Sorbonne Université, Faculté de Médecine.
APHP, Hôpital Salpêtrière, Département de Neurologie, Paris, France.
Curr Opin Neurol. 2018 Aug;31(4):484-490. doi: 10.1097/WCO.0000000000000577.
The present study will highlight recent advances in the field of myoclonus-dystonia with a focus on clinical aspects, pathogenesis, and treatment. We will also discuss genetics, classification issues, and diagnostic criteria.
Myoclonus-dystonia is a clinical syndrome corresponding to the phenotype linked to SGCE, the main causative gene. Childhood-onset myoclonus that predominates over dystonia with prominent upper body involvement, an absence of truncal dystonia, associated anxiety or compulsivity, and a positive family history are helpful diagnostic clues. Recent studies demonstrated that zonisamide is an interesting therapeutic option in myoclonus-dystonia, and that bilateral pallidal stimulation has major and lasting therapeutic effects. Accumulating evidence suggests that an alteration in cerebello-thalamic pathway function may play a prominent role and that this is possibly related to a GABAergic deficit reflecting Purkinje cell dysfunction. Impaired striatal plasticity and disturbed serotonin homeostasis may also be implicated. Newly available cellular and rodent models may further assist in investigating the pathogenesis of this disorder.
Comprehensive analysis of the phenotype and precise classification are important in patients with myoclonus and dystonia to identify homogeneous groups of patients. This is critical to guide tailored therapeutic strategies and promote effective research.
本研究将重点关注肌阵挛-肌张力障碍领域的最新进展，包括临床方面、发病机制和治疗方法。我们还将讨论遗传学、分类问题和诊断标准。
肌阵挛-肌张力障碍是一种临床综合征，与 SGCE 相关，后者是主要的致病基因。儿童期起病、以肌阵挛为主、上半身受累明显、无躯干性肌张力障碍、伴发焦虑或强迫、阳性家族史有助于诊断。最近的研究表明，唑尼沙胺是治疗肌阵挛-肌张力障碍的一种有趣的选择，双侧苍白球刺激具有显著和持久的治疗效果。越来越多的证据表明，小脑-丘脑通路功能的改变可能起重要作用，这可能与反映浦肯野细胞功能障碍的 GABA 能缺陷有关。纹状体可塑性受损和 5-羟色胺稳态紊乱也可能与此有关。新出现的细胞和啮齿动物模型可能有助于进一步研究这种疾病的发病机制。
对肌阵挛和肌张力障碍患者的表型进行全面分析和精确分类对于识别同质患者群体非常重要。这对于指导针对性的治疗策略和促进有效的研究至关重要。
