Dilena Robertino, Striano Pasquale, Gennaro Elena, Bassi Laura, Olivotto Sara, Tadini Laura, Mosca Fabio, Barbieri Sergio, Zara Federico, Fumagalli Monica
Service of Pediatric Epileptology - Unit of Clinical Neurophysiology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini" University of Genova, Genoa, Italy.
Brain Dev. 2017 Apr;39(4):345-348. doi: 10.1016/j.braindev.2016.10.015. Epub 2016 Nov 19.
Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction.
A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident.
Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate.
近期临床证据支持基于分子功能障碍对遗传性癫痫性脑病采取靶向治疗方法。
一名2日龄男婴，患有癫痫性脑病，脑电图背景为爆发抑制，伴有强直阵挛性游走性部分性发作。该病情对苯巴比妥、吡哆醇、磷酸吡哆醛和左乙拉西坦治疗无效，但视频脑电图监测显示静脉注射负荷剂量苯妥英钠有显著反应。数周内，成功将苯妥英钠换为卡马西平，以预防因难以维持苯妥英钠适当血药浓度而导致的癫痫复发。基因分析在SCN2A基因中发现一个新的新生杂合突变（c.[4633A>G]p.[Met1545Val]）。在两岁零三个月大时，患者服用卡马西平仍无癫痫发作，尽管有明显发育迟缓。
钠通道阻滞剂是确诊或疑似SCN2A相关癫痫性脑病的一线治疗药物。在具有相符电临床特征的严重病例中，我们提出一种治疗方案，即先进行高剂量静脉注射苯妥英钠试验性治疗，若有阳性反应则继以卡马西平治疗，后者更适合长期维持治疗。鉴于此类疾病罕见，需要开展合作研究，以根据电临床特征和推测的潜在遗传基础制定EIEE的共享治疗方案。
