Meta-Analysis Highlights Benefits of Repetitive Transcranial Magnetic Stimulation in Cerebellar Ataxia

Qiang Gao, MD, PhD

A recently published systematic review and meta-analysis revealed that repetitive transcranial magnetic stimulation (rTMS) over the cerebellar may be an efficacious treatment option for patients with cerebellar ataxia, a neurodegenerative disorder with limited symptomatic therapies available. This approach was also shown to be safe, well-attended, and did not result in unanticipated negative adverse events (AEs).¹

Senior author Qiang Gao, MD, PhD, senior physiotherapist at West China Hospital, and colleagues, included 7 randomized controlled trials in the quantitative review, each of which assessed real and sham-rTMS interventions. All told, the utilization of rTMS on cerebellum improved scores on the Assessment and Rating of Ataxia (SARA) scale (standardized mean difference [SMD], –0.87; 95% CI, –1.41 to –0.34; P = .001; I² = 62%) the International Cooperative Ataxia Rating Scale (ICARS)(SMD, –1.06; 95% CI, –1.47 to –0.64; P <.00001; I² = 0%) and Berg Balance Scale (BBS)(SMD, 0.76; 95% CI, 0.33-1.19; P = .0005; I² = 39%).

A subgroup analysis assessing high-frequency rTMS demonstrated similar positive effects (SMD, –1.28; 95% CI, –1.82 to –0.74; P <.00001; I2 = 0%). As for safety, the incidence of AEs between rTMS and sham were not significantly different (OR, 1.73; 95% CI, 0.55-5.46; P = .35; I2 = 0%). Although these results highlight the impacts of rTMS on patients with cerebellar ataxia, investigators noted that they should be taken with caution, as the study included a limited amount of evidence, using only 7 studies.

rTMS targeting cerebellar structures enables modulation of cortical excitability and is capable of inducing long-lasting changes in the excitability of cerebello-thalamo-cortical pathways. Previous studies have shown that the magnetic resonance spectroscopy (MRS) provides a non-ionizing and non-invasive method to measure the alteration of cerebellar metabolism, and thus its application before and after the rTMS has been considered suitable.

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This approach has gained more attention over the years, with more studies coming out not just in ataxia but across other neurologic conditions. In 2022, a prospective, randomized, double-blind, sham-controlled study was conducted to investigate the effects of low-frequency rTMS on local intracerebral metabolism in patients with spinocerebellar ataxia type 3 (SCA3) as well as the possible correlation between the alteration of cerebellar ataxia and the improvement of ataxia. The trial, included 9 patients assigned to real stimulation and 9 on sham for 15 consecutive days.

After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05).²

REFERENCES
1. Efficacy and safety of repetitive transcranial magnetic stimulation in cerebellar ataxia: a systematic review and meta-analysis. The Cerebellum. 2024;(23):243-254. doi:10.1007/s12311-022-01508-y
2. Manor B, Greenstein PE, Davila-Perez P, Wakefield S, Zhou J, Pascual-Leone A. Repetitive transcranial magnetic stimulation in spinocerebellar ataxia: a pilot randomized controlled trial. Front Neurol. 2019;(10). doi:10.3389/fneur.2019.00073