Skip to main content

Advertisement

SpringerLink
Log in

Effects of Non-invasive Brain Stimulation on Hereditary Ataxia: a Systematic Review and Meta-analysis

  • Review
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data analyzed in this study are included in published article or its supplementary information files.

Abbreviations

NIBS:

Non-invasive brain stimulation

HAs:

Hereditary ataxias

SCA:

Spinocerebellar ataxia

RCTs:

Random controlled trials

TMS:

Transcranial magnetic stimulation

tDCS:

transcranial direct current stimulation

rTMS:

repetitive pulse TMS

tACS:

transcranial alternating current stimulation

iTBS:

intermittent theta burst stimulation

SARA:

The Scale for the Assessment and Rating of Ataxia

ICARS:

International Cooperative Ataxia Rating Scale

BBS:

Berg Balance Scale

MD:

mean difference

CI:

confidence interval

References

  1. Jayadev S, Bird TD. Hereditary ataxias: overview. Genet Med. 2013;15(9):673–83.

    Article  CAS  PubMed  Google Scholar 

  2. Yang QH, Zhang YH, Du SH, Wang YC, Fang Y, Wang XQ. Non-invasive Brain Stimulation for Central Neuropathic Pain. Front Mol Neurosci. 2022;15:879909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shimizu H, Tsuda T, Shiga Y, Miyazawa K, Onodera Y, Matsuzaki M, et al. Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration. Tohoku J Exp Med. 1999;189(3):203–11.

    Article  CAS  PubMed  Google Scholar 

  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).

  5. Franca C, de Andrade DC, Teixeira MJ, Galhardoni R, Silva V, Barbosa ER, et al. Effects of cerebellar neuromodulation in movement disorders: A systematic review. Brain Stimulat. 2018;11(2):249–60.

    Article  Google Scholar 

  6. Qiu YT, Chen Y, Tan HX, Su W, Guo QF, Gao Q. Efficacy and safety of repetitive transcranial magnetic stimulation in cerebellar ataxia: a Systematic review and meta-analysis. Cerebellum. 2023.

  7. Salcı Y, Fil A, Keklicek H, Çetin B, Armutlu K, Dolgun A, et al. Validity and reliability of the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) in multiple sclerosis patients with ataxia. Mult Scler Relat Disord. 2017;18:135–40.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Storey E, Tuck K, Hester R, Hughes A, Churchyard A. Inter-rater reliability of the International Cooperative Ataxia Rating Scale (ICARS). Mov Disord. 2004;19(2):190–2.

    Article  PubMed  Google Scholar 

  10. Winser SJ, Smith C, Hale LA, Claydon LS, Whitney SL. Balance outcome measures in cerebellar ataxia: a Delphi survey. Disabil Rehabil. 2015;37(2):165–70.

    Article  PubMed  Google Scholar 

  11. Chen XY, Lian YH, Liu XH, Sikandar A, Li MC, Xu HL, et al. Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3. Front Aging Neurosci. 2022;14:827993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Qian H. The efficacy of repetitive transcranial magnetic stimulation in the treatment of spinocerebellar ataxia (Master degree). Hangzhou Normal University; 2020.

    Google Scholar 

  13. Sikandar A, Liu XH, Xu HL, Li Y, Lin YQ, Chen XY, et al. Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: a prospective, randomized, double-blind, sham-controlled study. Parkinsonism Related Disord. 2023;106:105236.

    Article  CAS  Google Scholar 

  14. Manor B, Greenstein PE, Davila-Perez P, Wakefield S, Zhou JH, Pascual-Leone A. Repetitive transcranial magnetic stimulation in spinocerebellar Ataxia:A Pilot randomized controlled trial. Front Neurol. 2019;10.

  15. Wei FF, Zheng LJ, Wang J, Fan BQ, Sun DD, Peng Y, Cai HA. Efficacy of high-frequency repetitive transcranial magnetic stimulation on motor symptoms in patients with Spinocerebellar ataxia 3(SCA3). Chin Manipul Rehabilit Med. 2018;9:14–5. https://doi.org/10.19787/j.issn.1008-1879.2018.16.007.

    Article  Google Scholar 

  16. Qiu MQ. Clinical efficacy and MRS analysis of repetitive transcranial magnetic stimulation in the treatment of SCA3 (Master degree). Hangzhou Normal University; 2022.

    Google Scholar 

  17. Nakamura Y, Yamada I, Sakamoto H. Repetitive transcranial magnetic stimulation treatment on hereditary spino-cerebellar degeneration. J Neurol. 2010;257:S92.

    Google Scholar 

  18. Gandini J, Manto M, Bremova-Ertl T, Feil K, Strupp M. The neurological update: therapies for cerebellar ataxias in 2020. J Neurol. 2020;267(4):1211–20.

    Article  CAS  PubMed  Google Scholar 

  19. Liu B, Yang A, Gao W, Chen Y, Wang Y, Liu X, et al. Altered cerebral blood flow in patients with spinocerebellar degeneration. Front Neurosci. 2022;16:977145.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Shiga Y, Tsuda T, Itoyama Y, Shimizu H, Miyazawa KI, Jin K, et al. Transcranial magnetic stimulation alleviates truncal ataxia in spinocerebellar degeneration. J Neurol Neurosurg Psychiat. 2002;72(1):124–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Spampinato DA, Celnik PA, Rothwell JC. Cerebellar-Motor Cortex Connectivity: One or Two Different Networks? J Neurosci. 2020;40(21):4230–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rodríguez-Labrada R, Velázquez-Pérez L, Ziemann U. Transcranial magnetic stimulation in hereditary ataxias: Diagnostic utility, pathophysiological insight and treatment. Clin Neurophysiol. 2018;129(8):1688–98.

    Article  PubMed  Google Scholar 

  23. Diana M, Raij T, Melis M, Nummenmaa A, Leggio L, Bonci A. Rehabilitating the addicted brain with transcranial magnetic stimulation. Nat Rev Neurosci. 2017;18(11):685–93.

    Article  CAS  PubMed  Google Scholar 

  24. Fierro B, Giglia G, Palermo A, Pecoraro C, Scalia S, Brighina F. Modulatory effects of 1 Hz rTMS over the cerebellum on motor cortex excitability. Exp Brain Res. 2007;176(3):440–7.

    Article  PubMed  Google Scholar 

  25. Popa T, Russo M, Meunier S. Long-lasting inhibition of cerebellar output. Brain Stimul. 2010;3(3):161–9.

    Article  CAS  PubMed  Google Scholar 

  26. França C, de Andrade DC, Silva V, Galhardoni R, Barbosa ER, Teixeira MJ, et al. Effects of cerebellar transcranial magnetic stimulation on ataxias: A randomized trial. Parkinsonism Relat Disord. 2020;80:1–6.

    Article  PubMed  Google Scholar 

  27. Maas R, Teerenstra S, Toni I, Klockgether T, Schutter D, van de Warrenburg BPC. Cerebellar Transcranial Direct Current Stimulation in Spinocerebellar Ataxia Type 3: a Randomized, Double-Blind. Sham-Controlled Trial. Neurotherapeutics. 2022;19(4):1259–72.

    PubMed  Google Scholar 

  28. Ashizawa T, Figueroa KP, Perlman SL, Gomez CM, Wilmot GR, Schmahmann JD, et al. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;8:177.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Yasui K, Yabe I, Yoshida K, Kanai K, Arai K, Ito M, et al. A 3-year cohort study of the natural history of spinocerebellar ataxia type 6 in Japan. Orphanet J Rare Dis. 2014;9:118.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jacobi H, du Montcel ST, Bauer P, Giunti P, Cook A, Labrum R, et al. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. Lancet Neurol. 2015;14(11):1101–8.

    Article  PubMed  Google Scholar 

  31. Grimaldi G, Taib NOB, Manto M, Bodranghien F. Marked reduction of cerebellar deficits in upper limbs following transcranial cerebello-cerebral DC stimulation: Tremor reduction and re-programming of the timing of antagonist commands. Front Syst Neurosci. 2014;8.

  32. Benussi A, Cantoni V, Manes M, Libri I, Dell'Era V, Datta A, et al. Motor and cognitive outcomes of cerebello-spinal stimulation in neurodegenerative ataxia. Brain. 2021;144(8):2310–21.

    Article  PubMed  Google Scholar 

  33. Krewer C, Thibaut A. Non-invasive brain stimulation for treatment of severe disorders of consciousness in people with acquired brain injury. Cochrane Databas System Rev. 2020;(2).

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, The First Hospital of China Medical University, Shenyang City, 110001, Liaoning Province, China

    Ye Liu, Yiming Ma, Jing Zhang, Xuejing Yan & Yi Ouyang

  2. Department of Neurology, The Fifth People’s Hospital of Datong, Datong City, Shanxi Province, China

    Jing Zhang

Authors
  1. Ye Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yiming Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuejing Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YL, YM and JZ conducted the study selection process, retrieved data and performed analyses. YL contributed to writing the original manuscript draft. XY and OY contributed to data interpretation and manuscript revisions. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yi Ouyang.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Ma, Y., Zhang, J. et al. Effects of Non-invasive Brain Stimulation on Hereditary Ataxia: a Systematic Review and Meta-analysis. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01638-x

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12311-023-01638-x

Keywords

Search

Navigation