Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures
Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures
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DOI：
10.1111/epi.14727
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发表时间：
2019-05-01
期刊：
影响因子：
5.6
通讯作者：
Milh, Mathieu
中科院分区：
文献类型：
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作者：
Denis, Julien;Villeneuve, Nathalie;Milh, Mathieu
目的：了解scn8a相关性重度癫痫的发病模式，以便早期识别，并最终采用钠通道阻滞剂进行早期治疗。方法：我们回顾了携带SCN8A基因突变的患者的表型，在638名患者的多中心队列中，由几位儿科神经学家前瞻性随访。我们关注临床医生对癫痫性脑病的诊断方式、最初的症状、脑电图（EEG）结果和癫痫发作类型。我们基于癫痫相关错义变异在蛋白质上的定位进行了基因型/表型相关性。结果：我们发现19例患者携带SCN8A新发突变，占我们队列的3%，其中9例为新发突变。癫痫发病年龄为1天至16个月。我们发现两种起病模式：12例患者缓慢起病，罕见和/或轻微癫痫发作，间歇脑电图正常（1组）。第一个事件是急性全身性强直-阵挛性发作（GTCS， 1a组，n = 6）或肌阵挛性抽搐发作，常被误认为与睡眠相关的运动或其他运动障碍（1b组，n = 6）。7例患者突发性频繁强直性发作或癫痫性痉挛伴间期脑电图异常，可快速诊断为癫痫性脑病。钠通道阻滞剂在大多数情况下有效或不加重。意义：SCN8A是第三大最常见的早发性癫痫性脑病基因，与两种癫痫发作模式相关。
Objective: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers.Methods: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types. We made genotypic/phenotypic correlation based on epilepsy-associated missense variant localization over the protein.Results: We found 19 patients carrying a de novo mutation of SCN8A, representing 3% of our cohort, with 9 mutations being novel. Age at onset of epilepsy was 1 day to 16 months. We found two modes of onset: 12 patients had slowly emerging onset with rare and/or subtle seizures and normal interictal EEG (group 1). The first event was either acute generalized tonic-clonic seizure (GTCS; Group 1a, n = 6) or episodes of myoclonic jerks that were often mistaken for sleep-related movements or other movement disorders (Group 1b, n = 6). Seven patients had a sudden onset of frequent tonic seizures or epileptic spasms with abnormal interictal EEG leading to rapid diagnosis of epileptic encephalopathy. Sodium channel blockers were effective or nonaggravating in most cases.Significance: SCN8A is the third most prevalent early onset epileptic encephalopathy gene and is associated with two modes of onset of epilepsy.