Nakken K O, Magnusson A, Steinlein O K
Statens senter for epilepsi, Sandvika.
Tidsskr Nor Laegeforen. 1998 Feb 20;118(5):716-8.
We describe a Norwegian family with clusters of brief nocturnal motor seizures with hyperkinetic or tonic manifestations. Seizures started in childhood. Neurological examination and neuroimaging were normal. Interictal EEG registrations were mostly normal, ictal EEG registrations disclosed left frontal epileptiform discharges in two of three patients examined and just shallow arousal preceding the attack in one of the three patients. Segregation analysis indicated an autosomal dominant inheritance pattern, and the patients were subsequently diagnosed as having autosomal dominant nocturnal frontal lobe epilepsy, a disorder first described in 1995. A missense mutation in the gene for the alpha-4 subunit of the neuronal nicotinergic acetylcholine receptor was recently described in an Australian family with this disorder. Our Norwegian family proved to have a novel insertion mutation (776ins3) in the same gene. This mutation affects the second transmembrane domain (M2) which forms the critical section of the ion channel. This is the first case of idiopathic partial epilepsy where the underlying molecular defect has been found. The fact that a dysfunction of the nicotinergic acetylcholine receptor may give rise to frontal epileptic seizures was surprising and may shed new light on the basic mechanisms of epileptogenesis. Manipulations of the cholinergic system may open up a new therapeutic approach.
我们描述了一个挪威家庭，该家庭存在成群的夜间短暂运动性发作，伴有运动过多或强直表现。发作始于童年。神经系统检查和神经影像学检查均正常。发作间期脑电图记录大多正常，发作期脑电图记录显示，在接受检查的3例患者中，有2例出现左侧额叶癫痫样放电，3例中的1例在发作前仅有轻度觉醒。分离分析表明为常染色体显性遗传模式，这些患者随后被诊断为常染色体显性夜间额叶癫痫，这是一种于1995年首次被描述的疾病。最近在一个患有该疾病的澳大利亚家庭中发现了神经元烟碱型乙酰胆碱受体α-4亚基基因中的一个错义突变。我们的挪威家庭被证实该基因存在一个新的插入突变（776ins3）。此突变影响形成离子通道关键部分的第二个跨膜结构域（M2）。这是第一例发现潜在分子缺陷的特发性局灶性癫痫病例。烟碱型乙酰胆碱受体功能障碍可能引发额叶癫痫发作这一事实令人惊讶，可能为癫痫发生的基本机制提供新的线索。对胆碱能系统的调控可能开辟一种新的治疗方法。
