Original article| Volume 56, 103218, November 2021

Perturbation practice in multiple sclerosis: Assessing generalization from support surface translations to tether-release tasks

Published:August 16, 2021DOI:


      • People with MS may generalize improvements in protective steps across balance tasks.
      • Mediation analyses may be a unique approach to assess generalization via rehabilitation.
      • Generalization of protective stepping supports further study of step training in MS.



      To determine whether improvements in protective stepping experienced after repeated support surface translations generalize to a different balance challenge in people with multiple sclerosis (PwMS)


      MS affects almost 1 million people in the United States and impairs balance and mobility. Perturbation practice can improve aspects of protective stepping in PwMS, but whether these improvements generalize is unknown.


      Fourteen PwMS completed two visits, 24hrs apart. The balance tasks included tether-release trials and support surface translations on a treadmill eliciting backward protective stepping. Margin of stability, step length, and step latency were calculated. Generalization was assessed via multilevel mediation models (MLMM) with bootstrapping to produce percentile and bias corrected confidence intervals


      There were no mediated effects for margin of stability or step latency; however, mediation was observed for step length, indicating that participants increased step length throughout the treadmill trials, and this generalized to tether-release trials


      MLMM may be useful for evaluating generalization of motor training to novel balance situations, particularly in small sample sizes. Using these analyses, we observed PwMS generalized improvements in step length, suggesting that aspects of protective step training may translate to improvements in other reactive balance tasks in PwMS.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Amato MP
        • Grimaud J
        • Achiti I
        • Bartolozzi ML
        • Adeleine P
        • Hartung HP
        • Kappos L
        • Thompson A
        • Trojano M
        • Vukusic S
        • Confavreux C.
        Evaluation of the EDMUS system (EVALUED) Study Group. European validation of a standardized clinical description of multiple sclerosis.
        J. Neurol. 2004; 251: 1472-1480
        • Bazelier MT
        • Van Staa TP
        • Uitdehaag BMJ
        • et al.
        Risk of fractures in patients with multiple sclerosis: A population-based cohort study.
        Neurology. 2012; 78: 1967-1973
        • Bhatt T
        • Pai YC.
        Generalization of gait adaptation for fall prevention: from moveable platform to slippery floor.
        J. Neurophysiol. 2009; 101: 948-957
        • Bolger N
        • Laurenceau JP.
        Intensive longitudinal methods: An introduction to diary and experience sampling research.
        Guilford Publications, Inc, New York2013
        • Cameron MH
        • Lord S.
        Postural control in multiple sclerosis: Implications for fall prevention.
        Curr. Neurol. Neurosci. Rep. 2010; 10: 407-412
        • Cameron MH
        • Horak FB
        • Herndon RR
        • Bourdette D.
        Imbalance in multiple sclerosis: a result of slowed spinal somatosensory conduction.
        Somatosen. Mot. Res. 2008; 25: 113-122
        • Carty CP
        • Cronin NJ
        • Nicholson D
        • Lichtwark GA
        • Mills PM
        • Kerr G
        • Barrett RS.
        Reactive stepping behaviour in response to forward loss of balance predicts future falls in community-dwelling older adults.
        Age Ageing. 2014; 44 (...): 109-115
        • Cattaneo D
        • De Nuzzo C
        • Fascia T
        • Macalli M
        • Pisoni I
        • Cardini R.
        Risks of falls in subjects with multiple sclerosis.
        Arch. Phys. Med. Rehabil. 2002; 83: 864-867
        • de Kam D
        • Roelofs JM
        • Geurts AC
        • Weerdesteyn V.
        Body configuration at first stepping-foot contact predicts backward balance recovery capacity in people with chronic stroke.
        PLoS One. 2018; 13e0192961
      1. Ender P. ml_mediation. 2014. Retrieved from

        • Franchignoni F
        • Horak F
        • Godi M
        • Nardone A
        • Giordano A.
        Using psychometric techniques to improve the Balance Evaluation Systems Test: the mini-BESTest.
        J. Rehabilit. Med. 2010; 42: 323-331
        • Fritz MS
        • MacKinnon DP.
        Required sample size to detect the mediated effect.
        Psychol. Sci. 2007; 18: 233-239
        • Gera G
        • Fling BW
        • Van Ooteghem K
        • Cameron M
        • Frank JS
        • Horak FB
        Postural motor learning deficits in people with MS in spatial but not temporal control of center of mass.
        Neurorehab. Neural. Re. 2016; 30: 722-730
        • Grabiner MD
        • Lou Bareither M
        • Gatts S
        • Marone J
        • Troy KL
        Task-specific training reduces trip-related fall risk in women.
        Med. Sci. Sports Exerc. 2012; 44: 2410-2414
        • Gunn H
        • Markevics S
        • Haas B
        • Marsden J
        • Freeman J.
        Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults with Multiple Sclerosis.
        Arch. Phys. Med. Rehabil. 2015; 96: 1898-1912
        • Hof AL.
        The ‘extrapolated center of mass’ concept suggests a simple control of balance in walking.
        Hum. Mov. Sci. 2008; 27: 112-125
        • Humm AM
        • Magistris MR
        • Truffert A
        • Hess CW
        • Rösler KM.
        Central motor conduction differs between acute relapsing–remitting and chronic progressive multiple sclerosis.
        Clin. Neurophys. 2003; 114: 2196-2203
        • Kjølhede T
        • Vissing K
        • Dalgas U.
        Multiple sclerosis and progressive resistance training: A systematic review.
        Mult. Scler. J. 2012; 18: 1215-1228
        • Koo TK
        • Li MY.
        A guideline of selecting and reporting intraclass correlation coefficients for reliability research.
        J. Chiropr. Med. 2016; 15: 155-163
        • Krull JL
        • MacKinnon DP.
        Multilevel modeling of individual and group level mediated effects.
        Multivariate Behav. Res. 2001; 36: 249-277
        • Lee A
        • Bhatt T
        • Pai YC.
        Generalization of treadmill perturbation to overground slip during gait: Effect of different perturbation distances on slip recovery.
        J. Biomech. 2016; 49: 149-154
        • Lurie J D
        • Zagaria AB
        • Ellis L
        • Pidgeon D
        • Gill-Body KM
        • Burke C
        • McDonough CM.
        Surface perturbation training to prevent falls in older adults: a highly pragmatic, randomized controlled trial.
        Phys. Ther. 2020; (...) (E-pub ahead of print)
        • MacKinnon DP
        • Lockwood CM
        • Hoffman JM
        • West SG
        • Sheets V.
        A comparison of methods to test mediation and other intervening variable effects.
        Psychol. Methods. 2002; 7: 83-117
        • MacKinnon D.
        Introduction to statistical mediation analysis.
        Routledge, New York2012
        • Mansfield A
        • Peters AL
        • Liu BA
        • Maki BE.
        Effect of a Perturbation-Based Balance Training Program on Compensatory Stepping and Grasping Reactions in Older Adults: A Randomized Controlled Trial.
        Phys. Ther. 2010; 90: 476-491
        • Mansfield A
        • Wong JS
        • Bryce J
        • Knorr S
        • Patterson KK.
        Does Perturbation-Based Balance Training Prevent Falls? Systematic Review and Meta-Analysis of Preliminary Randomized Controlled Trials.
        Phys. Ther. 2014; 95: 700-709
        • Mansfield A
        • Wong JS
        • McIlroy WE
        • et al.
        Do measures of reactive balance control predict falls in people with stroke returning to the community?.
        Physiother (United Kingdom). 2015; 101: 373-380
        • McNeish D.
        Multilevel mediation with small samples: A cautionary note on the multilevel structural equation modeling framework.
        Struct. Equ. Model. 2017; 24: 609-625
        • Nasreddine ZS
        • Phillips NA
        • Bedirian V
        • Charbonneau S
        • Whitehead V
        MoCA: a brief screening tool for mild cognitive impairment.
        J. Am. Geriat. Soc. 2005; 53: 695-699
        • Pai YC
        • Bhatt T
        • Yang F
        • Wang E
        • Kritchevsky S.
        Perturbation training can reduce community-dwelling older adults’ annual fall risk: a randomized controlled trial.
        J. Gerontol. A Biol. Sci. Med. Sci. 2014; 69: 1586-1594
        • Peterson EW
        • Cho CC
        • von Koch L
        • Finlayson ML.
        Injurious Falls Among Middle Aged and Older Adults With Multiple Sclerosis.
        Arch. Phys. Med. Rehabil. 2008; 89: 1031-1037
        • Peterson DS
        • Huisinga JM
        • Spain R
        • Horak FB.
        Characterization of Compensatory Stepping in People with Multiple Sclerosis.
        Arch. Phys. Med. Rehabil. 2016; 97 (Percutaneous): 513-521
        • Peterson DS
        • Dijkstra BW
        • Horak FB.
        Postural motor learning in People with Parkinson’s disease.
        J. Neurol. 2016; 5: 1-8
        • Shen X
        • Mak MKY.
        Technology-assisted balance and gait training reduces falls in patients with Parkinson’s disease: A randomized controlled trial with 12-month follow-up.
        Neurorehabil. Neural Repair. 2015; 29: 103-111
        • Singer ML
        • Smith LK
        • Dibble LE
        • Foreman KB.
        Age-Related difference in postural control during recovery from posterior and anterior perturbations.
        Anat. Rec. 2015; 298: 346-353
        • Snook EM
        • Motl RW.
        Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis.
        Neurorehabil. Neural. Re. 2009; 23 (Epub 2008 Oct 23): 108-116
        • Van Liew C
        • Dibble LE
        • Hunt GR
        • Foreman KB
        • Peterson DS.
        Protective stepping in multiple sclerosis: Impacts of a single session of in-place perturbation practice.
        Mult. Scler. Relat. Disord. 2018; 2019 (October): 17-24
        • Wallin MT
        • Culpepper WJ
        • Campbell JD
        • et al.
        The prevalence of MS in the United States: A population-based estimate using health claims data.
        Neurology. 2019; 92: E1029-E1040
        • Wang TY
        • Bhatt T
        • Yang F
        • Pai YC.
        Generalization of motor adaptation to repeated-slip perturbation across tasks.
        Neuroscience. 2011; 180: 85-95
        • Yang F
        • Bhatt T
        • Pai Y-C.
        Generalization of treadmill-slip training to prevent a fall following a sudden (novel) slip in over-ground walking.
        J. Biomech. 2013; 46: 63-69
        • Zwibel HL.
        Contribution of impaired mobility and general symptoms to the burden of multiple sclerosis.
        Adv. Ther. 2009; 26: 1043-1057