Efficacy of lamotrigine in refractory neonatal seizures

doi:10.1016/S0887-8994(98)00125-8

Pediatric Neurology

Volume 20, Issue 2, February 1999, Pages 161-163

https://doi.org/10.1016/S0887-8994(98)00125-8 Get rights and content

Abstract

A newborn infant with seizures of unknown etiology that were refractory to treatment with phenobarbitone, phenytoin, midazolam, clonazepam, and vigabatrin is reported. The introduction of the new antiepileptic drug lamotrigine was followed by rapid and sustained control of the seizures.

Introduction

The usual recommended drug treatment for neonatal seizures is phenobarbital followed by phenytoin, if a second antiepileptic drug (AED) is required [1]. Other AEDs have also been used effectively, notably the benzodiazepines clonazepam [2], lorazepam [3], and midazolam [4]. There have also been reports of primidone [5], [6], lidocaine [7], thiopental [8], paraldehyde [9], and sodium valproate [10] being used successfully in newborn infants with seizures. The present report concerns a newborn infant with seizures of unknown etiology that were refractory to treatment with phenobarbital, phenytoin, midazolam, clonazepam, and vigabatrin. The introduction of the new antiepileptic drug, lamotrigine, was followed by rapid and sustained control of the seizures.

Section snippets

Case report

The infant, a female, was a spontaneous vaginal birth at 40 weeks gestation, with a birth weight of 2,840 gm and a head circumference of 35 cm. Her mother was a 35-year-old gravida VI para III woman who gave a history of intermittent tonic-clonic seizures starting soon after birth and continuing for 2 years, 6 months. The seizures were thought to have been the result of perinatal asphyxia and were treated with AEDs. The current pregnancy was normal, but the labor was complicated by late

Discussion

The infant described suffered from neonatal seizures of unknown etiology. Perinatal hypoxic-ischemic encephalopathy seemed an unlikely explanation given the normal Apgar scores and the delay in seizure onset until 43 hours of age. The history of seizures in the mother raised the possibility of benign familial neonatal convulsions, although the infant’s abnormal interictal behavior and refractory seizure state were atypical for this disorder [1].

The infant’s seizures were not controlled with the

Acknowledgements

The authors thank Dr. Abe Chutorian for this critical review of the manuscript.

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The immature brain is intrinsically hyperexcitable, a feature that, despite being crucial for learning, synaptogenesis and neuronal plasticity, predisposes the neonate to seizures. Seizures represent the most common neurologic manifestation of impaired brain function in this age group. Importantly, although seizure-induced neuronal injury is minimal in the “healthy” neonatal brain, the “metabolically-compromised” brain appears more vulnerable. Even in the “healthy” brain, however, seizures result in impaired learning, enhanced susceptibility to further seizures, and increased risk of brain injury with seizures later in life, as a result of altered hippocampal circuitry. Given these findings, an aggressive approach to neonatal seizures appears warranted. However, our current conventional therapies (including phenobarbital, phenytoin, and benzodiazepines), even when used in combination, are often ineffective in controlling seizures. Lidocaine may yield better efficacy but requires more study. Recent animal data suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonists such as topiramate may have a neuroprotective role. However, further work is needed to confirm the safety of excitatory amino acid antagonists in neonates because there remains a prevailing concern that such agents may impair normal neurodevelopmental processes.
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Case ReportsEfficacy of lamotrigine in refractory neonatal seizures

Abstract

Introduction

Section snippets

Case report

Discussion

Acknowledgements

J Pediatr

Pediatr Neurol

J Pediatr

Brain Dev

Neonatal seizures

Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures

Eur J Clin Pharmacol

Lorazepam in the treatment of refractory neonatal seizures

J Child Neurol

Case Reports
Efficacy of lamotrigine in refractory neonatal seizures