Efficacy of Lamotrigine in Refractory Neonatal Seizures Peter A. Barr, MB, BS*, Vera E. Buettiker, MD*, and Jayne H. Antony, MD † A newborn infant with seizures of unknown etiology that were refractory to treatment with phenobarbi- tone, phenytoin, midazolam, clonazepam, and vigaba- trin is reported. The introduction of the new antiepi- leptic drug lamotrigine was followed by rapid and sustained control of the seizures. © 1999 by Elsevier Science Inc. All rights reserved. Barr PA, Buettiker VE, Antony JH. Efficacy of lam- otrigine in refractory neonatal seizures. Pediatr Neurol 1999;20:161-163. 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 benzo- diazepines 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 refrac- tory to treatment with phenobarbital, phenytoin, midazo- lam, clonazepam, and vigabatrin. The introduction of the new antiepileptic drug, lamotrigine, was followed by rapid and sustained control of the seizures. 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 decelerations of the fetal heart rate and thick meconium staining of the amniotic fluid. The infant had Apgar scores of 8 and 9 recorded at 1 and 5 minutes, respectively, and ventilatory resuscitation was not required. She developed early onset respiratory distress that lasted for 3 hours and required a maximum oxygen concentration of 30% via a head box. She was apparently well when discharged from hospital the following day. The infant was admitted to her local district hospital after an episode of generalized stiffening with apnea and cyanosis lasting for 2 minutes at 43 hours of age. Generalized tonic-clonic seizures, with apnea and cyanosis, commenced 3 hours after her admission and recurred fre- quently for the next 4 hours. During this period, she received the following intravenous AEDs in total dosage: phenobarbital 40 mg/kg, diazepam 175 g/kg, midazolam 300 g/kg, and pyridoxine 100 mg. Her seizures persisted, and she was mechanically ventilated, sedated with morphine, and given a continuous infusion of midazolam, 5 g/kg/ minute, before transfer to the Royal Alexandra Hospital for Children at 3 days of age for further investigation and treatment of status epilepticus. The seizures recurred shortly after admission to the newborn intensive care unit and remained refractory to treatment for the next 2 weeks. The following seizure types were observed: subtle (fixed staring gaze, eyelid flutters and eye deviation, limb cycling, and autonomic disturbance, including hypertension and tachycardia); tonic (tonic posturing of the trunk often associated with flushing, apnea, and cyanosis or arterial oxygen desaturation); and clonic (jerking of limbs, face, and eyelids). Interictally the infant was limp and unresponsive. The electroencephalogram (EEG) when the infant was 4 days of age demonstrated a burst-suppression pattern, with irregular bursts of 4-6 Hz and 6-8 Hz interspersed with 3- to 4-second periods of flattening. In addition, seizures were evident that probably arose from the central regions and then spread more generally (Fig 1). The administration of intravenous pyridoxine, 100 mg, during the EEG did not produce any noteworthy change in the recording. A second EEG at 10 days of age demonstrated a low-voltage background, with bursts of 6-7 Hz and 15-18 Hz and no sharp activity (Fig 2). The infant was treated with phenobarbital from 3-5 days of age, with a therapeutic plasma concentration (99 mol/L [normal, 40-130 mol/ L]); phenobarbital and vigabatrin (105 mg/kg/day) from 6-8 days of age; vigabatrin (210 mg/kg/day) from 9-11 days of age; and phenytoin and vigabatrin from 12-16 days of age. The plasma phenytoin concentrations were low (4 and 8 mol/L [normal, 40-80 mol/L]), after a total intravenous loading dose of 20 mg/kg and an oral maintenance dose of 8 mg/kg/day. The infant also received 1-3 intravenous bolus doses of clonazepam, 100 g/kg every day, except for 1-2 days of seizure-free periods that followed the introduction of vigabatrin and phenytoin when she was 6 and 12 days of age, respectively. Empiric treatment with pyridoxine, 100 mg daily, and biotin, 5 mg daily, was commenced at 10 days of age. From the Departments of *Neonatology and † Neurology; Royal Alexandra Hospital for Children; Westmead, NSW, Australia. Communications should be addressed to: Dr. Barr; Department of Neonatology; Royal Alexandra Hospital for Children; PO Box 3515; Parramatta, NSW 2124, Australia. Received July 16, 1998; accepted October 16, 1998. 161 © 1999 by Elsevier Science Inc. All rights reserved. Barr et al: Lamotrigine in Neonatal Seizures PII S0887-8994(98)00125-8 ● 0887-8994/99/$20.00