Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto, Canada.
Department of Clinical Movement Disorders and Motor Neuroscience, University College London (UCL), Institute of Neurology, Queen Square, London, United Kingdom.
Neurobiol Dis. 2019 Dec;132:104462. doi: 10.1016/j.nbd.2019.05.001. Epub 2019 May 9.
Dystonia and Parkinson's disease are closely linked disorders sharing many pathophysiological overlaps. Dystonia can be seen in 30% or more of the patients suffering with PD and sometimes can precede the overt parkinsonism. The response of early dystonia to the introduction of dopamine replacement therapy (levodopa, dopamine agonists) is variable; dystonia commonly occurs in PD patients following levodopa initiation. Similarly, parkinsonism is commonly seen in patients with mutations in various DYT genes including those involved in the dopamine synthesis pathway. Pharmacological blockade of dopamine receptors can cause both tardive dystonia and parkinsonism and these movement disorders syndromes can occur in many other neurodegenerative, genetic, toxic and metabolic diseases. Pallidotomy in the past and currently deep brain stimulation largely involving the GPi are effective treatment options for both dystonia and parkinsonism. However, the physiological mechanisms underlying the response of these two different movement disorder syndromes are poorly understood. Interestingly, DBS for PD can cause dystonia such as blepharospasm and bilateral pallidal DBS for dystonia can result in features of parkinsonism. Advances in our understanding of these responses may provide better explanations for the relationship between dystonia and Parkinson's disease.
肌张力障碍和帕金森病是密切相关的疾病,它们具有许多重叠的病理生理学特征。30%或更多的帕金森病患者会出现肌张力障碍,有时它可能先于明显的帕金森病出现。早期肌张力障碍对多巴胺替代疗法(左旋多巴、多巴胺激动剂)的反应是多变的;左旋多巴治疗开始后,帕金森病患者常出现肌张力障碍。同样,各种 DYT 基因突变的患者也常出现帕金森病,包括涉及多巴胺合成途径的基因突变。多巴胺受体的药理学阻断可引起迟发性肌张力障碍和帕金森病,这些运动障碍综合征也可发生在许多其他神经退行性、遗传、毒性和代谢疾病中。过去的苍白球切开术和目前主要涉及 GPi 的深部脑刺激是肌张力障碍和帕金森病的有效治疗选择。然而,这两种不同的运动障碍综合征反应的生理机制尚不清楚。有趣的是,DBS 治疗帕金森病可引起眼睑痉挛等肌张力障碍,双侧苍白球 DBS 治疗肌张力障碍可导致帕金森病特征。对这些反应的深入了解可能为肌张力障碍和帕金森病之间的关系提供更好的解释。