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
Article first published online: 26 JAN 2010
© 2010 Japanese Society of Neuropathology
Volume 30, Issue 5, pages 501–514, October 2010
How to Cite
Wang, X., Wang, H., Xia, Y., Jiang, H., Shen, L., Wang, S., Shen, R., Xu, Q., Luo, X. and Tang, B. (2010), 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. Neuropathology, 30: 501–514. doi: 10.1111/j.1440-1789.2009.01094.x
- Issue published online: 26 JAN 2010
- Article first published online: 26 JAN 2010
- Received 5 June 2009; revised and accepted 2 December 2009; published online 26 January 2010.
- precerebellar nuclei;
- spinocerebellar ataxias 6;
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.