Dystonia - new advances in classification, genetics, pathophysiology and treatment
Dystonia - new advances in classification, genetics, pathophysiology and treatment
复制标题
DOI：
10.1111/ane.12231
复制
发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Skogseid, I. M.
中科院分区：
文献类型：
--
作者：
Skogseid, I. M.
肌张力障碍是一种异质性运动障碍，被定义为“一种持续肌肉收缩的综合征，经常导致扭曲和重复的运动，或不正常的姿势”。肌张力障碍的分类随着知识的增加而发展，并提出了不同的方案，包括发病年龄、身体分布和病因作为主要的鉴别因素。肌张力障碍的新定义和新分类现已由一组顶尖的肌张力障碍专家提出，并将在此提及。通过比较显性携带者和未显性携带者的神经生理学，以及对突变基因产物的分子生物学研究，发现了导致原发性全身性肌张力障碍的前两个基因突变(DYT1-TOR1A和DYT6-THAP1)，为研究原发性肌张力障碍的发病机制和病理生理学提供了便利。近年来，还发现了其他几种导致原发性肌张力障碍、肌张力障碍+和阵发性肌张力障碍的基因突变。仅在去年，通过使用全外显子测序技术，在以颈部肌张力障碍为主的家系中发现了三种不同基因的突变，这可能有助于更好地了解更常见的局灶性肌张力障碍的发病机制。在过去的二十年里，肉毒杆菌神经毒素(BONT)和脑深部刺激(DBS)彻底改变了对症治疗肌张力障碍的方法，并继续改进以提高疗效并扩大其适应症。不幸的是，肌张力障碍的口服药物治疗没有取得任何进展。目前和未来对肌张力障碍的发病机制和病理生理学机制的新见解有望很快在这一领域得到改善。
Dystonia is a heterogeneous movement disorder and has been defined as 'a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements, or abnormal postures'. The classification of dystonia has developed along with increasing knowledge, and different schemes have been suggested, including age at onset, body distribution, and etiology as the main differentiating factors. A revised definition and a new classification of dystonia have now been proposed by a group of leading dystonia experts and will be referred here. The discovery of the first two gene mutations causing primary generalized dystonia (DYT1-TOR1A and DYT6-THAP1) has facilitated studies on pathogenesis and pathophysiology of primary dystonias, by comparing neurophysiology between manifesting and non-manifesting carriers, and by studying the molecular biology of the mutant gene products. During recent years, several other gene mutations causing primary dystonia, dystonia-plus, and paroxysmal dystonia disorders have been discovered. Only during the last year, by the use of whole-exome sequencing techniques, mutations in three different genes in families with predominantly cervical dystonia were found, which may lead to improved insight into the pathogenesis also of the more frequent focal dystonias. Botulinum neurotoxin (BoNT) and deep brain stimulation (DBS) have revolutionized the symptomatic treatment for dystonia during the last two decades and continue to be refined to improve efficacy and expand their indications. Unfortunately, no progress has been made in the oral medication of dystonia. Current and future new insights into pathogenetic and pathophysiological mechanisms of dystonia will hopefully lead to improvement also in this area soon.