Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia (SCA02)

Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxias: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase

Neurodegenerative cerebellar ataxias represent a group of disabling disorders which currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. In this randomized, double-blind, sham-controlled study followed by an open-label phase, the investigators will evaluate whether a repetition of two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS, after a three months interval, may further outlast clinical improvement in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term.

Neurodegenerative cerebellar ataxias represent a heterogeneous group of disabling disorders in which progressive ataxia of gait, limb dysmetria, oculomotor deficits, dysarthria and kinetic tremor are the prominent clinical manifestations. Both the hereditary and sporadic forms usually present in young adulthood, and are characterized by atrophy of cerebellar or brainstem structures. Currently, cerebellar ataxia lack effective disease-modifying therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present randomized, double-blind, sham-controlled study followed by an open-label phase will investigate a repetition of two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS, after a three months interval, may further outlast clinical improvement in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term. In addition the investigators will evaluate if tDCS intervention might improve cerebellar cognitive-affective syndrome in patients with ataxia.

Ataxia, Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Multiple System Atrophy, Ataxia With Oculomotor Apraxia, CANVAS

Transcranial direct current stimulation, Transcranial magnetic stimulation, Spinocerebellar ataxia, Cerebellar ataxia

10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)

10 sessions of sham cerebellar and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks).

10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)

10 sessions of sham cerebellar and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks)

International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia).

Scale for the Assessment and Rating of Ataxia (SARA): 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia).

CCAS/Schmahmann syndrome scale: 120 point scale, yielding a total score of 0 (most severe cognitive impairment) to 120 (no cognitive impairment).

International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia).

Scale for the Assessment and Rating of Ataxia (SARA): 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia).

CCAS/Schmahmann syndrome scale: 120 point scale, yielding a total score of 0 (most severe cognitive impairment) to 120 (no cognitive impairment).

Cerebellar brain inhibition (CBI) is expressed as motor evoked potential amplitude (average of 10 recordings). Lower values reflect higher inhibition and thus reduced impairment.

The Italian version of the Short-Form Health Survey 36 (SF-36): consists of 36 scaled score, yielding a total score of 0 (more disability) to 100 (less disability).

Inclusion Criteria: Patients with a cerebellar syndrome and quantifiable cerebellar atrophy Exclusion Criteria: Severe head trauma in the past History of seizures History of ischemic stroke or hemorrhage Pacemaker Metal implants in the head/neck region Severe comorbidity Intake of illegal drugs Pregnancy

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