Balance control in spino-cerebellar ataxia type 6: Vestibular processing unravelled

The spino-cerebellar ataxias (SCAs) are a group of inherited and neurologically degenerative disorders that frequently cause atrophy of the cerebellum [1]. SCA6 is clinically characterised with impaired balance and ataxia of movement, frequently causing falls [2], and is considered to be one of the SCA types with the purest pathology due to the relatively localised signs of neuronal damage in the cerebellum. The disordered control processes responsible for the balance impairment in this group remain undetermined and consequently no management guidelines exist [1]. Animal experimentation has suggested that areas of the cerebellum, such as the anterior cerebellar vermis, flocculus and spino-cerebellum have roles in vestibular gain control, sensory integration and timing [3]. Dysfunction of these areas could cause poorly scaled, directed or timed balance responses, any of which could be responsible for impaired balance control. Since SCA6 is known to involve Purkinje cell atrophy particularly in the anterior and superior cerebellar hemispheres and vermis [1], it is reasonable to hypothesise that poor balance may result from impaired vestibular processing associated with these regions. Here we investigate whether SCA subjects can use vestibular information appropriately to control balance, in particular to integrate vestibular information with other sensory inputs. Seventeen subjects with SCA6 were recruited together with a group of seventeen matched healthy controls. Subjects stood quietly on force plates (Kistler) with their feet 8cm apart and with different head yaw directions (head forward or right/left 90 degrees). Clusters of infrared-emitting diodes were fixed securely to each of the body segments and body motion was recorded in 3D using Coda (Charnwood Dynamics). Galvanic vestibular stimulation (GVS, 1mA bipolar R+L-/R-L+) was used to provide a standardised and repeatable vestibular balance perturbation and visual conditions (vision intact/obscured) were varied using liquid crystal spectacles (Plato). In both groups, average responses to GVS were normally timed and normally directed (along the intra-aural line, towards the anodal ear). Furthermore, average response magnitudes typically increased with removal of vision, as did baseline instability measures in both groups. However, despite these many similarities to healthy controls, in all conditions SCA6 response magnitudes were consistently larger than those of the healthy control group. These results suggest that abnormal vestibular processing is probably not the main determinant of SCA6 instability. However, SCA6 subjects’ ‘over-response’ to GVS could contribute to instability and may be due either to an abnormal increase in gain of the vestibular channel of balance control or an epiphenomenon of the subjects’ greater baseline instability. [1] Schols,L. et al., Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. The Lancet Neurology. 2004; 3(5):291-304 [2] van de Warrenburg,B.P. et al., Falls in degenerative cerebellar ataxias. Movement Disorders. 2005; 20(4):497-500 [3] Manzoni, D. et al., Changes in gain and spatiotemporal properties of the vestibulospinal reflex after injection of a gaba-A agonist in the cerebellar anterior vermis. Journal of Vestibular Research 1997; 7(1):7-20