Progressive axonal dysfunction and clinical impairment in amyotrophic lateral sclerosis
Progressive axonal dysfunction and clinical impairment in amyotrophic lateral sclerosis
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DOI：
10.1016/j.clinph.2012.06.020
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发表时间：
2012-12-01
影响因子：
4.7
通讯作者：
Kiernan, Matthew C.
中科院分区：
文献类型：
--
作者：
Cheah, Benjamin C.;Lin, Cindy S. Y.;Kiernan, Matthew C.
目的：目的：探讨肌萎缩侧索硬化（ALS）患者轴索功能的纵向变化及其与运动单位丢失和功能损害的关系。（年龄53.7 ± 1.7岁; 22名男性）在基线和12周随访时使用轴突兴奋性技术进行了研究。兴奋性参数的纵向测量表明，随着去极化阈值电紧张的进一步增加，K+通道功能障碍增加（90-100 ms，基线，46.8 +/- 1.0%;随访，48.7 +/- 0.8%; P = 0.02）和超兴奋（基线，-24.0 +/- 1.2%; 12周，-26.0 +/- 1.2%; P = 0.04）。随访时复合肌肉动作电位（CMAP）振幅保留的患者比CMAP从基线下降的患者轴突兴奋性发生更严重的变化，这表明ALS患者中最明显的疾病影响是在轴突丧失之前对运动轴突的影响。精细运动功能下降与轴突兴奋性的严重变化相关，提示功能损害与轴突功能障碍有关。结论：ALS患者轴突兴奋性的纵向变化提示运动轴突中K+通道功能障碍增加。轴突兴奋性研究能够调查轴突离子通道功能障碍的纵向变化，从而可能导致ALS中轴突变性的过程。(C)2012年国际临床神经生理学联合会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Objective: To elucidate longitudinal changes in axonal function in amyotrophic lateral sclerosis (ALS) patients, and to relate such changes with motor unit loss and functional impairment.Methods: 37 ALS patients (age, 53.7 +/- 1.7 years; 22 males) were studied using axonal excitability techniques at baseline and 12 weeks follow-up.Results: Longitudinal measurements across excitability parameters suggested increasing K+ channel dysfunction, with further increases in depolarising threshold electrotonus (90-100 ms, baseline, 46.8 +/- 1.0%; follow-up, 48.7 +/- 0.8%; P = 0.02) and superexcitability (baseline, -24.0 +/- 1.2%; 12 weeks, -26.0 +/- 1.2%; P = 0.04). Patients with preserved compound muscle action potential (CMAP) amplitude at follow-up developed more severe changes in axonal excitability than those in whom CMAP decreased from baseline, suggesting that the most pronounced disease effects were on motor axons immediately prior to axonal loss in ALS patients. Fine motor decline was associated with more severe changes in axonal excitability, suggesting that functional impairment was related to axonal dysfunction.Conclusions: Longitudinal changes in axonal excitability in ALS patients suggest increasing K+ channel dysfunction in motor axons.Significance: Axonal excitability studies enable investigation of longitudinal changes in axonal ion channel dysfunction, and thereby the processes that potentially contribute to axonal degeneration in ALS. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.