Spinocerebellar ataxia type 6: Systematic patho-anatomical study reveals different phylogenetically defined regions of the cerebellum and neural pathways undergo different evolutions of the degenerative process.
Spinocerebellar ataxia type 6 is a late onset autosomal dominantly inherited ataxic disorder, and previous patho-anatomical studies have only reported neurodegeneration in SCA6 as being confined to the cerebellar cortex, dentate nucleus and inferior olive. However, the characteristics of cerebellar symptoms and many poorly understood "extracerebellar" symptoms reveal the three cerebellar regions and the corresponding precerebellar nuclei may undergo differing evolution of the degenerative process, and a more widespread brainstem degeneration in SCA6. We carried out a detailed immunohistochemical study in two SCA6 patients who had rather early onset and short disease duration with 25 CAG repeats, which is atypical for SCA-6. We investigated the severity of neurodegeneration in each of the cerebellar regions and the corresponding precerebellar nuclei, and further characterize the extent of brain degeneration. This study confirmed that vestibulocerebellar, spinocerebellum and pontocerebellar are consistent targets of the pathological process of SCA6, but the severity of neurodegeneration in each of them was different. Vestibulocerebellum and the inferior cerebellar peduncle undergo the most severe neurodegeneration, while neurodegeneration in the pontocerebellar is less severe. Furthermore, we observed obvious neurodegeneration in layers II and III of the primary motor cortex, vestibular nuclei, inferior olivary nucleus, nucleus proprius and posterior spinocerebellar tract. Our detailed postmortem findings confirmed that SCA6 was not a simple "pure" cerebellar disease, but a complex neurodegenerative disease in which the three cerebellar regions underwent different evolutions of neurodegeneration process, and the corresponding precerebellar nuclei and the neural pathway were all involved.
Wang
Xuejing
X
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Wang
Hui
H
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Xia
Yujun
Y
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Jiang
Hong
H
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Shen
Lu
L
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Wang
Shoubiao
S
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Shen
Ruowu
R
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Xu
Qian
Q
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Luo
Xuegang
X
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
Tang
Beisha
B
Department of Neurology, Xiangya Hospital,Department of Anatomy & Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, andDepartment of Anatomy, Qing Dao University, QingDao, Shandong, China.
D000293:Adolescent; D001933:Brain Stem / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000473:pathology*; D019680:Trinucleotide Repeat Expansion