Motor and cognitive outcomes of cerebello-spinal stimulation in neurodegenerative ataxia

Abstract

Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks, with a 14-week (T3), 24-week (T4), 36-week (T5) and 52-week follow-up (T6) (open-label phase). At each time point, a clinical, neuropsychological and neurophysiological evaluation was performed. Cerebellar-motor cortex connectivity was evaluated using transcranial magnetic stimulation (TMS). We observed a significant improvement in all motor scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale), in cognition (evaluated with the cerebellar cognitive affective syndrome scale), in quality-of-life scores, in motor cortex excitability and in cerebellar inhibition after real tDCS compared to sham stimulation and compared to baseline (T0), both at short and long-term. We observed an addon-effect after two repeated treatments with real tDCS compared to a single treatment with real tDCS. The improvement at motor and cognitive scores correlated with the restoration of cerebellar inhibition evaluated with TMS. Cerebello-spinal tDCS represents a promising therapeutic approach for both motor and cognitive symptoms in patients with neurodegenerative ataxia, a still orphan disorder of any pharmacological intervention.

The cognitive profile of Friedreich ataxia: a systematic review and meta-analysis

“…A potential way to confirm this hypothesis could be through resting state connectivity (rsFC) in FRDA patients. Indeed, ctDCS has been found recently to improve cognitive performances in a population of patients (one FRDA) with cerebellar ataxia of mixed origins [ 65 ], supporting the role of the cerebellum in their modulation.…”

Non‐invasive electrical stimulation in patients with neurodegenerative ataxia and spasticity: A systematic review and meta‐analysis of randomized controlled trials

“…When restricted to the two studies with unique NCT identifiers at http://clinicaltrials.gov [16,17], the total sample size was 81, and the meta‐analytic estimates remained similar to the results reported above. CBI was found to remain significantly reduced at an MD of −0.36% (95% CI −0.39 to −0.32, p < 0.001) but with significant heterogeneity ( I 2 = 82%, p for Cochran's Q test 0.019).…”

“…Another three studies involving 101 patients reported a poststimulation change in CBI (Figure 1b) [16][17][18], and the randomeffects analysis found post-treatment improvement to be an MD of −0.34% (95% CI −0.37 to −0.32, p < 0.001), with substantial heterogeneity detected (I 2 = 79%, p for Cochran's Q test 0.009). Despite the high heterogeneity observed for the change in CBI, no notable differences were noticed with regard to baseline characteristics of the patient population (type of neurodegenerative ataxia, age and proportion of females included).…”

Cerebellar Transcranial Direct Current Stimulation in Spinocerebellar Ataxia Type 3: a Randomized, Double-Blind, Sham-Controlled Trial

“…Three randomized controlled trials from the same group have recently demonstrated substantial clinical improvement in ataxia patients with mixed etiologies following a two-week regimen of daily cerebellar anodal or cerebello-spinal tDCS sessions [ 19 – 21 ]. In the first two studies, the reported reduction in ataxia severity was found to persist throughout the three-month follow-up period, accompanied by a restoration of functional cerebellothalamocortical tract connectivity [ 20 , 21 ].…”

“…In the first two studies, the reported reduction in ataxia severity was found to persist throughout the three-month follow-up period, accompanied by a restoration of functional cerebellothalamocortical tract connectivity [ 20 , 21 ]. In their third study, the investigators extended the randomized, double-blind phase with an open-label phase, demonstrating the add-on effect of a second round of cerebello-spinal tDCS after three months on both motor and cognitive outcomes [ 19 ]. Albeit encouraging, further trials are required to evaluate the effects of similar treatment protocols in etiologically homogeneous cohorts.…”