Meta-Analysis Highlights Benefits of Noninvasive Brain Stimulation in Cerebellar Ataxia Care

A recently published systematic review and meta-analysis of randomized controlled trials (RCTs) assessing noninvasive brain stimulation (NIBS) techniques in patients with cerebellar ataxia revealed that these approaches are safe and effective in improving motor coordination in this patient group. In addition, transcranial direct current stimulation (tDCS) outperformed repetitive transcranial magnetic stimulation (rTMS) in treating patients.¹

Led by Yun Luo, Department of Rehabilitation Medicine, First Affiliated Hospital of Gannan Medical University, the published analysis included 14 RCTs with low-risk bias comprising 406 patients with cerebellar ataxia. Although the trials had an intermediate level of evidence, results showed that cerebellar NIBS, including tDCS and rTMS, was effective in reducing the Scale for the Assessment and Rating of Ataxia (SARA) scores (mean difference, –3.45; 95% CI, –4.85 to –2.50; P <.05) in this patient population vs controls.

Cerebellar ataxias encompass a heterogenous group of acquired and hereditary disorders with diverse clinical presentations. Currently, the majority of degenerative ataxias lack effective pharmacologic disease-modifying therapies and there is growing interest in finding innovative therapeutic approaches to improve clinical symptoms in patients with this spectrum of disorders. In addition to tDCS, and rTMS, other types of NIBS techniques include transcranial alternating current stimulation (tACS), theta burst stimulation, and transcranial magnetic stimulation.

Results from the meta-analysis also revealed that NIBS techniques reduced International Cooperative Ataxia Rating Scale (ICARS) scores in patients with cerebellar ataxia when compared with controls (MD, –10.87; 95% CI, –14.46 to –7.28; P <.05). Between tDCS and rTMS, patient data revealed statistical differences in SARA scores but not on ICARS. In addition, patients’ etiology played a factor into the efficacy of NIBS, with statistically significant differences seen throughout.

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Over the years, there has been an increased effort to better understand these treatment approaches and their mechanism of action in cerebellar ataxia. Some studies have shown that the effects of iTBS might be more relevant than those obtained after rTMS, and encouraging results have been achieved in the treatment of gait and balance recovery in patients with stroke after cerebellar iTBS.² Furthermore, tACS has also emerged as a new technique to modulate cortical oscillations and entrain brain rhythms in specific frequencies.³

A 2020 literature review by Alberto Benussi et al on noninvasive cerebellar stimulation in neurodegenerative ataxia pointed to several areas of need, including “the inclusion of etiologically homogenous group of patients, perhaps in multicenter studies; defining the optimal timing of follow-up stimulation sessions and the effects of repeated sessions over time; the effects on cognition and emotions; the feasibility of at-home remotely supervised stimulation in larger cohorts; and if these effects may be intensified by concurrent motor training interventions or pharmacologic therapies."⁴

They added, "Critically, evaluation of target engagement using imaging or physiologic biomarkers, as well as the assessment of “dose” by using modelling to calculate the induced currents in the brain to define individual stimulation parameters, would be essential. Moreover, the cerebellum can show significant structural changes in term of climbing fiber Purkinje cell and parallel fiber Purkinje cell wirings in cerebellar ataxia and other disorders, and some wiring features can be rapidly changed within days and affect cerebellar synchronization."

REFERENCES
1. Gong C, Long Y, Peng XM, et al. Efficacy and safety of noninvasive brain stimulation for patients with cerebellar ataxia: a systematic review and meta-analysis of randomized controlled trials. Journal of Neurol. 2023;270:4782-4799. doi:10.1007/s00415-023-11799-8
2. Blumberger D.M., Vila-Rodriguez F., Thorpe K.E., et al. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): A randomised non-inferiority trial. Lancet. 2018;391:1683–1692. doi: 10.1016/S0140-6736(18)30295-2
3. Antal A., Boros K., Poreisz C., Chaieb L., Terney D., Paulus W. Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul. 2008 doi: 10.1016/j.brs.2007.10.001.
4. Benussi A, Pascual-Leone A, Borroni B. Non-invasive cerebellar stimulation in neurodegenerative ataxia: a literature review. Int J Mol Sci. 2020;21(6):1948. doi:10.3390.ijms21061948