Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial

Abstract

Spinocerebellar ataxia (SCA) is a neurodegenerative disorder caused by dysfunction of the cerebellum and its connected neural networks. There is currently no cure for SCA and symptomatic treatment remains limited. We aimed here to examine the effects of a repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum on clinical impression, postural control and gait in patients with SCA. In this randomized, double-blinded and sham-controlled study, 20 individuals aged 18-75 years with SCA confirmed by genetic testing completed rTMS or sham intervention comprising 20 sessions of MRI-guided stimulation over the cerebellum. Baseline assessments included the Standard Ataxia Rating Assessment (SARA), the 9-hole peg test of manual dexterity, the Timed Up-and-Go (TUG) test, standing postural control with eyes-open and eyes-closed, and gait. Immediate (within 1-week) and 1-month follow-ups were completed. Intervention compliance was high (19 ± 2 of 20 sessions) and no rTMS-related adverse events were reported. rTMS, compared to sham, was associated with greater percent improvement in SARA total score from baseline to the 1-month follow-up (p = 0.008). Secondary analyses of individual SARA items revealed that rTMS improved performance within the "stance" sub-score only (p = 0.002). This functional change was accompanied by improvement to several objective metrics of postural sway during eyes-open and eyes-closed standing (p < 0.008). rTMS did not influence the 9-hole peg test, TUG, or gait kinematics. A 20-session rTMS intervention is safe and feasible for those with SCA. Additional research is warranted to confirm the observed longer-term benefits of this intervention on standing postural control. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01975909.

Keywords: Standard Ataxia Rating Assessment; cerebellum; rTMS; spinocerebellar ataxia; standing postural control.

Figure 1

Study CONSORT diagram. One hundred and ten individuals were screened. Seventy-nine were ineligible and 11 were uninterested. The remaining 20 completed baseline testing. Ten were randomized to the rTMS intervention and ten to sham. All of them completed the intervention and both follow-ups.

Figure 2

The effects of cerebellar rTMS on the clinical assessment of ataxia and standing postural control (mean ± SE). Both groups exhibited relatively-large improvement (i.e., percent reduction) in SARA total score from baseline to the immediate follow-up (A). The rTMS group, however, exhibited greater percent improvement in this outcome, as compared to the sham group, at the 1-month follow-up. Secondary analyses revealed that compared to sham, the rTMS group exhibited greater improvements specifically within the SARA “stance” sub-score (B), yet no other SARA item (outcomes not pictured). Moreover, rTMS improved postural sway speed (i.e., sway speed decreased) during both eyes-open (C) and eyes-closed (D) standing. ^*Indicates significant main effects of group within two-way, repeated-measures ANCOVAs adjusted for age, sex, and intervention compliance.

Figure 3

Individual effects of cerebellar rTMS intervention on standing postural control. The average speed of standing postural sway fluctuations for each participant when standing with eyes open (top) and eyes closed (bottom) at baseline and at the immediate and 1-month follow-up assessments. Two participants with extremely high sway speed values at baseline (out of the mean ± 2XS.D.) were excluded from the figure for better visual effects.