Electrophysiology in spinocerebellar ataxia Diagnostic value and progression marker

Spinocerebellar ataxia (SCA) is the collective term introduced by the genetic classification to autosomal dominantly inherited cerebellar ataxias. SCA comprises a clinically and genetically heterogeneous group of neurodegenerative disorders with ataxia as key symptom (for review see Schöls et al. 2004). SCA does not necessarily mean that degeneration involves the spinal cord or is restricted to spinocerebellar systems. Some SCA subtypes are restricted to pure cerebellar degeneration (e.g. SCA6) while others spread to pontine nuclei, basal ganglia, retina, cerebral cortex, spinal tracts or peripheral nerves (Figure 1). Earlier pathoanatomical classifications tried to categorize variability of neurodegeneration in SCAs by introducing terms describing spread of pathoanatomic changes like cerebellar cortical atrophy (CCA), olivopontocerebellar atrophy (OPCA), spinocerebellar atrophy (here meant as a pathological description not as a collective term for the whole group), dentatorubral atrophy or spinal ataxia (Greenfield 1954). This neuropathological classification fell through because of its restricted applicability post mortem and, even more important, because of the variability of the diseases leading to different classification (e.g. as CCA, SCA or OPCA) of the same disorder (e.g. SCA3) sometimes even within the same family. Molecular genetics facilitates a precise, cheap and early (even prenatal) diagnosis and a classification linked to the molecular cause of the disease and thus to pathophysiology and – hopefully in the not too far future – causal therapy. However, genetic classification is not interested in phenotypic and clinical aspects of the diseases. Thorough clinical characterization of the phenotype is mandatory i) to direct genetic analyses (Figure 1) and enable a cost-saving genetic diagnosis and ii) to analyze complex clinical pictures and introduce symptomatic treatment alleviating Parkinsonian features, dystonia, spasticity, bladder dysfuntion, sleep disturbance or peripheral neuropathy and iii) to monitor the course of the disease. In this sense, neurophysiological investigations are used in SCA to search for spreading of the disease to non-cerebellar systems, to guide direct genetic testing and as potential progression markers for therapeutical trials in the future.