Eficacia y seguridad de la estimulación magnética transcraneal en el tratamiento de la ataxia espinocerebelosa. Revisión sistemática

Introduction Spinocerebellar ataxias (SCA) are a group of neurodegenerative genetic diseases characterized by cerebellar degeneration and transmitted through autosomal dominant inheritance. This degeneration causes a progressive loss of coordination of movements, making it difficult to walk, speak, and perform daily tasks. Symptoms usually appear in adulthood and worsen over time, although each type of SCA has its own characteristics and rate of progression. SCA lacks a definitive cure, so research approaches for new therapeutic pathways are being developed. In this regard, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure that can play an important role in the treatment of patients with SCA. Objective To assess the efficacy and safety of rTMS in patients with SCA. Methods To identify relevant studies, specific search strategies were developed and the following electronic databases were consulted: Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Physiotherapy Evidence Database (PEDRO), Science Citation Index expanded (SCI), Cumulative Index of Nursing and Allied Literature Complete (CINHAL), The International Network of Agencies for Health Technology Assessment (INAHTA), National Institute for Health and Care Excellence (NICE), Canada’s Drug and Health Technology Agency (CADTH), Agency for Health Care Research and Quality (AHRQ), Spanish Network of Agencies for Health Technology Assessment and National Health System Benefits (RedETS), Trip medical database, International Clinical Trials Registry Platform (ICTRP) Search Portal, and clinicalTrials.gov. Clinical trials published in any language were included, analyzing the effect of NMES on efficacy outcomes (changes from baseline in ataxia, postural control, gait, and quality of life) and safety (tolerance or acceptability of treatment and adverse effects) in people with SCA and compared with conventional treatment or simulated NMES. Two independent reviewers conducted the selection of studies and the extraction of relevant data, while also assessing the risk of bias using the Cochrane Collaboration's Risk of Bias (version 2) tool for clinical trials. Whenever possible, a meta-analysis of the treatment effects was conducted using a random-effects model, and statistical heterogeneity was estimated. The GradePro tool was used to assess the quality of the evidence. Results Nine clinical trials published between 2018 and 2024 and conducted in various countries in Asia, America, and Europe were included, analyzing a total of 300 patients. The mean age of the participants ranged from 34 to 53 years, and the mean score on the baseline severity level of ataxia was 13.3 (±6.4) and 34.7 (±18.0) points as measured by the SARA and ICARS questionnaires, respectively. The included studies evaluated different modalities of rTMS and with various key stimulation parameters (intensity, duration, and number of sessions). All of them used sham rTMS as a comparator. The follow-up of patients in the included studies ranged from the period immediately after the completion of treatment to 4 weeks post-treatment. As a result, in terms of efficacy, the accumulated analyses showed significant differences in favor of EMTr compared to the simulation in terms of overall improvement of ataxia symptoms (MD: -1.55; 95 % CI: -2.65 to 0.44; 7 trials; 263 participants; p = 0.006; I2: 91 % for the SARA scale-very low certainty- and MD: -4.07; 95 % CI: -5.50 to -2.64; 5 trials; 207 participants; p < 0.00001; I2: 56 % for the ICARS scale-low certainty), as well as for the improvement of specific subdomains of the ICARS scale on posture and gait (MD: -1.53; 95 % CI: -1.98 to -1.09; 4 trials; 163 participants; p < 0.00001; I2: 0 %-moderate certainty), limb function (MD: -3.59; 95 % CI: -4.49 to 2.68; 4 trials; 163 participants; p < 0.00001; I2: 14 %- moderate certainty), and oculomotor disorders (MD: -0.44; 95 % CI: -0.60 to -0.29; 4 trials; 163 participants; p < 0.00001; I2: 84 %-very low certainty) immediately after the intervention. However, the certainty is very low regarding the effect of rTMS on the improvement of scores in the ICARS subdomain that evaluates the improvement of oculomotor disorders. We did not identify any consistent and significant impact for factors such as the type of rTMS or the total stimulation time in the subgroup analyses conducted. We identified a qualitative subgroup effect suggesting a potential benefit restricted to the SCA3 subgroup of patients from EMTr in the improvement of ataxia measured with the SARA questionnaire, but the validity of these results is uncertain due to the presence of substantial unexplained heterogeneity and imbalances between the subgroups. Sensitivity analyses revealed results similar to those of the overall analysis. In terms of safety, we found no evidence of a significant effect of rTMS compared to sham stimulation regarding the number of dropouts/losses (low-certainty evidence) (RR: 1.21; 95 % CI: 0.49 to 3.03; 7 trials; 282 patients; p = 0.68; I2: 0 %). Overall, rTMS was described as a well-tolerated procedure and not associated with clinically significant adverse events. In patients treated with EMTr, more common adverse events reported were mild headache and nausea. None of the included studies reported the occurrence of any serious adverse event. Conclusions Low/very low certainty evidence indicates that rTMS, compared to sham rTMS, may slightly improve the severity of ataxia, as well as posture, gait, and limb function in patients with SCA, immediately after completing the stimulation program with comparable results in terms of tolerability and safety. However, low-quality evidence does not show significant differences in favor of rTMS for particular subdomains related to speech problems. The evidence is insufficient to evaluate the effects of rTMS on outcomes such as quality of life and during long-term follow-up. More studies with rigorous methods that minimize the risk of bias and provide long-term follow-up are needed.

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