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Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Cerebellar Ataxia: a Systematic Review and Meta-analysis

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Abstract

Cerebellar ataxia(CA) is defined as a degenerative disease of the nervous system. Repetitive transcranial magnetic stimulation (rTMS) has been a promising treatment for neurological and psychiatric diseases. Hence, to find out whether cerebellar rTMS impacts CA as a potential therapy, we performed a systematic review and meta-analysis. Qualified studies through a systematic search were retrieved for randomized controlled trials (RCTs) using acknowledged databases. Review Manager 5.4 software was employed to synthesize the data. A total of seven studies were identified as eligible and included in the quantitative review. Comparing real and sham-rTMS interventions, the utilization of rTMS on cerebellum improved the scale for the assessment and rating of ataxia (SARA) (SMD − 0.87, 95% CI − 1.41 to − 0.34; P = 0.001; I2 = 62%), the International Cooperative Ataxia Rating Scale (ICARS) (SMD − 1.06, 95% CI − 1.47 to − 0.64; P < 0.00001; I2 = 0%) and Berg balance Scale (BBS) (SMD 0.76, 95% CI 0.33 to 1.19; P = 0.0005; I2 = 39%). The subgroup analysis demonstrated high-frequency of rTMS had a positive effect (SMD − 1.28, 95% CI − 1.82 to − 0.74; P < 0.00001; I2 = 0%). For the safety, the incidence of adverse events between the two groups was not significantly different (OR 1.73, 95% CI 0.55 to 5.46; P = 0.35; I2 = 0%). In conclusion, this meta-analysis provided limited evidence, suggesting a possible strategy that rTMS over the cerebellum could be a viable therapy for symptoms associated with CA. Besides, rTMS intervention was well-attended and did not result in unanticipated negative effects.

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Data Availability

All data generated or analyzed during this study are included in this article and its supplementary information files.

Abbreviations

rTMS:

Repetitive transcranial magnetic stimulation

CA:

Cerebellar ataxia

NICS:

Non-invasive cerebellar stimulation

SCA:

Spinocerebellar ataxia

AT:

Ataxia telangiectasia

PC:

Purkinje cell

RCT:

Randomized controlled trial

SARA:

Scale for the Assessment and Rating of Ataxia

ICARS:

International Cooperative Ataxia Rating Scale

BBS:

Berg Balance Scale

TBS:

Theta-burst stimulation

tDCS:

Transcranial direct current stimulation

tACS:

Transcranial alternating current stimulation

SMD:

Standardized mean difference

95% CI:

95% Confidence interval

ROB:

Risk of bias

References

  1. Marsden JF. Cerebellar ataxia [J]. Handb Clin Neurol. 2018;159:261–81.

    Article  PubMed  Google Scholar 

  2. Manto MUE. Cerebellar disorders: a practical approach to diagnosis and management [M]. Cambridge: Cambridge University Press; 2010.

    Book  Google Scholar 

  3. Yap KH, Azmin S, HAMZAH CJ, et al. Pharmacological and non-pharmacological management of spinocerebellar ataxia: a systematic review [J]. J Neurol. 2022;269(5):2315–37.

    Article  PubMed  Google Scholar 

  4. Billeri L, Naro A. A narrative review on non-invasive stimulation of the cerebellum in neurological diseases [J]. Neurol Sci. 2021;42(6):2191–209.

    Article  PubMed  Google Scholar 

  5. Gomez CM, Thompson RM, Gammack JT, et al. Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset [J]. Ann Neurol. 1997;42(6):933–50.

    Article  CAS  PubMed  Google Scholar 

  6. Kasumu A, Bezprozvanny I. Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias [J]. Cerebellum (London, England). 2012;11(3):630–9.

    Article  CAS  PubMed  Google Scholar 

  7. Jiang D, Zhang Y, Hart RP, et al. Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency [J]. Brain J Neurol. 2015;138(12):3520–36.

    Article  Google Scholar 

  8. Li J, Hart RP, Mallimo EM, et al. EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia [J]. Nat Neurosci. 2013;16(12):1745–53.

    Article  PubMed  PubMed Central  Google Scholar 

  9. D’Angelo E. Physiology of the cerebellum [J]. Handb Clin Neurol. 2018;154:85–108.

    Article  PubMed  Google Scholar 

  10. Hoxha E, Balbo I, Miniaci MC, et al. Purkinje cell signaling deficits in animal models of ataxia [J]. Front Synaptic Neurosci. 2018;10:6.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Klomjai W, Katz R, Lackmy-Vallée A. Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) [J]. Ann Phys Rehabil Med. 2015;58(4):208–13.

    Article  PubMed  Google Scholar 

  12. Lefaucheur J-P, André-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) [J]. Clin Neurophysiol. 2014;125(11):2150–206.

    Article  PubMed  Google Scholar 

  13. Maas RPPWM, Helmich RCG, Van De Warrenburg BPC. The role of the cerebellum in degenerative ataxias and essential tremor: insights from noninvasive modulation of cerebellar activity [J]. Mov Disord. 2020;35(2):215–27.

    Article  PubMed  Google Scholar 

  14. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews [J]. BMJ (Clinical research ed). 2021;372: n71.

    PubMed  Google Scholar 

  15. Perez-Lloret S, van de Warrenburg B, Rossi M, et al. Assessment of ataxia rating scales and cerebellar functional tests: critique and recommendations [J]. Mov Disord. 2021;36(2):283–97.

    Article  PubMed  Google Scholar 

  16. Saute JAM, Donis KC, Serrano-Munuera C, et al. Ataxia rating scales–psychometric profiles, natural history and their application in clinical trials [J]. Cerebellum (London, England). 2012;11(2):488–504.

    Article  PubMed  Google Scholar 

  17. Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale [J]. Neurology. 2006;66(11):1717–20.

    Article  PubMed  Google Scholar 

  18. Trouillas P, Takayanagi T, Hallett M, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology [J]. J Neurol Sci. 1997;145(2):205–11.

    Article  CAS  PubMed  Google Scholar 

  19. Winser SJ, Chan AYY, Chung R, et al. Validity of balance measures in cerebellar ataxia: a prospective study with 12‐month follow‐up [J]. PM&R. 2022 [published online ahead of print]. https://doi.org/10.1002/pmrj.12826.

  20. Winser SJ, Smith CM, Hale LA, et al. Clinical assessment of balance using BBS and SARAbal in cerebellar ataxia: synthesis of findings of a psychometric property analysis [J]. Hong Kong Physiother J. 2018;38(1):53–61.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bürk K, Sival DA. Scales for the clinical evaluation of cerebellar disorders [J]. Handb Clin Neurol. 2018;154:329–39.

    Article  PubMed  Google Scholar 

  22. Hedges LV, Olkin I. Statistical methods for meta-analysis [M]. Saint Louis: Elsevier Science; 2014.

  23. Higgins JPT, Li T, Deeks JJ (editors). Chapter 6: choosing effect measures and computing estimates of effect. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). Cochrane; 2022. Available from www.training.cochrane.org/handbook.

  24. Luo D, Wan X, Liu J, et al. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range [J]. Stat Methods Med Res. 2018;27(6):1785–805.

    Article  MathSciNet  PubMed  Google Scholar 

  25. Shi J, Luo D, Wan X, et al. Detecting the skewness of data from the sample size and the five-number summary [J]. arXiv. 2020 Oct 12[arXiv preprint]. https://doi.org/10.48550/arXiv.2010.0574

  26. Shi J, Luo D, Weng H, et al. Optimally estimating the sample standard deviation from the five-number summary [J]. Res Synth Methods. 2020;11(5):641–54.

    Article  PubMed  Google Scholar 

  27. Wan X, Wang W, Liu J, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range [J]. BMC Med Res Methodol. 2014;14:135.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Cohen J. Statistical power analysis for the behavioral sciences [M]. New York: Academic Press; 1977.

    Google Scholar 

  29. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses [J]. BMJ (Clinical research ed). 2003;327(7414):557–60.

    Article  PubMed  Google Scholar 

  30. Greenland S, Robins JM. Estimation of a common effect parameter from sparse follow-up data [J]. Biometrics. 1985;41(1):55–68.

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  31. Sterne JAC, Sutton AJ, Ioannidis JPA, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials [J]. BMJ (Clinical research ed). 2011;343:d4002.

    Article  PubMed  Google Scholar 

  32. Pascual-Leone A, Valls-Solé J, Wassermann EM, et al. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex [J]. Brain. 1994;117(4):847–58.

    Article  PubMed  Google Scholar 

  33. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group; 2013. Available from guidelinedevelopment.org/handbook.

  34. Chen X-Y, Lian Y-H, Liu X-H, et al. Effects of repetitive transcranial magnetic stimulation on cerebellar metabolism in patients with spinocerebellar ataxia Type 3 [J]. Front Aging Neurosci. 2022;14:827993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Manor B, Greenstein PE, Davila-Perez P, et al. Repetitive transcranial magnetic stimulation in spinocerebellar ataxia: a pilot randomized controlled trial [J]. Front Neurol. 2019;10:73.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Qian H. The efficacy of repetitive transcranial magnetic stimulation in the treatment of spinocerebellar ataxia [D]. Hangzhou Normal University; 2020. https://doi.org/10.27076/d.cnki.ghzsc.2020.000785

  37. Arif S. Short time efficacy of repetitive transcranial magnetic stimulation in Spinocerebellar ataxia type 3 (SCA3): a prospective, randomized, double-blind, sham-controlled study [D]. Fujian Medical University; 2020. https://doi.org/10.27020/d.cnki.gfjyu.2020.000003

  38. Wei FF, Zheng LJ, Wang J, et al. Efficacy of high-frequency repetitive transcranial magnetic stimulation on motor symptoms in patients with Spinocerebellar ataxia 3(SCA3) [J]. Chinese Manipulation & Rehabilitation Medicine, 2018;9(16):14–15+18. https://doi.org/10.19787/j.issn.1008-1879.2018.16.007

  39. Kim W, Jung S, Oh M, et al. Effect of repetitive transcranial magnetic stimulation over the cerebellum on patients with ataxia after posterior circulation stroke: a pilot study [J]. J Rehabil Med. 2014;46(5):418–23.

    Article  PubMed  Google Scholar 

  40. França C, de Andrade DC, Silva V, et al. Effects of cerebellar transcranial magnetic stimulation on ataxias: a randomized trial [J]. Parkinsonism Relat Disord. 2020;80:1–6.

    Article  PubMed  Google Scholar 

  41. Nollet H, Van Ham L, Deprez P, et al. Transcranial magnetic stimulation: review of the technique, basic principles and applications [J]. Vet J (London, England 1997). 2003;166(1):28–42.

    Article  CAS  Google Scholar 

  42. Fernandez L, Major BP, Teo W-P, et al. The impact of stimulation intensity and coil type on reliability and tolerability of cerebellar brain inhibition (CBI) via dual-coil TMS [J]. Cerebellum (London, England). 2018;17(5):540–9.

    Article  PubMed  Google Scholar 

  43. Fleming MK, Sorinola IO, Newham DJ, et al. The effect of coil type and navigation on the reliability of transcranial magnetic stimulation [J]. IEEE Trans Neural Syst Rehabil Eng. 2012;20(5):617–25.

    Article  PubMed  Google Scholar 

  44. Spampinato D, Ibáñez J, Spanoudakis M, et al. Cerebellar transcranial magnetic stimulation: the role of coil type from distinct manufacturers [J]. Brain Stimul. 2020;13(1):153–6.

    Article  PubMed  Google Scholar 

  45. Daskalakis ZJ, Paradiso GO, Christensen BK, et al. Exploring the connectivity between the cerebellum and motor cortex in humans [J]. J Physiol. 2004;557(Pt 2):689–700.

    Article  CAS  PubMed  Google Scholar 

  46. Fierro B, Giglia G, Palermo A, et al. Modulatory effects of 1 Hz rTMS over the cerebellum on motor cortex excitability [J]. Exp Brain Res. 2007;176(3):440–7.

    Article  PubMed  Google Scholar 

  47. Oliveri M, Koch G, Torriero S, et al. Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans [J]. Neurosci Lett. 2005;376(3):188–93.

    Article  CAS  PubMed  Google Scholar 

  48. Qiu D-L, knöpfel T. An NMDA receptor/nitric oxide cascade in presynaptic parallel fiber-Purkinje neuron long-term potentiation [J]. J Neurosci. 2007;27(13):3408–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang D-J, Su L-D, Wang Y-N, et al. Long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses requires presynaptic and postsynaptic signaling cascades [J]. J Neurosci. 2014;34(6):2355–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mitoma H, Buffo A, Gelfo F, et al. Consensus paper Cerebellar. reserve: from cerebellar physiology to cerebellar disorders [J]. Cerebellum (London, England). 2020;19(1):131–53.

    Article  CAS  PubMed  Google Scholar 

  51. Grimaldi G, Argyropoulos GP, Boehringer A, et al. Non-invasive cerebellar stimulation–a consensus paper [J]. Cerebellum (London, England). 2014;13(1):121–38.

    Article  CAS  PubMed  Google Scholar 

  52. Chen TX, Yang C-Y, Willson G, et al. The efficacy and safety of transcranial direct current stimulation for cerebellar ataxia: a systematic review and meta-analysis [J]. The Cerebellum. 2021;20(1):124–33.

    Article  CAS  PubMed  Google Scholar 

  53. Benussi A, Pascual-Leone A, Borroni B. Non-invasive cerebellar stimulation in neurodegenerative ataxia: a literature review [J]. Int J Mol Sci. 2020;21(6):E1948.

    Article  Google Scholar 

  54. Song P, Li S, Wang S, et al. Repetitive transcranial magnetic stimulation of the cerebellum improves ataxia and cerebello-fronto plasticity in multiple system atrophy: a randomized, double-blind, sham-controlled and TMS-EEG study [J]. Aging. 2020;12(20):20611–22.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wessel MJ, Hummel FC. Non-invasive cerebellar stimulation: a promising approach for stroke recovery? [J]. Cerebellum (London, England). 2018;17(3):359–71.

    Article  PubMed  Google Scholar 

  56. Sun YM, Lu C, Wu ZY. Spinocerebellar ataxia: relationship between phenotype and genotype - a review [J]. Clin Genet. 2016;90(4):305–14.

    Article  CAS  PubMed  Google Scholar 

  57. Cook AA, Fields E, Watt AJ. Losing the beat: contribution of Purkinje cell firing dysfunction to disease, and its reversal [J]. Neuroscience. 2021;462:247–61.

    Article  CAS  PubMed  Google Scholar 

  58. Louis ED, Kerridge CA, Chatterjee D, et al. Contextualizing the pathology in the essential tremor cerebellar cortex: a patholog-omics approach [J]. Acta Neuropathol. 2019;138(5):859–76.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study is funded by the NSFC 82172540 from the National Natural Science Foundation of China.

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Author notes

  1. Yi-Tong Qiu and·Yi Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Sichuan Province, Chengdu, China

    Yi-Tong Qiu, Yi Chen, Hui-Xin Tan, Wei Su, Qi-Fan Guo & Qiang Gao

  2. Key Laboratory of Rehabilitation Medicine of Sichuan Province, Chengdu, Sichuan Province, China

    Yi-Tong Qiu, Yi Chen, Hui-Xin Tan, Wei Su, Qi-Fan Guo & Qiang Gao

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  1. Yi-Tong Qiu
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Contributions

All authors reviewed the manuscript. Study design and planning of systematic review: all authors. Literature search: QYT, CY. Figures: QYT, SW. Tables: QYT, GQF. Data collection and analysis: QYT, THX; query resolved by all authors. Data interpretation: QYT, CY, GQF. Writing: QYT, THX, SW. Corrections and final approval of manuscript: all authors.

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Correspondence to Qiang Gao.

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Qiu, YT., Chen, Y., Tan, HX. et al. Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Cerebellar Ataxia: a Systematic Review and Meta-analysis. Cerebellum 23, 243–254 (2024). https://doi.org/10.1007/s12311-022-01508-y

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