Department of Pediatric Neurology, University Children's Hospital Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Eur J Paediatr Neurol. 2011 Jan;15(1):1-7. doi: 10.1016/j.ejpn.2010.10.003. Epub 2010 Nov 19.
Neonatal seizures are common, especially in prematurity. Phenobarbital (PB) currently represents the antiepileptic drug (AED) of choice, despite being related to increased neuronal apoptosis in animal models and cognitive impairment in human subjects. Levetiracetam (LEV) may have a more favorable profile since it does not cause neuronal apoptosis in infant rodents.
In a prospective feasibility study, LEV was applied as first-line treatment in 38 newborns with EEG-confirmed seizures, after ruling out hypoglycemia, hypocalcaemia, hypomagnesaemia and pyridoxin dependency. Initial intravenous doses of 10 mg/kg LEV were gradually increased to 30 mg/kg over 3 days with a further titration to 45-60 mg/kg at the end of the week. Acute intervention with up to 2 intravenous doses of PB 20 mg/kg was tolerated during LEV titration. LEV was switched to oral as soon as the infants' condition allowed. Based on clinical observation, EEG tracings (aEEG/routine EEGs), and lab data, drug safety and anticonvulsant efficacy were assessed over 12 months.
In 19 newborns a single PB dose of 20 mg/kg was administered, while 3 newborns received 2 PB doses. 30 infants were seizure free under LEV at the end of the first week and 27 remained seizure free at four weeks, while EEGs markedly improved in 24 patients at 4 weeks. In 19 cases, LEV was discontinued after 2-4 weeks, while 7 infants received LEV up to 3 months. No severe adverse effects were observed.
These results illustrate the safety of LEV treatment in neonatal seizures, including prematurity and suggest LEV anticonvulsant efficacy. Additional PB treatment admittedly constitutes a methodological shortcoming due to the prolonged anticonvulsive efficacy of PB. Double blind prospective controlled studies and long-term evaluation of cognitive outcome are called for.
新生儿癫痫发作很常见，尤其是早产儿。苯巴比妥（PB）目前是抗癫痫药物（AED）的首选药物，尽管在动物模型中与神经元凋亡增加有关，在人类受试者中与认知障碍有关。左乙拉西坦（LEV）可能具有更有利的特征，因为它不会导致婴儿啮齿动物的神经元凋亡。
在一项前瞻性可行性研究中，在排除低血糖、低钙血症、低镁血症和吡哆醇依赖性后，LEV 被用作 38 例脑电图证实的癫痫发作新生儿的一线治疗药物。初始静脉注射剂量为 10mg/kg LEV，逐渐增加至 3 天内 30mg/kg，第 7 天结束时再滴定至 45-60mg/kg。在 LEV 滴定过程中，可耐受多达 2 次静脉注射 20mg/kg PB 的急性干预。一旦婴儿病情允许，即转换为口服 LEV。基于临床观察、脑电图描记（aEEG/常规 EEG）和实验室数据，在 12 个月内评估药物安全性和抗惊厥疗效。
19 例新生儿单次给予 20mg/kg PB 剂量，3 例新生儿给予 2 次 PB 剂量。第 1 周结束时，30 例婴儿在 LEV 下无癫痫发作，第 4 周时 27 例仍无癫痫发作，而 24 例患者在第 4 周时脑电图明显改善。19 例在 2-4 周后停用 LEV，7 例婴儿接受 LEV 治疗至 3 个月。未观察到严重不良反应。
这些结果说明了 LEV 治疗新生儿癫痫发作的安全性，包括早产儿，并表明 LEV 具有抗惊厥作用。由于 PB 的抗惊厥作用延长，额外的 PB 治疗确实构成了一种方法学上的缺陷。需要进行双盲前瞻性对照研究和认知结局的长期评估。
