Identification of the SCA21 disease gene: remaining challenges and promising opportunities.

ant measures to establish a post-ganglionic lesion site. Another important avenue of research will be the establishment of symptomatic treatment of autonomic changes in CANVAS. There is good cause to believe that symptomatic treatments established in other autonomic neuropathies (e.g. diabetic autonomic neuropathy) will also mitigate autonomic symptoms in CANVAS. However, given the lack of data regarding this approach in CANVAS, treatment decisions will need to be made on an individual basis and extensive monitoring will be required. In summary, the study by Wu et al. provides evidence that sympathetic and parasympathetic autonomic failure is an integral part of CANVAS. In clinical practice this finding adds to difficulties in the differential diagnosis of adult-onset, progressive ataxias. Additional studies assessing the safety and efficacy of existing drugs for counteracting autonomic symptoms in CANVAS are urgently required. Finally, from a scientific point of view, it will be interesting to establish the site of the lesion in CANVAS-associated autonomic failure, and we are convinced that future clinical and pathological studies in CANVAS will shed light on the pathomechanisms involved.