Thursday, May 23, 2024 10:00am-5:00pm ET
Acute Symptomatic Neonatal Seizures:
Biomarkers and impact of acute anticonvulsant therapy on risk of future epileptogenesis
Conference Co-Chairs: Brenda Banwell, Josh Bonkowsky, Amy Brooks-Kayal
Conference Speakers: Janet Soul, Adam Numis, Courtney Wusthoff, Betsy Pilon
Unmet Need: The NN Pediatric Consortium, consisting of Pediatric Neurologists from current NN sites, identified the need for effective management and identification of biomarkers predictive of epileptogenesis in acute symptomatic neonatal seizures as a key unmet need. Current treatments, including phenobarbital, have not changed outcomes in several decades. Long-term implications of acute clinical and subclinical seizures in neonates remain incompletely understood and prognostication is hindered by a lack of laboratory, electroencephalographic and neuroimaging biomarkers that predict risk for future epilepsy. The majority of research on outcomes post-acute seizures in neonates have focused on neurodevelopmental outcomes and have often been limited to specific populations, such as infants with hypoxic ischemic encephalopathy (HIE). Therapeutic studies have included protocols for cooling which have demonstrated efficacy in mitigating risk for neurodevelopmental disability in term infants with HIE. A recent comparator study of Levetiracetam demonstrated inferiority in seizure control compared to phenobarbital. Given concerns for the long-term impact of phenobarbital on brain tissue, and short-term risks for sedation, impairment in feeding, and prolongation of hospitalization, there remains an imperative to identify superior antiseizure therapies.
Conference Objective: To convene a key stakeholder one day virtual conference focused on designing a clinical trial comparing phenobarbital to a less neurotoxic antiseizure medicine (ASM) in neonates with acute symptomatic seizures inclusive of key biomarkers (laboratory, EEG and MRI). The trial will have a primary short-term outcome (cessation or reduction in total seizure burden measured in minutes/day) and a primary long-term (4 year) outcome (development of epilepsy).
Conference Outcome: Following the day’s discussion, a clinical trial proposal was designed by Dr. Janet Soul, who is working to submit the trial for consideration by NINDS to be conducted in the NeuroNEXT network.