Kanai Kazuaki, Kuwabara Satoshi, Arai Kimihito, Sung Jia-Ying, Ogawara Kazue, Hattori Takamichi
Department of Neurology, Chiba University School of Medicine, Chiba, Japan.
Brain. 2003 Apr;126(Pt 4):965-73. doi: 10.1093/brain/awg073.
Machado-Joseph disease is one of the most common hereditary spinocerebellar degenerative disorders with a wide range of clinical manifestations. Pathology studies have shown mild to moderate loss of anterior horn cells and, in terms of spinal pathology, Machado-Joseph disease is regarded as a type of lower motoneuron disease. Muscle cramps are often associated with lower motoneuron disorders, but features of cramps in Machado-Joseph disease patients have never been studied. We investigated the incidence and nature of muscle cramps in Machado-Joseph disease patients, the excitability properties of motor axons [strength-duration time constant (tau(SD)), threshold electrotonus, refractoriness and supernormality] using threshold tracking and the effects of mexiletine hydrochloride on those cramps. Of 20 consecutive patients, 16 (80%) had frequent, severe muscle cramps in the legs, trunk or arms that disturbed their daily activities. The frequency of pathological muscle cramps was similar to that for patients with amyotrophic lateral sclerosis (68%) and higher than those for patients with spinal muscular atrophy (33%) or peripheral axonal neuropathy (24%). Threshold-tracking studies showed that tau(SD), which in part reflects Na(+) conductance at the resting membrane potential, was significantly greater in the Machado-Joseph disease patients than in normal subjects; severe muscle cramps were associated with a longer tau(SD). Threshold electrotonus, refractoriness and supernormality were not significantly different between Machado-Joseph disease patients and normal subjects. Eight Machado-Joseph disease patients with severe cramps, who received mexiletine treatment, experienced nearly complete relief with a partial normalization of tau(SD) (P = 0.08). Muscle cramps are a very frequent and disabling factor in Machado-Joseph disease. Pathological muscle cramps responded well to mexiletine treatment, and this is consistent with the hypothesis that they are caused by an increase in persistent Na(+) conductance, possibly associated with axonal regeneration or collateral sprouting.
马查多-约瑟夫病是最常见的遗传性脊髓小脑退行性疾病之一，临床表现多样。病理学研究显示前角细胞有轻度至中度缺失，就脊髓病理学而言，马查多-约瑟夫病被视为一种下运动神经元疾病。肌肉痉挛常与下运动神经元疾病相关，但马查多-约瑟夫病患者的痉挛特征从未被研究过。我们调查了马查多-约瑟夫病患者肌肉痉挛的发生率和性质、使用阈值跟踪法检测运动轴突的兴奋性特性[强度-时间常数（tau(SD)）、阈下电紧张、不应期和超常期]以及盐酸美西律对这些痉挛的影响。在连续的20例患者中，16例（80%）在腿部、躯干或手臂频繁出现严重的肌肉痉挛，影响了他们的日常活动。病理性肌肉痉挛的发生率与肌萎缩侧索硬化症患者（68%）相似，高于脊髓性肌萎缩症患者（33%）或周围轴索性神经病患者（24%）。阈值跟踪研究表明，tau(SD)（部分反映静息膜电位时的钠电导）在马查多-约瑟夫病患者中显著高于正常受试者；严重的肌肉痉挛与更长的tau(SD)相关。马查多-约瑟夫病患者与正常受试者之间的阈下电紧张、不应期和超常期无显著差异。8例接受美西律治疗的严重痉挛的马查多-约瑟夫病患者痉挛几乎完全缓解，tau(SD)部分恢复正常（P = 0.08）。肌肉痉挛是马查多-约瑟夫病中非常常见且导致残疾的因素。病理性肌肉痉挛对美西律治疗反应良好，这与它们由持续性钠电导增加引起的假说一致，可能与轴突再生或侧支发芽有关。
