Comparison of sensory - motor and virtual reality interventions on indicators of gait, balance and quality of life of MS patients: a randomized trial

Comparison of sensory - motor and virtual reality interventions on indicators of gait, balance and quality of life of MS patients: a randomized trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparison of sensory - motor and virtual reality interventions on indicators of gait, balance and quality of life of MS patients: a randomized trial seyed hadi asghari, saeed Ilbeigi, Mohsen Mohammadnia Ahmadi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5192596/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Jun, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Introduction Multiple sclerosis (MS) is a neurological disorder that affects the central nervous system, causing inflammation and damage to the myelin sheath, leading to balance and gait impairments. Sensory-motor (SN) and virtual reality (VR) interventions have shown promise in addressing these balance issues by engaging all three components of the balance control systems. This study aimed to compare the effectiveness of SN and VR training on the functional status and quality of life of MS patients. Methods In this study, 36 MS patients receiving Rituximab therapy with an EDSS of 2 to 6 were randomly assigned to three groups: SN (n = 10), VR (n = 8) and a control group (n = 10). The SN and VR groups underwent 8 weeks of intervention, with 3 sessions per week, while the control group continued routine care. Assessments using Timed Up and Go (TUG), Timed 25-Foot Walk (T25FW), Multiple Sclerosis Quality of Life 54 Instrument (MSQOL54), and Pittsburgh Sleep Quality Index (PSQI) were conducted at baseline and after eight weeks. Results Considerable progress was made in all major and secondary variables after SN and VR training in comparison to the baseline settings. Furthermore, compared to the control group, the experimental groups showed a statistically significant improvement in both the primary and secondary outcomes. There were no significant differences in other variables between the SN and VR groups in the comparison of the experimental groups, with the exception of the PSQI, which showed significant changes in favor of the SN group. Conclusions The VR with a head-mounted display (HMD) serves as a motivational training tool, while SN training is an affordable and accessible technique. Both interventions can positively impact the functional status of MS patients by improving balance and gait through their task-oriented, dual-task, and multisensory nature. Biological sciences/Neuroscience Health sciences/Health care SN VR TUG T25FW MS Figures Figure 1 Figure 2 Introduction Multiple sclerosis (MS) is the primary cause of non-traumatic neurological dysfunction in young and middle-aged individuals. It is a degenerative inflammatory disease of the central nervous system (CNS) ( 1 ), which frequently affects women ( 2 ).This common and chronic neurological disorder is characterized by inflammatory demyelination, axonal damage and gray matter atrophy. Therefore, postural control abnormalities, abnormal gait, and cognitive impairment arise as a result of neuronal destruction in areas of the CNS relevant to motor and cognitive activities ( 3 ). Disturbance in balance is one of the common movement disorders of MS patients which limits daily activities and chores and has a detrimental impact on the patient's quality of life ( 4 ). Balance disorders are also thought to negatively affect walking performance so that most MS patients with gait disorders also report balance problems ( 5 ). Evaluation and treatment of balance and walking disorders in MS patients is particularly significant in the scientific community since balance and gait require integration of signals from visual, vestibular and proprioceptive sensory systems ( 6 ). The central integration of sensory afferents is disrupted in MS patients due to disorders in many CNS regions, including injury to the brain stem, spinal cord, and cerebellum, which slow down the body's sensory conduction, pyramidal, vestibular, and visual pathways ( 7 ). Therefore, the disturbance in the Central integration of sensory afferents affects the postural response in maintaining correct balance ( 8 ). Consequently, the central integration process allows for a unique response strategy for postural control during balance and gait ( 5 ). Most modulating treatments for MS patients use pharmacological strategies aimed at preventing relapse or reversing disability. However, these treatments are associated with side effects such as an increased risk of immune suppression. Therefore, other non-pharmacological interventions that have no known side effects may have additional benefits ( 9 ). In this regard, the World Health Organization 2020 guidelines have strongly recommended moderate or high intensity balance exercises to improve functional ability and prevent falls in people with chronic diseases such as MS ( 10 ). However, these interventions often lack optimal content. Optimal content in balance exercises refers to challenging of all the sensory, motor and cognitive components of the balance control system during balance intervention ( 11 ). Although, previous studies have introduced challenging balance exercises but they have emphasized only on the motor components (such as the center of body mass movement, and narrowing of the base of support) of the balance control system ( 12 ). Therefore, increase the training stimulus from other balance control systems (i.e., motor, sensory, and cognitive components) is necessary to achieve gradual improvement in other components of balance training. Sensory-motor exercises are a recent approach to balance training that emphasizes the integration of sensory (including vestibular, visual and somatosensory systems), motor (including limits of stability, anticipatory motor strategies, reactive motor strategies, and control of dynamics) and cognitive (including divided attention with additional motor or cognitive tasks such as dual-tasking) components of the balance control system ( 11 ). On the other hand, the repetitive and lengthy nature of traditional rehabilitation may reduce patients' long-term adherence to the rehabilitation program ( 13 ). Nowadays, unlike traditional methods, in order to enjoy the long-term rehabilitation process, exercise interventions can be performed through virtual reality (VR) applications ( 1 ). Virtual reality applications enable high-intensity, task-oriented multisensory feedback practice ,encouraging participants to engage in challenging tasks that integrate motor and cognitive demands ( 14 ). In addition, virtual reality interventions can enhance patients' sensory processing and integration systems and allows them to repeatedly: - exercise; - receive information feedback; - improve the motivation of training; and improve visual, auditory and tactile inputs ( 15 ). According to recent findings, sensory-motor exercises and virtual reality have been proposed as two models of balance training that employ different components of the balance control system in a different way ( 11 ). Although, In the field of SN exercises study by Callesen et al 2020, observed a significant improvement in the T25FW parameter in MS patients with EDSS 2 to 6.5 after ten weeks of balance and motor control training (twice a week) ( 16 ). Also, a study by molhemi et al 2021, has shown that 6 weeks of VR training significantly improved the TUG and 10 meters walking performance in MS patients with EDSS below 6 ( 13 ). However, so far, no study has compared two balance training models that emphasize the three components of the balance control system. Therefore, the main goal of the current study is to investigate the effectiveness of SN training compared to VR training on functional indicators of MS patients. Considering both SN and VR training programs were expected to be beneficial on the performance criteria of MS patients due to the sensory-oriented (multisensory) and integrated nature of the current exercise protocols. But the primary difficulty lies in determining which rehabilitation approach will be more effective on functional indicators and quality of life. Materials and methods Study design This research is an 8-week, single-blind, randomized experiment. Eligible MS patients were recruited in 3 phases: pre-test, intervention and post-test. The intervention phase included two sensory-motor exercises and virtual reality exercises for 8 weeks, three sessions per week which was carried out under the supervision of experts in neurology, sports biomechanics and exercise physiology at the institute of sports science and health of University of birjand. The MS patients in the control group received standard care during the intervention phase and were not permitted to engage in any physical activity. After familiarizing with the phases of the study, written informed consent was taken from the patients to enter the study. Moreover, the study was conducted in accordance with the Declaration of Helsinki. Ethics approval for the current research was also obtained by the Research Ethics Committee of Birjand University with code IR.BIRJAND.REC.1402.002. The present study has been registered with the trial ID 79224 in the Iranian Registry of Clinical Trials (IRCT) Center and is awaiting approval from this center. Also, this study is derived from an extensive research in MS patients. Earlier, other article taken from this comprehensive research (using the same exercise interventions and the same patients as in our study) titled "Effect of alpha lipoic acid supplement intake together with neuromuscular training on joints kinematics and muscles electrical activity involved at the Gait initiation in patients with Multiple sclerosis: A randomized control trial" in the IRCT Center registered and approved under the number of IRCT20190618043934N21(Trial registration number: IRCT20190618043934N21, Registration date: 2023-09-27). Participants The current study included MS patients who were treated with rituximab. As a result, patients sent to Razi Birjand Hospital were used to obtain homogenous patients (those receiving rituximab treatment). The sample size was computed using G.power version 3.1.9.7 with the following data: (α = 0.05; β-1 = 0.8; number of groups = 3; number of variables = 3; and average effect size of Kramer's V = 0.25) of 33 participants and 36 people with the option of dropping out. After reviewing the files of MS patients, 36 patients were identified who were treated with rituximab. Then, these patients were screened in terms of eligibility by a neurologist, so that 6 patients did not meet the inclusion criteria. Finally, 30 patients who matched the inclusion criteria were randomly allocated into three groups (using Randomizer Random Pick software by a person who was not involved in the evaluation of the variables and the implementation of the exercises): 1- SN training (n = 10); and 2- VR training (n = 10) 3- MS control (n = 10). Study inclusion criteria included: MS patients between 18 and 65 years; Relapsing-remitting MS patients treated with rituximab with high disease activity, patients with EDSS from 2 to 6 and Ability to walk without assistance and at least 100 meters. Study exclusion criteria are also included: Patients' personal unwillingness to continue the exercises, absence in more than 3 training sessions, Failure to answer the phone call to continue the treatment. Study procedures Following the division of the patients into experimental and control groups, the experimental groups were given a two-hour familiarization session in one day to familiarize them with the study procedures. Then, on two successive days between 4 and 8 PM, individuals in the SN and VR groups were directed to Institute of Sport Science and Health at University of Birjand for gait and dynamic balancing tests. In addition, patients were asked to complete questionnaires on their quality of life and sleep quality during the same session. Two days after measuring primary and secondary outcomes, SN and VR groups performed their respective exercises. After completing the relevant training protocols, 25-foot and TUG tests and quality of life and sleep quality questionnaires were reevaluated. The control group was not allowed to engage in any physical activity during the trial time, but were encouraged to conduct SN and VR activities after the study was completed. Study procedures are shown in Fig. 1 . Outcomes The study employed a single-blind design, where the examiner assessing the outcomes was unaware of the group assignments (experimental or control). To ensure consistency in the measurements, all outcomes were evaluated between 4 and 8 pm for both the experimental and control groups T25FW In this test, the individual walked 7.5 meters in a straight line without assistance in the shortest amount of time possible. T25FW is a reliable tool (ICC = 0.99) for measuring MS patients' walking speed ( 17 ). This test was repeated twice, and the walking speed was calculated as the average of the two tests ( 18 ). During the test, the test taker remained close the patient to avoid falling or any other incident. TUG The TUG test was designed to assess balance and capability for dynamic mobility. A stopwatch was used in this test to measure the time it took the subject to stand up from the armchair and travel a distance of 3 meters as quickly as possible, then turn around and seat back in the chair and lean back. The examiner remains near the patient to keep them from falling ( 19 ). MSQOL54 The 54-item quality of life questionnaire for MS patients was used to evaluate the quality of life of these patients. The MSQoL-54 questionnaire is a health-related self-assessment tool with two components: physical health and mental health scores. The physical health score is obtained from eight subscales of physical function, health perceptions, energy/fatigue, Role limitations - physical, pain, sexual function, social function and health distress. Meanwhile, the mental health score is obtained from five subscales of Health distress, overall quality of life, Emotional well-being, Role limitations - emotional and Cognitive function. Composite scores were calculated by converting item scores to a scale of zero to 100 where zero indicates the worst health condition and 100 indicates the best health condition ( 20 ). Also, the sum of two subscale scores of mental health and physical health was used to calculate the overall score of MSQoL-54. PSQI The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of MS patients. PSQI consists of 9 items that measure seven different aspects including sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disorders, use of sleeping pills and daytime dysfunction. The PSQI score ranges from 0 to 21, with higher scores indicating lower sleep quality. In general, a PSQI score more than 5 indicates poor quality sleep ( 21 ). Experimental interventions Each training session for the SN and VR groups lasted between 30 and 60 minutes, three days per week and for 8 consecutive weeks. In the SN group, several exercise patterns were considered for each exercise station so that the complexity of the exercises increased according to the progress of the patient. For the VR group, the complexity of the games was applied by increasing the speed of the games in accordance with the progress of the patient. Also, eye movements (in Table 1 ) were also designed for both exercise groups, which the patients voluntarily performed during the rest time between exercise stations ( 22 ). During the trial period, the patients in the exercise groups were prohibited from performing any other physical rehabilitation activities. In addition, during the intervention period, the patients took their medicines according to the doctor's orders. Finally, training sessions were conducted in groups of two to three people, and the progress observed in each training session was recorded separately for each patient. Table 1 Eye exercises Type of exercise Description Saccades Fast eye movement between 2 fixed objects horizontally, vertically and diagonally Smooth pursuit Eye tracking of a moving object horizontally, vertically and diagonally Vestibular ocular reflex Eye focus on a fixed object while turning the head side to side, up and down. SN intervention The sensorimotor training was a modified training protocol based on previous studies ( 5 , 23 ), in which the participants performed 18 training stations in a circular manner in each session. The exercises were divided into static and dynamic categories. The static part included 12 stations and the dynamic part (in the form of walking) also included 6 training stations. Static exercises including external destabilization and self-destabilization patterns which were performed on the floor surface and cushion foam in three conditions: eyes open, closed and with a helmet. During external stabilization exercises, the practitioner pushed (shifted) the patient's pelvis forward and sideways, in this situation the patient had to maintain his balance quickly. In self-destabilizing activities, patients shifted their weight from one leg to the other to deliberately modify their center of gravity. During the walking exercises, the patient was also given cognitive activities such as counting numbers, subtracting numbers, and remembering certain human or animal names. Each training session began with the patients warming up for 10 minutes. The final five minutes of each training session were spent to cooling down. The duration of each station from the first to the sixth week was 30, 35, 40, 45, 50, 55 seconds, and 60 seconds in the seventh and eighth weeks. The work-to-rest ratio was likewise regarded similar from the first to the eighth week. The sensorimotor training protocol is detailed in Table 2 . Table 2 Sensorimotor intervention Type of exercise surface eye condition static/dynamic ED open eyes ground static ED close eyes ground static Walk1 open eyes ground dynamic ED helmet ground static SD open eyes ground static walk2 open eyes ground dynamic SD close eyes ground static SD helmet ground static walk3 open eyes ground dynamic ED open eyes foam cushion static ED close eyes foam cushion static Walk4 open eyes ground dynamic ED helmet foam cushion static SD open eyes foam cushion static Walk5 open eyes ground dynamic SD close eyes foam cushion static SD helmet foam cushion static Walk6 open eyes foam cushion dynamic ED : External destabilization, SD : Self destabilization, walk1 : Heel-toe walking with head turning, walk2 : Throw the ball in different directions with visual tracking of the ball while walking. Walk3 : Walking on command (stop - move - turn in - turn out), walk4 : Walking between conical obstacles, walk5 : Zigzag walking between obstacles, walk6 : Walking on foam cushion. VR intervention The current study's VR methodology was carried out using the RAGU system. The RAGU system requires the Microsoft Kinect for image analysis and the Oculus VR glasses for 3D imaging. This system included a motion sensor to regulate the patient's motions during picture analysis (Microsoft KinectV2). The patient performed exercises in the virtual environment created with a HMD (head mounted display) that had 3D images (Oculus VR glasses). The sound system and motion sensors contributed to a stronger sense of reality. VR training in the current study was also a modified exercise protocol which was formed based on previous research ( 24 , 25 ). Virtual reality games included two components: dynamic and static. Dynamic games included one pattern or more than one pattern from the 12 gaiting patterns presented in Table 3 . The primary priority for the dynamic component of VR was to select games that recruited 12 different gaiting patterns during a VR training session. The virtual games considered for the dynamic component included Plank rich, Pistol whip, Boxing, walking dead, Temple run. Static VR games were also performed in such a way that 6 static movement patterns were recruited during a VR training session. This component also included Beat saber, Power beat saber, OHSHIP games. The duration of each VR station and rest between stations was equivalent but different from the SN protocol. However, the total duration of a training session was similar to the SN protocol and was 18, 21, 24, 27, 30, 33 minutes for weeks 1 to 6 and 36 minutes for weeks 7 and 8, respectively. All virtual reality games were played in a 10 x 10 room. A comprehensive description related to dynamic and static movement patterns is shown in Table 3 . Table 3 Virtual reality intervention movement patterns explanation Walking usual walking Simple walking on a walking path without the marker appearing avoid obstacles Avoiding obstacles or signs by lifting the leg When suddenly appear in a person's walking path acceleration/deceleration Stopping suddenly behind signs appearing while walking and starting quickly as soon as the signs disappear. Symmetrical Walking precisely on the feet marks that are arranged in a special order along the walking path Asymmetrical Walking precisely on the feet marks that are not arranged in a particular order along the walking path narrow path Walk in a walking path with less length and width than normal incremental speed setting A sign appearing one meter in front of the person while walking and touching it before turning off Slalom Walking around moving obstacles that approach the person Tandem Walking heel-toe 90-degree turn The appearance of a half-turn sign to the person while walking and a quick 90-degree turn to the starting point 180 degree turn The appearance of a half-turn sign to the person while walking and a quick 180 degree turn to the starting point Multi/dual task Performing two virtual tasks (auditory or cognitive tasks or two walking tasks) while walking Static Walking in place Walking in place in different directions Reaching virtual objects the appearance of virtual objects on both sides of the person and touching them with hands Stepping on virtual objects Lifting the healthy feet to avoid hitting virtual obstacles (e.g. bananas on the floor) and then returning to the starting position shifting weight steer an avatar in different directions to collect points or coins and avoid virtual collisions Rising on toes Steering an avatar up and down and avoiding obstacles by rising on the toes and returning to its original position (i.e. shifting body weight in anterior-posterior directions) Squats Avoid hitting virtual obstacles by sitting down and then standing up and vice versa Statically analysis Statistical analysis of the data was done using IBM SPSS Statistics 27 software. The normality of data distribution was evaluated through the Kolmogorov–Smirnov/Shapiro–Wilk tests or standard graphs (box plots and histograms). Descriptive analysis was expressed by giving mean and standard deviation for continuous variables and numbers for categorical variable (gender). The baseline comparisons of basic demographic and clinical characteristics among groups were performed using one-way ANOVA. Paired t-tests were used to discover the effect of time or changes from baseline to 8 weeks. Comparison between groups in outcome measures were performed through the general linear model approach (multivariate analysis of variance or multivariate ANOVA) using Bonferroni correction for post hoc comparisons. The effect size within groups (within groups' pre-post differences) was evaluated based on Cohen's d standards. Effect size results were interpreted as small (≥ 0.2), medium (≥ 0.5), or large (≥ 0.8). Also, Partial Eta squared (η2) was used to evaluate of the intergroup ES where η² ≥ 0.01. η² ≥ 0.06 and η² ≥ 0.14 are considered as small, medium and higher ESs, respectively. The significance level was set at p < 0.05. In addition, the figures were designed in GraphPad Prism software (version Graphpad Prism 8.4.3). Results In this study, 36 patients treated with rituximab participated which 6 patients did not meet the inclusion criteria and two patients from the VR group withdrew from the VR project due to a nervous attack before the start of this intervention and difficulty in transferring to the study location. Finally, 28 patients remained for the final evaluation. Table 4 presents demographic information separately for three categories. According to the results of the Shapiro Wilk and Levene test, there was no significant difference between the research groups in terms of age, height, weight, BMI and EDSS in basic conditions. Table 4 Clinical and demographic characteristics of the groups at baseline Variables VR (n = 8) M ± SD SN (n = 10) M ± SD CON(n = 10) M ± SD P Age (y) 36.25 ± 9.98 40.00 ± 6.63 34.10 ± 4.72 0.20 Gender F/M 3/5 1/9 2/8 - Weight (kg) 73.50 ± 19.89 62.80 ± 16.470 66.10 ± 12.81 0.39 Height (m) 1.67 ± 0.08 1.58 ± 0.06 1.673 ± 0.06 0.01 BMI (kg/m 2 ) 26.12 ± 6.98 24.89 ± 6.27 23.48 ± 3.65 0.62 EDSS 4.56 ± 0 .72 4.9500 ± 0.72 4.40 ± .45 0.16 MS diagnosis duration (y) 10.37 ± 2.61 11.5 + 3.95 10.12 ± 0.28 0.57 TUG (s) 13.66 ± 8.59 14.97 ± 10.41 10.79 ± 2.021 0.48 T25FW (m/s) 10.24 ± 7.87 12.94 ± 8.24 7.12 ± 1.53 0.15 MSQOL54-T 78.98 ± 28.11 72.61 ± 24.13 109.55 ± 30.32 0.02 MSQOL54-P 41.85 ± 12.83 35.39 ± 12.41 61.99 ± 17.82 0.001 MSQOL54-M 47.37 ± 16.32 37.23 ± 12.47 47.87 ± 14.28 0.20 PSQI 5.62 ± 2.92 8.60 ± 3.30 6.30 ± 2.71 0.10 VR : Virtual reality group; SN : Sensory motor group; CON : Control group y: Year; F/M : Female/Male; Kg : Kilogram; m : Meter; BMI : Body mass index; kg/m 2 : Kilogram / Meter 2 S : Second; TUG : Timed Up and Go; T25FW : Timed 25-Foot Walk ; MSQOL54 : Multiple Sclerosis Quality of Life − 54 Instrument ; MSQOL54-T : Multiple Sclerosis Quality of Life − 54 Instrument Total score: MSQOL54-P : Physical Health component score MSQOL54; MSQOL54-M : Mental Health component score MSQOL54; PSQI : Pittsburgh Sleep Quality Index; M ± SD : mean ± standard deviation; Significant data are set at p < 0.05. Result outcomes Intra-group and inter-group changes of performance indicators are shown in Table 5 and Fig. 2 . Within-group changes showed that both SN and VR interventions showed significant improvement (P < 0.05) in primary (T25FW, TUG) and secondary (MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQI) outcomes compared to baseline conditions. Whereas, the control group only showed significant improvements (P < 0.05) in secondary outcomes (MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQI) compared to baseline conditions. Table 5 intra and inter group results of primary and secondary outcomes variables Groups Pre M ± SD Post M ± SD Δ M ± SD Intragroup P intragroup ES η 2 TUG (S) VR SN CON 13.66 ± 8.59 14.97 ± 10.41 10.79 ± 2.02 8.98 ± 7.07 9.46 ± 6.88 9.96 ± 1.936 − 4.67 ± 2.58–5.51 ± 4.78 − 0.83 ± 1.20 0.005 0.001 0.05 -0.54 -0.52 -0.41 0.315 T25FW (m/s) VR SN CON 10.24 ± 7.87 12.94 ± 8.24 7.12 ± 1.53 7.06 ± 6.28 8.67 ± 6.28 6.96 ± 1.27 − 3.18 ± 1.77 − 4.27 ± 3.17 -0.15 ± 0.88 0.001 < 0.001 0 . 5 -0.40 -0.51 -0.10 0.429 MSQOL54-T VR SN CON 87.98 ± 28.11 72.61 ± 24.13 109.55 ± 30.32 144.36 ± 19.46 143.63 ± 20.38 128.51 ± 21.28 56.37 ± 20.55 71.02 ± 26.99 18.96 ± 19.61 < 0.001 < 0.001 0.01 2.00 2.94 0.62 0.524 MSQOL54-P VR SN CON 41.85 ± 12.83 35.39 ± 12.41 61.99 ± 17.82 67.86 ± 11.02 70.40 ± 9.57 70.78 ± 11.80 26.00 ± 9.81 35.00 ± 10.05 8.79 ± 9.96 < 0.001 < 0.001 0.02 2.02 2.82 0.49 0.588 MSQOL54-M VR SN CON 47.37 ± 16.32 37.23 ± 12.47 47.87 ± 14.28 78.74 ± 12.66 73.24 ± 14.55 57.67 ± 11.50 31.36 ± 13.22 36.00 ± 19.09 9.80 ± 10.35 < 0.001 < 0.001 0.01 1.92 2.88 0.68 0.412 PSQI VR SN CON 5.62 ± 2.92 8.60 ± 3.30 6.30 ± 2.71 3.62 ± 3.92 3.10 ± 2.68 4.70 ± 1.70 − 2.00 ± 2.32 -5.50 ± 3.34 − 1.60 ± 1.77 < 0.001 < 0.001 0.01 -0.68 -1.66 -0.59 0.350 VR : Virtual reality group; SN : Sensory motor group; CON : Control group Y : Year; Δ : Changes ; η 2 Partial Eta squared; S : Second; TUG : Timed Up and Go; T25FW : Timed 25-Foot Walk ; ; MSQOL54 : Multiple Sclerosis Quality of Life − 54 Instrument ; MSQOL54-T : Multiple Sclerosis Quality of Life − 54 Instrument Total score: MSQOL54-P : Physical Health component score MSQOL54; MSQOL54-M : Mental Health component score MSQOL54; PSQI : Pittsburgh Sleep Quality Index; ES : Effect size M ± SD : mean ± standard deviation; Significant data are set at p < 0.05; Inter-group changes also shown in Table 5 and Fig. 2 . The SN and VR interventions showed significant superiority (P 0.05) to each other in functional indices except PSQI (significant improvement in favor of the SN group) (P < 0.05). However, SN intervention showed a higher ES compared to VR in T25FW, MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQ T25FW and VR intervention also showed a higher ES in TUG than SN. Discussion The results of the present study showed that both SN and VR interventions significantly improved performance indicators compared to the control group. However, the PSQI showed a significant improvement only in the SN group compared to VR., while no significant difference was found in other measures between SN and VR groups. In terms of effect size, SN intervention generally reported higher values, except for the TUG index where VR showed a higher effect size., In other performance indicators SN intervention reported a higher effect size. T25FW The significant improvement in walking speed (T25FW) after the SN intervention can be attributed to the inclusion of walking patterns in this intervention, which aligns with the principle of exercise specificity in creating functional adaptations ( 26 ). Most of the SN intervention was dedicated to external destabilizing and self-destabilizing exercises, which probably affected the retraining of impaired feedback and feedforward mechanisms of gait control, and may be justified by the improvement of walking speed through these static exercise patterns. This suggests that static exercises can play a role in improving walking speed. On the other hand, stimulating the proprioceptive inputs by performing exercises on the foam has improved the efficiency of the feedback and forward control of walking and plays an important role in improving walking speed ( 27 ). The current study demonstrates that sensory-motor interventions significantly enhance the performance of the 25-foot walk and exhibit a high effect size. Diverging from previous studies that mainly concentrated on P values, this study underscores the importance of effect size and advocates for its prioritization as an important statistical measure in future research. Although, the present investigation revealed a significant impact of SN exercises on enhancing T25FW efficacy, other studies have documented contradictory outcomes regarding T25FW proficiency following SN protocol ( 16 , 26 , 28 , 29 ). Although balance control systems were comprehensively involved in these studies, but the positive effect of SN intervention on walking performance may be largely dependent on the degree of disability of MS patients. Probably, the high EDSS degree creates a potential stimulus to improve T25FW performance after SN exercises ( 16 , 28 ). Meanwhile, MS people with low EDSS may not benefit from the benefits of SN interventions on improving T25FW performance ( 26 , 29 ). Setting aside previous studies that were all focused on P-values, this study revealed a high ES from SN intervention on improving the T25FW and supports prioritizing it as an important statistical measure in future research. In general, the improvement of walking speed caused by SN intervention may be the result of improving the integration of sensory and motor inputs, and these effects are likely to be greater in MS patients with a high degree of disability. The improvement in walking speed after VR can be attributed to the reduced cognitive load of VR-induced gait impairment. Because the three-dimensional and panoramic view of VR with HMD causes the patient to be immersed in the virtual environment and this factor facilitates distraction from the real environment ( 30 ). As a result, the distraction caused by VR reduces the cognitive load of walking disorder and provides a rich environment for repetitive practice of walking tasks ( 31 ). Repeated execution of walking tasks in the form of virtual reality strengthens the mirror neuron system and causes recall stored motor plans and thus improves walking performance ( 32 ). The current study has reported a high ES (-0.40) and a significant impact of VR on the T25FW task. In the same context, some studies have also reported significant effects and high ES of VR on the walking speed of MS patients ( 13 , 31 ). The use of walking patterns in combination with VR is likely to justify the high ES and significant outcomes of these interventions ( 13 , 31 ). While, performing VR interventions in a static state has shown a low ES and an insignificant effect on improving walking speed ( 25 , 33 ). TUG The significant reduction in TUG time after SN intervention can be justified based on the approach of retraining the disrupted sensory systems ( 34 ). Since MS patients face abnormal fluctuations while standing quietly with their eyes open and these fluctuations intensify when their eyes are closed, especially on the foam, therefore, self-destabilizing and external destabilizing exercises with open and closed eyes on the surface the ground and cushion foam provide a wonderful stimulus for retraining patients' depth and visual sensory inputs that are naturally impaired ( 34 ). Also, 40 to 70% of MS patients have cognitive disorders, which impairs the speed of information processing and maintaining balance in challenging situations such as dual tasks. Therefore, in the present study, the use of cognitive-motor tasks provide the opportunity to retrain the cognitive components of the balance control system ( 35 ). Also, performing walking exercises with vertical and horizontal rotations can help to retrain the impaired vestibular system. Retraining the vestibular system is likely to develop vestibule-ocular reflexes that are responsible for stabilizing and changing gaze direction and maintaining dynamic balance ( 36 ). Current study demonstrated significant improvement and high ES in TUG performance after SN intervention. In most studies, lack of improvement in TUG performance after SN intervention has been shown using p-values, without discussing effect size ( 4 , 37 ). Although, these interventions extensively engaged the sensory, motor, and cognitive aspects of balance, the absence of an intensive, multimodal SN intervention(applied statically) could explain the lack of notable progress in the TUG results ( 4 , 37 ). However, the multisensory nature of the SMIT intervention and the high level of EDSS in MS patients in Pavlikova et al.'s (2020) study did not lead to a significant improvement in TUG ( 38 ). It is possible that the patients initially chosen for this study had better outcomes in the TUG test and required less intervention with SMIT ( 38 ). Overall, the retraining of impaired sensory systems through the integration of somatosensory, visual, and vestibular inputs may be the most important mechanism of TUG improvement after SN intervention. The improvement in TUG performance resulting from the VR intervention can be attributed to the cognitive-motor nature of VR. The cognitive-motor nature of VR allows the patient to develop fall prevention strategies such as attention, concentration, motor planning, and problem solving, thereby improving balance ( 1 ). VR-induced repetitive feedback increases patient motor knowledge related to TUG performance ( 32 ). Also, VR provides immediate feedback on performance, which helps to learn new motor strategies and possibly improve TUG performance ( 32 ). Our study demonstrated a high ES (-0.54) and statistical significance of VR intervention on TUG performance. In the same context, other VR interventions performed in both static and dynamic modes also reported a significant improvement in TUG performance after VR intervention ( 13 , 32 , 33 ). Although, these studies reached statistical significance, they differed in terms of ES. A low ES (Cohen’s d = -0.35) of VR on TUG performance was obtained from interventions performed with the Wii Fit Balance Board (in stationary mode) ( 33 ), while VR interventions combined with a treadmill ( 32 ) or floor walking ( 13 ) reported medium (Cohen’s d = -0.60) and high ES (Cohen’s d = -1.58), respectively. T25FW, TUG (SN vs VR) Although, SN and VR interventions significantly improved T25FW and TUG compared to the control group, however, no significant difference was observed between the two training models. Both SN and VR interventions seem to affect walking speed and balance through similar mechanisms but in different ways. Improving the integration of sensory inputs is one of the potential mechanisms for improving walking and balance after these interventions ( 34 ). Different implementation situations (static, dynamic) with eyes open and closed on ground and foam surfaces along with vertical and horizontal rotations in the head have provided the necessary stimulation to improve integration of sensory input through SN training ( 34 , 36 ). The inconsistency (mismatched) of the visual data obtained from the VR environment with the somatosensory and vestibular sensory data makes the patient have to better integrate the somatosensory and vestibular sensory systems ( 1 ). Also, both exercise interventions had a task-oriented nature, which means that both of them used exercise patterns that specifically targeted balance and walking ( 16 ). One of the important mechanisms of improving balance and walking is neural plasticity, which is probably improved due to the task-oriented nature of SN and VR interventions ( 25 , 39 ). Finally, both training interventions included dual tasks. The inclusion of cognitive-motor dual tasks simulates the real conditions of balance and walking in daily life and thus seeks to improve these measurements ( 3 ). MSQOL54-M The MSQOL54-M score showed a significant increase after SN and VR interventions. The improvement of the MSQOL54-M score after SN exercises can be related to the involvement of the cognitive component of the balance control system and the inclusion of cognitive-motor dual tasks. In this context, interventions that have reported significant improvements in MSQOL54-M scores have also highlighted the crucial role of cognitive elements in balance control and the execution of dual cognitive-motor tasks ( 26 , 28 ). Conversely, studies that did not report significant improvement in MSQOL54-M scores did not emphasize these cognitive and dual-task components ( 5 , 27 ). Although our study demonstrated a very high ES and significant of SN interventions on MSQOL54-M scores, other studies merely focused on p-values rather than ES. The VR intervention in our study demonstrated a very high ES on MSQOL54-M. Although other studies have also shown a significant impact of VR interventions on MSQOL54-M ( 25 , 31 ), our study reported a much higher ES on MSQOL54-M compared to these studies ( 25 , 31 ). The assumption is that VR systems based on HMDs (like our study) likely impose a higher cognitive load (due to increased immersion and more natural interaction) on patients compared to VR systems without the use of HMDs ( 25 , 31 ). This factor may explain the larger ES observed in our study compared to these other studies. MSQOL54-P both SN and VR interventions significantly improved the MSQOL54-P score. Challenging the different components of the balance control system through SN exercises may be an effective factor in the significant improvement of the MSQOL54-P score ( 22 , 27 , 28 ). While our study showed very high ES (2.82) for SN on MSQOL54-P score, other studies related to SN interventions have only reported MSQOL54-P score based on p-values. All these studies, which had a similar nature to our SN protocol, did not consistently show significant improvements in MSQOL54-P scores. Probably, the Less frequency of training sessions in some of studies did not show the effect of SN exercises on MSQOL54-P scores ( 5 , 26 ), Meanwhile, Studies with high-frequency training sessions have shown a significant effect of SN training on the MSQOL54-P score ( 22 , 27 , 28 ). The present study demonstrated a significant improvement in the MSQOL54-P score with a very high ES after VR intervention. Although Munari et al.'s 2020 study showed a medium ES (0.59) and Khalil et al.'s 2018 study also developed the MSQOL54-P score with a high ES (0.88) ( 25 , 31 ), the present study demonstrated a much higher ES (2.02) compared to these studies. This higher ES in the MSQOL54-P score can be attributed to higher-frequency exercise sessions, the use of VR models with HMD and higher disability level of patients in our study. MSQOL54-M, MSQOL54-P (SN vs VR) The lack of significant difference in MSQOL54-M score between SN and VR groups can be attributed to the cognitive-motor nature of these two training protocols because both training interventions emphasize the cognitive components of the balance control system in a different way ( 32 , 35 ). Finally, the lack of significant differences in MSQOL54-P scores between SN and VR groups can be attributed to the task-oriented nature of both exercise protocols, as both exercise interventions included exercises or games that specifically focused on balance and walking ( 25 , 39 ), which led to the same perception of physical health after two training interventions. Limitations The current study's limitations include the utilization of MS patients treated with rituximab (a particular treatment), which limits access to additional people. Also, the distribution of patients in the intervention groups was not equal in terms of gender, which may be the reason for the larger effect size of SN intervention compared to VR on most performance indicators. The lack of a follow-up period is another limitation that may affect the durability of the effect of sensory interventions on performance measures. The majority of the patients in this trial were women with relapsing-remitting MS, which may make it difficult to Generalisability the findings to other MS groups. Application recommendations The T25FW test is an important criterion for evaluating walking disorders in clinical settings, but it only evaluates walking speed; future studies should focus on walking subtasks such as gait initiation, gait termination, and spatiotemporal parameters. Furthermore, neuroimaging methods should be used to reveal the effect of SN and VR interventions on neural plasticity in the future. Also, it is recommended to evaluate the actual performance of walking and balance in daily life through the evaluation of motor-cognitive dual tasks or cognitive evaluations. Finally, the use of sensory integration tests will be important in determining the role of sensory interactions in balance control. Conclusion The present study showed significant improvement in walking speed, dynamic balance, quality of life and sleep quality of MS patients after 8 weeks of SN and VR interventions. Experimental interventions significantly increased performance measures compared to the control group. With the exception of sleep quality, which reported a significant improvement in favor of the SN group, there was no significant difference in other performance indicators between the two intervention groups. Therefore, SN training as a cost-effective and highly accessible training approach and virtual reality with HMD as a motivational training approach can affect the functional status of MS patients. Probably, the task-oriented, dual-task and multi-sensory aspects of both interventions most likely enhanced balance and walking in these individuals by improving anticipatory mechanisms and postural control . Declarations Data availability Data is provided within the supplementary information files. Conflict of interest The authors declare no competing interests. Acknowledgements We are grateful for the efforts of Razi Birjand Hospital and Sports Science and Health Research Institute of Birjand University in supporting this research project. Funding None. Author Contribution H.A ,S.I and M.M.M conceived and designed research. H.A, M.M.A, and M.Y conducted the experiment. H.A, M.M.A, and M.Y analyzed data. H.A, and S.I wrote the manuscript. All authors read and approved the manuscript. 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Ther. 91 (8), 1166–1183 (2011). Sokhangu, M. K., Rahnama, N., Etemadifar, M., Rafeii, M. & Saberi, A. Effect of neuromuscular exercises on strength, proprioceptive receptors, and balance in females with multiple sclerosis. Int. J. Prev. Med. ; 12 . (2021). Geerse, D. J., Roerdink, M., Marinus, J. & van Hilten, J. J. Assessing walking adaptability in stroke patients. Disabil. Rehabil. 43 (22), 3242–3250 (2021). Khalil, H. et al. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): a feasibility study. NeuroRehabilitation . 43 (4), 473–482 (2018). Kasser, S. L., Jacobs, J. V., Ford, M. & Tourville, T. W. Effects of balance-specific exercises on balance, physical activity and quality of life in adults with multiple sclerosis: a pilot investigation. Disabil. Rehabil. 37 (24), 2238–2249 (2015). Gandolfi, M. et al. Sensory integration balance training in patients with multiple sclerosis: a randomized, controlled trial. Multiple Scler. J. 21 (11), 1453–1462 (2015). Hebert, J. R., Corboy, J. R., Vollmer, T., Forster, J. E. & Schenkman, M. Efficacy of balance and eye-movement exercises for persons with multiple sclerosis (BEEMS). Neurology . 90 (9), e797–e807 (2018). Tramontano, M. 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. Restor. Neurol. Neurosci. 36 (6), 709–718 (2018). Winter, C. et al. Immersive virtual reality during gait rehabilitation increases walking speed and motivation: a usability evaluation with healthy participants and patients with multiple sclerosis and stroke. J. Neuroeng. Rehabil. 18 (1), 68 (2021). Munari, D. et al. Effects of robot-assisted gait training combined with virtual reality on motor and cognitive functions in patients with multiple sclerosis: A pilot, single-blind, randomized controlled trial. Restor. Neurol. Neurosci. 38 (2), 151–164 (2020). Calabrò, R. S. et al. Robotic gait training in multiple sclerosis rehabilitation: Can virtual reality make the difference? Findings from a randomized controlled trial. J. Neurol. Sci. 377 , 25–30 (2017). Nilsagård, Y. E., Forsberg, A. S. & von Koch, L. Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study. Mult Scler. 19 (2), 209–216 (2013). Cattaneo, D., Jonsdottir, J., Regola, A. & Carabalona, R. Stabilometric assessment of context dependent balance recovery in persons with multiple sclerosis: a randomized controlled study. J. Neuroeng. Rehabil . 11 , 100 (2014). Galperin, I. et al. Treadmill training with virtual reality to enhance gait and cognitive function among people with multiple sclerosis: a randomized controlled trial. J. Neurol. 270 (3), 1388–1401 (2023). Carpinella, I. et al. Walking With Horizontal Head Turns Is Impaired in Persons With Early-Stage Multiple Sclerosis Showing Normal Locomotion. Front. Neurol. 12 , 821640 (2021). Cattaneo, D. et al. Falls prevention and balance rehabilitation in multiple sclerosis: a bi-centre randomised controlled trial. Disabil. Rehabil . 40 (5), 522–526 (2018). Pavlikova, M. 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. Mult Scler. Relat. Disord . 40 , 101974 (2020). Callesen, J., Cattaneo, D., Brincks, J. & Dalgas, U. How does strength training and balance training affect gait and fatigue in patients with Multiple Sclerosis? A study protocol of a randomized controlled trial. NeuroRehabilitation . 42 (2), 131–142 (2018). Additional Declarations No competing interests reported. Supplementary Files Rawdata.xlsx Cite Share Download PDF Status: Published Journal Publication published 26 Jun, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 03 Feb, 2025 Reviews received at journal 14 Jan, 2025 Reviewers agreed at journal 05 Jan, 2025 Reviewers agreed at journal 05 Dec, 2024 Reviews received at journal 19 Nov, 2024 Reviewers agreed at journal 13 Nov, 2024 Reviewers invited by journal 11 Nov, 2024 Editor assigned by journal 11 Nov, 2024 Editor invited by journal 04 Nov, 2024 Submission checks completed at journal 02 Nov, 2024 First submitted to journal 02 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5192596","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":377609532,"identity":"af2e6afc-202f-4ddd-bbbf-7aad77c2d4cd","order_by":0,"name":"seyed hadi asghari","email":"","orcid":"","institution":"University of Birjand","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"seyed","middleName":"hadi","lastName":"asghari","suffix":""},{"id":377609533,"identity":"656a7a3d-c7ff-4a83-80e4-4c24f98eccdb","order_by":1,"name":"saeed Ilbeigi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYLACHgYJGQP2BiDLwIJ4LTwGPAdAWiSI1sLAYyCRAGISoUW+/fDBB28YLHjMJZ9f3fCjQIKBv707Aa8WgzNpyYZzgA6znJ1TdrMH6DCJM2c34NfCkGMmDfbL7Zy0G0DnAb2Ti1+LfP/777/BWm6eSbv5hxgtDDdy2JjBWm6wH7tNlC0GN54ZS84xAPqlJ4fttgyQQdAv8v3JDz+8qaiTM2c//uzmmz82cvztvQQcBrELRPBASCKUwwH7A1JUj4JRMApGwQgCAOWzQDFgjIddAAAAAElFTkSuQmCC","orcid":"","institution":"University of Birjand","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"saeed","middleName":"","lastName":"Ilbeigi","suffix":""},{"id":377609534,"identity":"1653f8ec-f9a8-406d-8721-94ce5352573b","order_by":2,"name":"Mohsen Mohammadnia Ahmadi","email":"","orcid":"","institution":"University of Birjand","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohsen","middleName":"Mohammadnia","lastName":"Ahmadi","suffix":""},{"id":377609535,"identity":"6be7f552-d77e-442c-9bcf-02271b04f0bd","order_by":3,"name":"Mohammad Yousefi","email":"","orcid":"","institution":"University of Birjand","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Yousefi","suffix":""},{"id":377609536,"identity":"a09955d1-102c-490d-a661-3f88d9930fe1","order_by":4,"name":"Mohammad Mousavi Mirzaei","email":"","orcid":"","institution":"Birjand University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Mousavi","lastName":"Mirzaei","suffix":""}],"badges":[],"createdAt":"2024-10-02 11:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5192596/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5192596/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-05048-3","type":"published","date":"2025-06-26T15:57:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70296962,"identity":"44ce2926-535b-4775-a5b6-78113d62cace","added_by":"auto","created_at":"2024-12-02 00:43:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":145329,"visible":true,"origin":"","legend":"\u003cp\u003eStudy procedures\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5192596/v1/da3460ed31688c2df65c51a4.png"},{"id":70297402,"identity":"f29d154d-1359-4962-b731-73b4002b260d","added_by":"auto","created_at":"2024-12-02 00:51:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73647,"visible":true,"origin":"","legend":"\u003cp\u003eIntergroup comparison of variables.A: TUG; B: T25FW; C: MSQOL54-T; D: MSQOL54-P; E: MSQOL54-M; F: PSQI. ✱: Significant difference in favor of SN; ✱✱: Significant difference in favor of VR; ns: No significant difference between groups; Significant data are set at p \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5192596/v1/29d1aabe8092858e433a3a5e.png"},{"id":85686109,"identity":"c003ed37-1bff-4138-87b2-eb6ebba34537","added_by":"auto","created_at":"2025-06-30 16:03:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1329915,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5192596/v1/ac45c119-687c-45d1-820c-52477ac765f8.pdf"},{"id":70296964,"identity":"4dc1c1e5-c999-4cdc-a1bf-c06c9c9b4dcc","added_by":"auto","created_at":"2024-12-02 00:43:28","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":13046,"visible":true,"origin":"","legend":"","description":"","filename":"Rawdata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5192596/v1/aa1da5ea32eac99e130369eb.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of sensory - motor and virtual reality interventions on indicators of gait, balance and quality of life of MS patients: a randomized trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is the primary cause of non-traumatic neurological dysfunction in young and middle-aged individuals. It is a degenerative inflammatory disease of the central nervous system (CNS) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), which frequently affects women (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).This common and chronic neurological disorder is characterized by inflammatory demyelination, axonal damage and gray matter atrophy. Therefore, postural control abnormalities, abnormal gait, and cognitive impairment arise as a result of neuronal destruction in areas of the CNS relevant to motor and cognitive activities (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Disturbance in balance is one of the common movement disorders of MS patients which limits daily activities and chores and has a detrimental impact on the patient's quality of life (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBalance disorders are also thought to negatively affect walking performance so that most MS patients with gait disorders also report balance problems (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Evaluation and treatment of balance and walking disorders in MS patients is particularly significant in the scientific community since balance and gait require integration of signals from visual, vestibular and proprioceptive sensory systems (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The central integration of sensory afferents is disrupted in MS patients due to disorders in many CNS regions, including injury to the brain stem, spinal cord, and cerebellum, which slow down the body's sensory conduction, pyramidal, vestibular, and visual pathways (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Therefore, the disturbance in the Central integration of sensory afferents affects the postural response in maintaining correct balance (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Consequently, the central integration process allows for a unique response strategy for postural control during balance and gait (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost modulating treatments for MS patients use pharmacological strategies aimed at preventing relapse or reversing disability. However, these treatments are associated with side effects such as an increased risk of immune suppression. Therefore, other non-pharmacological interventions that have no known side effects may have additional benefits (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In this regard, the World Health Organization 2020 guidelines have strongly recommended moderate or high intensity balance exercises to improve functional ability and prevent falls in people with chronic diseases such as MS (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, these interventions often lack optimal content. Optimal content in balance exercises refers to challenging of all the sensory, motor and cognitive components of the balance control system during balance intervention (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Although, previous studies have introduced challenging balance exercises but they have emphasized only on the motor components (such as the center of body mass movement, and narrowing of the base of support) of the balance control system (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Therefore, increase the training stimulus from other balance control systems (i.e., motor, sensory, and cognitive components) is necessary to achieve gradual improvement in other components of balance training. Sensory-motor exercises are a recent approach to balance training that emphasizes the integration of sensory (including vestibular, visual and somatosensory systems), motor (including limits of stability, anticipatory motor strategies, reactive motor strategies, and control of dynamics) and cognitive (including divided attention with additional motor or cognitive tasks such as dual-tasking) components of the balance control system (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the other hand, the repetitive and lengthy nature of traditional rehabilitation may reduce patients' long-term adherence to the rehabilitation program (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Nowadays, unlike traditional methods, in order to enjoy the long-term rehabilitation process, exercise interventions can be performed through virtual reality (VR) applications (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Virtual reality applications enable high-intensity, task-oriented multisensory feedback practice ,encouraging participants to engage in challenging tasks that integrate motor and cognitive demands (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In addition, virtual reality interventions can enhance patients' sensory processing and integration systems and allows them to repeatedly: - exercise; - receive information feedback; - improve the motivation of training; and improve visual, auditory and tactile inputs (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). According to recent findings, sensory-motor exercises and virtual reality have been proposed as two models of balance training that employ different components of the balance control system in a different way (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough, In the field of SN exercises study by Callesen et al 2020, observed a significant improvement in the T25FW parameter in MS patients with EDSS 2 to 6.5 after ten weeks of balance and motor control training (twice a week) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Also, a study by molhemi et al 2021, has shown that 6 weeks of VR training significantly improved the TUG and 10 meters walking performance in MS patients with EDSS below 6 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, so far, no study has compared two balance training models that emphasize the three components of the balance control system. Therefore, the main goal of the current study is to investigate the effectiveness of SN training compared to VR training on functional indicators of MS patients. Considering both SN and VR training programs were expected to be beneficial on the performance criteria of MS patients due to the sensory-oriented (multisensory) and integrated nature of the current exercise protocols. But the primary difficulty lies in determining which rehabilitation approach will be more effective on functional indicators and quality of life.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis research is an 8-week, single-blind, randomized experiment. Eligible MS patients were recruited in 3 phases: pre-test, intervention and post-test. The intervention phase included two sensory-motor exercises and virtual reality exercises for 8 weeks, three sessions per week which was carried out under the supervision of experts in neurology, sports biomechanics and exercise physiology at the institute of sports science and health of University of birjand. The MS patients in the control group received standard care during the intervention phase and were not permitted to engage in any physical activity. After familiarizing with the phases of the study, written informed consent was taken from the patients to enter the study. Moreover, the study was conducted in accordance with the Declaration of Helsinki. Ethics approval for the current research was also obtained by the Research Ethics Committee of Birjand University with code IR.BIRJAND.REC.1402.002. The present study has been registered with the trial ID 79224 in the Iranian Registry of Clinical Trials (IRCT) Center and is awaiting approval from this center. Also, this study is derived from an extensive research in MS patients. Earlier, other article taken from this comprehensive research (using the same exercise interventions and the same patients as in our study) titled \"Effect of alpha lipoic acid supplement intake together with neuromuscular training on joints kinematics and muscles electrical activity involved at the Gait initiation in patients with Multiple sclerosis: A randomized control trial\" in the IRCT Center registered and approved under the number of IRCT20190618043934N21(Trial registration number: IRCT20190618043934N21, Registration date: 2023-09-27).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eThe current study included MS patients who were treated with rituximab. As a result, patients sent to Razi Birjand Hospital were used to obtain homogenous patients (those receiving rituximab treatment). The sample size was computed using G.power version 3.1.9.7 with the following data: (α\u0026thinsp;=\u0026thinsp;0.05; β-1\u0026thinsp;=\u0026thinsp;0.8; number of groups\u0026thinsp;=\u0026thinsp;3; number of variables\u0026thinsp;=\u0026thinsp;3; and average effect size of Kramer's V\u0026thinsp;=\u0026thinsp;0.25) of 33 participants and 36 people with the option of dropping out. After reviewing the files of MS patients, 36 patients were identified who were treated with rituximab. Then, these patients were screened in terms of eligibility by a neurologist, so that 6 patients did not meet the inclusion criteria. Finally, 30 patients who matched the inclusion criteria were randomly allocated into three groups (using Randomizer Random Pick software by a person who was not involved in the evaluation of the variables and the implementation of the exercises): 1- SN training (n\u0026thinsp;=\u0026thinsp;10); and 2- VR training (n\u0026thinsp;=\u0026thinsp;10) 3- MS control (n\u0026thinsp;=\u0026thinsp;10). Study inclusion criteria included: MS patients between 18 and 65 years; Relapsing-remitting MS patients treated with rituximab with high disease activity, patients with EDSS from 2 to 6 and Ability to walk without assistance and at least 100 meters. Study exclusion criteria are also included: Patients' personal unwillingness to continue the exercises, absence in more than 3 training sessions, Failure to answer the phone call to continue the treatment.\u003c/p\u003e\n\u003ch3\u003eStudy procedures\u003c/h3\u003e\n\u003cp\u003eFollowing the division of the patients into experimental and control groups, the experimental groups were given a two-hour familiarization session in one day to familiarize them with the study procedures. Then, on two successive days between 4 and 8 PM, individuals in the SN and VR groups were directed to Institute of Sport Science and Health at University of Birjand for gait and dynamic balancing tests. In addition, patients were asked to complete questionnaires on their quality of life and sleep quality during the same session.\u003c/p\u003e \u003cp\u003eTwo days after measuring primary and secondary outcomes, SN and VR groups performed their respective exercises. After completing the relevant training protocols, 25-foot and TUG tests and quality of life and sleep quality questionnaires were reevaluated. The control group was not allowed to engage in any physical activity during the trial time, but were encouraged to conduct SN and VR activities after the study was completed. Study procedures are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe study employed a single-blind design, where the examiner assessing the outcomes was unaware of the group assignments (experimental or control). To ensure consistency in the measurements, all outcomes were evaluated between 4 and 8 pm for both the experimental and control groups\u003c/p\u003e\n\u003ch3\u003eT25FW\u003c/h3\u003e\n\u003cp\u003eIn this test, the individual walked 7.5 meters in a straight line without assistance in the shortest amount of time possible. T25FW is a reliable tool (ICC\u0026thinsp;=\u0026thinsp;0.99) for measuring MS patients' walking speed (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This test was repeated twice, and the walking speed was calculated as the average of the two tests (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). During the test, the test taker remained close the patient to avoid falling or any other incident.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTUG\u003c/h2\u003e \u003cp\u003eThe TUG test was designed to assess balance and capability for dynamic mobility. A stopwatch was used in this test to measure the time it took the subject to stand up from the armchair and travel a distance of 3 meters as quickly as possible, then turn around and seat back in the chair and lean back. The examiner remains near the patient to keep them from falling (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMSQOL54\u003c/h3\u003e\n\u003cp\u003eThe 54-item quality of life questionnaire for MS patients was used to evaluate the quality of life of these patients. The MSQoL-54 questionnaire is a health-related self-assessment tool with two components: physical health and mental health scores. The physical health score is obtained from eight subscales of physical function, health perceptions, energy/fatigue, Role limitations - physical, pain, sexual function, social function and health distress. Meanwhile, the mental health score is obtained from five subscales of Health distress, overall quality of life, Emotional well-being, Role limitations - emotional and Cognitive function. Composite scores were calculated by converting item scores to a scale of zero to 100 where zero indicates the worst health condition and 100 indicates the best health condition (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Also, the sum of two subscale scores of mental health and physical health was used to calculate the overall score of MSQoL-54.\u003c/p\u003e\n\u003ch3\u003ePSQI\u003c/h3\u003e\n\u003cp\u003eThe Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of MS patients. PSQI consists of 9 items that measure seven different aspects including sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disorders, use of sleeping pills and daytime dysfunction. The PSQI score ranges from 0 to 21, with higher scores indicating lower sleep quality. In general, a PSQI score more than 5 indicates poor quality sleep (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eExperimental interventions\u003c/h2\u003e \u003cp\u003eEach training session for the SN and VR groups lasted between 30 and 60 minutes, three days per week and for 8 consecutive weeks. In the SN group, several exercise patterns were considered for each exercise station so that the complexity of the exercises increased according to the progress of the patient. For the VR group, the complexity of the games was applied by increasing the speed of the games in accordance with the progress of the patient. Also, eye movements (in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) were also designed for both exercise groups, which the patients voluntarily performed during the rest time between exercise stations (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). During the trial period, the patients in the exercise groups were prohibited from performing any other physical rehabilitation activities. In addition, during the intervention period, the patients took their medicines according to the doctor's orders. Finally, training sessions were conducted in groups of two to three people, and the progress observed in each training session was recorded separately for each patient.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEye exercises\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of exercise\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSaccades\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFast eye movement between 2 fixed objects horizontally, vertically and diagonally\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmooth pursuit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEye tracking of a moving object horizontally, vertically and diagonally\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVestibular ocular reflex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEye focus on a fixed object while turning the head side to side, up and down.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSN intervention\u003c/h2\u003e \u003cp\u003eThe sensorimotor training was a modified training protocol based on previous studies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), in which the participants performed 18 training stations in a circular manner in each session. The exercises were divided into static and dynamic categories. The static part included 12 stations and the dynamic part (in the form of walking) also included 6 training stations. Static exercises including external destabilization and self-destabilization patterns which were performed on the floor surface and cushion foam in three conditions: eyes open, closed and with a helmet. During external stabilization exercises, the practitioner pushed (shifted) the patient's pelvis forward and sideways, in this situation the patient had to maintain his balance quickly. In self-destabilizing activities, patients shifted their weight from one leg to the other to deliberately modify their center of gravity. During the walking exercises, the patient was also given cognitive activities such as counting numbers, subtracting numbers, and remembering certain human or animal names. Each training session began with the patients warming up for 10 minutes. The final five minutes of each training session were spent to cooling down. The duration of each station from the first to the sixth week was 30, 35, 40, 45, 50, 55 seconds, and 60 seconds in the seventh and eighth weeks. The work-to-rest ratio was likewise regarded similar from the first to the eighth week. The sensorimotor training protocol is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSensorimotor intervention\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of exercise\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003esurface\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eeye condition\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic/dynamic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eclose eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalk1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ehelmet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ewalk2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eclose eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ehelmet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ewalk3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eclose eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalk4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ehelmet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalk5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eground\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eclose eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ehelmet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estatic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalk6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eopen eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003efoam cushion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003edynamic\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eED\u003c/b\u003e: External destabilization, \u003cb\u003eSD\u003c/b\u003e: Self destabilization, \u003cb\u003ewalk1\u003c/b\u003e: Heel-toe walking with head turning, \u003cb\u003ewalk2\u003c/b\u003e: Throw the ball in different directions with visual tracking of the ball while walking. \u003cb\u003eWalk3\u003c/b\u003e: Walking on command (stop - move - turn in - turn out), \u003cb\u003ewalk4\u003c/b\u003e: Walking between conical obstacles, \u003cb\u003ewalk5\u003c/b\u003e: Zigzag walking between obstacles, \u003cb\u003ewalk6\u003c/b\u003e: Walking on foam cushion.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eVR intervention\u003c/h2\u003e \u003cp\u003eThe current study's VR methodology was carried out using the RAGU system. The RAGU system requires the Microsoft Kinect for image analysis and the Oculus VR glasses for 3D imaging. This system included a motion sensor to regulate the patient's motions during picture analysis (Microsoft KinectV2). The patient performed exercises in the virtual environment created with a HMD (head mounted display) that had 3D images (Oculus VR glasses). The sound system and motion sensors contributed to a stronger sense of reality.\u003c/p\u003e \u003cp\u003eVR training in the current study was also a modified exercise protocol which was formed based on previous research (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Virtual reality games included two components: dynamic and static. Dynamic games included one pattern or more than one pattern from the 12 gaiting patterns presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The primary priority for the dynamic component of VR was to select games that recruited 12 different gaiting patterns during a VR training session. The virtual games considered for the dynamic component included Plank rich, Pistol whip, Boxing, walking dead, Temple run. Static VR games were also performed in such a way that 6 static movement patterns were recruited during a VR training session. This component also included Beat saber, Power beat saber, OHSHIP games. The duration of each VR station and rest between stations was equivalent but different from the SN protocol. However, the total duration of a training session was similar to the SN protocol and was 18, 21, 24, 27, 30, 33 minutes for weeks 1 to 6 and 36 minutes for weeks 7 and 8, respectively. All virtual reality games were played in a 10 x 10 room. A comprehensive description related to dynamic and static movement patterns is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVirtual reality intervention\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003emovement patterns\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eexplanation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eusual walking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSimple walking on a walking path without the marker appearing\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eavoid obstacles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvoiding obstacles or signs by lifting the leg When suddenly appear in a person's walking path\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eacceleration/deceleration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStopping suddenly behind signs appearing while walking and starting quickly as soon as the signs disappear.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymmetrical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalking precisely on the feet marks that are arranged in a special order along the walking path\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsymmetrical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalking precisely on the feet marks that are not arranged in a particular order along the walking path\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enarrow path\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalk in a walking path with less length and width than normal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eincremental speed setting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA sign appearing one meter in front of the person while walking and touching it before turning off\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlalom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalking around moving obstacles that approach the person\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTandem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalking heel-toe\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-degree turn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe appearance of a half-turn sign to the person while walking and a quick 90-degree turn to the starting point\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e180 degree turn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe appearance of a half-turn sign to the person while walking and a quick 180 degree turn to the starting point\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMulti/dual task\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerforming two virtual tasks (auditory or cognitive tasks or two walking tasks) while walking\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalking in place\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalking in place in different directions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReaching virtual objects\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ethe appearance of virtual objects on both sides of the person and touching them with hands\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStepping on virtual objects\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLifting the healthy feet to avoid hitting virtual obstacles (e.g. bananas on the floor) and then returning to the starting position\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eshifting weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esteer an avatar in different directions to collect points or coins and avoid virtual collisions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRising on toes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSteering an avatar up and down and avoiding obstacles by rising on the toes and returning to its original position (i.e. shifting body weight in anterior-posterior directions)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquats\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvoid hitting virtual obstacles by sitting down and then standing up and vice versa\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eStatically analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eStatistical analysis of the data was done using IBM SPSS Statistics 27 software. The normality of data distribution was evaluated through the Kolmogorov\u0026ndash;Smirnov/Shapiro\u0026ndash;Wilk tests or standard graphs (box plots and histograms). Descriptive analysis was expressed by giving mean and standard deviation for continuous variables and numbers for categorical variable (gender). The baseline comparisons of basic demographic and clinical characteristics among groups were performed using one-way ANOVA. Paired t-tests were used to discover the effect of time or changes from baseline to 8 weeks. Comparison between groups in outcome measures were performed through the general linear model approach (multivariate analysis of variance or multivariate ANOVA) using Bonferroni correction for post hoc comparisons. The effect size within groups (within groups' pre-post differences) was evaluated based on Cohen's d standards. Effect size results were interpreted as small (\u0026ge;\u0026thinsp;0.2), medium (\u0026ge;\u0026thinsp;0.5), or large (\u0026ge;\u0026thinsp;0.8). Also, Partial Eta squared (η2) was used to evaluate of the intergroup ES where η\u0026sup2; \u0026ge; 0.01. η\u0026sup2; \u0026ge; 0.06 and η\u0026sup2; \u0026ge; 0.14 are considered as small, medium and higher ESs, respectively. The significance level was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. In addition, the figures were designed in GraphPad Prism software (version Graphpad Prism 8.4.3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, 36 patients treated with rituximab participated which 6 patients did not meet the inclusion criteria and two patients from the VR group withdrew from the VR project due to a nervous attack before the start of this intervention and difficulty in transferring to the study location. Finally, 28 patients remained for the final evaluation. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents demographic information separately for three categories. According to the results of the Shapiro Wilk and Levene test, there was no significant difference between the research groups in terms of age, height, weight, BMI and EDSS in basic conditions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and demographic characteristics of the groups at baseline\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSN (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCON(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.25\u0026thinsp;\u0026plusmn;\u0026thinsp;9.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender F/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.80\u0026thinsp;\u0026plusmn;\u0026thinsp;16.470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.10\u0026thinsp;\u0026plusmn;\u0026thinsp;12.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.673\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.12\u0026thinsp;\u0026plusmn;\u0026thinsp;6.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.89\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.48\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0 .72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9500\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.40\u0026thinsp;\u0026plusmn;\u0026thinsp;.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMS diagnosis duration (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.5\u0026thinsp;+\u0026thinsp;3.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTUG (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.66\u0026thinsp;\u0026plusmn;\u0026thinsp;8.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.97\u0026thinsp;\u0026plusmn;\u0026thinsp;10.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.79\u0026thinsp;\u0026plusmn;\u0026thinsp;2.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT25FW (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.24\u0026thinsp;\u0026plusmn;\u0026thinsp;7.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.94\u0026thinsp;\u0026plusmn;\u0026thinsp;8.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.98\u0026thinsp;\u0026plusmn;\u0026thinsp;28.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.61\u0026thinsp;\u0026plusmn;\u0026thinsp;24.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109.55\u0026thinsp;\u0026plusmn;\u0026thinsp;30.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.85\u0026thinsp;\u0026plusmn;\u0026thinsp;12.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.39\u0026thinsp;\u0026plusmn;\u0026thinsp;12.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.99\u0026thinsp;\u0026plusmn;\u0026thinsp;17.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.37\u0026thinsp;\u0026plusmn;\u0026thinsp;16.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.23\u0026thinsp;\u0026plusmn;\u0026thinsp;12.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.87\u0026thinsp;\u0026plusmn;\u0026thinsp;14.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.60\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eVR\u003c/b\u003e: Virtual reality group; \u003cb\u003eSN\u003c/b\u003e: Sensory motor group; \u003cb\u003eCON\u003c/b\u003e: Control group y: Year; \u003cb\u003eF/M\u003c/b\u003e: Female/Male; \u003cb\u003eKg\u003c/b\u003e: Kilogram; \u003cb\u003em\u003c/b\u003e: Meter; \u003cb\u003eBMI\u003c/b\u003e: Body mass index; \u003cb\u003ekg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e: Kilogram / Meter\u003csup\u003e2\u003c/sup\u003e \u003cb\u003eS\u003c/b\u003e: Second; \u003cb\u003eTUG\u003c/b\u003e: Timed Up and Go; \u003cb\u003eT25FW\u003c/b\u003e: Timed 25-Foot Walk ; \u003cb\u003eMSQOL54\u003c/b\u003e: Multiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 Instrument ; \u003cb\u003eMSQOL54-T\u003c/b\u003e: Multiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 Instrument Total score: \u003cb\u003eMSQOL54-P\u003c/b\u003e : Physical Health component score MSQOL54; \u003cb\u003eMSQOL54-M\u003c/b\u003e: Mental Health component score MSQOL54; \u003cb\u003ePSQI\u003c/b\u003e: Pittsburgh Sleep Quality Index; \u003cb\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e: mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; Significant data are set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eResult outcomes\u003c/h2\u003e \u003cp\u003eIntra-group and inter-group changes of performance indicators are shown in Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Within-group changes showed that both SN and VR interventions showed significant improvement (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in primary (T25FW, TUG) and secondary (MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQI) outcomes compared to baseline conditions. Whereas, the control group only showed significant improvements (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in secondary outcomes (MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQI) compared to baseline conditions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eintra and inter group results of primary and secondary outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003evariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePre\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePost\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eΔ\u003c/p\u003e \u003cp\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntragroup\u003c/p\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eintragroup ES\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eη\u003c/em\u003e2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTUG (S)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.66\u0026thinsp;\u0026plusmn;\u0026thinsp;8.59\u003c/p\u003e \u003cp\u003e14.97\u0026thinsp;\u0026plusmn;\u0026thinsp;10.41\u003c/p\u003e \u003cp\u003e10.79 \u0026plusmn; 2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.98\u0026thinsp;\u0026plusmn;\u0026thinsp;7.07\u003c/p\u003e \u003cp\u003e9.46\u0026thinsp;\u0026plusmn;\u0026thinsp;6.88\u003c/p\u003e \u003cp\u003e9.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.58\u0026ndash;5.51\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78\u003c/p\u003e \u003cp\u003e\u0026minus;\u0026thinsp;0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.54\u003c/p\u003e \u003cp\u003e-0.52\u003c/p\u003e \u003cp\u003e-0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT25FW (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.24\u0026thinsp;\u0026plusmn;\u0026thinsp;7.87\u003c/p\u003e \u003cp\u003e12.94\u0026thinsp;\u0026plusmn;\u0026thinsp;8.24\u003c/p\u003e \u003cp\u003e7.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e \u003cp\u003e8.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e \u003cp\u003e6.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;3.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e \u003cp\u003e\u0026minus;\u0026thinsp;4.27\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17\u003c/p\u003e \u003cp\u003e-0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e.\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.40\u003c/p\u003e \u003cp\u003e-0.51\u003c/p\u003e \u003cp\u003e-0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.98\u0026thinsp;\u0026plusmn;\u0026thinsp;28.11\u003c/p\u003e \u003cp\u003e72.61\u0026thinsp;\u0026plusmn;\u0026thinsp;24.13\u003c/p\u003e \u003cp\u003e109.55\u0026thinsp;\u0026plusmn;\u0026thinsp;30.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144.36\u0026thinsp;\u0026plusmn;\u0026thinsp;19.46\u003c/p\u003e \u003cp\u003e143.63\u0026thinsp;\u0026plusmn;\u0026thinsp;20.38\u003c/p\u003e \u003cp\u003e128.51\u0026thinsp;\u0026plusmn;\u0026thinsp;21.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.37\u0026thinsp;\u0026plusmn;\u0026thinsp;20.55\u003c/p\u003e \u003cp\u003e71.02\u0026thinsp;\u0026plusmn;\u0026thinsp;26.99\u003c/p\u003e \u003cp\u003e18.96\u0026thinsp;\u0026plusmn;\u0026thinsp;19.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt; 0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt; 0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003cp\u003e2.94\u003c/p\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.85\u0026thinsp;\u0026plusmn;\u0026thinsp;12.83\u003c/p\u003e \u003cp\u003e35.39\u0026thinsp;\u0026plusmn;\u0026thinsp;12.41\u003c/p\u003e \u003cp\u003e61.99\u0026thinsp;\u0026plusmn;\u0026thinsp;17.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.86\u0026thinsp;\u0026plusmn;\u0026thinsp;11.02\u003c/p\u003e \u003cp\u003e70.40\u0026thinsp;\u0026plusmn;\u0026thinsp;9.57\u003c/p\u003e \u003cp\u003e70.78\u0026thinsp;\u0026plusmn;\u0026thinsp;11.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.00\u0026thinsp;\u0026plusmn;\u0026thinsp;9.81\u003c/p\u003e \u003cp\u003e35.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.05\u003c/p\u003e \u003cp\u003e8.79\u0026thinsp;\u0026plusmn;\u0026thinsp;9.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003cp\u003e2.82\u003c/p\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMSQOL54-M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.37\u0026thinsp;\u0026plusmn;\u0026thinsp;16.32\u003c/p\u003e \u003cp\u003e37.23\u0026thinsp;\u0026plusmn;\u0026thinsp;12.47\u003c/p\u003e \u003cp\u003e47.87\u0026thinsp;\u0026plusmn;\u0026thinsp;14.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.74\u0026thinsp;\u0026plusmn;\u0026thinsp;12.66\u003c/p\u003e \u003cp\u003e73.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.55\u003c/p\u003e \u003cp\u003e57.67\u0026thinsp;\u0026plusmn;\u0026thinsp;11.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.36\u0026thinsp;\u0026plusmn;\u0026thinsp;13.22\u003c/p\u003e \u003cp\u003e36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;19.09\u003c/p\u003e \u003cp\u003e9.80\u0026thinsp;\u0026plusmn;\u0026thinsp;10.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.92\u003c/p\u003e \u003cp\u003e2.88\u003c/p\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVR\u003c/p\u003e \u003cp\u003eSN\u003c/p\u003e \u003cp\u003eCON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.92\u003c/p\u003e \u003cp\u003e8.60\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e \u003cp\u003e6.30\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;3.92\u003c/p\u003e \u003cp\u003e3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68\u003c/p\u003e \u003cp\u003e4.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e \u003cp\u003e-5.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.34\u003c/p\u003e \u003cp\u003e\u0026minus;\u0026thinsp;1.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.68\u003c/p\u003e \u003cp\u003e-1.66\u003c/p\u003e \u003cp\u003e-0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.350\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cb\u003eVR\u003c/b\u003e: Virtual reality group; \u003cb\u003eSN\u003c/b\u003e: Sensory motor group; \u003cb\u003eCON\u003c/b\u003e: Control group \u003cb\u003eY\u003c/b\u003e: Year; \u003cb\u003eΔ\u003c/b\u003e: Changes ; \u003cem\u003eη\u003c/em\u003e2 Partial Eta squared; \u003cb\u003eS\u003c/b\u003e: Second; \u003cb\u003eTUG\u003c/b\u003e: Timed Up and Go; \u003cb\u003eT25FW\u003c/b\u003e: Timed 25-Foot Walk ; ; \u003cb\u003eMSQOL54\u003c/b\u003e: Multiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 Instrument ; \u003cb\u003eMSQOL54-T\u003c/b\u003e: Multiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 Instrument Total score: \u003cb\u003eMSQOL54-P\u003c/b\u003e : Physical Health component score MSQOL54; \u003cb\u003eMSQOL54-M\u003c/b\u003e: Mental Health component score MSQOL54; \u003cb\u003ePSQI\u003c/b\u003e: Pittsburgh Sleep Quality Index; \u003cb\u003eES\u003c/b\u003e: Effect size \u003cb\u003eM\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e: mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; Significant data are set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eInter-group changes also shown in Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The SN and VR interventions showed significant superiority (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in all primary (T25FW, TUG) and secondary (MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQI) outcomes (except the index) compared to the control group. SN and VR groups were not significantly superior (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) to each other in functional indices except PSQI (significant improvement in favor of the SN group) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, SN intervention showed a higher ES compared to VR in T25FW, MSQOL54-T, MSQOL54-P, MSQOL54-M, PSQ T25FW and VR intervention also showed a higher ES in TUG than SN.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of the present study showed that both SN and VR interventions significantly improved performance indicators compared to the control group. However, the PSQI showed a significant improvement only in the SN group compared to VR., while no significant difference was found in other measures between SN and VR groups. In terms of effect size, SN intervention generally reported higher values, except for the TUG index where VR showed a higher effect size., In other performance indicators SN intervention reported a higher effect size.\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eT25FW\u003c/h2\u003e \u003cp\u003eThe significant improvement in walking speed (T25FW) after the SN intervention can be attributed to the inclusion of walking patterns in this intervention, which aligns with the principle of exercise specificity in creating functional adaptations (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Most of the SN intervention was dedicated to external destabilizing and self-destabilizing exercises, which probably affected the retraining of impaired feedback and feedforward mechanisms of gait control, and may be justified by the improvement of walking speed through these static exercise patterns. This suggests that static exercises can play a role in improving walking speed. On the other hand, stimulating the proprioceptive inputs by performing exercises on the foam has improved the efficiency of the feedback and forward control of walking and plays an important role in improving walking speed (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The current study demonstrates that sensory-motor interventions significantly enhance the performance of the 25-foot walk and exhibit a high effect size. Diverging from previous studies that mainly concentrated on P values, this study underscores the importance of effect size and advocates for its prioritization as an important statistical measure in future research. Although, the present investigation revealed a significant impact of SN exercises on enhancing T25FW efficacy, other studies have documented contradictory outcomes regarding T25FW proficiency following SN protocol (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Although balance control systems were comprehensively involved in these studies, but the positive effect of SN intervention on walking performance may be largely dependent on the degree of disability of MS patients. Probably, the high EDSS degree creates a potential stimulus to improve T25FW performance after SN exercises (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Meanwhile, MS people with low EDSS may not benefit from the benefits of SN interventions on improving T25FW performance (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Setting aside previous studies that were all focused on P-values, this study revealed a high ES from SN intervention on improving the T25FW and supports prioritizing it as an important statistical measure in future research. In general, the improvement of walking speed caused by SN intervention may be the result of improving the integration of sensory and motor inputs, and these effects are likely to be greater in MS patients with a high degree of disability.\u003c/p\u003e \u003cp\u003eThe improvement in walking speed after VR can be attributed to the reduced cognitive load of VR-induced gait impairment. Because the three-dimensional and panoramic view of VR with HMD causes the patient to be immersed in the virtual environment and this factor facilitates distraction from the real environment (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). As a result, the distraction caused by VR reduces the cognitive load of walking disorder and provides a rich environment for repetitive practice of walking tasks (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Repeated execution of walking tasks in the form of virtual reality strengthens the mirror neuron system and causes recall stored motor plans and thus improves walking performance (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). The current study has reported a high ES (-0.40) and a significant impact of VR on the T25FW task. In the same context, some studies have also reported significant effects and high ES of VR on the walking speed of MS patients (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The use of walking patterns in combination with VR is likely to justify the high ES and significant outcomes of these interventions (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). While, performing VR interventions in a static state has shown a low ES and an insignificant effect on improving walking speed (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eTUG\u003c/h2\u003e \u003cp\u003eThe significant reduction in TUG time after SN intervention can be justified based on the approach of retraining the disrupted sensory systems (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Since MS patients face abnormal fluctuations while standing quietly with their eyes open and these fluctuations intensify when their eyes are closed, especially on the foam, therefore, self-destabilizing and external destabilizing exercises with open and closed eyes on the surface the ground and cushion foam provide a wonderful stimulus for retraining patients' depth and visual sensory inputs that are naturally impaired (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Also, 40 to 70% of MS patients have cognitive disorders, which impairs the speed of information processing and maintaining balance in challenging situations such as dual tasks. Therefore, in the present study, the use of cognitive-motor tasks provide the opportunity to retrain the cognitive components of the balance control system (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Also, performing walking exercises with vertical and horizontal rotations can help to retrain the impaired vestibular system. Retraining the vestibular system is likely to develop vestibule-ocular reflexes that are responsible for stabilizing and changing gaze direction and maintaining dynamic balance (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrent study demonstrated significant improvement and high ES in TUG performance after SN intervention. In most studies, lack of improvement in TUG performance after SN intervention has been shown using p-values, without discussing effect size (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Although, these interventions extensively engaged the sensory, motor, and cognitive aspects of balance, the absence of an intensive, multimodal SN intervention(applied statically) could explain the lack of notable progress in the TUG results (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). However, the multisensory nature of the SMIT intervention and the high level of EDSS in MS patients in Pavlikova et al.'s (2020) study did not lead to a significant improvement in TUG (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). It is possible that the patients initially chosen for this study had better outcomes in the TUG test and required less intervention with SMIT (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Overall, the retraining of impaired sensory systems through the integration of somatosensory, visual, and vestibular inputs may be the most important mechanism of TUG improvement after SN intervention.\u003c/p\u003e \u003cp\u003eThe improvement in TUG performance resulting from the VR intervention can be attributed to the cognitive-motor nature of VR. The cognitive-motor nature of VR allows the patient to develop fall prevention strategies such as attention, concentration, motor planning, and problem solving, thereby improving balance (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). VR-induced repetitive feedback increases patient motor knowledge related to TUG performance (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Also, VR provides immediate feedback on performance, which helps to learn new motor strategies and possibly improve TUG performance (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study demonstrated a high ES (-0.54) and statistical significance of VR intervention on TUG performance. In the same context, other VR interventions performed in both static and dynamic modes also reported a significant improvement in TUG performance after VR intervention (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Although, these studies reached statistical significance, they differed in terms of ES. A low ES (Cohen\u0026rsquo;s d = -0.35) of VR on TUG performance was obtained from interventions performed with the Wii Fit Balance Board (in stationary mode) (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), while VR interventions combined with a treadmill (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) or floor walking (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) reported medium (Cohen\u0026rsquo;s d = -0.60) and high ES (Cohen\u0026rsquo;s d = -1.58), respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eT25FW, TUG (SN vs VR)\u003c/h2\u003e \u003cp\u003eAlthough, SN and VR interventions significantly improved T25FW and TUG compared to the control group, however, no significant difference was observed between the two training models. Both SN and VR interventions seem to affect walking speed and balance through similar mechanisms but in different ways. Improving the integration of sensory inputs is one of the potential mechanisms for improving walking and balance after these interventions (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Different implementation situations (static, dynamic) with eyes open and closed on ground and foam surfaces along with vertical and horizontal rotations in the head have provided the necessary stimulation to improve integration of sensory input through SN training (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). The inconsistency (mismatched) of the visual data obtained from the VR environment with the somatosensory and vestibular sensory data makes the patient have to better integrate the somatosensory and vestibular sensory systems (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Also, both exercise interventions had a task-oriented nature, which means that both of them used exercise patterns that specifically targeted balance and walking (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). One of the important mechanisms of improving balance and walking is neural plasticity, which is probably improved due to the task-oriented nature of SN and VR interventions (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Finally, both training interventions included dual tasks. The inclusion of cognitive-motor dual tasks simulates the real conditions of balance and walking in daily life and thus seeks to improve these measurements (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eMSQOL54-M\u003c/h2\u003e \u003cp\u003eThe MSQOL54-M score showed a significant increase after SN and VR interventions. The improvement of the MSQOL54-M score after SN exercises can be related to the involvement of the cognitive component of the balance control system and the inclusion of cognitive-motor dual tasks. In this context, interventions that have reported significant improvements in MSQOL54-M scores have also highlighted the crucial role of cognitive elements in balance control and the execution of dual cognitive-motor tasks (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Conversely, studies that did not report significant improvement in MSQOL54-M scores did not emphasize these cognitive and dual-task components (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Although our study demonstrated a very high ES and significant of SN interventions on MSQOL54-M scores, other studies merely focused on p-values rather than ES.\u003c/p\u003e \u003cp\u003eThe VR intervention in our study demonstrated a very high ES on MSQOL54-M. Although other studies have also shown a significant impact of VR interventions on MSQOL54-M (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), our study reported a much higher ES on MSQOL54-M compared to these studies (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The assumption is that VR systems based on HMDs (like our study) likely impose a higher cognitive load (due to increased immersion and more natural interaction) on patients compared to VR systems without the use of HMDs (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). This factor may explain the larger ES observed in our study compared to these other studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eMSQOL54-P\u003c/h2\u003e \u003cp\u003eboth SN and VR interventions significantly improved the \u003cb\u003eMSQOL54-P\u003c/b\u003e score. Challenging the different components of the balance control system through SN exercises may be an effective factor in the significant improvement of the \u003cb\u003eMSQOL54-P\u003c/b\u003e score (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). While our study showed very high ES (2.82) for SN on \u003cb\u003eMSQOL54-P\u003c/b\u003e score, other studies related to SN interventions have only reported \u003cb\u003eMSQOL54-P\u003c/b\u003e score based on p-values. All these studies, which had a similar nature to our SN protocol, did not consistently show significant improvements in MSQOL54-P scores. Probably, the Less frequency of training sessions in some of studies did not show the effect of SN exercises on MSQOL54-P scores (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), Meanwhile, Studies with high-frequency training sessions have shown a significant effect of SN training on the MSQOL54-P score (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present study demonstrated a significant improvement in the MSQOL54-P score with a very high ES after VR intervention. Although Munari et al.'s 2020 study showed a medium ES (0.59) and Khalil et al.'s 2018 study also developed the MSQOL54-P score with a high ES (0.88) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), the present study demonstrated a much higher ES (2.02) compared to these studies. This higher ES in the MSQOL54-P score can be attributed to higher-frequency exercise sessions, the use of VR models with HMD and higher disability level of patients in our study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eMSQOL54-M, MSQOL54-P (SN vs VR)\u003c/h2\u003e \u003cp\u003eThe lack of significant difference in \u003cb\u003eMSQOL54-M\u003c/b\u003e score between SN and VR groups can be attributed to the cognitive-motor nature of these two training protocols because both training interventions emphasize the cognitive components of the balance control system in a different way (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Finally, the lack of significant differences in \u003cb\u003eMSQOL54-P\u003c/b\u003e scores between SN and VR groups can be attributed to the task-oriented nature of both exercise protocols, as both exercise interventions included exercises or games that specifically focused on balance and walking (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), which led to the same perception of physical health after two training interventions.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe current study's limitations include the utilization of MS patients treated with rituximab (a particular treatment), which limits access to additional people. Also, the distribution of patients in the intervention groups was not equal in terms of gender, which may be the reason for the larger effect size of SN intervention compared to VR on most performance indicators. The lack of a follow-up period is another limitation that may affect the durability of the effect of sensory interventions on performance measures. The majority of the patients in this trial were women with relapsing-remitting MS, which may make it difficult to Generalisability the findings to other MS groups.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eApplication recommendations\u003c/h2\u003e \u003cp\u003eThe T25FW test is an important criterion for evaluating walking disorders in clinical settings, but it only evaluates walking speed; future studies should focus on walking subtasks such as gait initiation, gait termination, and spatiotemporal parameters. Furthermore, neuroimaging methods should be used to reveal the effect of SN and VR interventions on neural plasticity in the future. Also, it is recommended to evaluate the actual performance of walking and balance in daily life through the evaluation of motor-cognitive dual tasks or cognitive evaluations. Finally, the use of sensory integration tests will be important in determining the role of sensory interactions in balance control.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present study showed significant improvement in walking speed, dynamic balance, quality of life and sleep quality of MS patients after 8 weeks of SN and VR interventions. Experimental interventions significantly increased performance measures compared to the control group. With the exception of sleep quality, which reported a significant improvement in favor of the SN group, there was no significant difference in other performance indicators between the two intervention groups. Therefore, SN training as a cost-effective and highly accessible training approach and virtual reality with HMD as a motivational training approach can affect the functional status of MS patients. Probably, the task-oriented, dual-task and multi-sensory aspects of both interventions most likely enhanced balance and walking in these individuals by improving anticipatory mechanisms and postural control\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is provided within the supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful for the efforts of Razi Birjand Hospital\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eand Sports Science and Health Research Institute of Birjand University in supporting this research project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH.A ,S.I and M.M.M conceived and designed research. H.A, M.M.A, and M.Y conducted the experiment. H.A, M.M.A, and M.Y analyzed data. H.A, and S.I wrote the manuscript. All authors read and approved the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOzkul, C., Guclu-Gunduz, A., Yazici, G., Guzel, N. A. \u0026amp; Irkec, C. Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: A single-blinded randomized controlled trial. \u003cem\u003eEur. J. Integr. Med.\u003c/em\u003e \u003cb\u003e35\u003c/b\u003e, 101092 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLearmonth, Y. et al. Safety of exercise training in multiple sclerosis: a protocol for an updated systematic review and meta-analysis. \u003cem\u003eSyst. Reviews\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 1\u0026ndash;10 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorelli, N. \u0026amp; Morelli, H. 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Surveying sleep quality and fatigue in multiple sclerosis patients at a multiple sclerosis center in Kermanshah, Iran, in 2017. \u003cem\u003eNeurobiol. sleep. circadian rhythms\u003c/em\u003e. \u003cb\u003e8\u003c/b\u003e, 100050 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHebert, J. R., Corboy, J. R., Manago, M. M. \u0026amp; Schenkman, M. Effects of vestibular rehabilitation on multiple sclerosis\u0026ndash;related fatigue and upright postural control: a randomized controlled trial. \u003cem\u003ePhys. Ther.\u003c/em\u003e \u003cb\u003e91\u003c/b\u003e (8), 1166\u0026ndash;1183 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSokhangu, M. K., Rahnama, N., Etemadifar, M., Rafeii, M. \u0026amp; Saberi, A. Effect of neuromuscular exercises on strength, proprioceptive receptors, and balance in females with multiple sclerosis. \u003cem\u003eInt. J. Prev. Med.\u003c/em\u003e ;\u003cb\u003e12\u003c/b\u003e. (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeerse, D. J., Roerdink, M., Marinus, J. \u0026amp; van Hilten, J. J. Assessing walking adaptability in stroke patients. \u003cem\u003eDisabil. Rehabil.\u003c/em\u003e \u003cb\u003e43\u003c/b\u003e (22), 3242\u0026ndash;3250 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalil, H. et al. The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): a feasibility study. \u003cem\u003eNeuroRehabilitation\u003c/em\u003e. \u003cb\u003e43\u003c/b\u003e (4), 473\u0026ndash;482 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKasser, S. L., Jacobs, J. V., Ford, M. \u0026amp; Tourville, T. W. Effects of balance-specific exercises on balance, physical activity and quality of life in adults with multiple sclerosis: a pilot investigation. \u003cem\u003eDisabil. 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Falls prevention and balance rehabilitation in multiple sclerosis: a bi-centre randomised controlled trial. \u003cem\u003eDisabil. Rehabil\u003c/em\u003e. \u003cb\u003e40\u003c/b\u003e (5), 522\u0026ndash;526 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePavlikova, M. 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. \u003cem\u003eMult Scler. Relat. Disord\u003c/em\u003e. \u003cb\u003e40\u003c/b\u003e, 101974 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCallesen, J., Cattaneo, D., Brincks, J. \u0026amp; Dalgas, U. How does strength training and balance training affect gait and fatigue in patients with Multiple Sclerosis? A study protocol of a randomized controlled trial. \u003cem\u003eNeuroRehabilitation\u003c/em\u003e. \u003cb\u003e42\u003c/b\u003e (2), 131\u0026ndash;142 (2018).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SN, VR, TUG, T25FW, MS","lastPublishedDoi":"10.21203/rs.3.rs-5192596/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5192596/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e \u003cp\u003eMultiple sclerosis (MS) is a neurological disorder that affects the central nervous system, causing inflammation and damage to the myelin sheath, leading to balance and gait impairments. Sensory-motor (SN) and virtual reality (VR) interventions have shown promise in addressing these balance issues by engaging all three components of the balance control systems. This study aimed to compare the effectiveness of SN and VR training on the functional status and quality of life of MS patients.\u003c/p\u003e \u003cp\u003eMethods\u003c/p\u003e \u003cp\u003eIn this study, 36 MS patients receiving Rituximab therapy with an EDSS of 2 to 6 were randomly assigned to three groups: SN (n\u0026thinsp;=\u0026thinsp;10), VR (n\u0026thinsp;=\u0026thinsp;8) and a control group (n\u0026thinsp;=\u0026thinsp;10). The SN and VR groups underwent 8 weeks of intervention, with 3 sessions per week, while the control group continued routine care. Assessments using Timed Up and Go (TUG), Timed 25-Foot Walk (T25FW), Multiple Sclerosis Quality of Life 54 Instrument (MSQOL54), and Pittsburgh Sleep Quality Index (PSQI) were conducted at baseline and after eight weeks.\u003c/p\u003e \u003cp\u003eResults\u003c/p\u003e \u003cp\u003eConsiderable progress was made in all major and secondary variables after SN and VR training in comparison to the baseline settings. Furthermore, compared to the control group, the experimental groups showed a statistically significant improvement in both the primary and secondary outcomes. There were no significant differences in other variables between the SN and VR groups in the comparison of the experimental groups, with the exception of the PSQI, which showed significant changes in favor of the SN group.\u003c/p\u003e \u003cp\u003eConclusions\u003c/p\u003e \u003cp\u003eThe VR with a head-mounted display (HMD) serves as a motivational training tool, while SN training is an affordable and accessible technique. Both interventions can positively impact the functional status of MS patients by improving balance and gait through their task-oriented, dual-task, and multisensory nature.\u003c/p\u003e","manuscriptTitle":"Comparison of sensory - motor and virtual reality interventions on indicators of gait, balance and quality of life of MS patients: a randomized trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-02 00:43:23","doi":"10.21203/rs.3.rs-5192596/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-02-03T05:12:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-14T18:17:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18318002135470889844640981877258263061","date":"2025-01-05T16:31:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251854902535669847398456825471477642865","date":"2024-12-05T14:07:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-19T12:54:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144255689365470541007157625499915416510","date":"2024-11-13T10:20:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-11T14:50:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-11T14:38:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-11-04T10:02:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-02T05:48:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-10-02T11:23:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e1bbc42-37f1-40e8-aad7-66ae389f701b","owner":[],"postedDate":"December 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":40202579,"name":"Biological sciences/Neuroscience"},{"id":40202580,"name":"Health sciences/Health care"}],"tags":[],"updatedAt":"2025-06-30T15:59:18+00:00","versionOfRecord":{"articleIdentity":"rs-5192596","link":"https://doi.org/10.1038/s41598-025-05048-3","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-06-26 15:57:10","publishedOnDateReadable":"June 26th, 2025"},"versionCreatedAt":"2024-12-02 00:43:23","video":"","vorDoi":"10.1038/s41598-025-05048-3","vorDoiUrl":"https://doi.org/10.1038/s41598-025-05048-3","workflowStages":[]},"version":"v1","identity":"rs-5192596","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5192596","identity":"rs-5192596","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}