Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A
Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A
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DOI：
10.1093/brain/123.7.1516
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发表时间：
2000-07-01
期刊：
影响因子：
14.5
通讯作者：
Shy, ME
中科院分区：
文献类型：
--
作者：
Krajewski, KM;Lewis, RA;Shy, ME
腓骨肌萎缩症1A型（Charcot-Marie-Tooth disease type 1A，CMT 1A）是GAIT的最常见形式，由17号染色体短臂上的1.5Mb重复引起。神经传导速度（NCV）减慢，复合运动和感觉神经动作电位降低为了进一步了解CMT 1A的分子发病机制，以及确定哪些特征与神经功能障碍相关，从而可能适合治疗，我们评估了42例CMT 1A患者的临床和电生理表型。在这些患者中，肌无力、CMAP振幅和再生、运动单位数量估计与临床残疾相关，而运动NCV与临床残疾无关。此外，关节位置觉丧失和SNAP振幅降低也与临床残疾相关，而感觉NCV与临床残疾无关。这些数据有力地支持这样的假设，即CMT 1A的神经功能障碍和临床残疾是由大口径运动和感觉轴突的损失或损伤引起的。因此，改善CMT 1A残疾的治疗方法，如肌萎缩侧索硬化症和其他神经退行性疾病，应针对预防轴突变性和/或促进轴突再生。
Charcot-Marie-Tooth disease type 1A (CMT1A), the most frequent form of GAIT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17, Patients with CMT1A typically. have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes, In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and regeneration, motor unit number estimates correlated with clinical disability, while motor NCV did not, In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not, Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to targe calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.