Anodal Cerebellar Transcranial Direct Current Stimulation Reduces Motor and Cognitive Symptoms in Friedreich's Ataxia: A Randomized, Sham‐Controlled Trial

Naeije, Gilles; Rovaï, Antonin; Destrebecq, Virginie; Trotta, Nicolas; Tiège, Xavier De

doi:10.1002/mds.29453

Cited by 6 publications

(2 citation statements)

References 51 publications

(149 reference statements)

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“…The general rule of anodal being excitatory and cathodal inhibitory is probably an oversimplification of the physiological mechanisms underlying tDCS, as numerous factors can turn facilitatory changes into inhibitory, and vice versa. 21 However, although we did not measure cerebellar-brain inhibition to prove our hypothesis, many studies have demonstrated that anodal tDCS increases the inhibitory action of the cerebellum to M1, 23-26 while the dual tDCS effect over the cerebellum has also been confirmed by behavioural studies. 52 We do not believe that the paradoxical response could be attributed to cerebellar atrophy because only two patients had reduced cerebellar volume and these patients’ results were in line with the trend of the whole group.…”

Section: Discussionmentioning

confidence: 80%

“… 19 Although the tDCS effect is not always predictable, as it also depends on the orientation of the underlying neurons and the sensitivity of their compartments to exogenous current, 20 previous studies have shown that cerebellar tDCS can modulate, in a polarity-specific fashion, the excitability of cerebellar cortical neurons and, consequently, the output from cerebellar nuclei to the motor cortex 17 , 21 , 22 ; more specifically, it has been observed that anodal tDCS increases the inhibitory action of the cerebellum to the motor cortex. 23-26 …”

Section: Introductionmentioning

confidence: 99%

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Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability

Latorre,

Rocchi,

Paparella

et al. 2023

Brain

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Cortical myoclonus is produced by abnormal neuronal discharges within the sensorimotor cortex, as demonstrated by electrophysiology. Our hypothesis is that the loss of cerebellar inhibitory control over the motor cortex, via cerebello-thalamo-cortical connections, could induce the increased sensorimotor cortical excitability that eventually causes cortical myoclonus. To explore this hypothesis, in the present study we applied anodal transcranial direct current stimulation over the cerebellum of patients affected by cortical myoclonus and healthy controls and assessed its effect on sensorimotor cortex excitability. We expected that anodal cerebellar transcranial direct current stimulation would increase the inhibitory cerebellar drive to the motor cortex and therefore reduce the sensorimotor cortex hyperexcitability observed in cortical myoclonus. Ten patients affected by cortical myoclonus of various aetiology and 10 aged-matched healthy controls were included in the study. All participants underwent somatosensory evoked potentials, long-latency reflexes, and short-interval intracortical inhibition recording at baseline and immediately after 20 min session of cerebellar anodal transcranial direct current stimulation. In patients, myoclonus was recorded by the means of surface electromyography before and after the cerebellar stimulation. Anodal cerebellar transcranial direct current stimulation did not change the above variables in healthy controls, while it significantly increased the amplitude of somatosensory evoked potential cortical components, long-latency reflexes and decreased short-interval intracortical inhibition in patients; alongside, a trend towards worsening of the myoclonus after the cerebellar stimulation was observed. Interestingly, when dividing patients in those with and without giant somatosensory evoked potentials, the increment of the somatosensory evoked potential cortical components was observed mainly in those with giant potentials. Our data showed that anodal cerebellar transcranial direct current stimulation facilitates, and does not inhibit, sensorimotor cortex excitability in cortical myoclonus syndromes. This paradoxical response might be due to an abnormal homeostatic plasticity within the sensorimotor cortex, driven by dysfunctional cerebello-thalamo-cortical input to the motor cortex. We suggest that the cerebellum is implicated in the pathophysiology of cortical myoclonus and that these results could open the way to new forms of treatment or treatment targets.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability

Latorre,

Rocchi,

Paparella

et al. 2023

Brain

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Effects of Non‐Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta‐Analysis

Matsugi,

Ohtsuka,

Bando

et al. 2024

Movement Disord Clin Pract

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BackgroundThis systematic review and meta‐analysis aimed to assess the effectiveness of non‐invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192).ObjectiveWe aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients.MethodsThe PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta‐analysis was performed.ResultsSeventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = −2.49, [95% confidence interval: −3.34, −1.64]) and ICARS (−5.27 [−7.06, −3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia.ConclusionNon‐invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high‐quality RCTs are required.

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Cerebellar Transcranial Direct Current Stimulation in the Cerebellar Cognitive Affective Syndrome: A Randomized, Double‐Blind, Sham‐Controlled Trial

Reumers,

Maas,

Schutter

et al. 2024

Movement Disorders

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BackgroundThe cerebellar cognitive affective syndrome (CCAS) encompasses cognitive and affective symptoms in patients with cerebellar disorders, for which no proven treatment is available.ObjectivesOur primary objective was to study the effect of cerebellar anodal transcranial direct current stimulation (tDCS) on cognitive performance in CCAS patients. Secondary effects on ataxia severity, mood, and quality of life were explored.MethodsWe performed a randomized, double‐blind, sham‐controlled trial. Thirty‐five patients with CCAS were included and received 10 sessions of 20 minutes sham (n = 17) or real (n = 18) tDCS, with a current of 2 mA. Cognitive performance was assessed using executive function subtests of the computerized Test of Attentional Performance (TAP), with the composite as primary endpoint. Secondary outcomes were ataxia severity, mood, and quality of life. Outcomes were evaluated 1, 3, 6, and 12 months post‐intervention.ResultsCerebellar tDCS was well tolerated and no serious adverse events related to the intervention occurred. No significant tDCS effect was found on cognitive performance. Improvement on the TAP was observed in the sham group 1 month post‐treatment (estimate = −0.248, 95% CI, −0.49 to −0.01), but not clinically relevant. A positive tDCS effect was observed for ataxia severity 1 month post‐treatment (estimate = −0.985, 95% CI, −1.94 to −0.03).ConclusionsTen sessions of 20 minutes cerebellar anodal tDCS did not prove efficacious for CCAS‐related cognitive impairment, but a significant positive effect of tDCS was found for ataxia severity, aligning with previous findings indicative of tDCS as a therapeutic neuromodulation tool in cerebellar disorders. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Anodal Cerebellar Transcranial Direct Current Stimulation Reduces Motor and Cognitive Symptoms in Friedreich's Ataxia: A Randomized, Sham‐Controlled Trial

Cited by 6 publications

References 51 publications

Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability

Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability

Effects of Non‐Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta‐Analysis

Cerebellar Transcranial Direct Current Stimulation in the Cerebellar Cognitive Affective Syndrome: A Randomized, Double‐Blind, Sham‐Controlled Trial

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