Department of Neurology, Movement Disorders Division, Duke University (NBP), Durham, NC, United States.
Department of Neurology, NYU Grossman School of Medicine (SJF), New York, NY, United States.
Handb Clin Neurol. 2023;196:425-442. doi: 10.1016/B978-0-323-98817-9.00005-3.
Dystonia is a hyperkinetic movement disorder with a unique motor phenomenology that can manifest as an isolated clinical syndrome or combined with other neurological features. This chapter reviews the characteristic features of dystonia phenomenology and the syndromic approach to evaluating the disorders that may allow us to differentiate the isolated and combined syndromes. We also present the most common types of isolated and combined dystonia syndromes. Since accelerated gene discoveries have increased our understanding of the molecular mechanisms of dystonia pathogenesis, we also present isolated and combined dystonia syndromes by shared biological pathways. Examples of these converging mechanisms of the isolated and combined dystonia syndromes include (1) disruption of the integrated response pathway through eukaryotic initiation factor 2 alpha signaling, (2) disease of dopaminergic signaling, (3) alterations in the cerebello-thalamic pathway, and (4) disease of protein mislocalization and stability. The discoveries that isolated and combined dystonia syndromes converge in shared biological pathways will aid in the development of clinical trials and therapeutic strategies targeting these convergent molecular pathways.
肌张力障碍是一种运动障碍，具有独特的运动表现，可表现为孤立的临床综合征或与其他神经特征合并。本章回顾了肌张力障碍表现的特征性特征和评估可能导致我们区分孤立性和合并性综合征的综合征的综合征方法。我们还介绍了最常见的孤立性和合并性肌张力障碍综合征类型。由于加速的基因发现增加了我们对肌张力障碍发病机制的分子机制的理解，我们还通过共同的生物学途径介绍了孤立性和合并性肌张力障碍综合征。这些孤立性和合并性肌张力障碍综合征的趋同机制的示例包括（1）通过真核起始因子 2α信号破坏综合反应途径，（2）多巴胺能信号传导疾病，（3）小脑丘脑通路改变，以及（4）蛋白质定位和稳定性疾病。孤立性和合并性肌张力障碍综合征在共同的生物学途径上趋同的发现将有助于针对这些趋同分子途径的临床试验和治疗策略的发展。
