Thankfully, neonatal seizures are not something that we identify frequently in veterinary medicine. Unfortunately, neonatal seizures are one of the most common reasons for presentation to the ER in human medicine. Among full term infants, seizures account for 1-3.5% of the cases for infant presentation to ER. To date, phenobarbital (PB) has been the anti-epileptic drug (AED) of choice, however levetiracetam (LEV) was evaluated in a meta-analysis in 202. (REF) The findings are interesting…read on to learn more!
Some Background
Human infants with seizures generally have a good prognosis. Phenobarbital has been reported to control 43-80% of electrical seizures, with the added benefit of reducing brain metabolism. The downside is that it has been shown to cause neuronal apoptosis in animal models (aka our patients). LEV has a seizure control rate of 35-86% for neonatal seizures and has been shown to have a neuroprotective effect without evidence of neuronal apoptosis or synaptic development. As we well know, LEV also has a lower side effect profile in our patients. This is true for human infants however the adverse effects monitored are slightly different. In this population, blood pressure and respiratory depression are more significant and are what are reported in studies evaluating adverse effects.
The Results
Most studies reported no significant difference in efficacy between LEV and PB however 1 study showed that LEV was more effective for clinical seizures (seizures we can see) and not significantly different with electrical seizures (those we can only see on EEG). Another study reported that high dose (20-40 mg/kg/d) PB was more effective than LEV, but regular dose (20-30 mg/kg/d) was inferior to LEV. The seizure control rate in 1 study was 86% with LEV, and 62% with PB. However, the meta-analysis identified that overall, no significant difference was found between the two drugs.
Levetiracetam was the winner in terms of adverse effects! In most studies, LEV had a lower incidence of hypotension and respiratory depression than PB. Neurodevelopment scores (motor, cognitive and language scores) were similar among the two groups with a slightly higher language score in infants that had been treated with PB.
Despite all of this, PB is still the first-line treatment for neonatal seizures according to the WHO (2021) because it controls most seizures, from most etiology, and also decreases the metabolic rate. This might seem trivial, but reduced metabolic rate can improve outcome fairly strongly due to a lack of “work” that the brain must do during the post ictal phase.
What do I think? Based on this data, I would favor intravenous LEV at 30-60 mg/kg single dose for neonatal seizures in our patients FIRST, followed by diazepam + phenobarbital second if seizures aren’t controlled.
Thanks for reading! I hope you have a wonderful week and I look forward to working with you soon.
