Feasibility and Safety of a Powered Exoskeleton for Balance Training for People living with Multiple Sclerosis. A Single-Group Preliminary Study (RAPPER III)

Abstract 

Objective 

The aim of this study was to evaluate the feasibility, usability, safety, and potential health benefits of using an exoskeleton device for the rehabilitation of people living with Multiple Sclerosis.  

Design 

Single-group preliminary study. 

Subjects 

Eleven adults living with Multiple Sclerosis were recruited with Expanded Disability Status Scores that ranged from 6 to 7.5 (mean age 54.2 years (11.8)). 

Methods 

Individual participants undertook a balance rehabilitation exercise program using the Rex Rehab robotic exoskeleton device. Each participant undertook 4 x 45-60 minute supervised, balance exercise sessions.  Primary outcomes measured were: 1) Number of participants who completed the trial protocol safely, and 2) Number and nature of Adverse Events reported. Secondary outcomes assessed mobility; balance; spasticity; sleep; functional independence; quality of life and device satisfaction. 

Results 

10 out of 11 participants completed the trial protocol safely. Four adverse events were recorded (one serious) all of which were deemed to be unrelated to the trial.  

Secondary outcomes showed allied improvements in balance, joint mobility, spasticity and quality of life. All participants found the device acceptable to use. 

Conclusion 

These results suggest it is feasible and safe to use the Rex Rehab exoskeleton device to assist with balance rehabilitation for people living with Multiple Sclerosis. 

Key Words: Feasibility, Safety, Balance, Multiple Sclerosis, Rehabilitation, Robotic Exoskeleton Device, Abdominal Muscles, Mobility 

Lay abstract 

Multiple sclerosis (MS) is a chronic neurological disease that can lead to symptoms including muscle weakness and balance issues. The incidence of falls in people living with MS (PwMS) is three times higher than that in older people.  To try to reduce this vulnerability to falls, this study aimed to evaluate the feasibility, safety, and potential health benefits of using an exoskeleton device for a balance exercise programme.  11 PwMS undertook 4 x 45-60 minute supervised, balance exercise sessions using the exoskeleton. Feasibility and safety were assessed by identifying the number of participants who completed the trial safely; consideration of any issues experienced during the trial and how these were resolved.   10 participants completed the trial (1 withdrew due to their MS)  and only 4 issues were reported, all of which were unrelated to the trial.  Some participants also experienced improvements in balance, mobility and quality of life.  

Introduction 

Multiple sclerosis (MS) is a common neurological disorder characterised by an autoimmune response causing inflammation and demyelination of nerve cells within the brain and spinal cord (1).  Approximately, 80% of people living with MS (PwMS) experience gait and mobility impairments, while 75% suffer from balance disorders (2).  Balance impairment may be related to a variety of factors including muscle weakness, in-co-ordination, sensory disturbances, spasticity and cerebellar symptoms (3). 

While it is recognised that many PwMS have poor balance that is associated with falls (4), there is a growing body of research evidence, which identifies the many benefits of exercise, including better balance (5-7).  However, given that balance issues like increased postural sway (8) have been identified as contributory risk factors for falls, it is important to find ways that PwMS can exercise safely and effectively. Rehabilitation using assistive technology has been identified as one effective means of addressing this problem (9). 

Building on a preliminary study that used the current Rex Rehab exoskeleton device for people with spinal cord injury (10), this study aimed to assess the feasibility and safety of using the same exoskeleton device (11), to support a balance rehabilitation program for PwMS. 

Feasibility was assessed in the relatively broad manner adopted by other stage 1 trials (12-13), which have addressed aspects of process, management, scientific outcome and resources. 

Safety was assessed by comprehensively documenting the number and nature of adverse events and how effectively the trial team identified, managed and resolved them (Table 1).  Secondary objectives sought to determine whether there may be health benefits associated with undertaking a balance exercise treatment intervention supported within a Rex Rehab exoskeleton. Alongside this, we sought simple feedback comments from participants about their experiences of the trial. 

Methods 

The study utilised a prospective, open label, single arm, non-randomized design, and was approved by the East of England-Cambridgeshire and Hertfordshire Health Research Authority Ethics panel (REC reference: 16/EE/0553) IRAS reference: 219334. The trial was registered with CTN: NCT05102682 via ClinicalTrials.gov and with the National Institute for Health and Care Research reference: NEUR 33236. Organizational registration via East Kent University Hospitals NHS Foundation Trust  Research and Innovation ref: 2016/NEURO/10.  (A copy of the Protocol, participant consent and information sheets are provided in Supplemental material files). An outline of the study components is provided in a flow chart (Figure 1). 

Setting and Participants 

The trial was conducted in an Outpatient setting on a University campus.  Participants self-referred following an advertisement placed with MS services, charities, East Kent Neuro-rehabilitation Unit and social media platforms.  All applicants were screened by questionnaire on the telephone against the trial inclusion and exclusion criteria identified in Table 2. Eleven individuals enrolled from April to July 2017 and provided written informed consent on trial entry. 

Equipment 

A Rex Rehab exoskeleton was used, supplied by Rex Bionics Ltd. PO Box 316-063. Auckland 0760, New Zealand. 

Study Outcomes 

All outcome measurements were performed by the same neuro-physiotherapist at the beginning and end of the intervention period and training sessions were spaced at 1 week intervals, which enabled ample recovery time between sessions.(18) 

The primary feasibility measurement outcomes were:  

1. Proportion of individuals who were eligible for inclusion following screening process 

2. Number of participants who completed the trial 

3. Dropout Rate – percentage of participants who dropped out of the trial 

4. Time taken for an individual to transfer into the Rex device  

5.  Level of assistance required with the transfer 

6. Time taken to complete sit to stand inside the device 

The primary safety outcomes were: 

1. Number of Adverse Events recorded 

2. The severity and nature of Adverse Events reported 

An Adverse event (AE) is defined as an event associated with a medical device that led to death or serious injuries of a patient, or may lead to such if the event recurs (19).  

The secondary outcome measures were the Berg Balance Scale (BBS) (20), Modified Ashworth Scale (MAS) (17), Modified Falls Efficacy Scale (MFES) (21),  Multiple Sclerosis Impact Scale (MSIS-29) (22), Health related Quality of Life Scale EQ-5D-5L (23), Psychosocial Impact of Assistive Devices Scale (PIADS) (24), Activities-Specific Balance Confidence Scale (ABC) (25), Multiple Sclerosis Walking Scale (MSWS-12) (26), Arm Activity Measure (ArmA) (27), Epworth Sleepiness Scale (28), and the Visual Analogue Scale for Pain (VAS) (29). Passive joint range of motion (ROM) for ankles, knees and hips was measured using a standard goniometer and standard principles for joint measurement were followed (30). For all outcome measures used, standard procedures were followed which included the use of a standard chair (for example, as defined in the BBS scale) and standard plinth, which were adjusted as deemed suitable by the trial team. This enabled standardisation of all testing measurements across all testing sessions.  All participants recruited were living with chronic advanced MS and presented  with a variable degree of paresis.  A decision was made to have a detailed functional assessment taken instead of using the Medical Research Council Muscle Power Scale (31), which is an impairment focused scale. Further information on mobility; walking aids; ataxia; relevant anti-spasticity medication and ongoing treatment is presented in Table 2. Outcome measure questionnaires were presented in the same order across all participants.  A 15 minute interview was conducted 10 days post-trial with participants and their care-giver if available to gain feedback on individual experiences. Interviews were audio recorded and transcribed by the interviewer.  

Intervention 

The balance exercise program was designed to focus on strengthening leg extensor and abdominal muscles, recommended as important for PwMS (32-331).  The program also included a focus on maintaining an optimal upright posture, when standing in the Rex and performing dynamic balance exercises (34), [See Appendix 1 for exercise programme].  Given the absence of Cochrane guidelines (35) on the optimal type, duration, intensity and frequency of exercise training sessions for PwMS, the intervention was delivered in 4 exercise sessions (with data collected before and after). This number of sessions exceeded the single session applied in the previous SCI study (10) and was constrained by the resources to hand.  The time schedule between each training session was an interval of one week. Spasticity was measured before the training intervention, at the beginning of session 3 and at the end of the fourth session. Individual participants were offered and supported with appointment times as flexibly as possible within the available weekend diary slots of the team.  As spasticity can vary throughout the day for numerous reasons, when feasible, it is recommended that therapies take place at the same period of the day.  

The Rex device used is a robust powered exoskeleton which covers the waist, pelvis and lower limbs of the individual (16 and Figure 2).

The individual user is supported securely within the device using a pelvic harness, thigh and calf cuffs, and an abdominal pad (Figure 3).

The Rex is designed for use in a clinical environment under the supervision of a Rex-trained clinician and is operated by a keypad and joystick. 

Individuals transferred into the Rex with the appropriate level of assistance as risk assessed by the trial team.  Optimal postural alignment and positioning of the individual within the device was ensured by the trial neuro-physiotherapist.  Following a verbal briefing, the clinician then switched on the device and used the joystick to bring the individual up from a sitting to standing position.  From the standing position, the appropriate functionality mode was selected (e.g. move forward). The device was then operated via “hands on” assistance from the trial neuro-physiotherapist, which enabled the participant to relax their arms and concentrate on their posture. The trial neuro-physiotherapist always held onto the Rex device to stabilise it when moving, a technique termed “spotting” taught as part of the device training (16).  

Statistical Analysis 

Descriptive statistics are provided for the primary outcome measures and safety data (Table 1 - Adverse Events). Categorical variables were summarised by the number and percentage of responses in each category, whilst the mean and standard deviation were used to summarise continuous variables. Analyses of secondary outcome measures were conducted using paired t-tests to examine changes in scores from pre-trial to post-trial time points. The distribution of changes in scores was assessed visually and found to be approximately normally distributed for all outcomes.  Where outcomes were measured on more than two occasions, two-way ANOVA was used for to compare between timepoints (with participant and time being the two factors). For the PIADS scale, measured once post-treatment, a one-sample t-test was used to indicate if the results varied significantly from zero, in relation to whether using the Rex device in the trial had a positive or negative impact on the rated domains. All statistical tests were performed with a two-sided 95% significance level. The software package Stata (Version 15.1) was used for all analyses. 

Results 

11 individuals were enrolled into the trial from a sample of 21 PwMS who were screened, which equates to 52%. Table 4 provides participant demographic data.  The most common reason for exclusion at screening was when a potential participant’s calf muscle bulk exceeded 375 mm in circumference (this measurement is taken at a fixed point 80 mm below the knee), as identified in the Manual (16), which was identified on 6 occasions during screening.  The other reasons were low blood pressure, back pain, history of osteoporotic fractures, short tibial length and sacral lesions.  

Primary Outcome Measures 

10 out of 11 participants (91%) completed the trial, and only one participant chose to withdraw due to a reported relapse of their MS.  All 11 participants completed the transfer into the device with a mean time of 3 minutes 35 seconds. Five individuals managed to transfer into the exoskeleton device independently after instruction from the trial team.  One required verbal support and supervision from the neuro-physiotherapist, 4 required “hands on” physical assistance from the neuro-physiotherapist and 1 required the assistance of 2 trained team members and the use of a hoist.  All participants completed the sit to stand task within the device with assistance from the neuro-physiotherapist. 

Adverse Events 

A total of 4 AEs  were recorded (Table 1), only 1 of which was categorised as serious, and none were directly attributable to the trial.  

Secondary Outcome Measures 

Tables 5, 6, 7, 8, 9 and 10 report the statistically significant changes between the baseline and post-trial measurements taken.  

Passive Joint ROM (Table 5) 

The mean left ankle inversion ROM reduced by 7 degrees and the mean right knee flexion increased by 9 degrees at the end of the trial.  

Balance (Tables 6 and 7) 

4 participants achieved a clinically significant improvement in balance over the course of the trial. This was determined by calculating whether a sufficient increase in points had been made by the individual relative to their initial BBS score (36) (Table 6). 

MSIS-29 (Table 7) 

There was a positive change for all but 2 participants in how MS was perceived to impact on their daily lives during the trial.  

EQ-5D-5L (Table 7)  

Scores increased over time by a mean of 0.17 units, with all but 3 participants reporting an improvement and none showing a decline.  

Spasticity (Table 8) 

Statistically significant reductions in spasticity were detected in the left ankle plantarflexors and dorsiflexors and right ankle dorsiflexors.  

PIADS (Table 9) 

Participants consistently reported that taking part in the trial had made a significant positive impact on the 3 individual components of competence, adaptability  and self-esteem. 

ABC/ArmA/VAS (Pain)/ESS/MSWS-12/MFES (Tables 7 and 10)  

There was no significant change between timepoints for the ABC, ArmA, VAS pain, ESS scores, MSWS-12 and MFES during the trial. 

The improvements observed above accorded with informal feedback from participants’ and, in some cases, their carers (See Appendix 2 for all feedback). 

Discussion 

The main findings from this study are that it is feasible and safe to use this exoskeleton to support and enable the performance of a balance exercise programme by PwMS provided that there is a specialist team with an advanced level of clinical knowledge and expertise available to support participants.  Taken together and mindful of the criteria (37) on what constitutes a successful feasibility study, the outcomes showed that the intervention and assessment protocols were well-tolerated and not associated with any serious study-related adverse events.   

There were only three minor adverse events and one serious adverse event, which were not directly related to the study, and which did not consume an excessive amount of unanticipated time or resource. Individuals diagnosed with relapsing remitting MS can experience a relapse at any time and taking part in a clinical research trial would not prevent such an event.  This accounts for the first AE in Table 1. AEs two (suspected deep vein thrombosis) and three (back pain) were likewise un-associated with trial participation. Recording and resolving these AEs demonstrated the effectiveness of our risk assessment and safety monitoring process, given that they were quickly picked up when the participants arrived for their sessions.  Direct access to the Principal Investigator within the team via telephone communication enabled swift access to expert knowledge and clinical decision making to establish the most appropriate and safe course of action to be taken.   AE four involved a participant who reported that they had fallen at home. It is known that the incidence of falls is three times higher in PwMS compared to older people (38) and this context is relevant and can account for this incident alone.  It is perhaps notable that none of these AEs were connected to the use of the device or exercise programme.  We suggest that this was partly due to the advanced level of clinical expertise and specialism within the trial research team, which meant for example, that individual participants were optimally positioned within the exoskeleton by the trial neuro-physiotherapist and thereon kept under continuous, careful observation. An advanced level of expertise also enabled dynamic advanced risk assessment of participants, which enabled optimal safety throughout all trial exercise sessions.    

We are aware of only one other feasibility and safety research trial which examined the use of a different powered exoskeleton for PwMS (13).  This trial concluded that the exoskeleton used was feasible and safe for only 4 people out of the sample population of 13 participants.  Conversely, our trial demonstrated that with an experienced trial team using the Rex exoskeleton, it was feasible for all 10 individuals to participate and complete the trial safely.   Our result accords with those of two other studies that examined the feasibility and safety of two different exoskeletons for people with SCI (10, 39), with both studies reporting safe, study protocol completion.  Future studies could also compare different training regimes with or without powered exoskeleton devices.  In terms of changes and improvements in participant independence and required assistance during the exercise sessions, it could also be useful to consider including a broader outcome measure to detect and record these changes over the trial period in future research. 

A recent systematic review on the use of robot-assisted training for balance training for patients affected by stroke reported that robot-assisted therapy offers significant improvement of balance when compared with traditional therapy (40).  This endorses and supports our study as analysis of the secondary outcome measures revealed a clinically meaningful improvement in balance for 4 participants.  This clinical change was endorsed by their subjective feedback and care-giver comments (Appendix 2).  With regards to balance, relevant research has found that PwMS who are able to walk have decreased core muscle strength when compared to individuals in a matched control group (41).  PwMS also find it more challenging to maintain postural stability when challenged by external forces (42) and experience delays in postural adjustments (3) and fear of falls (8).  Importantly, clinical research evidence demonstrates that training core abdominal muscles improves anticipatory postural adjustments and balance, and also reduces the associated fear of falls (43, 44).  Accordingly, the practise adopted in this study of encouraging participants to actively contract their abdominal muscles prior to and during movement may have helped their balance (see Intervention details in Appendix 1).We also note that there were improvements during the study in the passive joint ROM at the left ankle and right knee, and a significant reduction in muscle spasticity in both left and right ankle dorsiflexor muscles and left ankle plantarflexor muscles. Such improvements could also have a positive influence on balance (9).  One participant in our group of ten, was unable to stand independently and unable to walk.  In future research, it could be worth considering the potential inclusion of a functional sitting balance measurement scale, for example, the Function In Sitting Test (FIST), (45) for individuals who are not able to walk, which would enable more relevant data to be collected for such individuals. 

For some participants, improvements translated into other benefits. For example, one participant was able to pick up a shoe from the ground, which he had previously been unable to do and thus was extremely meaningful for him.  There were also allied improvements in perceived individual competence, adaptability and self-esteem recorded via PIADS for all participants with some individuals starting new activities for example, going to the gym and gliding, which they attributed to their positive experience of taking part in the trial. There were also statistically significant improvements in perceived health and quality of life and a reduction in the perceived impact of MS on day-to-day life, although it is noted that there were numerous secondary outcomes and due to multiple testing, changes in some outcomes may have been expected due to chance. 

Study Limitations 

This study has several limitations. The broad study eligibility criteria meant that participants varied from being independently mobile with a walking aid to being a wheelchair user and requiring a hoist for transfers.  This heterogeneity made it challenging to identify group patterns during the trial and further research would benefit from recruiting a larger sample to allow participant stratification.  Beyond the primary focus of the trial, the true magnitude of secondary health benefits detected for some participants could potentially be more accurately uncovered by increasing the number and frequency of treatment sessions, which were limited by resource availability. That said, at the end of each exercise session participants were physically and cognitively tired reflecting the demands of the intervention, so spacing sessions to enable recovery is important.  In future research, it would also be useful to include an initial Outpatient measuring appointment, where the individual has an opportunity to try the device. This would improve screening process efficiency and might also reduce the anxiety commonly expressed by participants when they tried out the device for the first time. Given that PwMS are a vastly heterogenous group, and that the focus of this trial was feasibility and safety, the measured improvements in secondary outcomes for participants need to be understood as simply that these are key outcome measures for use in a larger trial, which could enable a more precise and in-depth comparison to individual baselines.  There was no control group to exclude potential equivalent benefit from the treatment sessions without the exoskeleton device. And finally, to improve insight and understanding of what is meaningful and relevant to individual participants, it would be extremely valuable to include a qualitative research study in any future research study, as what matters most to the individual is not always easily captured in quantitative feasibility research studies.  PwMS are a vulnerable group of individuals, who experience balance issues and are at high risk of falls, which would impact negatively on their quality of life and have implications for health and social care systems throughout the world.  The clinical significance of this study is that specialist teams can safely support and enable the practice of a balance exercise programme using this exoskeleton device.  We think that it is important that PwMS are supported and enabled to access and use equipment that can help and we think that future research needs to consider the availability and access to specialist teams in countries throughout the world, given that qualifications, experience and skills are highly variable. 

Conclusion 

This study demonstrates that it is feasible and safe to use the Rex Rehab exoskeleton device to assist with a balance rehabilitation exercise program for PwMS, provided that there is a specialist team in support with an advanced level of clinical knowledge and expertise.   

This study provides preliminary evidence, of measurable physical and psychological health benefits for some participants after only 4 treatment sessions.  These findings justify further research to gain insight into ‘dose’ response and treatment efficacy by refining the protocol to focus on those secondary outcome measures that showed evidence of improvement. In addition, it would be valuable to explore the experiences of trial participants in more depth via qualitative methodology. 

Acknowledgements 

We gratefully acknowledge the assistance provided by colleagues and students from the Schools of Engineering and Digital Arts and Psychology  at the University of  Kent .  We also gratefully acknowledge the support and assistance from Rex Bionics Ltd. PO Box 316-063. Auckland 0760, for the provision of the Rex exoskeleton device, training and device maintenance throughout the trial. 

The authors report that there are no competing interests to declare. 

REFERENCES 

1. Barker RA, Cicchetti F. Neuroanatomy and Neuroscience at a Glance. 4^th Ed. Chichester. Wiley-Blackwell (2012). 

2. Straudi S, Fanciullacci C, Martinuzzi C, Pavarelli C, Rossi B, Chisari C et al. The effects of robot-assisted gait training in progressive multiple sclerosis: A randomised controlled trial. Journal of Multiple Sclerosis 2015; 22;3: 373-384. https://doi.org/10.1177/1352458515620933  

3. Cameron MH, Lord S. Postural control in Multiple Sclerosis: Implications for fall prevention. Curr Neurol Neuroscience Rep 2010; 10 ;5:407-412 

https://doi.org/10.1007/s11910-010-0128-0  

4. Comber L, Sosnoff JJ, Galvin R, Coote S. Postural Control Deficits in people with Multiple Sclerosis: A systematic review and meta-analysis.  Gait and Posture 2018; 61:445-452. https://doi.org/10.1016/j.gaitpost.2018.02.018  

5. Stevens V, Goodman K, Rough K, Kraft GH. Gait impairment and optimizing mobility in multiple sclerosis. Physical Medicine and Rehabilitation Clinics 2013;1;24;4:573-592. https://doi.org/10.1016/j.pmr.2013.07.002  

6. Motl RW, Sandroff BM. Benefits of Exercise Training in MS. Curr Neurol Neuroscience Rep 2015; 15:62 https://doi.org/10.1007/s11910-015-0585-6  

7. Dalgas U. Rehabilitation and MS: Hot topics in the preservation of physical functioning. Journal of the Neurological Sciences 2011;311: S1 S43–S47. https://doi.org/10.1016/s0022-510x(11)70008-9  

8. Gunn H, Cameron M, Hoang P, Lord S, Shaw S, Freeman J. Relationship  

between Physiological and Perceived Fall Risk in People With Multiple Sclerosis:  

Implications for Assessment and Management. Archives of Physical Medicine and 

Rehabilitation 2018; 99:2022-2029. https://doi.org/10.1016/j.apmr.2018.03.019  

9. Bethoux F, Bennett S. Introduction: Enhancing mobility in Multiple Sclerosis. International Journal of MS care 2011;13;1: 1-3. https://doi.org/10.7224/1537-2073-13.1.1  

10. Birch N, Sakel M, Graham J, Priestley T, Heywood C, Gall A et al. Results of the First Interim Analysis of the Rapper II trial in patients with spinal cord injury: ambulation and functional exercise programs in the Rex powered walking aid.  Journal of NeuroEngineering and Rehabilitation 2017; 14;60: 2-10. https://doi.org/10.1186/s12984-017-0274-6  

11. Rex Bionics. (Internet) 2022. Available from https://www.rexbionics.com/product-information  (Accessed May 2022). 

12. Learmonth YC, Motl RW. Important considerations for feasibility studies in physical activity research involving persons with multiple sclerosis: a scoping systematic review and case study. Pilot and feasibility studies. 2018 ;4;1:1-1. https://doi.org/10.1186/s40814-017-0145-8  

13. Kozlowski AJ, Fabian M, Lad D, Delgado AD.  Feasibility and Safety of a Powered Exoskeleton for Assisted Walking for Persons With Multiple Sclerosis: A Single-Group Preliminary Study Archives of Physical Medicine and Rehabilitation 2017; 98:1300-1307. https://doi.org/10.1016/j.apmr.2017.02.010  

14. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M et al. Diagnostic criteria for MS: 2010 revisions to the “McDonald” criteria. Annals of Neurology2011; 69; 2:292-302. https://doi.org/10.1002/ana.22366  

15. Kurtzke JF. Rating neurological impairment in MS: An expanded disability status scale (EDSS). Neurology. 1983; 33;11: 1444-1452. https://doi.org/10.1212/wnl.33.11.1444  

16. Rex Bionics Ltd. Rex Bionics Training Manual. 2016. Volume 3.0. January.  

17. Gregson JM, Leathley M, Moore P, Sharma AK, Smith TL, Watkins CL.  Reliability of the Tone Assessment Scale and the Modified Ashworth Scale as Clinical Tools for Assessing Poststroke Spasticity.  Archives of Physical Medicine and Rehabilitation1999; 80: 1013 – 1016.  https://doi.org/10.1016/s0003-9993(99)90053-9  

18. White LJ Dressendorfer RH. Exercise and Multiple Sclerosis. Sports Med 2004;34(15):1077-100.  doi: 10.2165/00007256-200434150-00005. 

19. He Y, Eguren D, Luu, TP, Contreras-Vidal JL. Risk management and regulations for lower limb exoskeletons: a review. Medical Devices: Evidence and Research 2017;10: 89–107. https://doi.org/10.2147/mder.s107134  

20. Downs S. The Berg Balance Scale.  An Appraisal. Journal of Physiotherapy 2015; 61:46. https://doi.org/10.1016/j.jphys.2014.10.002  

21. Hill KD, Schwarz JA, Kalogeropolous AJ, Gibson SJ. Fear of Falling Revisited.  Archives of Physical Medicine and Rehabilitation1996;77: 1025-1029. https://doi.org/10.1016/s0003-9993(96)90063-5  

22. Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The Multiple Sclerosis Impact Scale (MSIS-29).  A new patient based outcome measure.  Brain 2001; 124: 962-973. https://doi.org/10.1093/brain/124.5.962  

23. Brooks R. EuroQol: the current state of play. Health Policy1996;37; 1:53-72. https://doi.org/10.1016/0168-8510(96)00822-6  

24. Jutai J, Day H. Measuring the Psychosocial Impact of an Assistive Devices: the PIADS.  Canadian Journal of Rehabilitation  1996; 9;2: 159-168. https://doi.org/10.1037/t45599-000  

25. Powell LE, Myers AM. The Activities-specific Balance Confidence (ABC) Scale.  Journal of Gerontology Medical Science 1995; 50;1:M28-34. https://doi.org/10.1093/gerona/50a.1.m28     

26. McGuigan C, Hutchinson M.  Confirming the validity and responsiveness of the Multiple Sclerosis Walking Scale-12 (MSWS-12). Neurology2004; 62; (15184625): 2103-2105. https://doi.org/10.1212/01.wnl.0000127604.84575.0d  

27. Ashford S, Turner-Stokes L, Siegert R, Slade M.  Initial psychometric evaluation of the Arm Activity Measure (ArmA): a measure of activity in the hemiparetic arm.  Clinical Rehabilitation 2013; 27; 8: 728-740. https://doi.org/10.1177/0269215512474942  

28. Johns MW.  A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale.  Sleep 1991;14:50-55. https://doi.org/10.1093/sleep/14.6.540  

29. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS) and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP).  American College of Rheumatology 2011; Arthritis Care and Research; 63; Number S11:  S240-S252.a  https://doi.org/10.1002/acr.20543 lly 

30. Physiopedia. Category Goniometry.  Available at: https://www.physio-pedia.com/Category:Goniometry    Accessed May 2022 

31. Firman G. Medical Research Council for Muscle Strength. 2009. Available at: https://medicalcriteria.com/web/neuromrc/  Accessed October 2022. 

32. Bowser B, O’Rourke S, Brown CN, White LW, Simpson KJ. Sit to stand  

      biomechanics of individuals with MS. Clinical Biomechanics 2015; 30; 8:788-794. https://doi.org/10.1016/j.clinbiomech.2015.06.012  

33. Keser I, Kirdi N, Meric A, Kurne AT, Karabudak R. Comparing routine  

neurorehabilitation program with trunk exercises based on Bobath concept in  

multiple sclerosis: Pilot study JRRD 2013;50;1:133-https://doi.org/10.1682/jrrd.2011.12.0231  

34. Cattaneo D, Jonsdottir J, Zocchi M and Regola A. Effects of balance exercises  

on people with multiple sclerosis: a pilot study. Clinical Rehabilitation 2007; 21: 771- 

781. https://doi.org/10.1177/0269215507077602  

35. Amatya B, Khan F, Galea M. Rehabilitation for people with MS: an overview of Cochrane systematic reviews (Protocol). Cochrane Database of systematic reviews 2019; 7 Art. No: CD012732.  https://doi.org/10.1002/14651858.CD012732.pub2 

36. Donoghue D. Physiotherapy Research and Older People (PROP) group, Stokes, EK. How much change is true change? The minimum detectable change of the Berg Balance Scale in elderly people. Journal Rehab Medicine 2009; 41;5:343-346. https://doi.org/10.2340/16501977-0337  

37. Thabane L, Ma J, Chu R, Cheng J, Ismaila, A, Rios, LP et al. A Tutorial on Pilot Studies: The What, Why and How. BMC Medical Research Methodology 2010; 10;1:1. https://doi.org/10.1186/1471-2288-10-1  

38. Hayes S, Kennedy C, Galvin R, Finlayson M, McGuigan C, Walsh CD et al.  Interventions for the prevention of falls in people with MS (Protocol). Cochrane database of systematic reviews. 2017;1; Art. No.: CD012475. https://doi.org/10.1002/14651858.cd012475  

39. Xiang X-N, Ding M-F, Zong H-Y, Liu Y, Cheng H, He C-Q et al. The safety and feasibility of a new rehabilitation robotic exoskeleton for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI): an observational study. Spinal Cord2020;58:787–794. https://doi.org/10.1038/s41393-020-0423-9  

40. Wang L, Zheng Y, Dang Y, Teng M, Zhang  X. Cheng Y. et al. Effects of Robot-assisted training on balance function in patients with Stroke: A Systematic Review and Metanalysis. J Rehabil Medicine 2021;53;4 https://doi.org/10.2340/16501977-2815  

41. Yoosefinejad AK, Motealleh A, Khademi S, Hosseini S.F.  Lower Endurance and Strength of Core Muscles in Patients with Multiple Sclerosis.  Int Journal of MS Care 2017;  19;2: 100-104. https://doi.org/10.7224/1537-2073.2015-064  

42. Comber L, Sosnoff JJ, Galvin R, Coote S. Postural Control Deficits in people with Multiple Sclerosis: A systematic review and meta-analysis.  Gait and Posture 2018; 61:445-452. https://doi.org/10.1016/j.gaitpost.2018.02.018  

43. Lee NG, You JSH, Yi CH, Jeon HS, Choi BS, Lee DR et al.  Best Core Stabilization for Anticipatory Postural Adjustment and Falls in Hemiparetic Stroke. Archives Physical Medicine Rehabilitation 2018; 99;11: 2168 – 2174. https://doi.org/10.1016/j.apmr.2018.01.027  

44. 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. European Journal of Physical and Rehabilitation Medicine 2019;55;2:199-208. https://doi.org/10.23736/s1973-9087.18.04778-0  

45. Gorman SL, Rivera M, McCarthy L. Reliability of the Function in sitting test. Rehab Research in Practice. 2014. 1-6.  

    http://dx.doi.org/10.1155/2014/593280

TABLES

Table 1: Adverse Events 

Table 2. Trial inclusion and exclusion criteria 

Table 3. Mobility, ataxia, medication and ongoing treatment.

Table 4: Participant demographics and clinical characteristics 

Table 5: Secondary outcome measure - Passive joint range of movement 

Table 6: Clinically significant change in individual Berg Balance Scale scores during the trial 

Table 7: Secondary outcome measures 

Table 8: Secondary outcome measure - Modified Ashworth Scale - Muscle spasticity 

(*) 3, 24 degrees of freedom due to missing data values 

(+) 3, 11 degrees of freedom due to missing data values 

Table 9: Secondary outcome measure - Psychosocial Impact Assistive Devices Scale (PIADS)