Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Clinical Research Education, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ann Clin Transl Neurol. 2022 Nov;9(11):1702-1714. doi: 10.1002/acn3.51667. Epub 2022 Oct 8.
Patients with spinal and bulbar muscular atrophy (SBMA) often experience muscular weakness under cold exposure.
In our previously conducted observational study, we assessed nerve conduction and grip strength to examine the effect of cold exposure on motor function, based on which we conducted a randomized controlled trial to evaluate the efficacy and safety of mexiletine hydrochloride in SBMA (MEXPRESS).
In the observational study, 51 consecutive patients with SBMA and 18 healthy controls (HCs) were enrolled. Of the patients with SBMA, 88.0% experienced cold paresis. Patients with SBMA exhibited greater prolongation of ulnar nerve distal latency under cold (SBMA, 5.6 ± 1.1 msec; HC, 4.3 ± 0.6 msec; p <0.001); the change in the distal latencies between room temperature and cold exposure conditions correlated with the change in grip power. In the MEXPRESS trial, 20 participants took mexiletine or lactose, three times a day for 4 weeks with a crossover design. There was no difference in distal latencies at room temperature and under cold exposure between mexiletine and placebo groups as the primary endpoint. However, tongue pressure and 10-sec grip and release test under cold exposure were improved in the mexiletine group. There were no serious adverse events throughout the study period.
Cold paresis is common and associated with prolongation of distal latency in SBMA. The results of the phase II clinical trial revealed that mexiletine showed short-term safety, but it did not restore cold exposure-induced prolongation of distal latency.
患有脊髓延髓肌萎缩症（SBMA）的患者在寒冷暴露下常出现肌肉无力。
在我们之前进行的观察性研究中，我们评估了神经传导和握力，以检查寒冷暴露对运动功能的影响，在此基础上，我们进行了一项随机对照试验，以评估盐酸美西律在 SBMA（MEXPRESS）中的疗效和安全性。
在观察性研究中，纳入了 51 例连续的 SBMA 患者和 18 例健康对照者（HCs）。88.0%的 SBMA 患者出现寒冷性瘫痪。与 HCs 相比，SBMA 患者在寒冷时尺神经远端潜伏期延长更大（SBMA，5.6±1.1 msec；HC，4.3±0.6 msec；p<0.001）；室温与寒冷暴露条件下远端潜伏期的变化与握力的变化相关。在 MEXPRESS 试验中，20 名参与者采用交叉设计，每天三次服用美西律或乳糖，持续 4 周。作为主要终点，室温下和寒冷暴露下的远端潜伏期在美西律组和安慰剂组之间没有差异。然而，在寒冷暴露下，舌压和 10 秒握力和释放测试得到改善。在整个研究期间没有发生严重不良事件。
寒冷性瘫痪很常见，与 SBMA 中远端潜伏期延长有关。二期临床试验结果表明，美西律具有短期安全性，但不能恢复寒冷暴露引起的远端潜伏期延长。
