Kuo Sheng-Han
Continuum (Minneap Minn). 2019 Aug;25(4):1036-1054. doi: 10.1212/CON.0000000000000753.
This article reviews the symptoms, laboratory and neuroimaging diagnostic tests, genetics, and management of cerebellar ataxia.
Recent advances in genetics have led to the identification of novel genetic causes for ataxia and a more comprehensive understanding of the biological pathways critical for normal cerebellar function. When these molecular pathways become dysfunctional, patients develop cerebellar ataxia. In addition, several ongoing clinical trials for Friedreich ataxia and spinocerebellar ataxia will likely result in novel symptomatic and disease-modifying therapies for ataxia. Antisense oligonucleotides for spinocerebellar ataxias associated with CAG repeat expansions might be a promising therapeutic strategy.
Cerebellar ataxias include heterogeneous disorders affecting cerebellar function, leading to ataxic symptoms. Step-by-step diagnostic workups with genetic investigations are likely to reveal the underlying causes of ataxia. Some disease-specific therapies for ataxia exist, such as vitamin E for ataxia with vitamin E deficiency and thiamine for Wernicke encephalopathy, highlighting the importance of recognizing these forms of ataxia. Finally, genetic diagnosis for patients with ataxia will accelerate clinical trials for disease-modifying therapy and will have prognostic value and implications for family planning for these patients.
本文综述小脑性共济失调的症状、实验室及神经影像学诊断检查、遗传学及治疗。
遗传学方面的最新进展已导致发现共济失调的新遗传病因，并对正常小脑功能所必需的生物学途径有了更全面的认识。当这些分子途径功能失调时，患者会出现小脑性共济失调。此外，针对弗里德赖希共济失调和脊髓小脑性共济失调的几项正在进行的临床试验可能会产生针对共济失调的新的对症治疗和疾病修正治疗方法。针对与CAG重复扩增相关的脊髓小脑性共济失调的反义寡核苷酸可能是一种有前景的治疗策略。
小脑性共济失调包括影响小脑功能的异质性疾病，导致共济失调症状。通过基因检测进行逐步诊断检查可能会揭示共济失调的潜在病因。存在一些针对共济失调的疾病特异性治疗方法，如用于维生素E缺乏性共济失调的维生素E和用于韦尼克脑病的硫胺素，这凸显了识别这些形式的共济失调的重要性。最后，对共济失调患者进行基因诊断将加速疾病修正治疗的临床试验，并对这些患者的预后及计划生育具有指导意义。
