Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites |
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| Authors: | K Gierga H J Schelhaas† E R Brunt‡ K Seidel W Scherzed R Egensperger§ R A I de Vos¶ W den Dunnen P F Ippel†† E Petrasch-Parwez‡‡ T Deller L Schöls§§ U Rüb |
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| Institution: | Institute of Clinical Neuroanatomy, J. W. Goethe University, Frankfurt/Main,;Center of Neuropathology and Prion Research, Ludwig-Maximilians-University of München, München,;Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, Bochum, and;Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany;;Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen,;Departments of Neurology,;Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen,;Laboratorium Pathologie Oost Nederland, Enschede, and;Department of Medical Genetics, University Hospital Utrecht, Utrecht, the Netherlands |
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| Abstract: | Aims: Spinocerebellar ataxia type 6 (SCA6) is a late onset autosomal dominantly inherited ataxic disorder, which belongs to the group of CAG repeat, or polyglutamine, diseases. Although, it has long been regarded as a 'pure' cerebellar disease, recent clinical studies have demonstrated disease signs challenging the view that neurodegeneration in SCA6 is confined to the well-known lesions in the cerebellum and inferior olive. Methods: We performed a systematic pathoanatomical study throughout the brains of three clinically diagnosed and genetically confirmed SCA6 patients. Results: This study confirmed that brain damage in SCA6 goes beyond the known brain predilection sites. In all of the SCA6 patients studied loss of cerebellar Purkinje cells and absence of morphologically intact layer V giant Betz pyramidal cells in the primary motor cortex, as well as widespread degeneration of brainstem nuclei was present. Additional damage to the deep cerebellar nuclei was observed in two of three SCA6 patients. Conclusions: In view of the known functional role of affected central nervous grey components it is likely that their degeneration at least in part is responsible for the occurrence of a variety of SCA6 disease symptoms. |
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| Keywords: | channelopathies pathoanatomy polyglutamine diseases spinocerebellar ataxia type 6 spinocerebellar ataxias |
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