Manto Mario, Gandini Jordi, Feil Katharina, Strupp Michael
Cerebellar Ataxia Unit, Department of Neurology, CHU-Charleroi, Charleroi.
Department of Neuroscience, University of Mons, Mons, Belgium.
Curr Opin Neurol. 2020 Feb;33(1):150-160. doi: 10.1097/WCO.0000000000000774.
Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum.
Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias.
Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.
提供关于小脑性共济失调的病理生理学、病因、诊断及治疗的最新进展。这是一组散发或遗传性疾病，临床表现多样，在许多情况下对日常生活有显著影响。患者可能表现为单纯小脑型表型，或小脑功能缺陷与影响中枢/外周神经系统的小脑外功能缺陷的各种组合。相关动物模型为多种影响小脑的疾病的合理治疗铺平了道路。
临床上，小脑综合征现根据一种新的临床量表分为小脑运动综合征、前庭小脑综合征和小脑认知情感综合征。这种基于三个基石的细分得到了解剖学发现和神经影像学的支持。现已确定，基底神经节和小脑这两个主要的皮质下节点通过双突触通路相连，确保双向通信。遗传性共济失调包括常染色体隐性小脑性共济失调（ARCA）、常染色体显性脊髓小脑性共济失调、发作性共济失调和X连锁共济失调。除了运动障碍协会对ARCA的基因分类外，小脑与共济失调研究协会对ARCA的分类代表了这一复杂的小脑性共济失调亚组的重大进展。新一代测序技术的出现拓宽了小脑性共济失调的范围。
小脑性共济失调的诊断和管理需要多学科方法。小脑与基底神经节之间解剖关系的证明影响了对小脑-基底神经节-丘脑-皮质系统的理解。针对有害通路的新型疗法，如作用于RNA的疗法，正在研发中。
