Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Medical Genetics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Neuropathology. 2023 Apr;43(2):135-142. doi: 10.1111/neup.12860. Epub 2022 Aug 17.
Spinocerebellar ataxia type 3 (SCA3) is a form of autosomal dominant cerebellar ataxia with a wide range of clinical manifestations, including ataxia and pyramidal and extrapyramidal signs. A few SCA3 patients have been noticed to be predisposed to the development of inclusion body myositis. It is still unknown whether muscle can be primarily involved in the pathogenesis of SCA3. This study reported an SCA3 family in which the index patient initially presented with parkinsonism, sensory ataxia, and distal myopathy but the absence of cerebellar and pyramidal symptoms. The clinical and electrophysiological studies implied a possible combination of distal myopathy and sensory-motor neuropathy or neuronopathy. MRI muscle showed selective fat infiltration and absence of denervated edema-like changes, indicating the distal muscle weakness had a myopathic origin. Muscle pathology showed the myopathic involvement, besides neurogenic involvement, characterized by chronic myopathic changes with multiple autophagic vacuoles. Genetic screening revealed expanded CAG of 61 repeats in the ATXN3 gene, which showed co-segregation in the family. Besides the neurogenic origin, the myopathic origin may be partly attributed to the limb weakness of SCA3 patients, which expands the spectrum of the clinical manifestation of SCA3.
脊髓小脑性共济失调 3 型（SCA3）是一种常染色体显性遗传性小脑共济失调，具有广泛的临床表现，包括共济失调和锥体外系及锥体系体征。一些 SCA3 患者易发生包涵体肌炎。目前尚不清楚肌肉是否会成为 SCA3 发病机制的主要部位。本研究报道了一个 SCA3 家系，该家系的先证者最初表现为帕金森病、感觉性共济失调和远端肌病，但无小脑和锥体系症状。临床和电生理研究提示可能存在远端肌病和感觉运动神经病或神经元病的组合。MRI 肌肉显示选择性脂肪浸润，无去神经支配性水肿样改变，表明远端肌无力具有肌病起源。肌肉病理学显示除神经源性受累外，还存在肌病性受累，特征为慢性肌病改变伴多个自噬空泡。基因筛查显示 ATXN3 基因的 CAG 重复扩展 61 次，在家系中存在共分离。除神经源性起源外，肌病性起源可能部分归因于 SCA3 患者的肢体无力，这扩大了 SCA3 的临床表现谱。
