Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites.

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.