Transcranial Stimulation in Spino-Cerebellar Ataxia

描述（由申请人提供）：脊髓小脑性共济失调（SCA）是指一个家族的遗传性疾病，导致步态和平衡的进行性问题，以及其他衰弱症状。尽管我们知道导致许多SCA亚型的基因是已知的，尽管我们知道它们都与小脑和大脑其他特定部位的损伤有关，但SCA无法治愈，我们仍然缺乏有效的对症治疗。我们提出一种新的方法，使用无创经颅磁刺激（TMS）来改善SCA患者的平衡、步态和姿势。我们将招募20名基因证实的SCA患者。其中一半将被随机分配到真正的干预组，另一半则被随机分配到虚假（即控制）干预组。经颅磁刺激干预将包括20次刺激，为期四周。在基线和随访时，所有患者都将接受全面的评估，包括几个SCA评分量表，以及复杂的平衡测试（即行走、站立和肌肉协调）。患者还将完成一系列神经生理学测试，以评估干预前后小脑及其连接的功能。这将有助于我们测试干预的临床效用，并获得关于SCA残疾基础的新知识。在初步研究中，我们已经证明经颅磁刺激应用于小脑是安全的，它可以改善患者的平衡。我们现在将进行一个更系统、更大、更仔细控制的原理证明临床试验。我们预计，接受真正的rTMS的患者会表现出更好的平衡、更少的跌倒和改善的活动能力，而接受假刺激的患者则没有任何好处。如果我们的预测是正确的，这项研究将为一种新的治疗方法提供循证支持，以改善SCA患者的生活，并且拟议的定量评估将为未来更大的多地点临床试验检查可能的客观终点。

DESCRIPTION (provided by applicant): Spinocerebellar ataxia (SCA) refers to a family of genetic diseases that cause progressive problems with gait and balance, as well as other debilitating symptoms. Even though the genes responsible for many of the SCA subtypes are known, and even though we know that they all are associated with damage of the cerebellum and other specific parts of the brain, there is no cure for SCA and we still lack an effective symptomatic treatment. We propose a novel approach using noninvasive transcranial magnetic stimulation (TMS) to improve balance, gait, and posture in patients with SCA. We will recruit 20 patients with genetically-confirmed SCA. Half will be randomly assigned to a real intervention, and half to a sham (i.e., control) intervention. The TMS intervention will consist of 20 stimulatio sessions over a four week period. At baseline and at follow-up, all patients will undergo comprehensive assessments including several SCA rating scales, along with sophisticated tests of balance (i.e., walking, standing and muscle coordination). Patients will also complete a series of neurophysiologic tests to evaluate the function of the cerebellum and its connections before and after the intervention. This will help us test the clinical utility of the intervention and als gain new knowledge about the basis for the disability in SCA. In pilot studies we have shown already that TMS is safe when applied to the cerebellum and that it can improve balance in patients. We now will conduct a more systematic, larger, carefully controlled proof- of-principle clinical trial We anticipate that patients receiving real rTMS will show better balance, fewer falls, and improved mobility while those undergoing sham stimulation will show no benefits. If our prediction is correct, this study will provide evidence-based support for a new treatment to improve the lives of patients with SCA, and the proposed quantitative evaluations will examine possible objective end-points for a future, larger multi-site clinical trial.