocols for neonatal seizures have become more standardized in recent years. Phenobarbital maintains its position as the first-line agent, typically beginning with a loading dose of 20 milligrams per kilogram. Second-line treatment decisions often depend on clinical context, with levetiracetam preferred in cardiac patients, and fosphenytoin considered when there’s a family history of channelopathy. For refractory cases, clinicians may need to progress to continuous midazolam infusion while addressing the underlying etiology.

The duration of antiseizure medication therapy should be individualized, though there’s growing evidence supporting early discontinuation in a case of acute symptomatic seizure. Many patients can be weaned safely from medications prior to NICU discharge, particularly when the underlying etiology has been adequately addressed and seizure resolution has been confirmed through clinical and electrographic monitoring.