Home Aerobic Training for Cerebellar Degenerative Diseases: a Randomized Controlled Trial

Scott Barbuto, Sheng-Han Kuo, Lauren Winterbottom, Seonjoo Lee, Yaakov Stern, Michael O'Dell, Joel Stein, Scott Barbuto, Sheng-Han Kuo, Lauren Winterbottom, Seonjoo Lee, Yaakov Stern, Michael O'Dell, Joel Stein

Abstract

Balance training has shown some benefits in cerebellar ataxia whereas the effects of aerobic training are relatively unknown. To determine whether a phase III trial comparing home aerobic to balance training in ambulatory patients with cerebellar ataxia is warranted, we conducted a single-center, assessor-blinded, randomized controlled trial. Nineteen subjects were randomized to aerobic training and 17 subjects to balance training. The primary outcome was improvement in ataxia as measured by the Scale for the Assessment and Rating of Ataxia (SARA). Secondary outcomes included safety, training adherence, and balance improvements. There were no differences between groups at baseline. Thirty-one participants completed the trial, and there were no training-related serious adverse events. Compliance to training was over 70%. There was a mean improvement in ataxia symptoms of 1.9 SARA points (SD 1.62) in the aerobic group compared to an improvement of 0.6 points (SD 1.34) in the balance group. Although two measures of balance were equivocal between groups, one measure of balance showed greater improvement with balance training compared to aerobic training. In conclusion, this 6-month trial comparing home aerobic versus balance training in cerebellar ataxia had excellent retention and adherence to training. There were no serious adverse events, and training was not interrupted by minor adverse events like falls or back pain. There was a significant improvement in ataxia symptoms with home aerobic training compared to balance training, and a phase III trial is warranted. Clinical trial registration number: NCT03701776 on October 8, 2018.

Keywords: Aerobic exercise; Ataxia; Balance training; Spinocerebellar degeneration.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Fig. 1
Fig. 1
Consort flow diagram
Fig. 2
Fig. 2
Box plot for post–pre change scores for SARA and DGI. Abbreviations: SARA, Scale for the Assessment and Rating of Ataxia. DGI, Dynamic Gait Index

References

    1. Salman MS. Epidemiology of cerebellar diseases and therapeutic approaches. The Cerebellum. 2018;17:4–11. doi: 10.1007/s12311-017-0885-2.
    1. Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019;5:24. doi: 10.1038/s41572-019-0074-3.
    1. Synofzik M, Nemeth AH. Recessive ataxias. Handb Clin Neurol. 2018;155:73–89. doi: 10.1016/B978-0-444-64189-2.00005-6.
    1. Durr A. Autosomal dominant cerebellar ataxia: polyglutamine expansions and beyond. Lancet Neurol. 2004;9:885–894. doi: 10.1016/S1474-4422(10)70183-6.
    1. Trujillo-Martin MM, Serrano-Aguilar P, Monton-Alvarez F, Carrillo-Fumero R. Effectiveness and safety of treatments for degenerative ataxias: a systematic review. Mov Disord. 2009;24:1111–1124. doi: 10.1002/mds.22564.
    1. De Silva R, Greenfield J, Cook A, et al. Guidelines on the diagnosis and management of the progressive ataxias. Orphanet J Rare Dis. 2019;14:51. doi: 10.1186/s13023-019-1013-9.
    1. Van de Warrenburg BPC, van Gaalen J, Boesch S, et al. EFNS/ENS consensus on the diagnosis and management of chronic ataxias in adulthood. Eur J Neurol. 2014;21:552–562. doi: 10.1111/ene.12341.
    1. Miyai I, Mizuki I, Hattori N, Mihara M, et al. Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases. Neurorehabil Neural Repair. 2012;26:515–522. doi: 10.1177/1545968311425918.
    1. Keller JL, Bastian AJ. A home balance exercise program improves walking in people with cerebellar ataxia. Neurorehabil Neural Repair. 2014;28:770–778. doi: 10.1177/1545968314522350.
    1. Ilg W, Synofzik M, Brotz D, Burkard S, et al. Intensive coordinative training improves motor performance in degenerative cerebellar disease. Neurology. 2009;73:1823–1830. doi: 10.1212/WNL.0b013e3181c33adf.
    1. Rodriguez-Diaz JC, Velazquez-Perez L, Labrada RR, Rodriguez RA, Perez DL, et al. Neurorehabilitation therapy in spinocerebellar ataxia type 2: a 24-week, rater-blinded, randomized, controlled trial. Mov Disord. 2018;33:1481–1487. doi: 10.1002/mds.27437.
    1. Tercero-Perez K, Cortes H, Torres-Ramos Y, Rodriguez-Labrada R, et al. Effects of physical rehabilitation in patients with spinocerebellar ataxia type 7. Cerebellum. 2019;18:397–405. doi: 10.1007/s12311-019-1006-1.
    1. Ilg W, Brotz D, Burkard S, Giese MA, Schols L, Synofzik M. Long-term effects of coordinative training in degenerative cerebellar disease. Mov Disord. 2010;25:2239–2246. doi: 10.1002/mds.23222.
    1. Barbuto S, Kuo S, Stein J. Investigating the clinical significance and research discrepancies of balance training in degenerative cerebellar disease: a systematic review. Am J Phys Med Rehabil. 2020;99:989–998. doi: 10.1097/PHM.0000000000001476.
    1. Ilg W, Schatton C, Schicks J, Giese M, Schols L, Synofzik M. Video game-based coordinative training improves ataxia in children with degenerative ataxia. Neurology. 2012;79:2056–2060. doi: 10.1212/WNL.0b013e3182749e67.
    1. Milne SC, Corben LA, Georgiou-Karistianis N, Delatycki MB, Yiu EM. Rehabilitation for individuals with genetic degenerative ataxia: a systematic review. Neurorehabil Neural Repair. 2017;31:609–622. doi: 10.1177/1545968317712469.
    1. Chang Y, Chou C, Huang W, Song C, et al. Cycling regimen induces spinal circuitry plasticity and improves leg muscle coordination in individuals with spinocerebellar ataxia. Arch Phys Med Rehabil. 2015;96:1006–1013. doi: 10.1016/j.apmr.2015.01.021.
    1. Schmitz-Hubsch T, Tezenas du Montcel S, Baliko L, et al. “Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients.” Mov Disord. 2006; 21: 699–704.
    1. Barbuto S, Martelli D, Omofuma IB, et al. Phase I randomized controlled study investigating the potential benefits of aerobic exercise in degenerative cerebellar disease. Clin Rehabil. 2020;34:584–594. doi: 10.1177/0269215520905073.
    1. Barbuto S, Martelli D, Omofuma IB, et al. Phase I single blind randomized controlled trial comparing balance and aerobic training in degenerative cerebellar disease. PMR. 2020;13:364–371. doi: 10.1002/pmrj.12401.
    1. Synofzik M, Ilg W. “Motor training in degenerative spinocerebellar disease: ataxia-specific improvements by intensive physiotherapy and exergames.” Biomed Res Int. 2014. 10.1155/2014/583507
    1. Lanza G, Casabona JA, Bellomo M, et al. “Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?” J Int Med Res. 2020. 48. 10.1177/0300060519854626.
    1. Burciu RG, Fritsche N, Granert O, et al. Brain changes associated with postural training in patients with cerebellar degeneration: a voxel-based morphometry study. J Neurosci. 2013;33:4594–4604. doi: 10.1523/JNEUROSCI.3381-12.2013.
    1. Sujkowski AL, Hong L, Wessells RH, Todi SV. “The protective role of exercise against age-related neurodegeneration.” Ageing Res Rev. 2021. 10.1016/j.arr.2021.101543
    1. Chirles TJ, Reiter K, Weiss LR, et al. Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders. J Alzheimers Dis. 2017;57:845–856. doi: 10.3233/JAD-161151.
    1. Talukdar T, Nikolaidis A, Zwilling CE, et al. Aerobic fitness explains individual differences in the functional brain connectome of healthy young adults. Cereb Cortex. 2018;28:3600–3609. doi: 10.1093/cercor/bhx232.
    1. Mang CS, Brown KE, Neva JL, et al. “Promoting motor cortical plasticity with acute aerobic exercise: a role for cerebellar circuits.” Neural Plast. 2016. 10.1155/2016/6797928
    1. Bruchhage MM, Amad A, Draper SB, et al. “Drum training induces long-term plasticity in the cerebellum and connected cortical thickness. Sci Rep. 2020;10(1):10116. doi: 10.1038/s41598-020-65877-2.
    1. Schitz-hubsch T, Du montcel ST, Baliko L, et al. “Scale for the assessment and rating of ataxia: development of a new clinical scale.” Neurology. 2006; 66:1717–1720.
    1. Pangman VC, Sloan J, Guse L. An examination of psychometric properties of the mini-mental status examination and the standardized mini-mental status examination: implications for clinical practice. Appl Nurs Res. 2000;13(4):209–213. doi: 10.1053/apnr.2000.9231.
    1. Yabe I, Matsushima M, Soma H, Basri R, Sasaki H. Usefulness of the Scale for Assessment and Rating of Ataxia (SARA) J Neurol Sci. 2008;266:164–166. doi: 10.1016/j.jns.2007.09.021.
    1. Lai RY, Tomishon D, Figueroa KP, Pulst SM, Perlman S, et al. “Tremor in the degenerative cerebellum: towards the understanding of brain circuitry for tremor.” Cerebellum. 2019. 10.1007/s12311-019-01016-6.
    1. Fox SM, Naughton JP, Haskell WL. Physical activity and the prevention of coronary heart disease. Ann Clin Res. 1971;3(6):404–432.
    1. McDermott AY, Mernitz H. Exercise and older patients: prescribing guidelines. Am Fam Physician. 2006;74:437–444.
    1. Deka P, Pozehl B, Williams MA, et al. Adherence to recommended exercise guidelines in patients with heart failure. Heart Fail Rev. 2017;22:41–53. doi: 10.1007/s10741-016-9584-1.
    1. Picorelli AM, Pereira LS, Pereira DS, et al. Adherence to exercise programs for older people is influenced by program characteristics and personal factors: a systematic review. J Physiother. 2014;60:151–156. doi: 10.1016/j.jphys.2014.06.012.
    1. Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar ataxia: a randomized, double blind, placebo-controlled trial. Lancet Neurol. 2015;14:985–991. doi: 10.1016/S1474-4422(15)00201-X.
    1. Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39:142–148. doi: 10.1111/j.1532-5415.1991.tb01616.x.
    1. Shumway-Cook A, Woollacott MH. “Motor control: theory and practical applications.” Williams & Wilkins Baltimore; 1995.
    1. Pardasaney PK, Latham NK, et al. Sensitivity to change and responsiveness for four balance measures for community-dwelling older adults. Phys Ther. 2012;92:388–397. doi: 10.2522/ptj.20100398.
    1. Ristori G, Romano S, Visconti A, et al. Riluzole in cerebellar ataxia. Neurology. 2010;74:839–845. doi: 10.1212/WNL.0b013e3181d31e23.
    1. Romano S, Coarelli G, Marcotulli C, et al. Riluzole in patients with hereditary cerebellar ataxia: a randomized, double-blind, placebo controlled trial. Lancet Neurol. 2015;14:985–991. doi: 10.1016/S1474-4422(15)00201-X.
    1. Dishman RK. “Exercise adherence: its impact on public health. Champaign: Human Kinetics Books; 1988
    1. Kahn EB, Ramsey LT, Brownson RC, et al. “The effectiveness of interventions to increase physical activity: a systematic review. Am J Prev Med. 2002;22:73–107. doi: 10.1016/S0749-3797(02)00434-8.
    1. Task Force on Community Preventive Services Recommendations to increase physical activity in communities. Am J Prev Med. 2001;22:67–72.
    1. Hillsdon M, Foster C, Thorogood M. “Interventions for promoting physical activity. Cochrane Database Syst Rev. 2005; CD003180.
    1. Milne SC, Corben LA, Roberts M, Murphy A, Tai G, Georgiou-Karistianis N, Yiu EM, Delatycki MB. Can rehabilitation improve the health and well-being in Friedreich's ataxia: a randomized controlled trial? Clin Rehabil. 2018;32:630–643. doi: 10.1177/0269215517736903.
    1. Blamey A, Mutrie N. “Changing the individual to promote health-enhancing physical activity: the difficulties of producing evidence and translating it into practice. J Sports Sci. 2004;22:741–754. doi: 10.1080/02640410410001712449.
    1. Cotman CW, Berchtold NC. Exercise: a behavorial intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25:295–301. doi: 10.1016/S0166-2236(02)02143-4.
    1. Mang CS, Campbell KL, Ross CJD, et al. Promoting neuroplasticity for motor rehabilitation after stroke. Phys Ther. 2013;93:1707–1716. doi: 10.2522/ptj.20130053.
    1. Ferrer-Uris B, Busquets A, Lopez-Alonso V, et al. Enhancing consolidation of a rotational visuomotor adaptation task through acute exercise. PLoS One. 2017;12:e0175296. doi: 10.1371/journal.pone.0175296.

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