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MOBILITY AND BALANCE REHABILITATION IN MULTIPLE SCLEROSIS: A SYSTEMATIC REVIEW AND DOSE-RESPONSE META-ANALYSIS

Open AccessPublished:November 21, 2022DOI:https://doi.org/10.1016/j.msard.2022.104424

      HIGHLIGHTS

      • The results of our review provide Level I evidence on the effects of balance intervention to improve mobility and balance in PwMS. Interventions satisfying task-oriented principles appear to be the best for improving mobility and balance rehabilitation.
      • High dosage of rehabilitation interventions lasting more than 40 minutes should be specifically delivered to improve balance impairments.
      • New taxonomy of rehabilitation interventions, high-quality experimental studies with large samples, and long follow-ups are needed to identify patients’ clinical features clusters and develop balance and gait treatment recommendations for clinicians.

      Abstract

      Objective

      To assess the benefits of neurological rehabilitation and the dose-response relationship for the treatment of mobility and balance in multiple sclerosis.

      Methods

      We included studies investigating the effects of neurological rehabilitation on mobility and balance with the following eligibility criteria for inclusion: Population, People with Multiple Sclerosis (PwMS); Intervention, method of rehabilitation interventions; Comparison, experimental (specific balance intervention) vs control (no intervention/no specific balance intervention); Outcome, balance clinical scales; Study Design, randomised controlled trials. We conducted a random effects dose-response meta-analysis to assess linear trend estimations and a one stage linear mixed effects meta-regression for estimating dose-response curves.

      Results

      We retrieved 196 studies from a list of 5020 for full text review and 71 studies (n subjects=3306) were included. One study was a cross-over and 70 studies were randomized controlled trials and the mean sample size per study was 46.5±28.6 (mean±SD) with a mean age of 48.3±7.8years, disease duration of 11.6±6.1years, and EDSS of 4.4±1.4points. Twenty-nine studies (40.8%) had the balance outcome as the primary outcome, while 42 studies (59.1%) had balance as secondary outcome or did not specify primary and secondary outcomes. Thirty-three trials (46.5%) had no active intervention as comparator and 38 trials (53.5%) had an active control group.
      Individual level data from 20 studies (n subjects=1016) were analyzed showing a medium pooled effect size for balance interventions (SMD=0.41; 95% CIs 0.22 to 0.59). Moreover, we analyzed 14 studies (n subjects=696) having balance as primary outcome and BBS as primary endpoint yielding a mean difference of 3.58 points (95% CIs 1.79 to 5.38, p<0.0001).
      Finally, we performed meta regression of the 20 studies showing an association between better outcome, log of intensity defined as minutes per session (β=1.26; SEβ=0.51; p=0.02) and task-oriented intervention (β=0.38; SEβ=0.17; p=0.05).

      Conclusion

      Our analyses provide level 1 evidence on the effect of balance intervention to improve mobility. Furthermore, according to principles of neurological rehabilitation, high intensity and task-specific interventions are associated with better treatment outcomes.

      Keywords

      1. Introduction

      Balance impairments, defined as the difficulties in maintaining the upright position during static, challenging, and reactive conditions of postural control, are common in People with Multiple Sclerosis (PwMS) (
      • Cameron MH
      • Nilsagard Y.
      Balance, gait, and falls in multiple sclerosis.
      ,
      • Cameron MH
      • Lord S.
      Postural Control in Multiple Sclerosis: Implications for Fall Prevention.
      ,
      • Scholz M
      • Haase R
      • Trentzsch K
      • Weidemann ML
      • Ziemssen T.
      Fear of falling and falls in people with multiple sclerosis: A literature review.
      ) leading to falls in 46% of PwMS over six months. (
      • Beghi E
      • Gervasoni E
      • Pupillo E
      • et al.
      Prediction of Falls in Subjects Suffering From Parkinson Disease, Multiple Sclerosis, and Stroke.
      )
      Balance disorders and falls highlighted the importance of balance rehabilitation (
      • Comber L
      • Sosnoff JJ
      • Galvin R
      • et al.
      Postural control deficits in people with Multiple Sclerosis: A systematic review and meta-analysis.
      ), setting of intervention, disability, and type of treatment, can modulate the effects of balance rehabilitation, however treatment approaches and dose of intervention are two key factors. In recent decades, several rehabilitation approaches have been developed to improve balance in PwMS (
      • Khan F
      • Amatya B
      • Galea MP
      • et al.
      Neurorehabilitation: applied neuroplasticity.
      ). Gunn et al. reported that the effect on balance outcomes was higher in interventions incorporating gait, balance, and functional training compared to other types of interventions (
      • Gunn H
      • Markevics S
      • Haas B
      • et al.
      Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults With Multiple Sclerosis.
      ), while Paltamaa et al. reported that progressive resistance and aerobic interventions have positive effects on mobility and balance in PwMS. (
      • Paltamaa J
      • Sjögren T
      • Peurala SH
      • et al.
      Effects of physiotherapy interventions on balance in multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.
      )
      Even though several rehabilitation approaches have proven to be effective, it is important to understand the magnitude of mobility and balance improvement gained by increasing therapeutic dose (
      • Dijkers MP
      • Hart T
      • Tsaousides T
      • et al.
      Treatment taxonomy for rehabilitation: past, present, and prospects.
      ). The dose can be defined as “the amount of active ingredient(s) expected to produce the desired effect and the frequency and duration at which the agent is taken”. (
      • Lang CE
      • Lohse KR
      • Birkenmeier RL.
      Dose and timing in neurorehabilitation: prescribing motor therapy after stroke.
      ) Dose is a critical complex element that contributes to the effectiveness of the therapeutic interventions including frequency, intensity, duration, and timing of interventions. (
      • Kwakkel G.
      Impact of intensity of practice after stroke: issues for consideration.
      )
      Understanding the optimal dose of a given therapeutic intervention is critical to the implementation of evidence-based practice and to increase the effectiveness of interventions. The challenge of finding the best dose for rehabilitation is that the active ingredients, their targets and mechanisms of action remain unclear hampering the development of theoretical models on rehabilitation. (
      • Dijkers MP
      • Hart T
      • Tsaousides T
      • et al.
      Treatment taxonomy for rehabilitation: past, present, and prospects.
      )
      Evidence about the appropriate dose of rehabilitation interventions is sorely lacking for neurological diseases. Only a few studies on stroke rehabilitation and brain injury have been carried out supporting contradictory results about the dose-response relationship between high intensity of practice and better outcome. (
      • Kwakkel G.
      Impact of intensity of practice after stroke: issues for consideration.
      ,
      • Shiel A
      • Burn JP
      • Henry D
      • et al.
      The effects of increased rehabilitation therapy after brain injury: results of a prospective controlled trial.
      ,
      • Chen CC
      • Heinemann AW
      • Granger CV
      • et al.
      Functional gains and therapy intensity during subacute rehabilitation: a study of 20 facilities.
      ,
      • Lohse KR
      • Lang CE
      • Boyd LA.
      Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation.
      ,
      • Kwakkel G
      • van Peppen R
      • Wagenaar RC
      • et al.
      Effects of augmented exercise therapy time after stroke: a meta-analysis.
      ) However, a review by Lohse et al. showed a strong positive relationship between dose and response, demonstrating that time spent in therapy is a robust predictor of recovery across different types of interventions in people with Stroke. (
      • Lohse KR
      • Lang CE
      • Boyd LA.
      Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation.
      )
      International clinical guidelines of rehabilitation in multiple sclerosis stress the lack of an appropriate dose for rehabilitation interventions. To our knowledge, only two reviews on balance intervention in PwMS suggest that rehabilitation programs achieving a high dose of challenging balance exercise may lead to the greatest benefit in balance outcomes (
      • Khan F
      • Amatya B
      • Galea MP
      • et al.
      Neurorehabilitation: applied neuroplasticity.
      ,
      • Gunn H
      • Markevics S
      • Haas B
      • et al.
      Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults With Multiple Sclerosis.
      ), although a formal analysis investigating dose-response relationship in mobility and balance interventions in PwMS is missing.
      Hence, our systematic review is aimed at: i) evaluating the effectiveness of balance interventions, ii) evaluating the relationship between dose and rehabilitation effect on balance outcomes, iii) uncovering variables that may influence balance interventions in PwMS.

      2. Methods

      2.1 Protocol and registration

      This systematic review was performed according to the Cochrane group recommendations (
      ). We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA2020) statement for the reporting. (
      • Liberati A
      • Altman DG
      • Tetzlaff J
      • et al.
      The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration.
      ) We also registered the protocol and details of this review into the International Prospective Register of Systematic Reviews—PROSPERO (https://www.crd.york.ac.uk/prospero/; register number CRD42020187247) that are publicly available.

      2.2 Eligibility criteria

      We included studies eligible according to the following PICOs:
      • (P) Population: participants who had a diagnosis of Multiple Sclerosis (MS) according to McDonald criteria (
        • Thompson AJ
        • Banwell BL
        • Barkhof F
        • et al.
        Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.
        ) without concomitant neurological pathologies
      • (I) Intervention; specific balance intervention, defined as all the interventions used in MS rehabilitation that specifically target balance and coordination using specific function-based activities to improve balance and stability (
        • Bowman T
        • Gervasoni E
        • Amico AP
        • Antenucci R
        • Benanti P
        • Boldrini P
        • Bonaiuti D
        • Burini A
        • Castelli E
        • Draicchio F
        • Falabella V
        • Galeri S
        • Gimigliano F
        • Grigioni M
        • Mazzon S
        • Mazzoleni S
        • FG Mestanza Mattos
        • Molteni F
        • Morone G
        • Petrarca M
        • Picelli A
        • Posteraro F
        • Senatore M
        • Turchetti G
        • Crea S
        • Cattaneo D
        • MC; Carrozza
        CICERONE" Italian Consensus Group for Robotic Rehabilitation. What is the impact of robotic rehabilitation on balance and gait outcomes in people with multiple sclerosis? A systematic review of randomized control trials.
        )
      • (C) Comparison: no intervention or no specific balance intervention, defined as any type of intervention, passive stretching, and general exercises (
        • Bowman T
        • Gervasoni E
        • Amico AP
        • Antenucci R
        • Benanti P
        • Boldrini P
        • Bonaiuti D
        • Burini A
        • Castelli E
        • Draicchio F
        • Falabella V
        • Galeri S
        • Gimigliano F
        • Grigioni M
        • Mazzon S
        • Mazzoleni S
        • FG Mestanza Mattos
        • Molteni F
        • Morone G
        • Petrarca M
        • Picelli A
        • Posteraro F
        • Senatore M
        • Turchetti G
        • Crea S
        • Cattaneo D
        • MC; Carrozza
        CICERONE" Italian Consensus Group for Robotic Rehabilitation. What is the impact of robotic rehabilitation on balance and gait outcomes in people with multiple sclerosis? A systematic review of randomized control trials.
        )
      • (O) Outcomes clinical scales whose area of assessment includes “balance (non-vestibular)” according to the Rehabilitation Measure Database (https://www.sralab.org/rehabilitation-measures);
      • (s) Study design: Randomised Controlled Trials (RCTs) and cross-over
      Additionally, we included only RCTs published in English when one or more independent variables (e.g., intensity and/or duration of training) were specified in the paper; conversely, we excluded non-randomized and non-controlled pre-experimental studies, protocols, conference papers, or unpublished materials and studies including multiple diagnoses without separate analysis of MS.

      2.2.1 Search Strategy

      We conducted a literature search from inception to January 2021 through the following databases: MEDLINE, Embase, Cochrane Library (CENTRAL database), Scopus, Web of Science, and PEDro Database. Suitable keywords and MeSH headings were generated through discussions amongst the study authors. Search strategies for each database were available in Supplementary Table 1.
      We also performed a manual search in the reference list of included articles and previously published reviews, to retrieve articles not covered by the databases search. The literature search was supplemented by examining citation lists of returned articles and through Google Scholar searches.

      2.3 Study Selection

      Two reviewers (GP and CC) independently screened all the titles and abstracts of the articles. After this step, potentially relevant articles were retrieved for full-text assessment, and the same reviewers independently evaluated all the potential full-text papers to identify eligible studies. In the event of disagreement, a third reviewer (EG) evaluated the article to achieve a joint consensus.

      2.4 Data extraction and quality assessment

      Studies were summarized by two authors (GP and CC). A planned spreadsheet was used to extract the following data:
      • The publication year and the first author's name
      • Sample size (n° of participants in the experimental group and the control group and drops out)
      • Clinical and demographic characteristics of the sample (Mean age, MS type, EDSS score, Disease duration)
      • Experimental and control intervention description
      • Intervention characteristics [setting, duration, frequency, intensity, and dose of intervention]
      • Timing of follow-up assessments
      • Balance related outcome measures (primary and secondary outcomes)
      In case of unavailable data, we sent an e-mail to the authors or we estimated required data when possible, otherwise, the study was excluded from meta-analysis. If data were presented as median and interquartile range, median was assimilated to mean and standard deviation (SD) was calculated considering that inter-quartile range = 1.35 × SD, (
      ) and clinical relevance was differently judged depending on the minimally clinically important difference (MCID) of the measured outcomes. (
      • McGlothlin AE
      • Lewis RJ.
      Minimal clinically important difference: defining what really matters to patients.
      ) The study with a crossover design was analyzed as parallel group RCT, by calculating effects before the point of crossover.

      2.5 Categories of balance intervention

      According to previous studies on the definition and classification of balance intervention (
      • Horak FB.
      Postural orientation and equilibrium: what do we need to know about neural control of balance to prevent falls?.
      ,
      • Forbes PA
      • Chen A
      • Blouin JS.
      Sensorimotor control of standing balance.
      ,
      • Cosentino C
      • Baccini M
      • Putzolu M
      • et al.
      Effectiveness of Physiotherapy on Freezing of Gait in Parkinson's Disease: A Systematic Review and Meta-Analyses.
      ,
      • Heine M
      • van de Port I
      • Rietberg MB
      • et al.
      Exercise therapy for fatigue in multiple sclerosis.
      ,

      Shumway-Cook A, Woollacott MH. Motor Control: Translating Research Into Clinical Practice. Wolters Kluwer, Lippincott Williams and Wilkins 2102.

      ), we defined and classified rehabilitation intervention of the selected studies in eight categories:
      • 1)
        Task-oriented training: individualized, client‐centered, and functional‐based interventions focused on motor relearning principles;
      • 2)
        Gaming exercises program: active console game interventions, exergames;
      • 3)
        General exercises program: general exercises challenging balance;
      • 4)
        Mixed exercises program: more than one intervention in the same group;
      • 5)
        Core stability training: yoga and pilates trained by a physical therapist;
      • 6)
        Aerobic and resistance training;
      • 7)
        Vibration therapy: vibration therapy
      • 8)
        Other types of training (e.g. aquatic training and hippotherapy)

      2.6 Risk of Bias assessment

      We assessed the methodological quality of the studies using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0, version of 15 March 2019). (
      • Sterne JAC
      • Savović J
      • Page MJ
      • et al.
      RoB 2: a revised tool for assessing risk of bias in randomised trials.
      ) Bias arising from the: randomization process, deviations from intended intervention (effect of assignment and adhering to intervention), missing outcome data, outcome measurement. The selection of the reported studies was considered for risk-of-bias assessment and labeled as “low risk of bias,” “high risk of bias,” or “some concerns” by two independent reviewers (GP, CC). Disagreements were resolved by a third author (EG). Traffic light plots of the domain-level judgments for each individual result and weighted bar plots of the distribution of risk-of-bias judgments within each bias domain are formatted according to the risk-of-bias assessment tool and built up through RobVis.

      2.7 Data synthesis and Analysis

      According to PICOs, all studies have been considered in a qualitative synthesis of the results (see Table 1). To limit heterogeneity, we did not include studies where the balance outcomes were assessed only by instruments (e.g. static and dynamic posturography) providing a wide range of instrumented variables.
      Table 1Summary of included studies.
      First Author[Ref], YearSpecified balance as primary outcome (Y/N)Sample size (drop out)Participant CharacteristicsExperimental interventionControl interventionBalance-related outcome measuresSettingDuration, weeksFrequency, sessions per weekIntensity, min per sessionDose, H totFU, weeks
      Abasıyanık, 2020NEG: 21 (5)
      CG: 21 (4)Mean age: 45.5

      MS type: RR, SP

      EDSS: 3.15

      Disease duration: 11.84
      Clinical PilatesHome exercise programTUG, ABC, FES-I, PosturographyOut8357.523/
      Afrasiabifar, 2018YEG1: 25 (1)

      EG2: 25 (2)

      CG: 25 (0)
      Mean age: 32.7

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: 27.6
      EG1: Cawthorne–Cooksey treatment

      EG2: Frenkel treatment
      Routine careBBSOut12360366
      Aidar, 2018NEG: 13 (2)

      CG: 13 (1)
      Mean age:43.2

      MS type:not specified

      EDSS <7.5

      Disease duration: not specified
      Resistance trainingNo physiotherapyBBS, TUGOut12352.531.5/
      Aidar, 2018NEG: 14 (1)

      CG: 14 (1)
      Mean age: 43.2

      MS type: not specified

      EDSS <7.5

      Disease duration: not specified
      Aquatic exercisesNo physiotherapyBBS, TUGOut12352.531.5/
      Amiri, 2019NEG: 36 (1)

      CG: 36 (2)
      Mean age: 31.61

      MS type: RR

      EDSS: 3.84

      Disease duration: not specified
      Core stability trainingConventional programs (not include training of balance function)PosturographyOut1036030/
      Armutlu, 2001YEG: 13 (0)

      CG: 13 (0)
      Mean age: 33.61

      MS type: PP, SP

      EDSS: 4.7

      Disease duration: 6.07
      Johnstone Pressure Splint in addition to neuromuscular rehabilitationNeuromuscular rehabilitation, mat activities with PNF techniques combined with balance trainingPosturographyIn43Not specifiedNot specified/
      Arntzen, 2019YEG: 40 (1)

      CG: 40 (0)
      Mean age:50.1

      MS type:not specified

      EDSS:2.36

      Disease duration:10.36
      Group-based, comprehensive core stability interventionStandard care on balance and trunk controlMini-BESTest, PosturographyOut63601812, 24
      Aydin, 2014NEG: 20 (4)

      CG: 20 (0)
      Mean age: 32.83

      MS type: not specified

      EDSS: 3.5

      Disease duration: 6.97
      Hospital-based calisthenic and relaxation exercisesHome-based calisthenic and relaxation exercisesBBSEG: In

      CG: Home
      1254040/
      Brichetto_1, 2013YEG: 18 (0)

      CG: 18 (0)
      Mean age: 41.95

      MS type: not specified

      EDSS: 4.1

      Disease duration: 11.75
      Wii exercisesBalance rehabilitationBBS, PosturographyOut436012/
      Brichetto_2, 2015YEG: 16 (0)

      CG: 16 (0)
      Mean age: 50.5

      MS type: RR, SP, PP

      EDSS: 3.7

      Disease duration: 10.5
      Sensory system impairment rehabilitationBalance rehabilitationBBS, PosturographyOut436012/
      Broekmans, 2010NEG: 11 (0)

      CG: 14 (2)
      Mean age: 47.9

      MS type: RR, SP, PP

      EDSS: 4.3

      Disease duration: not specified
      Leg muscle training on a vibration platformNo physiotherapyBBS, TUGOut2055083.5/
      Bulguroglu, 2017NEG1: 12

      EG2: 13

      CG: 13

      (7 drop out, groups not specified)
      Mean age: 40.6

      MS type: not specified

      EDSS: 1.6

      Disease duration: 4.16
      EG1: Mat Pilates

      EG2: Reformer Pilates
      Home-based relaxation and respiration exercisesTUG, ABCEG1,2: Out

      CG: Home
      826016/
      Cakt, 2010NEG1: 15 (1)

      EG2: 15 (5)

      CG: 15 (6)
      Mean age: 37.9

      MS type: not specified

      EDSS: not specified

      Disease duration: 7.3
      EG1: progressive resistance training on a bicycle ergometer and balance exercise

      EG2: home-based lower-limb strengthening and balance exercise
      No physiotherapyTUG, DGIEG1: Out

      EG2: Home
      8212332.8/
      Calabrò, 2017YEG: 20 (0)

      CG: 20 (0)
      Mean age:42.5

      MS type: RR

      EDSS: 4.57

      Disease duration: 11.5
      Robotic-assisted gait training +VRRobotic-assisted gait trainingBBS, TUGOut857046.6/
      Callesen, 2019YEG1: 23 (6)

      EG2: 28 (4)

      CG: 20 (2)
      Mean age: 52

      MS type: RR, SP, PP

      EDSS: 3.5

      Disease duration: 17
      EG1: Progressive resistance training of the lower extremities

      EG2: Balance and Motor Control Training that challenges gait function
      No physiotherapySSST, Mini-BESTest, ABC, PosturographyOut1026020/
      Carling, 2017YEG: 25 (2)

      CG: 26 (0)
      Mean age: 58

      MS type: RR, SP, PP

      EDSS: 6

      Disease duration: 20.85
      Core stability exercises, dual tasking and sensory strategies + tailored home exercise programmeNo physiotherapyBBS, FES-I,

      TUG, Posturography
      Out + Home726014/
      Cattaneo_1, 2007YEG1:23 (3)

      EG2:12 (1)

      CG:15 (2)
      Mean age:46

      MS type:RR,SP,PP

      EDSS:not specified

      Disease duration:13.8
      EG1: Balance rehabilitation to improve motor and sensory strategies

      EG2: Balance rehabilitation to improve motor strategy
      Conventional therapy, treatments not specifically aimed at improving balanceBBS, DGI, ABCIn33.5457.8/
      Cattaneo_2, 2014NEG: 25 (2)

      CG: 28 (7)
      Mean age: 48.35

      MS type: RR, SP, PP

      EDSS: 5

      Disease duration: not specified
      Balance rehabilitation aimed at improving motor and sensory strategiesRehabilitation treatment which did not include training of sensory strategiesPosturographyOut33456.7/
      Conroy, 2017NEG: 26 (10)

      CG: 25 (17)
      Mean age: 52.7

      MS type: RR, SP, PP

      EDSS:not specified

      Disease duration: 13.3
      Internet-based module, tele-management

      home exercise
      Home-based exercisesBBSHome247Not specifiedNot specified/
      DeBolt, 2004YEG: 19 (1)

      CG: 17 (0)
      Mean age: 50.7

      MS type: RR, SP, PP

      EDSS: 3.78

      Disease duration: 14.09
      Lower-extremity resistance training.No physiotherapyTUG, PosturographyHome10342.521.2/
      Eftekharsadat, 2015NEG: 15 (0)

      CG: 15 (0)
      Mean age: 35.2

      MS type: RR, SP

      EDSS:not specified

      Disease duration: 7.1
      Postural stability training program using the Biodex Balance System SDNo physiotherapyBBS, TUG, PosturographyOut122208/
      Fjeldstad-Pardo, 2018NEG: 10 (1)

      CG1:10 (0)

      CG2: 10 (0)
      Mean age: 54.7

      MS type: RR, SP, PP

      EDSS: 4.3

      Disease duration: not specified
      Home based exercises program plus in-person physical therapy at foundationCG1: Remote physical therapy supervised via audio/visual real-time telecommunication

      CG2: Unsupervised home based exercises program
      BBS, ABC, PosturographyEG: Home+out

      CG1,2: Home
      87Not specifiedNot specified/
      Forsberg, 2016YEG: 44 (9)

      CG: 43 (5)
      Mean age: 54.14

      MS type: RR, SP, PP

      EDSS:not specified

      Disease duration:15.5
      Group-based balance exercisesNo physiotherapyBBS, TUG, ABC, FSST, PosturographyOut725512.8/
      Freitas, 2018NEG: 9 (0)

      CG: 12 (0)
      Mean age:46.5

      MS type: RR

      EDSS: not specified

      Disease duration: not specified
      Whole-body vibrationSham whole-body vibrationBBS, TUG, PosturographyOut512.50.2/
      Frevel, 2015YEG: 9 (1)

      CG: 9 (1)
      Mean age: 45.5

      MS type: RR, SP

      EDSS: 3.8

      Disease duration: 19
      Internet-based home training (balance, postural control and strenght training)HippotherapyBBS, DGI, TUGEG: Home

      CG: Out
      1222510/
      Gandolfi_1, 2014YEG: 12 (2)

      CG: 14 (2)
      Mean age: 50.5

      MS type: RR, SP

      EDSS: 4.2

      Disease duration: 14.2
      Specific balance exercises aimed at improving the ability to integrate multisensory inputs during balance responsesEnd-effector system training and stretching exercisesBBS, ABC, PosturographyOut6250104
      Gandolfi_2, 2015YEG: 39 (7)

      CG: 41 (5)
      Mean age:48.38

      MS type:RR

      EDSS:3.3

      Disease duration:13.74
      Specific training to improve central integration of afferent sensory inputsConventional rehabilitationBBS, ABC, PosturographyOut535012.54
      Hayes, 2011NEG: 11 (2)

      CG: 11 (1)
      Mean age: 49

      MS type: not specified

      EDSS: 5.24

      Disease duration: 12.15
      Standard exercises and Renew training (high intensity lower extremity eccentric ergometric resistance exercise)Standard therapy: aerobic training, lower extremity stretching, upper extremity strenght training and balance exercisesTUG, BBSOut12352.531.5/
      Hebert_1, 2011YEG1: 12 (0)

      EG2: 13 (0)

      CG: 13 (0)
      Mean age: 46.53

      MS type: RR, SP

      EDSS: not specified

      Disease duration: 6.9
      EG1: Vestibular rehabilitation

      EG2: Bicycle endurance and stretching exercises
      No physiotherapyPosturographyOut6260124, 8
      Hebert_2, 2018YEG:44 (6)

      CG:44 (6)
      Mean age:44.75

      MS type:not specified

      EDSS:3.42

      Disease duration:7.16
      Vestibular rehabilitationNo physiotherapyPosturographyOut147Not specifiedNot specified/
      Hoang, 2016YEG: 28 (5)

      CG: 22 (1)
      Mean age: 52.4

      MS type: RR, SP, PP

      EDSS:4.15

      Disease duration:12.5
      Step training with two interactive exergamesNo physiotherapyTUG, PosturographyOut1223012/
      Hogan, 2014NEG1: 66 (18)

      EG2: 45 (10)

      EG3: 16 (3)

      CG: 19 (4)
      Mean age: 52

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: 14
      EG1: Group-based physiotherapy (balance and strengthening exercises)

      EG2: Individual physiotherapy

      EG3: Yoga
      No physiotherapyBBSOut1016010/
      Kalron_1, 2016NEG: 16 (1)

      CG: 16 (1)
      Mean age: 45.6

      MS type: RR

      EDSS: 4.2

      Disease duration: 11
      VR balance rehabilitationStretching exercises, static postural control, weight shifting and perturbations exercisesBBS, FSST, PosturographyOut62306/
      Kalron_2, 2017NEG:25 (3)

      CG:25 (2)
      Mean age:43.2

      MS type:RR

      EDSS:4.3

      Disease duration:11.85
      Pilates intervention + home exercise programPhysiotherapy sessions + home exercise programBBS, TUG, FSSTOut121306/
      Kargarfard, 2018NEG: 20 (3)

      CG: 20 (5)
      Mean age: 36.4

      MS type: RR

      EDSS: 3.6

      Disease duration: 6.2
      Aquatic training programNo physiotherapyBBSOut8352.521/
      Keser, 2013NEG: 10

      CG: 10

      (3 drop out, groups not specified)
      Mean age: 38.6

      MS type: not specified

      EDSS: 2.82

      Disease duration: 6.35
      Posture, mat, coordination, balance, walking, stepping and movement control, and strengthening exercises and trunk exercises based on the Bobath conceptRoutine neurorehabilitation program (posture, mat, coordination, balance, walking, stepping and move- ment control, and strengthening exercises)BBSOut836024/
      Khalil, 2018NEG: 20 (4)

      CG: 20 (4)
      Mean age: 37.37

      MS type: RR

      EDSS: 3

      Disease duration: 9.04
      VR trainingHome-based traditional balance exercises without the VRBBS, TUGEG: Out

      CG: Home
      63123.6/
      Kramer, 2014YEG1:21

      EG2:20

      CG:20

      (9 drop out, groups not specified)
      Mean age: 47

      MS type: not specified

      EDSS: 3

      Disease duration: not specified
      EG1: Exergame

      EG2: Posturomed training
      Conventional training groupPosturographyOut33304,5/
      Kucuk, 2016NEG: 11 (8)

      CG: 9 (4)
      Mean age: 48.45

      MS type: not specified

      EDSS: 3

      Disease duration: 14.5
      PilatesUsual care (traditional exercise program; strength, balance and coordination exercises)BBS, TUGOut8252.514/
      Lord, 1998NEG: 12 (16)

      CG: 11 (9)
      Mean age: 53,1

      MS type: RR, PP

      EDSS: not specified

      Disease duration: 16.15
      Facilitation (impairments-based) approachTask-oriented treatment for walking and functional mobilityBBSOut62.56015/
      Lozano-Quilis, 2014NEG: 6 (0)

      CG: 5 (1)
      Mean age: 44,82

      MS type: RR, SP

      EDSS: not specified

      Disease duration: 9.77
      Virtual rehabilitationUsual care (standard balance and gait rehabilitation exercises)BBS, TUG, POMAOut1016010/
      Mansour, 2013NEG: 12 (0)

      CG: 12 (0)
      Mean age: 41.04

      MS type: RR

      EDSS: 2,85

      Disease duration: not specified
      Treadmill trainingTreadmill training with 40% partial body weight supportTUGOut63309/
      Martini, 2018NEG: 20 (0)

      CG: 20 (0)
      Mean age: 55.4

      MS type: not specified

      EDSS: 6

      Disease duration: not specified
      Task-oriented trainingUsual medical careTUG, FSST, ABCOut61404/
      McAuley, 2015NEG: 24 (2)

      CG: 24 (0)
      Mean age: 59,7

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: 18,97
      DVD exercise intervention focusing on balance, strength, and flexibilityWatch the 85-minute DVD documentary and continue with their normal day to-day livesSPPBHome243Not specifiedNot specified/
      Monjezi, 2017NEG: 23 (4)

      CG: 24 (5)
      Mean age: 36

      MS type: RR

      EDSS: 2,8

      Disease duration: 7,35
      Dual-task balance training

      Single-task balance trainingABC, BBSOut434596
      Negahban, 2013NEG: 12 (0)

      CG: 12 (0)
      Mean age: 36,62

      MS type: RR, SP

      EDSS: 3,7

      Disease duration: 9,4
      EG 1:Swedish massage

      EG 2: Exercise therapy (strength, stretch, endurance treadmill and balance training exercises)

      EG 3: Exercise therapy plus massage
      Standard medical careBBS, TUGOut53307,5/
      Nilsagård, 2012YEG: 42 (1)

      CG: 42 (3)
      Mean age: 49,7

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: 12,35
      Balance exercise using Nintendo Wii Fit Plus®No physiotherapyTUG, FSST, DGI, ABCHome6.52306,5/
      Novotna, 2019YEG: 23 (0)

      CG: 16 (0)
      Mean age: 40,69

      MS Type: not specified

      EDSS: 3,8

      Disease duration: 14,76
      Tailored exercise training using Homebalance®No physiotherapyBBS, Mini-BESTest, TUG (part of Mini-BESTest),

      ABC, FES-I
      Home471574
      Ortiz Gutie ́rrez 2013NEG: 25 (1)

      CG: 25 (2)
      Mean age: 41,23

      MS type: RR

      EDSS: 3,3

      Disease duration: 10,27
      Telerehabilitation treatment using the Xbox 360®Physiotherapy treatment (stretching, low-loads strength exercises, propioception exercises and gait facilitation exercises)BBS, POMAHome10EG: 4

      CG: 2
      EG: 20

      CG: 40
      13.3/
      Ozgen, 2016YEG: 20 (0)

      CG: 20 (0)
      Mean age: 41

      MS Type: RR, SP, PP

      EDSS: 3,5

      Disease duration: 7,7
      Customized vestibular rehabilitationUsual medical careABC, TUG, BBS, DGI, PosturographyOut865544/
      Ozkul_1, 2020NEG1: 17 (4)

      EG2: 17 (4)

      CG: 17 (4)
      Mean age: 32,33

      MS type: RR

      EDSS: 1,3

      Disease duration: 4
      EG 1: Virtual reality Pilates

      EG 2: Pilates and balance training group
      Relaxation exercisesBBS, TUG, PosturographyEG 1,2: Out

      CG: Home
      82EG: 60

      CG: 20
      EG: 16

      CG: 5.3
      /
      Ozkul_2, 2020NEG: 12 (2)

      CG: 11 (1)
      Mean age: 43,75

      MS Type: RR, PP

      EDSS: 3,87

      Disease duration: 14,75
      Task-oriented circuit trainingRelaxation exercisesBBS, ABC, TUG, PosturographyOut626012/
      Pavlikova, 2020NEG: 114 (19)

      CG: 64 (9)
      Mean age: 46,63

      MS type: RR, SP, PP

      EDSS: 5,1

      Disease duration: 13,6
      Balance specific physiotherapy (motor program activating therapy and sensory motor integration trainingVojta and conventional dynamic strengthening exercisesBBS, TUGEG: In + Out

      CG: In + Out
      924012/
      Peruzzi, 2017NEG: 16 (2)

      CG: 15 (4)
      Mean age: 42,8

      MS Type: RR

      EDSS: 3,8

      Disease duration: 12,1
      VR Treadmill trainingVirtual reality-based treadmill trainingBBS, TUG, FSSTOut634513.5/
      Prokopiusova, 2020YEG: 22

      CG: 22

      (5 drop out, groups not specified)
      Mean age: 48,5

      MS type: RR, SP, PP

      EDSS: 4,7

      Disease duration: 12,8
      Functional Electric Stimulation in Posturally Corrected PositionNeuroproprioceptive facilitation and inhibition physiotherapyBBS, TUG, DGI, ABC, FSSTOut876056/
      Prosperini, 2013NEG: 18 (1)

      CG: 18 (1)
      Mean age: 36,2

      MS type: RR, SP

      EDSS: 3,25

      Disease duration: 10,75
      Balance exercise using Nintendo Wii Fit PlusNo physiotherapyFSST, PosturographyHome125303021
      Robinson, 2015YEG1: 20 (0)

      EG2: 18 (1)

      CG: 18 (3)
      Mean age: 52

      MS type: not specified

      EDSS: not specified

      Disease duration: not specified
      EG 1: Balance exercise using the Nintendo Wii Fit™

      EG2: Traditional balance training
      No physiotherapyPosturographyIn425074
      Russo, 2017NEG: 30 (0)

      CG: 15 (0)
      Mean age: 41,5

      MS type: RR

      EDSS: 5

      Disease duration: 11,69
      Lokomat-Pro + traditional trainingUsual care (general conditioning exercises, warming up, strengthening, gait and postural control)TUG, POMAOut1836054/
      Salci, 2017NEG1: 16 (2)

      EG2: 16 (2)

      CG: 16 (2)
      Mean age: 35,67

      MS type: RR, SP, PP

      EDSS: 3,5

      Disease duration: 7
      EG 1: Balance training (sensory and motor strategy facilitation techniques)

      EG 2: Lumbar stabilization exercises in addition to balance training
      Task-oriented training (Nine workstations: sit to stand, stepping, reaching, walking, running, hitting a ball)BBS, PosturographyOut634513.5/
      Samaei, 2011YEG: 17 (1)

      CG: 17 (2)
      Mean age: 33

      MS type: RR

      EDSS: not specified

      Disease duration: 4,65
      Downhill or uphill treadmill walkingDownhill or uphill treadmill walkingTUG, PosturographyOut433064
      Sangelaji, 2014NEG: 42 (7)

      CG: 30 (10)
      Mean age: 32,55

      MS Type: not specified

      EDSS: 1,83

      Disease duration: not specified
      Combination exercises (stretching, strengthening aerobics and balancing exercisesNot specifiedBBSOut1037537.5/
      Sangelaji, 2016NEG1: 10 (0)

      EG2: 10 (0)

      EG3: 10 (0)

      CG: 10 (0)
      Mean age: 33,66

      MS type: RR

      EDSS: 1,78

      Disease duration: 2
      Aerobic exercise training and resistance exercise training sessions in different ratiosNo physiotherapyBBS, TUGOut84Not specifiedNot specified/
      Schuhfried, 2005NEG: 6 (0)

      CG: 6 (0)
      Mean age: 47,1

      MS type: not specified

      EDSS: 3,8

      Disease duration: not specified
      Whole-body vibrationSham whole-body vibrationTUG, PosturographyOut1190.152
      Silkwood-Sherer, 2007YEG: 9 (0)

      CG: 6 (0)
      Mean age: 44,53

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: 11,03
      Hippo-therapy sessionsNo physiotherapyBBS, POMA, PosturographyOut141307/
      Spina, 2016YEG: 10 (1)

      CG: 10 (0)
      Mean age: 47,5

      MS type: RR, SP, PP

      EDSS: 3,8

      Disease duration: 6,97
      Whole-body vibrationSham whole-body vibrationBBS, DGI, PosturographyIn3560153
      Stephens, 2001NEG: 6 (not specified)

      CG: 6 (not specified)
      Mean age: 54

      MS Type: not specified

      EDSS: 4,75

      Disease duration: 7,61
      Awareness through movements trainingEducational classes on acupuncture treatment, new medications, benefits of exerciseABC, PosturographyOut10Not specifiedEG:180

      CG: 90
      Not specified/
      Tarakci, 2013YEG: 55 (4)

      CG: 57 (7)
      Mean age: 40,57

      MS type: RR, SP, PP

      EDSS: 4,29

      Disease duration: 8,71
      Flexibility, range of motion, strengthening, core stabilization, balance and coordination exercises and functional activitiesNo physiotherapyBBSOut1236036/
      Thomas, 2017NEG: 15 (1)

      CG: 15 (0)
      Mean age: 49,3

      MS type: RR, SP, PP

      EDSS: not specified

      Disease duration: not specified
      Balance exercise using the Nintendo Wii Fit™ (Wii Sports, Sports Resort and Fit Plus software)Usual medical careTUGEG: Home + Out

      CG: Out
      EG: 482Not specifiedNot specified/
      Tramontano, 2018NEG: 15 (2)

      CG: 15 (7)
      Mean age: 48,2

      MS Type: not specified

      EDSS: 6,5

      Disease duration: 14
      VR treatment (VRG): postural stability in standing position on a foam cushionStandard neurorehabilitation (stretching, postural alignment, mobilizations and neuromuscular facilitations, balance training in standing and dynamic tasks)BBS, POMAOut45EG: 100

      CG: 80
      EG: 33.3

      CG: 26.7
      4
      Vermohlen, 2018YEG: 32 (2)

      CG: 38 (1)
      Mean age: 51

      MS type: not specified

      EDSS: 5,4

      Disease duration: 17
      Hippotherapy and standard careStandard therapyBBSOut12EG: 1306/
      Yazgan, 2020YEG1: 16 (1)

      EG2: 16 (4)

      CG: 15 (0)
      Mean age: 43,73

      MS type: RR, SP, PP

      EDSS: 4,01

      Disease duration: 12,67
      EG 1: Balance exercise using Nintendo Wii Fit™

      EG 2: Balance Trainer
      No physiotherapyBBS, TUGOut826016/
      We included in the meta-analysis all the studies with available data comparing the experimental group (specific balance intervention classified into 8 categories) versus the control group (no intervention or no specific balance intervention). For each study, we entered only post-intervention scores to account for the expected heterogeneity between studies and outcome measures, as recommended by the Cochrane collaboration. In the case of two or more experimental groups, we considered only the balance group. Consequently, in the case of two experimental (balance) groups belonging to one of the eight categories listed above, we combined the experimental interventions into a single group. Conversely, in case of two experimental groups belonging to different categories, we examined the experimental group considered as the main active principle of efficacy by the authors.

      2.8 Statistical Analysis

      Random-effects models weighted by inverse variance were used to calculate the pooled effect size (ES) according to the DerSimonian and Laird procedure. Each study included in this meta-analysis was handled as a statistical unit.
      We estimated the pooled ES of interventions either as mean difference (MD) to summarize studies using the same balance scale or as standardized mean difference (SMD) to summarize studies using different balance scales. Given the small sample size of included studies, we applied the bias-corrected Hedges’ g to estimated SMD. This is equivalent to a Cohen's d with an additional correction factor for small samples, thus providing more conservative results. Positive ESs indicated greater improvement in balance with the experimental intervention than the control intervention. ESs were graded as small (g = 0.20), medium (g = 0.50) and large (g = 0.80).
      Between-study variance and heterogeneity were assessed by the Cochran's Q-value and I2 index, respectively; we considered an I2 ≤ 40% as marginal, 30 to 60% as moderate, and 50 to 90% as substantial heterogeneity. The risk of publication bias was assessed by the Egger's test of asymmetry and the Orwin's fail-safe N test for estimating the number of missing studies to be incorporated to make the observed ES trivial, on the assumption that studies demonstrating a lack of benefit might not have been published. We performed a sensitivity analysis to confirm our results when the balance was not set as the primary endpoint.
      Meta-regression analyses were run to explore which covariates or factors were associated (if any) with a greater ES of experimental interventions.
      We identified the following study variables as continuous (log10-transformed) covariates: mean age of participants, duration (overall treatment length in weeks), frequency (number of sessions per week), intensity (minutes spent in a single session) of intervention, and dose (total time rehabilitation intended as a product of duration, frequency and intensity in hours) as defined by Lohse et al.; (
      • Lohse KR
      • Lang CE
      • Boyd LA.
      Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation.
      ) or as categorical factors: setting (home-based or hospital-based), type of experimental intervention (non task-oriented or task-oriented), type of control intervention (none or alternative).
      Two-tailed p values less than 0.05 were considered significant. Data were analyzed by using the freeware software Revman 5.3 and JASP version 0.14 (JASP Team, 2020; www.jasp-stats.org).

      2.9 GRADE

      The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system was employed to score the overall quality of evidence. (
      • Guyatt GH
      • Oxman AD
      • Schünemann HJ
      • et al.
      GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology.
      ) An initially assumed high level of evidence was downgraded according to the following pre-defined criteria (
      • Andrews JC
      • Schunemann HJ
      • Oxman AD
      • et al.
      GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.
      ): risk of bias (limitations in study design and execution or methodological quality); inconsistency (significant between-study heterogeneity and I2 ≥ 40%); indirectness (> 50% of the participants were outside the target population); imprecision (< 400 participants,); publication/selection bias (asymmetry of the funnel plot). Consequently, the evidence could be ranked into four levels: very low, low, moderate, and high.

      3. Results

      3.1 Study selection

      The literature search identified a total of 5020 results, among which 1591 duplicates were removed, and 3233 studies were rejected according to title and abstract. A total of 196 unique full-text articles were assessed for eligibility. At the end of the screening phase, 125 studies were excluded (reasons for exclusion are reported in Figure 1), and then 71 studies were included in systematic review. (Figure 1).
      Figure 1
      Figure 1PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2009 flow diagram (www.prisma-statement.org).

      3.2 Studies Characteristics

      The total number of participants is sufficiently high (n = 3306), however, we observed a great heterogeneity of the sample size among the studies ranging from 12 to 178 participants with a mean (mean ± SD) sample size per study of 46.5 ± 28.6 participants. The mean age was 48.3 ± 7.8 years with a disease duration of 11.6 ± 6.1 years and an Expanded Disability Status Scale (EDSS) score of 4.4 ± 1.4 points.
      Thirteen studies (18.3%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,

      Spina E, Carotenuto A, Aceto MG, et al. The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study. Restor Neurol Neurosci;34(5):869-76. doi: 10.3233/RNN-160665. PMID: 27567760.

      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ) had follow-up assessment including 843 participants. Timing of follow-up assessments ranged from 4 to 24 weeks.
      A comprehensive summary of the trials and participants’ characteristics is reported in Table 1. All 71 studies included were randomized controlled studies: one (1.4%) (
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ) was crossover and 70 (98.6%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,

      Spina E, Carotenuto A, Aceto MG, et al. The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study. Restor Neurol Neurosci;34(5):869-76. doi: 10.3233/RNN-160665. PMID: 27567760.

      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Aydın T
      • Akif Sarıyıldız M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Zocchi M
      • et al.
      Effects of balance exercises on people with multiple sclerosis: a pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Regola A
      • et al.
      Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study.
      ,
      • Conroy SS
      • Zhan M
      • Culpepper 2nd, WJ
      • et al.
      Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait.
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Lozano-Quilis JA
      • Gil-Gómez H
      • Gil-Gómez JA
      • et al.
      Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • Martini DN
      • Zeeboer E
      • Hildebrand A
      • et al.
      ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ortiz-Gutiérrez R
      • Cano-de-la-Cuerda R
      • Galán-del-Río F
      • et al.
      A telerehabilitation program improves postural control in multiple sclerosis patients: a Spanish preliminary study.
      ,
      • Ozgen G
      • Karapolat H
      • Akkoc Y
      • et al.
      Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ,
      • Prokopiusova T
      • Pavlikova M
      • Markova M
      • et al.
      Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis.
      ,
      • Russo M
      • Dattola V
      • Logiudice AL
      • et al.
      The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ,
      • Silkwood-Sherer D
      • Warmbier H.
      Effects of hippotherapy on postural stability, in persons with multiple sclerosis: a pilot study.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ,
      • Vermöhlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) had a parallel design.
      Twenty-nine studies (40.8%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,

      Spina E, Carotenuto A, Aceto MG, et al. The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study. Restor Neurol Neurosci;34(5):869-76. doi: 10.3233/RNN-160665. PMID: 27567760.

      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Zocchi M
      • et al.
      Effects of balance exercises on people with multiple sclerosis: a pilot study.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ozgen G
      • Karapolat H
      • Akkoc Y
      • et al.
      Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial.
      ,
      • Prokopiusova T
      • Pavlikova M
      • Markova M
      • et al.
      Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ,
      • Vermöhlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) had the balance outcome as the primary outcome, while 42 studies (59.1%) (
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Aydın T
      • Akif Sarıyıldız M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.
      ,
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Regola A
      • et al.
      Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study.
      ,
      • Conroy SS
      • Zhan M
      • Culpepper 2nd, WJ
      • et al.
      Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait.
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Lozano-Quilis JA
      • Gil-Gómez H
      • Gil-Gómez JA
      • et al.
      Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • Martini DN
      • Zeeboer E
      • Hildebrand A
      • et al.
      ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Ortiz-Gutiérrez R
      • Cano-de-la-Cuerda R
      • Galán-del-Río F
      • et al.
      A telerehabilitation program improves postural control in multiple sclerosis patients: a Spanish preliminary study.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ,
      • Russo M
      • Dattola V
      • Logiudice AL
      • et al.
      The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ,
      • Silkwood-Sherer D
      • Warmbier H.
      Effects of hippotherapy on postural stability, in persons with multiple sclerosis: a pilot study.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ) had balance outcome as the secondary outcome or did not specify primary and secondary outcomes.
      Thirty-three trials (46.5%) (
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,

      Spina E, Carotenuto A, Aceto MG, et al. The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study. Restor Neurol Neurosci;34(5):869-76. doi: 10.3233/RNN-160665. PMID: 27567760.

      ,
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • Martini DN
      • Zeeboer E
      • Hildebrand A
      • et al.
      ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ,
      • Silkwood-Sherer D
      • Warmbier H.
      Effects of hippotherapy on postural stability, in persons with multiple sclerosis: a pilot study.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ,
      • Vermöhlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) had no active intervention as comparator and 38 trials (53.5%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Aydın T
      • Akif Sarıyıldız M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Zocchi M
      • et al.
      Effects of balance exercises on people with multiple sclerosis: a pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Regola A
      • et al.
      Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study.
      ,
      • Conroy SS
      • Zhan M
      • Culpepper 2nd, WJ
      • et al.
      Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Lozano-Quilis JA
      • Gil-Gómez H
      • Gil-Gómez JA
      • et al.
      Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • Ortiz-Gutiérrez R
      • Cano-de-la-Cuerda R
      • Galán-del-Río F
      • et al.
      A telerehabilitation program improves postural control in multiple sclerosis patients: a Spanish preliminary study.
      ,
      • Ozgen G
      • Karapolat H
      • Akkoc Y
      • et al.
      Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ,
      • Prokopiusova T
      • Pavlikova M
      • Markova M
      • et al.
      Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis.
      ,
      • Russo M
      • Dattola V
      • Logiudice AL
      • et al.
      The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ) had an active control group (Table 1).
      Figures 2A-C summarize studies’ assessment and treatment type (2A), dose (2B), and setting (2C) of the interventions.
      Figure 2
      Figure 2A: Studies characteristics in terms of treatment type and outcome measures, data are reported as counts.
      . B: Studies characteristics in terms of dose, duration, frequencies and intensity
      Dose =dose (split into bins of ten hours); Dur=duration (split into bins of 3 weeks); Freq=frequency (number of sessions per week); Int=intensity (split into bins of 10 minutes). n=number of studies.
      . C: Studies characteristics in terms of setting of the interventions.
      Out: outpatients; Home: home rehabilitation; In: Inpatients; Out+home: mix of outpatients and home rehabilitation; In+out: inpatients and outpatients. n=number of studies.
      Treatment type(blue bars): TO=task-oriented interventions; Gaming=active console game interventions; Mix= Mixed interventions Core S=trunk stability interventions; Aer/Str=strength and aerobic resistance training; Gener=general exercises, usual care; Vibr=vibration. n=number of study
      Outcome (red bars): BBS=Berg Balance Scale; TUG=timed up-and-go test; Platf=stabilometric platform; ABC=Activities-specific Balance Confidence Scale; FSST=Four-Step Square Test; DGI=Dynamic Gait Index; FES=Falls Efficacy scale; POMA=Performance Oriented Mobility Assessment; M_BEST=Mini-Balance Evaluation Systems Test. n=number of studies
      According to balance intervention (see the method section), we reported the types of intervention in the 71 selected trials (figure 2A): 23 studies (32.4%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Zocchi M
      • et al.
      Effects of balance exercises on people with multiple sclerosis: a pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Regola A
      • et al.
      Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • Martini DN
      • Zeeboer E
      • Hildebrand A
      • et al.
      ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ozgen G
      • Karapolat H
      • Akkoc Y
      • et al.
      Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ),provided task-oriented training, 12 studies (16.9%) (
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Lozano-Quilis JA
      • Gil-Gómez H
      • Gil-Gómez JA
      • et al.
      Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.
      ,
      • Ortiz-Gutiérrez R
      • Cano-de-la-Cuerda R
      • Galán-del-Río F
      • et al.
      A telerehabilitation program improves postural control in multiple sclerosis patients: a Spanish preliminary study.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) gaming exercises program, 4 studies (5.6%) (
      • Conroy SS
      • Zhan M
      • Culpepper 2nd, WJ
      • et al.
      Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ) general exercises program, 10 studies (14.1%) (
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ) (
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Russo M
      • Dattola V
      • Logiudice AL
      • et al.
      The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Vermöhlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).
      ) mixed exercises program, 6 studies (8.4%) (
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ) core stability training, 4 studies (5.6%) (
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aydın T
      • Akif Sarıyıldız M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ) strength exercises program, 8 studies (11.2%) (
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Prokopiusova T
      • Pavlikova M
      • Markova M
      • et al.
      Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis.
      ,
      • Silkwood-Sherer D
      • Warmbier H.
      Effects of hippotherapy on postural stability, in persons with multiple sclerosis: a pilot study.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ) others type of training (e.g. aquatic training and hippo therapy), and 4 studies (5.6%) (
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,

      Spina E, Carotenuto A, Aceto MG, et al. The effects of mechanical focal vibration on walking impairment in multiple sclerosis patients: A randomized, double-blinded vs placebo study. Restor Neurol Neurosci;34(5):869-76. doi: 10.3233/RNN-160665. PMID: 27567760.

      ,
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ) vibration program.

      3.3 Dose of the interventions

      The duration, frequency, and intensity of balance intervention for each trial significantly differed among the studies. The dose varies greatly from less than 1 hour in two studies (2.8%) (
      • Schuhfried O
      • Mittermaier C
      • Jovanovic T
      • et al.
      Effects of whole-body vibration in patients with multiple sclerosis: a pilot study.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ) to 83 hours in one study (1.4%) (
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ), with a median of 12 hours. Eight studies (11.3%) (
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Conroy SS
      • Zhan M
      • Culpepper 2nd, WJ
      • et al.
      Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ) provide information only about duration and/or frequency of intervention making it impossible to calculate the total dose. Due to the high heterogeneity of dose, we grouped studies into categorical subgroups (Figure 2B). For the vast majority of the reports (n = 60, 84.5%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Novotna K
      • Janatova M
      • Hana K
      • et al.
      Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.
      ,
      • Prosperini L
      • Fortuna D
      • Giannì C
      • et al.
      Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Tramontano M
      • Martino Cinnera A
      • Manzari L
      • et al.
      Vestibular rehabilitation has positive effects on balance, fatigue and activities of daily living in highly disabled multiple sclerosis people: A preliminary randomized controlled trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Aydın T
      • Akif Sarıyıldız M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Fjeldstad-Pardo C
      • Thiessen A
      • Pardo G.
      Telerehabilitation in Multiple Sclerosis: Results of a Randomized Feasibility and Efficacy Pilot Study.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Freitas EDS
      • Frederiksen C
      • Miller RM
      • et al.
      Acute and Chronic Effects of Whole-Body Vibration on Balance, Postural Stability, and Mobility in Women With Multiple Sclerosis.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The Effect of Community Exercise Interventions for People with MS Who Use Bilateral Support for Gait.
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Lozano-Quilis JA
      • Gil-Gómez H
      • Gil-Gómez JA
      • et al.
      Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • Martini DN
      • Zeeboer E
      • Hildebrand A
      • et al.
      ADSTEP: Preliminary Investigation of a Multicomponent Walking Aid Program in People With Multiple Sclerosis.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ortiz-Gutiérrez R
      • Cano-de-la-Cuerda R
      • Galán-del-Río F
      • et al.
      A telerehabilitation program improves postural control in multiple sclerosis patients: a Spanish preliminary study.
      ,
      • Ozgen G
      • Karapolat H
      • Akkoc Y
      • et al.
      Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ,
      • Prokopiusova T
      • Pavlikova M
      • Markova M
      • et al.
      Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial.
      ,
      • Stephens J
      • DuShuttle D
      • Hatcher C
      • et al.
      Use of Awareness Through Movement Improves Balance and Balance Confidence in People with Multiple Sclerosis: A Randomized Controlled Study.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ,
      • Vermöhlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO).
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) rehabilitation intervention lasted from 4 to 12 weeks, while frequency was around of 2/3 times per week in 48 studies (67.6%) (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Gandolfi M
      • Geroin C
      • Picelli A
      • et al.
      Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.
      ,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: A randomized, controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Monjezi S
      • Negahban H
      • Tajali S
      • et al.
      Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.
      ,
      • Robinson J
      • Dixon J
      • Macsween A
      • et al.
      The effects of exergaming on balance, gait, technology acceptance and flow experience in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and Downhill Walking in Multiple Sclerosis: A Randomized Controlled Trial.
      ,
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • Alghwiri AA
      • Al-Shorafat D
      • Khazaaleh S
      Abu Foul L. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): A feasibility study.
      ,
      • Abasıyanık Z
      • Ertekin Ö
      • Kahraman T
      • et al.
      The effects of Clinical Pilates training on walking, balance, fall risk, respiratory, and cognitive functions in persons with multiple sclerosis: A randomized controlled trial.
      ,
      • Aidar FJ
      • Carneiro AL
      • Costa Moreira O
      • et al.
      Effects of resistance training on the physical condition of people with multiple sclerosis.
      ,
      • Aidar FJ
      • Gama de Matos D
      • de Souza RF
      • et al.
      Influence of aquatic exercises in physical condition in patients with multiple sclerosis.
      ,
      • Amiri B
      • Sahebozamani M
      • Sedighi B.
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      ,
      • Armutlu K
      • Karabudak R
      • Nurlu G.
      Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study.
      ,
      • Brichetto G
      • Spallarossa P
      • de Carvalho ML
      • et al.
      The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.
      ,
      • Brichetto G
      • Piccardo E
      • Pedullà L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.
      ,
      • Broekmans T
      • Roelants M
      • Alders G
      • et al.
      Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis.
      ,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • Ozkul C
      • et al.
      The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.
      ,
      • Cakt BD
      • Nacir B
      • Genç H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      ,
      • Calabrò RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.
      ,
      • Cattaneo D
      • Jonsdottir J
      • Regola A
      • et al.
      Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study.
      ,
      • DeBolt LS
      • McCubbin JA.
      The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
      ,
      • Eftekharsadat B
      • Babaei-Ghazani A
      • Mohammadzadeh M
      • et al.
      Effect of virtual reality-based balance training in multiple sclerosis.
      ,
      • Forsberg A
      • von Koch L
      • Nilsagård Y.
      Effects on Balance and Walking with the CoDuSe Balance Exercise Program in People with Multiple Sclerosis: A Multicenter Randomized Controlled Trial.
      ,
      • Frevel D
      • Mäurer M.
      Internet-based home training is capable to improve balance in multiple sclerosis: a randomized controlled trial.
      ,
      • Hayes HA
      • Gappmaier E
      • LaStayo PC.
      Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.
      ,
      • Hebert JR
      • Corboy JR
      • Vollmer T
      • et al.
      Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS).
      ,
      • Hoang P
      • Schoene D
      • Gandevia S
      • et al.
      Effects of a home-based step training programme on balance, stepping, cognition and functional performance in people with multiple sclerosis–a randomized controlled trial.
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      ,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized Controlled Trial to Examine the Impact of Aquatic Exercise Training on Functional Capacity, Balance, and Perceptions of Fatigue in Female Patients With Multiple Sclerosis.
      ,
      • Keser I
      • Kirdi N
      • Meric A
      • et al.
      Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study.
      ,
      • Kramer A
      • Dettmers C
      • Gruber M.
      Exergaming with additional postural demands improves balance and gait in patients with multiple sclerosis as much as conventional balance training and leads to high adherence to home-based balance training.
      ,
      • Küçük F
      • Kara B
      • Poyraz EÇ
      • et al.
      Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.
      ,
      • Lord SE
      • Wade DT
      • Halligan PW.
      A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
      ,
      • Mansour WT
      • Atya MA
      • Aboumousa AM.
      Improving Gait and Balance in Multiple Sclerosis Using Partial Body Weight Supported Treadmill Training.
      ,
      • McAuley E
      • Wójcicki TR
      • Learmonth YC
      • et al.
      Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.
      ,
      • Negahban H
      • Rezaie S
      • Goharpey S.
      Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.
      ,
      • Nilsagård YE
      • Forsberg AS
      • von Koch L.
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial.
      ,
      • Pavlikova M
      • Cattaneo D
      • Jonsdottir J
      • et al.
      The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.
      ,
      • Peruzzi A
      • Zarbo IR
      • Cereatti A
      • et al.
      An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.
      ,
      • Russo M
      • Dattola V
      • Logiudice AL
      • et al.
      The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology.
      ,
      • Salcı Y
      • Fil A
      • Armutlu K
      • Yildiz FG
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      ,
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      ,
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      ,
      • Thomas S
      • Fazakarley L
      • Thomas PW
      • et al.
      Mii-vitaliSe: a pilot randomized controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
      ) and intensity ranged from 30 to 60 minutes in 53 studies (74.6%). (
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S.
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.