Seizures are one of the most common neurologic emergencies in neonates, arising in ~3/1000term live births and are associated with significant mortality and neuro-developmental disability (Soul et al, 2018). In contrast to seizures in older children, most neonatal seizures result from acute symptomatic etiologies rather than epilepsy. The most common etiologies include neonatal encephalopathy caused by hypoxic-ischemia (HIE), focal ischemia affecting one or more vascular territories (stroke), intracranial hemorrhage, infection, cerebral dysgenesis, and metabolic disturbances. (Soul et al, 2018, Venkatesan et al, 2016). Treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical studies. Globally, phenobarbital (PB) is standard of care as first-line therapy in neonatal seizures. Phenobarbital has shown efficacy (response usually defined as 80% to 100% reduction in seizure burden in sec/h) of between 50% and 80% in several small studies. Several other antiepileptic drugs (AEDs) have shown some efficacy as first-line treatment (eg, levetiracetam [LEV]vs. PB as first-line [Rao et al, 2018]) or as adjunct treatment, but gold standard evidence of efficacy or effectiveness is lacking for all compounds, and all AED-based treatments are currently off-label (Soul et al, 2018).
Lacosamide(LCM, VIMPAT®), is indicated for the treatment of partial-onset seizures (POS) in patients 4 years of age and older, and this indication is currently limited in the US to VIMPAT oral dosage forms (FilmCoated Tablets and Oral Solution). VIMPAT intravenous (iv) delivery is indicated for the treatment of POS in adults (17 years of age and older) in the US. Any AED use in neonates is off label and and the scant literature in the neonatal seizure population indicates variations in the care pathway with numerous AEDs utilized at varying doses according to underlying condition (Rennie et al, 2018; Glass et al, 2017; Venkatesan et al, 2016; Dizon et al, 2019).
Count data of LCM prescribing in neonates indicates scant usage: PEDSnet database n~27, PCORnet n ~ 13, Soul collaboration dataset n <50. A paper by Glass and colleagues indicates no usage (Glass et al, 2017), and an internal survey (Watson et al, 2019) shows no use in acute seizure and rarely in prophylaxis. These factors indicate the challenge in recruiting both physicians and parents for a clinical study, where to date no safety data exists in neonates. Based on these factors, UCB has decided to set up an epidemiological neonatal seizure study evaluating pharmacokinetics (PK) and effectiveness outcome to support development of a clinical study and provide evidence for the clinical and patient community. The study will include all neonates initially exposed to iv LCM in PEDSnet and PCORnet. Patients can later be switched to oral LCMduring follow up.