Authors :
Presenting Author: Samantha Parkhurst, MD – University of Tennessee Health Science Center
Madison Granberry, BS – Rhodes College; Amy Patterson, MD – Assistant Professor, Pediatric Neurology, University of Tennessee Health Science Center; Tracee Ridley-Pryor, DNP, APRN, PMHNP-BC – University of Tennessee Health Science Center; Andrew Schroeder, MD – Assistant Professor, Pediatric Neurology, University of Tennessee Health Science Center; Sarah Weatherspoon, MD – Associate Professor, Pediatric Neurology, University of Tennessee Health Science Center; James Wheless, BSc Pharm., MD, FAAP, FACP, FAAN, FAES – Professor and Chief of Pediatric Neurology, Pediatric Neurology, University of Tennessee Health Science Center; Marianna Rivas-Coppola, MD – Assistant Professor, Pediatric Neurology, University of Tennessee Health Science Center
Rationale:
The incidence of seizures in the neonatal period is 5 per 1000 live births, and in preterm neonates is 11 per 1000 live births1-2. High neonatal seizure burden has been associated with poor neurodevelopmental outcomes3. Multiple studies have shown that lacosamide (LCS) can be safe and effective for focal seizures in children 1 month or older4, but there are limited studies looking at the efficacy and safety of LCS in neonates. In this retrospective study, we analyzed the safety and efficacy of LCS in neonates with recurrent seizures.
Methods:
An IRB approved, retrospective study was conducted at Le Bonheur Children’s Hospital from January 2016 to July 2022 on neonates with clinical or electrographic seizures who had a corrected gestational age of 44 weeks or younger and no history of cardiac arrhythmias.
Results:
Thirty-eight neonates with clinical or electrographic seizures were identified, with a mean corrected gestational age of 36 + 6 weeks (Range: 23-41 weeks). Thirty-five patients (92.10%) were treated with an average of 1.79 meds (±0.99) prior to starting LCS, with phenobarbital (PHB) and levetiracetam (LEV) being the two most common medications used overall, and both were used concurrently in 22 patients prior to LCS. Four of 38 patients (10.53%) were premature when LCS was initiated (1 at 33 weeks and the other 3 at 35 weeks corrected gestation age). The average LCS loading dose was 9.19 mg/kg/day (±1.60) and average maintenance dose was 9.97 mg/kg/day (±3.99). Serum LCS levels were obtained in 24/38 patients (63.16%) with a mean of 8.18 ug/mL (±4.27). Repeat EEG was obtained in 31/38 patients within 10 days of LCS administration with 20/31 (64.52%) no longer demonstrating seizures (EEG or clinical). The other 7 patients had EEGs obtained greater than 24 days after LCS administration, all of which demonstrated no seizures. For patients whose seizures were due to an acute brain injury (infectious, ischemic, or hemorrhagic causes), there was a 50% reduction in seizures on EEG. However, for those patients whose seizures were related to genetic or structural abnormalities, there was only a 23.08% reduction in seizures on EEG. Sleepiness was the only adverse effect reported in 1/38 patients (2.63%) after LCS initiation.
Conclusions: Lacosamide was a safe and effective adjunctive therapy for neonatal seizures in our experience (including several premature neonates) with refractory acute symptomatic seizures. Further randomized clinical trials are warranted.
References:
1 Olson DM. Neonatal seizures. NeoReviews 2012; 13: 213-223.
2 Thibeault-Eybalin MP, Lortie A, Carmant L. Neonatal seizures: do they damage the brain? Pediatr Neurol 2009; 40: 175-180. 3. Holmes GL.
3 Efficacy of Levetiracetam and Phenobarbital as First-Line Treatment for Neonatal Seizures. Carmen Verwoerd, Jamie Limjoco, Victoria Rajamanickam, Andrew Knox J Child Neurology. 2022 Apr;37(5):401-409.
4 Use of Real-World Data and Pharmacometric Modeling in Support of Lacosamide Dosing in Pediatric Patients Under 4 years of Age. Pradeep B Lukka, Megan Woods, Rebecca Chhim, Stephanie J Phelps, James W Wheless, Bernd Meibohm Clin Pharmacol. 2021 Jul; 61 (7): 881-888.
Funding: None