Efficacy of Cerebellar Transcranial Direct Current Stimulation in Degenerative Ataxia. A Sham-controlled Clinical and Quantitative Analysis.

Degenerative cerebellar ataxias are a heterogeneous group of inherited and acquired disorders characterized by cerebellar atrophy and degeneration which leads to a wide range of clinical symptoms. Indeed, beside cerebellar symptoms such as gait ataxia, postural unbalance, dysmetria and nystagmus, patients may exhibit peripheral neuropathy, pyramidal and extrapyramidal signs and behavioural symptoms, depending on the aetiology of the disorder.

These disorders substantially affect autonomy and quality of life, yet effective disease-modifying or symptomatic treatments remain limited; their current management is largely supportive, including physical therapy and symptomatic pharmacological interventions.

Among non-pharmacological treatments, cerebellar transcranial direct current stimulation (tDCS), a non-invasive brain stimulation (NIBS) technique, has been employed in several studies with the aim to improve both motor and cognitive symptoms in different forms of ataxia, with conflicting results, so that, at present, it is not possible to determine its therapeutic potential with certainty. In this regard, it has been hypothesized that the large variability of clinical outcomes associated with such approach is due to several factors including, among the most relevant, the heterogeneity of ataxia aetiology, the significant differences in terms of protocols of stimulation and the lack of sensitive objective measures to be integrated with the scales traditionally employed in the clinical routine. Indeed, in the last years, quantitative analysis of movement (performed using either motion capture system or wearable inertial sensors) has shown to be a reliable approach to assess, in combination with clinical data, the existence and magnitude of possible positive effects induced by NIBS on basic motor functions (i.e., gait and balance) as well as to monitor real-world mobility and characterize physical activity patterns of people with ataxia.

The ability of cerebellar tDCS to influence the cerebellar-thalamus-cortical pathway has been demonstrated by the cerebellar-brain inhibition (CBI) TMS paradigm. Moreover, the cerebellar-cortical connectivity has been explored with NIBS combined with functional magnetic resonance imaging (fMRI) and EEG with online and offline paradigms. Several studies show that cerebellar NIBS is able to influence cortical oscillations and that an increase of beta power in frontal and parietal region is involved sensory-motor integration and motor control through the modulation of the cerebellar-thalums cortical circuit; the role of cortical gamma oscillation on motor activity following cerebellar stimulation is less characterized, but some evidence indicates that cortical gamma activity reflects excitatory action of the cerebellum on the motor thalamus and the motor cortex. However, in this case the results are controversial probably due to the heterogeneous methodological approaches.

Based on these observations, the aim of the present study was to assess the efficacy of cerebellar anodal tDCS in improving ataxia in different forms of degenerative ataxia with a sham-controlled approach, using validated clinical rating scales as well as quantitative techniques for human movement analysis focused on gait and upper limb functionality (i.e., hand-to-mouth task) as data on these motor tasks are already available for people with ataxia.