A study on pahtophysiology and non-invasive treatment of dystonia

肌张力障碍是一种持续的肌肉收缩综合征，经常引起重复或扭曲的运动或异常的姿势。这是一种常见的疾病，其发病率约为帕金森病的五分之一。作家痉挛是局灶性肌张力障碍，发病时仅影响写作。这种任务特异性为研究执行特定任务的正常运动控制机制提供了独特的机会。它也因对治疗的抵抗而臭名昭著。我们试图通过降低运动前皮层的兴奋性来治疗这些患有作家痉挛的患者，在之前的PET研究中，运动前皮层被认为是过度活跃的。为此，我们使用了阈下低频重复经颅磁刺激（rTMS），它可以抑制皮层。使用计算机系统来评估笔迹，我们证明了笔迹的显著改善和异常皮质沉默期的正常化。因此，运动前皮层是基底神经节的主要输出接收区之一，在肌张力障碍中表现出过度活跃，rTMS对其进行纠正可能为治疗这些患者提供一种有用的方法。另一方面，我们有机会检查7例x连锁隐性肌张力障碍-帕金森病尸检患者的免疫组织化学结果。我们发现新纹状体中纹状体神经元的早期丢失是这种疾病张力障碍期的病理标志。纹状体细胞抑制黑质致密部的黑纹状体多巴胺能投射，它们的丧失可能导致不受控制的多巴胺释放。因此，肌张力障碍可能是由过量的多巴胺引起的，多巴胺会抑制运动前区和其他皮质区域。

Dystonia is a syndrome of sustained muscle contractions frequently causing repetitive or twisting movement or abnormal posture. It is a common disorder with its incidence being approximately one fifth of that of Parkinson's disease. Writer's cramp is a focal dystonia, affecting only writing in its onset. This task-specificity provides a unique opportunity of investigating the mechanism of normal motor control for performing a specific task. It is also known notorious because of the resistance to treatment. We tried to treat these patients with writer's cramp by decreasing the excitability of the premotor cortex, which is known to be hyperactive in previous PET studies. For this, we used subthreshold low-frequency repetitive transcranial magnetic stimulation (rTMS), which inhibits the cortex. Using a computerized system for evaluating handwriting, we demonstrated significant improvement in handwriting and normalization of the abnormal cortical silent periods. Therefore the premotor cortex, one of the major output receptive areas from the basal ganglia, was shown hyperactive in dystonia, and its correction by rTMS may provide a useful method for treating these patients.We on the other hand had a chance to examine the immunohistochemichal findings in 7 autopsied patients with X-linked recessive dystonia-parkinsonism. We found the early loss of striosomal neurons in the neostriatum is the pathological hallmark of the dystonic phase of this disease. Striosomal cells are inhibiting the nigrastriatal dopaminergic projections from substantia nigra pars compacta, and their loss should lead to uncontrolled release of dopamine. Dystonia may therefore be caused by excess dopamine, which disinhibits premotor and other cortical areas.