Institute of Neurology, University College London, London WC1N 3BG, UK.
Brain. 2010 Dec;133(Pt 12):3530-40. doi: 10.1093/brain/awq318. Epub 2010 Nov 23.
Episodic ataxia type 1 is a neuronal channelopathy caused by mutations in the KCNA1 gene encoding the fast K(+) channel subunit K(v)1.1. Episodic ataxia type 1 presents with brief episodes of cerebellar dysfunction and persistent neuromyotonia and is associated with an increased incidence of epilepsy. In myelinated peripheral nerve, K(v)1.1 is highly expressed in the juxtaparanodal axon, where potassium channels limit the depolarizing afterpotential and the effects of depolarizing currents. Axonal excitability studies were performed on patients with genetically confirmed episodic ataxia type 1 to characterize the effects of K(v)1.1 dysfunction on motor axons in vivo. The median nerve was stimulated at the wrist and compound muscle action potentials were recorded from abductor pollicis brevis. Threshold tracking techniques were used to record strength-duration time constant, threshold electrotonus, current/threshold relationship and the recovery cycle. Recordings from 20 patients from eight kindreds with different KCNA1 point mutations were compared with those from 30 normal controls. All 20 patients had a history of episodic ataxia and 19 had neuromyotonia. All patients had similar, distinctive abnormalities: superexcitability was on average 100% higher in the patients than in controls (P < 0.00001) and, in threshold electrotonus, the increase in excitability due to a depolarizing current (20% of threshold) was 31% higher (P < 0.00001). Using these two parameters, the patients with episodic ataxia type 1 and controls could be clearly separated into two non-overlapping groups. Differences between the different KCNA1 mutations were not statistically significant. Studies of nerve excitability can identify K(v)1.1 dysfunction in patients with episodic ataxia type 1. The simple 15 min test may be useful in diagnosis, since it can differentiate patients with episodic ataxia type 1 from normal controls with high sensitivity and specificity.
发作性共济失调 1 型是一种神经元通道病，由编码快速 K(+)通道亚基 K(v)1.1 的 KCNA1 基因突变引起。发作性共济失调 1 型表现为短暂的小脑功能障碍和持续性肌强直，并伴有癫痫发病率增加。在有髓周围神经中，K(v)1.1 在近节段轴突中高度表达，钾通道在近节段轴突中限制去极化后电位和去极化电流的作用。对经基因证实的发作性共济失调 1 型患者进行轴突兴奋性研究，以描述 K(v)1.1 功能障碍对体内运动轴突的影响。在腕部刺激正中神经，从拇短展肌记录复合肌肉动作电位。采用阈值跟踪技术记录强度-时间常数、阈值电紧张、电流/阈值关系和恢复周期。将来自 8 个具有不同 KCNA1 点突变的家族的 20 例患者的记录与 30 例正常对照进行比较。所有 20 例患者均有发作性共济失调病史，19 例有肌强直。所有患者均有类似的、独特的异常：与对照组相比，患者的超兴奋性平均高 100%（P < 0.00001），在阈电紧张中，由于去极化电流（阈值的 20%）引起的兴奋性增加高 31%（P < 0.00001）。使用这两个参数，发作性共济失调 1 型患者和对照组可以清楚地分为两个不重叠的组。不同 KCNA1 突变之间的差异无统计学意义。神经兴奋性研究可以识别发作性共济失调 1 型患者的 K(v)1.1 功能障碍。由于该测试简单，只需 15 分钟，具有高灵敏度和特异性，可用于诊断，有助于将发作性共济失调 1 型患者与正常对照区分开来。
