Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial

Sarah C Milne^{1

2

3

4}, Melissa Roberts^{1

2}, Shannon Williams^{5

6}, Jillian Chua⁷, Alison C Grootendorst⁸, Genevieve Agostinelli⁸, Anneke C Grobler^{4

9}, Hannah L Ross², Amy Robinson¹⁰, Kristen Grove^{5

6}, Gabrielle Modderman¹¹, Annabel Price¹⁰, Megan Thomson², Libby Massey^{8

12}, Christina Liang^{13

14}, Kishore R Kumar^{15

16

17}, Kim Dalziel¹⁸, Joshua Burns¹⁹, Carolyn M Sue^{20

21

22}, Pubudu N Pathirana²³, Malcolm Horne^{24

25}, Nikki Gelfand²⁶, Helen Curd²⁶, David Szmulewicz^{24

27

28}, Louise A Corben^{1

4

29}, Martin B Delatycki^{1

4

30}

Affiliations

¹ Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Australia.
² Physiotherapy Department, Monash Health, Cheltenham, Australia.
³ School of Primary and Allied Health Care, Monash University, Frankston, Australia.
⁴ Department of Pediatrics, The University of Melbourne, Parkville, Australia.
⁵ Physiotherapy Department, Sir Charles Gairdner Hospital, Nedlands, Australia.
⁶ Physiotherapy Department, Royal Perth Hospital, Perth, Australia.
⁷ Ryde Hospital, Eastwood, Australia.
⁸ MJD Foundation, Darwin, Australia.
⁹ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia.
¹⁰ Physiotherapy Department, Royal North Shore Hospital, St Leonards, Australia.
¹¹ Rehabilitation Services, Royal Darwin and Palmerston Regional Hospital, Darwin, Australia.
¹² College of Public Health Medical and Veterinary Sciences, James Cook University, Townsville, Australia.
¹³ Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia.
¹⁴ Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
¹⁵ Molecular Medicine Laboratory and Department of Neurology, Concord Repatriation General Hospital, Concord Clinical School, The University of Syndey, Concord, Australia.
¹⁶ Translational Neurogenomics Group, Genomic and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, Australia.
¹⁷ St Vincent's Healthcare Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Kensington, Australia.
¹⁸ Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia.
¹⁹ Disability Prevention Program, St. Jude Children's Research Hospital, Memphis, TN, USA.
²⁰ Centre for Neurodegeneration, Neuroscience Research Australia, Sydney, Australia.
²¹ Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
²² Department of Neurology, Prince of Wales Hospital, Sydney, Australia.
²³ School of Engineering, Deakin University, Geelong, Australia.
²⁴ Bionics Institute, East Melbourne, Australia.
²⁵ Department of Medicine, St Vincent's Hospital, The University of Melbourne, Parkville, Australia.
²⁶ Monash Genetics, Monash Health, Clayton, Australia.
²⁷ Balance Disorders and Ataxia Service, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
²⁸ Monash Medical Centre, Monash Health, Clayton, Australia.
²⁹ Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia.
³⁰ Victorian Clinical Genetics Services, Melbourne, Australia.

PMID: 39520242
DOI: 10.1002/ana.27130

Randomized Controlled Trial

Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial

Sarah C Milne et al. Ann Neurol. 2025 Mar.

. 2025 Mar;97(3):409-424.

doi: 10.1002/ana.27130. Epub 2024 Nov 9.

Authors

Affiliations

¹ Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Australia.
² Physiotherapy Department, Monash Health, Cheltenham, Australia.
³ School of Primary and Allied Health Care, Monash University, Frankston, Australia.
⁴ Department of Pediatrics, The University of Melbourne, Parkville, Australia.
⁵ Physiotherapy Department, Sir Charles Gairdner Hospital, Nedlands, Australia.
⁶ Physiotherapy Department, Royal Perth Hospital, Perth, Australia.
⁷ Ryde Hospital, Eastwood, Australia.
⁸ MJD Foundation, Darwin, Australia.
⁹ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia.
¹⁰ Physiotherapy Department, Royal North Shore Hospital, St Leonards, Australia.
¹¹ Rehabilitation Services, Royal Darwin and Palmerston Regional Hospital, Darwin, Australia.
¹² College of Public Health Medical and Veterinary Sciences, James Cook University, Townsville, Australia.
¹³ Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia.
¹⁴ Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
¹⁵ Molecular Medicine Laboratory and Department of Neurology, Concord Repatriation General Hospital, Concord Clinical School, The University of Syndey, Concord, Australia.
¹⁶ Translational Neurogenomics Group, Genomic and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, Australia.
¹⁷ St Vincent's Healthcare Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Kensington, Australia.
¹⁸ Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia.
¹⁹ Disability Prevention Program, St. Jude Children's Research Hospital, Memphis, TN, USA.
²⁰ Centre for Neurodegeneration, Neuroscience Research Australia, Sydney, Australia.
²¹ Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
²² Department of Neurology, Prince of Wales Hospital, Sydney, Australia.
²³ School of Engineering, Deakin University, Geelong, Australia.
²⁴ Bionics Institute, East Melbourne, Australia.
²⁵ Department of Medicine, St Vincent's Hospital, The University of Melbourne, Parkville, Australia.
²⁶ Monash Genetics, Monash Health, Clayton, Australia.
²⁷ Balance Disorders and Ataxia Service, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
²⁸ Monash Medical Centre, Monash Health, Clayton, Australia.
²⁹ Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia.
³⁰ Victorian Clinical Genetics Services, Melbourne, Australia.

PMID: 39520242
DOI: 10.1002/ana.27130

Abstract

Objective: Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30-week goal-directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health-related quality of life, and balance in individuals with an HCA.

Methods: Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24-week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF-36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation.

Results: Seventy-one participants (rehabilitation, 37; standard-care, 34) were included in the intention-to-treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, p = 0.028) and SARA (-1.21, 95% CI: -2.32 to -0.11, p = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference -1.51, 95% CI: -2.76 to -0.27, p = 0.017), but not mFIM scores (1.74, 95% CI: -0.32 to 3.81, p = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls.

Interpretation: Goal-directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health-related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2025;97:409-424.

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References

1. Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 2014;42:174–183.
1. Gorcenco S, Karremo C, Puschmann A. Patients' perspective in hereditary ataxia. Cerebellum 2022;23:82–91.
1. Potashman MH, Mize ML, Beiner MW, et al. Ataxia rating scales reflect patient experience: an examination of the relationship between clinician assessments of cerebellar ataxia and patient‐reported outcomes. Cerebellum 2023;22:1257–1273.
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Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial

Affiliations

Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources