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Balance impairments are common in people with Multiple Sclerosis (PwMS). However, no studies have examined brain activation while performing balance tasks in PwMS. The present study aims to investigate hemodynamic response function (HRF) between Healthy Subjects (HS) and PwMS during the execution of balance tasks on a stabilometric platform using functional near-infrared spectroscopy (fNIRS). We recruited 18 PwMS with mean+standard deviation age of 42.1±10.6 years and Expanded Disability Status Scale (EDSS) of 2.0±1 points, and 18 age- and gender-matched HS aged 37.3±9.7 years. Participants underwent fNIRS recordings while maintaining upright standing on a foam with eyes open (EO) and closed (EC) for 30 seconds. We investigated frontal, occipital, and temporal cortices using the NIRSscoutX system to measure oxy- and deoxyhemoglobin levels for 44 measurement channels. We concurrently measured the Area of the centre of pressure. We used a t-test to compare between-group differences on Area (Platform variable), while we ran a linear mixed model (Area, channel, and group) to fit HRF changes between EO and EC conditions. We observed statistically significant between-group differences in Area in EO (p=0.04) and EC condition (p=0.02). Group means (standard error) adjusted for Area and multiple comparisons denotes statistically significant differences in 3 active channels (Broadman Area 21): right temporal (Channel 1, HS:1.41(0.23) uM; PwMS:0.41(0.26) uM) and left temporal (Channel 2, HS:1.47(0.23) uM; PwMS:0.30(0.25) uM; Channel 3, HS:1.76(0.23) uM; PwMS:0.98(0.26) uM). We did not observe differences in the other cortical areas. As expected, balance control is impaired in PwMS on foam with EC. The current study adds to the literature that the increase in HRF observed in EC condition in HS is reduced in PwMS. This reduction occurs explicitly symmetrically in the right and left temporal cortices. [ABSTRACT FROM AUTHOR]

Background: People with Multiple Sclerosis (PwMS) often experience imbalance, gait dysfunction, and fatigue. Circuit Training (CT) can be viable for improving balance, gait, and fatigue in MS. To the author's knowledge, no studies have systematically reviewed the existing literature evaluating the effectiveness of CT in PwMS., Objectives: To investigate the effectiveness of CT in improving balance, gait, and reducing fatigue in PwMS and provide a quantitative and qualitative synthesis of Randomized Controlled Trials (RCTs)., Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Google Scholar, and PEDro Database (Dec 2021 to May 2024)., Study Selection: RCTs using CT in PwMS including balance, gait, or fatigue outcomes., Data Synthesis: Search inclusion criteria were: i) available full text, ii) CT rehabilitation, iii) balance, gait, or fatigue measured as outcomes, and iv) articles in English. Full text articles were analyzed by two screeners. If there was disagreement regarding inclusion, a further reviewer was consulted. No discrepancies were found., Results: We identified 878 studies, 14 studies were eligible including 716 PwMS with a mean (standard deviation) age of 49.9 (10.9) years, disease duration of 10.8 (7.2) years, and Expanded Disability Status Scale score of 4.3 (0.9) points. RevMan 5.4.1 was used to run the meta-analysis. We found a significant overall effect on Berg Balance Scale (Mean Difference (MD) = 6.07 points, 95%CI:1.40,10.75; p = 0.01) and in Fatigue Severity Scale (MD = 0.98 points, 95%CI:0.30,1.66; p = 0.005) in favor of CT. We did not find a significant effect in Timed Up and Go (MD = 0.46 second, 95%CI:-0.04,0.96; p = 0.07), in Six-Minute Walk Test (MD = 17.46 m, 95%CI:-8.06,42.97; p = 0.18), and in Modified Fatigue Impact Scale (MD = 3.34 points, 95%CI:-0.41,7.09; p = 0.08) in favor of CT. We assessed methodological quality using RoB 2.0, and quality of evidence using GRADE., Limitations: Small number of studies, all identifying having some risk of bias., Conclusion: Circuit training can have positive effects on PwMS in terms of increasing balance, gait, and reducing fatigue. Further research is needed., Systematic Review Registration Number: PROSPERO CRD42021286834. CONTRIBUTION OF THE PAPER., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Reduced walking endurance is common in people with multiple sclerosis (PwMS), leading to reduced social participation and increased fall risk. This highlights the importance of identifying which gait aspects should be mostly targeted by rehabilitation to maintain/increase walking endurance in this population. A total of 56 PwMS and 24 healthy subjects (HSs) executed the 6 min walk test (6 MWT), a clinical measure of walking endurance, wearing three inertial sensors (IMUs) on their shanks and lower back. Five IMU-based digital metrics descriptive of different gait domains, i.e., double support duration, trunk sway, gait regularity, symmetry, and local dynamic instability, were computed. All metrics demonstrated moderate-high ability to discriminate between HSs and PwMS (AUC: 0.79-0.91) and were able to detect differences between PwMS at minimal (PwMS mFR ) and moderate-high fall risk (PwMS FR ). Compared to PwMS mFR , PwMS FR walked with a prolonged double support phase (+100%), larger trunk sway (+23%), lower stride regularity (-32%) and gait symmetry (-18%), and higher local dynamic instability (+24%). Normative cut-off values were provided for all metrics to help clinicians in detecting abnormal scores at an individual level. The five metrics, entered into a multiple linear regression model with 6 MWT distance as the dependent variable, showed that gait regularity and the three metrics most related to dynamic balance (i.e., double support duration, trunk sway, and local dynamic instability) were significant independent contributors to 6 MWT distance, while gait symmetry was not. While double support duration and local dynamic instability were independently associated with walking endurance in both PwMS mFR and PwMS FR , gait regularity and trunk sway significantly contributed to 6 MWT distance only in PwMS mFR and PwMS FR , respectively. Taken together, the present results allowed us to provide hints for tailored rehabilitation exercises aimed at specifically improving walking endurance in PwMS.

Context: Chronic Neurological Disorders (CNDs) are among the leading causes of disability worldwide, and their contribution to the overall need for rehabilitation is increasing. Therefore, the identification of new digital solutions to ensure early and continuous care is mandatory., Objective: This protocol proposes to test the usability, acceptability, safety, and efficacy of Telerehabilitation (TR) protocols with digital and robotic tools in reducing the perceived level of disability in CNDs including Parkinson's Disease (PD), Multiple Sclerosis (MS), and post-stroke patients., Design Setting and Subjects: This single-blinded, multi-site, randomized, two-treatment arms controlled clinical trial will involve PD (N = 30), MS (N = 30), and post-stroke (N = 30). Each participant will be randomized (1:1) to the experimental group (20 sessions of motor telerehabilitation with digital and robotic tools) or the active control group (20 home-based motor rehabilitation sessions according to the usual care treatment). Primary and secondary outcome measures will be obtained at the baseline (T0), post-intervention (T1, 5 weeks after baseline), and at follow-up (T2, 2 months after treatment)., Main Outcome Measures: a multifaceted evaluation including quality of life, motor, and clinical/functional measures will be conducted at each time-point of assessment. The primary outcome measures will be the change in the perceived level of disability as measured by the World Health Organization Disability Assessment Schedule 2.0., Conclusion: The implementation of TR protocols will enable a more targeted and effective response to the growing need for rehabilitation linked to CNDs, ensuring accessibility to rehabilitation services from the initial stages of the disease., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Limited longitudinal studies have been conducted on gait impairment progression overtime in non-disabled people with multiple sclerosis (PwMS). Therefore, a deeper understanding of gait changes with the progression of the disease is essential. The objective of the present study was to describe changes in gait quality in PwMS with a disease duration ≤ 5 years, and to verify whether a change in gait quality is associated with a change in disability and perception of gait deterioration. We conducted a multicenter prospective cohort study. Fifty-six subjects were assessed at baseline (age: 38.2 ± 10.7 years, Expanded Disability Status Scale (EDSS): 1.5 ± 0.7 points) and after 2 years, participants performed the six-minute walk test (6MWT) wearing inertial sensors. Quality of gait (regularity, symmetry, and instability), disability (EDSS), and walking perception (multiple sclerosis walking scale-12, MSWS-12) were collected. We found no differences on EDSS, 6MWT, and MSWS-12 between baseline and follow-up. A statistically significant correlation between increased EDSS scores and increased gait instability was found in the antero-posterior (AP) direction (r = 0.34, p = 0.01). Seventeen subjects (30%) deteriorated (increase of at least 0.5 point at EDSS) over 2 years. A multivariate analysis on deteriorated PwMS showed that changes in gait instability medio-lateral (ML) and stride regularity, and changes in ML gait symmetry were significantly associated with changes in EDSS (F = 7.80 (3,13), p = 0.003, R 2 = 0.56). Moreover, gait changes were associated with a decrease in PwMS perception on stability ( p < 0.05). Instrumented assessment can detect subtle changes in gait stability, regularity, and symmetry not revealed during EDSS neurological assessment. Moreover, instrumented changes in gait quality impact on subjects' perception of gait during activities of daily living.

Gait analysis is often used to study locomotor alterations in people with multiple sclerosis (PwMS), but the large number of extracted variables challenges the interpretability. In this paper, we analysed gait alterations by combining the Gait Profile Score (GPS), which summarizes kinematic locomotor deviations, and Statistical Parametric Mapping (SPM), which compares kinematics and kinetics over the whole gait cycle. Eleven PwMS and 11 speed-matched Healthy Controls (HC) underwent overground gait analysis. GPS were compared through independent-samples t-tests; sagittal-plane kinematics and power at hip, knee, and ankle were compared through SPM Hotelling's-T2 and SPM t-tests. Spearman's correlation coefficients (r) between GPS and clinical outcomes were also calculated. PwMS had higher GPS than HC (PwMS = 8.74 ± 2.13°; HC = 5.01 ± 1.41°;p < 0.001). Multivariate SPM found statistically significant differences at 0-49%, 70-80%, and 93-99% of stride (p < 0.05) and univariate analysis showed reduced ankle dorsiflexion, and lower knee flexion during pre-swing and swing. GPS correlated with Expanded Disability Status Scale (r = 0.65; 95%C.I.[0.04,0.91]; p = 0.04) and 2-Minute Walking Test (r = -0.65; 95%C.I.[-0.91,-0.04]; p = 0.04). GPS in conjunction with SPM revealed multi-joint kinematic alterations on sagittal plane involving distal joint angles, ankle and knee, during the stance phase with no changes at the proximal level. Gait deviations were more pronounced in PwMS with higher disability and walking limitations., (© 2023. The Author(s).)

Poor dynamic balance and impaired gait adaptation to different contexts are hallmarks of people with neurological disorders (PwND), leading to difficulties in daily life and increased fall risk. Frequent assessment of dynamic balance and gait adaptability is therefore essential for monitoring the evolution of these impairments and/or the long-term effects of rehabilitation. The modified dynamic gait index (mDGI) is a validated clinical test specifically devoted to evaluating gait facets in clinical settings under a physiotherapist's supervision. The need of a clinical environment, consequently, limits the number of assessments. Wearable sensors are increasingly used to measure balance and locomotion in real-world contexts and may permit an increase in monitoring frequency. This study aims to provide a preliminary test of this opportunity by using nested cross-validated machine learning regressors to predict the mDGI scores of 95 PwND via inertial signals collected from short steady-state walking bouts derived from the 6-minute walk test. Four different models were compared, one for each pathology (multiple sclerosis, Parkinson's disease, and stroke) and one for the pooled multipathological cohort. Model explanations were computed on the best-performing solution; the model trained on the multipathological cohort yielded a median (interquartile range) absolute test error of 3.58 (5.38) points. In total, 76% of the predictions were within the mDGI's minimal detectable change of 5 points. These results confirm that steady-state walking measurements provide information about dynamic balance and gait adaptability and can help clinicians identify important features to improve upon during rehabilitation. Future developments will include training of the method using short steady-state walking bouts in real-world settings, analysing the feasibility of this solution to intensify performance monitoring, providing prompt detection of worsening/improvements, and complementing clinical assessments., (© 2023. The Author(s).)

Dynamic balance disorders are common impairments in People with Multiple Sclerosis (PwMS) leading to gait disorders and a higher risk of falling. However, the assessment of dynamic balance is still challenging and instrumented indexes provide objective and quantitative data of CoM movement and Base of Support, which are considered that are two key factors describing dynamic balance. This study aims at validating recent instrumented indexes based on the inverted pendulum model and characterizing dynamic balance disorders in PwMS. We clinically assessed 20 PwMS and we collected instrumented gait data through an optoelectronic system. Data from 20 Healthy Subjects (HS) were also considered as normative reference. Margin of Stability by HoF (MoS&#95;Hof) and by Terry (MoS&#95;Terry) at midstance, and Foot Placement Estimator (D FPE ) at heel strike were calculated in mediolateral (ML) and anteroposterior (AP) directions, for both less affected and most affected sides for PwMS and for dominant and non-dominant side for HS. MoS&#95;HOF well discriminated between PwMS and HS, followed by MoS&#95;TERRY in ML direction (Mos&#95;HOF: PwMS = 130.0 ± 27.2 mm, HS = 106.5 ± 18.6 mm, p  < 0.001, MoS&#95;TERRY: PwMS = 75.1 ± 24.3 mm, HS = 56.5 ± 23.4 mm, p  < 0.02). MoS&#95;HOF and MoS&#95;TERRY discriminated between sides in both directions in PwMS. D FPE did not discriminate between groups and sides. Moderate correlations were found between all three indexes and clinical balance scales (from r  = 0.02 to r  = 0.66), energy recovery (from r  = -0.77 to r  = -0.11), single stance time (from r  = -0.11 to r  = 0.80) and step length (from r  = -0.83 to r  = -0.20). MoS&#95;HOF resulted in the best index to describe dynamic balance disorders in PwMS: they keep CoM position far from the lateral and as close as possible to the anterior boundary of the Base of Support as preventive strategies to control balance perturbations. Furthermore, PwMS seem to use different preventive strategies in accordance with the specific lower limb impairments. This alters the physiological gait mechanisms increasing the energy expenditure and decreasing gait quality and dynamic balance.

Objective: To assess the benefits of neurological rehabilitation and the dose-response relationship for the treatment of mobility and balance in multiple sclerosis., Methods: We included studies investigating the effects of neurological rehabilitation on mobility and balance with the following eligibility criteria for inclusion: Population, People with Multiple Sclerosis (PwMS); Intervention, method of rehabilitation interventions; Comparison, experimental (specific balance intervention) vs control (no intervention/no specific balance intervention); Outcome, balance clinical scales; Study Design, randomised controlled trials. We conducted a random effects dose-response meta-analysis to assess linear trend estimations and a one stage linear mixed effects meta-regression for estimating dose-response curves., Results: We retrieved 196 studies from a list of 5020 for full text review and 71 studies (n subjects=3306) were included. One study was a cross-over and 70 studies were randomized controlled trials and the mean sample size per study was 46.5 ± 28.6 (mean±SD) with a mean age of 48.3 ± 7.8years, disease duration of 11.6 ± 6.1years, and EDSS of 4.4 ± 1.4points. Twenty-nine studies (40.8%) had the balance outcome as the primary outcome, while 42 studies (59.1%) had balance as secondary outcome or did not specify primary and secondary outcomes. Thirty-three trials (46.5%) had no active intervention as comparator and 38 trials (53.5%) had an active control group. Individual level data from 20 studies (n subjects=1016) were analyzed showing a medium pooled effect size for balance interventions (SMD=0.41; 95% CIs 0.22 to 0.59). Moreover, we analyzed 14 studies (n subjects=696) having balance as primary outcome and BBS as primary endpoint yielding a mean difference of 3.58 points (95% CIs 1.79 to 5.38, p<0.0001). Finally, we performed meta regression of the 20 studies showing an association between better outcome, log of intensity defined as minutes per session (β=1.26; SEβ=0.51; p = 0.02) and task-oriented intervention (β=0.38; SEβ=0.17; p = 0.05)., Conclusion: Our analyses provide level 1 evidence on the effect of balance intervention to improve mobility. Furthermore, according to principles of neurological rehabilitation, high intensity and task-specific interventions are associated with better treatment outcomes., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Falls are a common and persistent concern among people with neurological disorders (PwND), as they frequently result in mobility deficits and may lead to loss of functional independence. This study investigated the ceiling and floor effects, internal consistency, and convergent validity of 2 patient-reported fall prevention strategy scales in PwND., Methods: This is a prospective cohort study. Two-hundred and ninety-nine PwND (111 people with multiple sclerosis, 94 people with Parkinson's disease, and 94 people with stroke) were seen for rehabilitation and assessed. The number of retrospective and prospective falls, use of walking assistive devices, scores on the Fall Prevention Strategy Survey (FPSS), Falls Behavioural Scale (FaB), and balance and mobility scales (Berg Balance Scale, Dynamic Gait Index, Timed Up and Go, 10-m walking test, and Activities-specific Balance Confidence) were analyzed., Results: Total score distributions showed negligible ceiling and floor effects for both the FPSS (ceiling: 0.3%, floor: 0.3%) and the FaB (ceiling: 0%, floor: 0%). The Cronbach α (CI) was of 0.87 (0.85-0.89) for the FPSS and 0.86 (0.84-0.88) for the FaB. In terms of convergent validity, the FPSS and FaB were moderately correlated (Spearman correlation coefficient = 0.65). Moreover, the correlations between the FPSS and FaB and balance and mobility scales ranged from 0.25 to 0.49 ( P < .01). Both scales are slightly better able to distinguish between retrospective fallers/nonfallers [area under the curve, AUC (95% CI): FPSS: 0.61 (0.5-0.7); FaB: 0.60 (0.5-0.6)] compared with prospective fallers/nonfallers [AUC (95% CI): FPSS: 0.56 (0.4-0.6); FaB: 0.57 (0.4-0.6)]. Both scales accurately identified individuals who typically required the use of a walking assistive device for daily ambulation [AUC (95% CI): FPSS: 0.74 (0.7-0.8); FaB: 0.69 (0.6-0.7)]. Multiple regression analysis showed that previous falls, use of an assistive device, and balance confidence significantly predicted participants' prevention strategies (FPSS: R2 = 0.31, F(8,159) = 10.5, P < .01; FaB: R2 = 0.31, F(8,164) = 10.89, P < .01)., Conclusion: The FPSS and the FaB appear to be valid tools to assess fall prevention strategies in people with neurological disorders. Both scales provide unique and added value in providing information on individual behavior for fall prevention., (Copyright © 2021 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

The balance of people with multiple sclerosis (PwMS) is commonly assessed during neurological examinations through clinical Romberg and tandem gait tests that are often not sensitive enough to unravel subtle deficits in early-stage PwMS. Inertial sensors (IMUs) could overcome this drawback. Nevertheless, IMUs are not yet fully integrated into clinical practice due to issues including the difficulty to understand/interpret the big number of parameters provided and the lack of cut-off values to identify possible abnormalities. In an attempt to overcome these limitations, an instrumented modified Romberg test (ImRomberg: standing on foam with eyes closed while wearing an IMU on the trunk) was administered to 81 early-stage PwMS and 38 healthy subjects (HS). To facilitate clinical interpretation, 21 IMU-based parameters were computed and reduced through principal component analysis into two components, sway complexity and sway intensity, descriptive of independent aspects of balance, presenting a clear clinical meaning and significant correlations with at least one clinical scale. Compared to HS, early-stage PwMS showed a 228% reduction in sway complexity and a 63% increase in sway intensity, indicating, respectively, a less automatic (more conscious) balance control and larger and faster trunk movements during upright posture. Cut-off values were derived to identify the presence of balance abnormalities and if these abnormalities are clinically meaningful. By applying these thresholds and integrating the ImRomberg test with the clinical tandem gait test, balance impairments were identified in 58% of PwMS versus the 17% detected by traditional Romberg and tandem gait tests. The higher sensitivity of the proposed approach would allow for the direct identification of early-stage PwMS who could benefit from preventive rehabilitation interventions aimed at slowing MS-related functional decline during neurological examinations and with minimal modifications to the tests commonly performed.

Background: People with Multiple Sclerosis (PwMS) show low levels of physical activity (PA), however there has been limited research on PA in early diagnosed and no/minimally impaired (<5 years, EDSS≤ 2.5) PwMS. The aims of the study were to objectively quantify PA levels in non-disabled PwMS, to compare the time spent daily at different PA levels (No activity (NPA), Light PA (LPA), Moderate PA (MPA), and Vigorous PA (VPA)) with healthy subjects (HS), and to examine the association of PA with disability, and clinical measures in PwMS., Methods: We assessed 58 PwMS (mean age±standard deviation, SD 39.1 ± 10.6years) and 20 HS (mean age±SD 39.3 ± 8.9 years). Demographic and clinical data were recorded at the hospital during the baseline assessment. Subjects wore the wrist GENEActiv accelerometer for 7-days. Data were collected at 100 Hz and summarized into a motor activity (MA) index using 60 s epochs with the following thresholds: MA NPA-LPA: 10mG, MA LPA-MPA : 100mG, MA MPA-VPA : 350mG., Results: PwMS show higher NPA and lower VPA compared to matched healthy subjects (NPA: Mean±SD, HS: 7.2 ± 0.9 h/day; PwMS: 8.1 ± 1.2 h/day, p<0.01; VPA: HS: 0.78± 0.42 h/day; PwMS: 0.50± 0.40 h/day, p = 0.01), while no between group differences were observed for LPA and MPA (p>0.05). Bivariate analysis showed that higher NPA was associated with fatigue (Fatigue Severity Scale, FSS score) in PwMS with EDSS 0-1.5 (r = 0.34, p = 0.05). In PwMS with EDSS 2-2.5, NPA was correlated with Six Minute Walk Test (6MWT, r=-0.45, p = 0.02) and CIQ (r=-0.41, p = 0.04), while VPA was more associated with FSS (R= -0.38, p = 0.06)., Conclusion: The PA level of PwMS differs from that of healthy subjects even in early diagnosed subjects. In PwMS with EDSS 0-1.5 only, fatigue is associated to prolonged inactive behavior. Conversely, in PwMS with EDSS 2-2.5 both inactivity and vigorous activities are modulated by fatigue, endurance and associated with different level of social participation., (Copyright © 2022. Published by Elsevier B.V.)

Background: Heat sensitivity occurs in a high percentage of people with multiple sclerosis (PwMS), in response to environmental or exercise-induced increase in body temperature. However, the kinetic and magnitude of adaptation of the internal load and of the core body temperature (CBT) to a submaximal continuous exercise has been poorly addressed in PwMS; this may be relevant for the brief exercise bouts usually occurring in normal daily life. The aim of this work was to evaluate whether multiple sclerosis influences the acute adaptation of the internal load, the CBT and the perceptual load in response to a constant submaximal work step., Methods: CBT has been continuously monitored (0.5 Hz) by a validated wearable heat-flux sensor and electrocardiography was recorded (250 Hz) by a wearable device during a standard 6-minute walk test (6MWT) in 14 PwMS (EDSS, 4.7 ± 1.2; disease duration: 13.0 ± 10.2 years; m ± SD) and 14 age, sex and BMI-matched healthy subjects (HS). The rate of perceived exertion (RPE) of the lower limbs was assessed during the 6MWT by the Borg scale (6-20)., Results: As expected, PwMS walked a significantly shorter distance (361 ± 98 m) than the HS group (613 ± 62 m, p<0.001 vs PwMS). However, the kinetics of adaptation of CBT and the magnitude of CBT change from baseline did not differ between groups. Similarly, heart rate (HR) kinetics and HR change from baseline were comparable between groups during the 6MWT. Finally, lower limbs RPE gradually increased during the exercise test, but without significant differences between groups., Conclusion: The internal load, the metabolic heat production, and the perceptive load due to a standard submaximal walking exercise seems to be preserved in PwMS, suggesting a comparable acute heat production and dissipation during exercise. Therefore, it is unlikely that the different distance achieved during the 6MWT may be caused by altered thermoregulatory responses to exercise. Rather, this appears to be a consequence of the known increased energy cost of locomotion in PwMS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gervasoni, Bertoni, Anastasi, Solaro, Di Giovanni, Grange, Gunga, Rovaris, Cattaneo, Maggioni and Merati.)

Background: Turning the head while walking (an action often required during daily living) is particularly challenging to maintain balance. It can therefore potentially reveal subtle impairments in early-stage people with multiple sclerosis who still show normal locomotion (NW-PwMS). This would help in identifying those subjects who can benefit from early preventive exercise aimed at slowing the MS-related functional decline., Objectives: To analyze if the assessment of walking with horizontal head turns (WHHT) through inertial sensors can discriminate between healthy subjects (HS) and NW-PwMS and between NW-PwMS subgroups. To assess if the discriminant ability of the instrumented WHHT is higher compared to clinical scores. To assess the concurrent validity of the sensor-based metrics., Methods: In this multicenter study, 40 HS and 59 NW-PwMS [Expanded Disability Status Scale (EDSS) ≤ 2.5, disease duration ≤ 5 years] were tested. Participants executed Item-6 of the Fullerton Advanced Balance scale-short (FAB-s) wearing three inertial sensors on the trunk and ankles. The item required to horizontally turn the head at a beat of the metronome (100 bpm) while walking. Signals of the sensors were processed to compute spatiotemporal, regularity, symmetry, dynamic stability, and trunk sway metrics descriptive of WHHT., Results: Mediolateral regularity, anteroposterior symmetry, and mediolateral stability were reduced in NW-PwMS vs. HS ( p ≤ 0.001), and showed moderate discriminant ability (area under the receiver operator characteristic curve [AUC]: 0.71-0.73). AP symmetry and ML stability were reduced ( p ≤ 0.026) in EDSS: 2-2.5 vs. EDSS: 0-1.5 subgroup (AUC: 0.69-0.70). The number of NW-PwMS showing at least one abnormal instrumented metric (68%) was larger ( p ≤ 0.002) than the number of participants showing abnormal FAB-s-Item6 (32%) and FAB-s clinical scores (39%). EDSS: 2-2.5 subgroup included more individuals showing abnormal instrumented metrics (86%) compared to EDSS: 0-1.5 subgroup (57%). The instrumented metrics significantly correlated with FAB-s-Item6 and FAB-s scores (|Spearman's r | ≥ 0.37, s | ≥ 0.37, p < 0.001), thus demonstrating their concurrent validity., Conclusion: The instrumented assessment of WHHT provided valid objective metrics that discriminated, with higher sensitivity than clinical scores, between HS and NW-PwMS and between EDSS subgroups. The method is a promising tool to complement clinical evaluation, and reveal subclinical impairments in persons who can benefit from early preventive rehabilitative interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carpinella, Gervasoni, Anastasi, Di Giovanni, Tacchino, Brichetto, Confalonieri, Solaro, Rovaris, Ferrarin and Cattaneo.)

Background: Balance and gait impairments increase fall rate and injury in people with neurological disorders(PwND). The modified Dynamic Gait Index(mDGI) is a scale assessing dynamic balance during walking, however its ability in identifying Fallers and Recurrent Fallers has not been studied., Research Question: To evaluate mDGI's ability in identifying retrospective Fallers and Recurrent Fallers establishing cut-off scores for its use in clinical practice., Method: In this cross-sectional study, the number of retrospective falls and mDGI scores were collected. PwND were categorised as Non-Fallers or Fallers (falls≥1) and as Recurrent Fallers(falls≥2) or Non-Recurrent/Non-Fallers(falls<2) according to their number of retrospective falls over two months. Two generalised linear logistic models were developed using a machine learning method to detect Fallers (Model 1) and Recurrent Fallers (Model 2) based on mDGI scores. ROC curves were used to identify mDGI cut-off scores to distinguish between different fall categories., Results: 58 PwND (mean ± standard deviation age: 63.4 ± 12 years) including 28 people with Multiple Sclerosis, 15 people with Parkinson's disease and 15 people with Stroke were analysed. The mDGI score(median (IQR)) for Non-Fallers, Fallers, Recurrent Fallers and Non-Recurrent/Non-Fallers was respectively 50(22), 37(22), 26.5(20.25) and 46.5(20.5)points. The cut-off to identify Fallers from Non-Fallers was 49 points(sensitivity:100 %, specificity:50 %, post-test probability with mDGI ≤ cut-off: 53.2 %, post-test probability with mDGI > cut-off: 0%, AUC:0.68), while 29 points(sensitivity:60 %, specificity:79 %, post-test probability with mDGI ≤ cut-off:52.1 %, post-test probability with mDGI > cut-off:16.1 %, AUC:0.70) was the best cut-off to identify Recurrent Fallers., Significance: People with mDGI score>49 points have low or minimal fall risk, while people with mDGI score≤49 points should be further investigated with other scales before starting a balance-focused rehabilitation intervention. People scoring ≤29 points on the mDGI scale may need a fall prevention intervention, regardless of the results of other balance clinical measures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Motor and cognitive disorders appear early in the course of multiple sclerosis (MS) and develop gradually over time., Objective: To study the frequency and pattern of subtle functional disorders in people with MS (PwMS) with no overt signs of disability in an early phase of the disease and their association with walking impairments in daily activities., Methods: In this cross-sectional study, we recruited PwMS with an Expanded Disability Status Scale (EDSS) score≤2.5 and disease duration≤5years. Participants were assessed with functional scales rating walking endurance (6-Min Walk Test), perceived walking ability (Twelve-item Multiple Sclerosis Walking Scale), balance (Fullerton Advanced Balance scale&#95;short), manual dexterity (Nine Hole Peg Test), fatigue (Fatigue Severity Scale), and cognitive impairments (Brief International Cognitive Assessment)., Results: About 90% of the 82 PwMS (mean [SD] EDSS score 1.5 [0.7] and disease duration 2.2 [1.7] years) showed endurance values below the expected score; almost 30% showed impairment, and for 57%, perceived walking ability score was abnormal. Balance was impaired in 48% of participants, as was manual dexterity (29%) and fatigue (24%), but only a few showed cognitive impairments. Only 11% of PwMS had no abnormal score on the scales used in the assessment. As compared with EDSS score 0 to 1.5, with EDSS score 2 to 2.5, performance was worse for endurance (difference±61.0m, P=0.016), perceived walking ability (-11 points, P=0.002), balance (+1.9 points, P=0.005), manual dexterity (-2.8 s, P=0.004), and fatigue (-1.3 points, P=0.013). Factors that predicted perceived walking ability were balance (B=-1.37, P<0.001) and fatigue (B=5.11, P<0.001) rather than endurance (B=-0.01, P=048)., Conclusion: Even PwMS with no clinical disability and classified as having "no problem walking" present walking and other functional deficits when assessed with specific functional tests. The addition of specific tools could better identify subtle motor and cognitive deficits. Finally, the assessment of balance disorders and fatigue is important to understand individuals' perceived walking impairments in daily activities., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The minimal clinically important difference (MCID) of modified Dynamic Gait Index (mDGI) has not yet been determined for People with Neurological Disorders (PwND)., Research Question: To establish the MCID of the mDGI to determine clinically meaningful improvement in balance and gait in PwND., Methods: In this longitudinal study from a randomised clinical trial, 55 participants both in and outpatients with neurological disorders, received fifteen 40-minute rehabilitation sessions. Inpatients received daily treatments over a period of three weeks while outpatients received three treatments/week over a period of five weeks. An anchor-based method using percentage rating of improvement in balance (Activities Balance Confidence scale, ABC) was used to determine the MCID of mDGI. The MCID was defined as the minimum change in mDGI total score (post - pre intervention) that was needed to perceive at least a 10 % improvement on the ABC scale. A Receiver Operating Characteristic curve was used to define the cut-off for the optimal MCID of the mDGI discriminating between improved and not improved participants., Results: The MCID of the mDGI total score was 6 points and Area under the Curve was 0.64. For the mDGI time sub-scores the MCID was 2 points and Area under the Curve was 0.6., Significance: The MCID of balance and gait improvement measured by mDGI was prudently establish at ≥7 points, meaning that this is the minimum improvement score PwND need to get to perceive a clinically relevant change in their balance and gait confidence. These reference values can be a tool incorporated into clinicians daily practice to interpret mDGI change scores helping to determine whether the intervention is effective; to develop clinical tailored intervention goals and to establish meaningful perceived change in PwND., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: The rapid development of electromechanical and robotic devices has profoundly influenced neurorehabilitation. Growth in the scientific and technological aspects thereof is crucial for increasing the number of newly developed devices, and clinicians have welcomed such growth with enthusiasm. Nevertheless, improving the standard for the reporting clinical, technical, and normative aspects of such electromechanical and robotic devices remains an unmet need in neurorehabilitation. Accordingly, this study aimed to analyze the existing literature on electromechanical and robotic devices used in neurorehabilitation, considering the current clinical, technical, and regulatory classification systems., Evidence Acquisition: Within the CICERONE Consensus Conference framework, studies on electromechanical and robotic devices used for upper- and lower-limb rehabilitation in persons with neurological disabilities in adulthood and childhood were reviewed. We have conducted a literature search using the following databases: MEDLINE, Cochrane Library, PeDro, Institute of Electrical and Electronics Engineers, Science Direct, and Google Scholar. Clinical, technical, and regulatory classification systems were applied to collect information on the electromechanical and robotic devices. The study designs and populations were investigated., Evidence Synthesis: Overall, 316 studies were included in the analysis. More than half (52%) of the studies were randomised controlled trials (RCTs). The population investigated the most suffered from strokes, followed by spinal cord injuries, multiple sclerosis, cerebral palsy, and traumatic brain injuries. In total, 100 devices were described; of these, 19% were certified with the CE mark. Overall, the main type of device was an exoskeleton. However, end-effector devices were primarily used for the upper limbs, whereas exoskeletons were used for the lower limbs (for both children and adults)., Conclusions: The current literature on robotic neurorehabilitation lacks detailed information regarding the technical characteristics of the devices used. This affects the understanding of the possible mechanisms underlying recovery. Unfortunately, many electromechanical and robotic devices are not provided with CE marks, strongly hindering the research on the clinical outcomes of rehabilitation treatments based on these devices. A more significant effort is needed to improve the description of the robotic devices used in neurorehabilitation in terms of the technical and functional details, along with high-quality RCT studies.

Maintaining a stable gait requires a dynamic balance control, that can be altered in persons with Multiple Sclerosis (MS), Stroke (ST), and Parkinson's disease (PD). The understanding of the strategy for Center of Mass (CoM) positioning adopted by patients during walking is important to be able to program treatments aimed at improving gait control and preventing falls. Forty-four persons with a mild-to-moderate neurological disorder (20 with MS, 14 with ST, 10 with PD) underwent clinical examination and gait analysis. Ten Healthy Subjects (HS) walking at matched speed provided the normative data. Dynamic balance was assessed using the margin of stability (MoS). It was calculated as the distance between the extrapolated Center of Pressure and the extrapolated CoM at mid-stance. The MoS values for lower limbs were calculated in patients and compared with speed-matched values of HS. Persons with neurological disorder showed increased MoS in the medio-lateral direction with respect to HS. Within-group comparison analysis showed a symmetry between lower limbs in HS (Mean (95%CI) [mm], dominant vs non-dominant limb, 43.3 (31.9-54.6) vs 42.9 (28.8-56.9)) and PD (less affected vs more affected limb, 71.1 (59.8-82.5) vs 72.5 (58.5-86.6)), while a significant asymmetry was found in MS (54.4 (46.4-62.4) vs 81.1 (71.2-91.1)) and ST (52.1 (42.6-61.7) vs 74.7 (62.8-86.6)) participants. The history of falls was comparable among PD, MS, and ST groups, and the MoS in the frontal plane showed a strong correlation with these records. Objective assessment of MoS revealed pathology-specific strategies showing different impacts in MS, ST, and PD on the ability to control CoM information to manage the balance between limbs during gait. MoS evaluation will provide useful information to address a tailored rehabilitation program and to monitor disease progression.

Background and Purpose: People with multiple sclerosis (PwMS) often report walking limitations even when the gold standard Expanded Disability Status Scale (EDSS) indicates normal walking endurance/autonomy. The present multicenter study on early-stage PwMS aims at analyzing which aspects are associated with patient-reported walking limitations measured with the 12-item Multiple Sclerosis Walking Scale (MSWS-12)., Methods: Eighty-two PwMS (EDSS ≤ 2.5) were assessed using the Fullerton Advanced Balance Scale-short (FAB-s), the Fatigue Severity Scale (FSS) and the 6-min Walk Test (6MWT), the latter administered also to 21 healthy subjects. Participants performed the 6MWT wearing three inertial sensors on ankles and trunk. Instrumented metrics describing gait velocity (stride length and frequency) and quality (regularity, symmetry, instability) were computed from sensor data. Fatigue (FSS), balance (FAB-s), walking endurance (6MWT) and instrumented metrics were entered in a multiple regression model with MSWS-12 as dependent variable., Results: Gait symmetry, gait instability, fatigue and balance were significantly associated with self-rated walking ability, whilst walking endurance and velocity were not. Fatigue, balance, gait symmetry and instability were more impaired in participants reporting mild-to-moderate (MS MM-PWL , 25 ≤ MSWS-12 < 75) compared to those reporting none-to-minimal (MS nm-PWL , 0 ≤ MSWS-12 ≤ 25) perceived walking limitations. Compared to healthy subjects, gait symmetry and stability were reduced in MS nm-PWL and MS MM-PWL , even in those participants with EDSS ≤ 1.5., Conclusion: Instrumentally assessed gait quality aspects (symmetry and instability) are associated with patient-reported walking ability in early-stage PwMS and seem sensitive biomarkers to detect subtle impairments even in the earliest stages of the disease (EDSS ≤ 1.5). Future studies should assess their ability to follow walking change due to MS progression or pharmacological/rehabilitation interventions., (© 2021 European Academy of Neurology.)

Wearable devices are used in rehabilitation to provide biofeedback about biomechanical or physiological body parameters to improve outcomes in people with neurological diseases. This is a promising approach that influences motor learning and patients' engagement. Nevertheless, it is not yet clear what the most commonly used sensor configurations are, and it is also not clear which biofeedback components are used for which pathology. To explore these aspects and estimate the effectiveness of wearable device biofeedback rehabilitation on balance and gait, we conducted a systematic review by electronic search on MEDLINE, PubMed, Web of Science, PEDro, and the Cochrane CENTRAL from inception to January 2020. Nineteen randomized controlled trials were included (Parkinson's n = 6; stroke n = 13; mild cognitive impairment n = 1). Wearable devices mostly provided real-time biofeedback during exercise, using biomechanical sensors and a positive reinforcement feedback strategy through auditory or visual modes. Some notable points that could be improved were identified in the included studies; these were helpful in providing practical design rules to maximize the prospective of wearable device biofeedback rehabilitation. Due to the current quality of the literature, it was not possible to achieve firm conclusions about the effectiveness of wearable device biofeedback rehabilitation. However, wearable device biofeedback rehabilitation seems to provide positive effects on dynamic balance and gait for PwND, but higher-quality RCTs with larger sample sizes are needed for stronger conclusions.

Introduction: In recent years, robot-assisted gait training (RAGT) has been proposed as therapy for balance and gait dysfunctions in people with multiple sclerosis (PwMS). Through this systematic review, we aimed to discuss the impact of RAGT on balance and gait outcomes. Furthermore, characteristics of the training in terms of robots used, participants characteristics, protocols and combined therapeutic approaches have been described., Evidence Acquisition: As part of the Italian Consensus on robotic rehabilitation "CICERONE" a systematic search was provided in PubMed, the Cochrane Library and PEDro to identify relevant studies published before December 2019. Only randomized control trials (RCT) involving RAGT for PwMS were included. PEDro scale was used to assess the risk of bias and the Oxford Center for Evidence-Based Medicine (OCEBM) was used to assess level of evidence of included studies., Evidence Synthesis: The search on databases resulted in 336 records and, finally, 12 studies were included. RAGT was provided with Exoskeleton in ten studies (6-40 session, 2-5 per week) and with end-effector in two studies (12 sessions, 2-3 per week) with large variability in terms of participants' disability. All the exoskeletons were combined with bodyweight support treadmill and movement assistance varied from 0% to 100% depending on participants' disability, two studies combined exoskeleton with virtual reality. The end-effector speed ranged between 1.3 and 1.8 km/h, with bodyweight support starting from 50% and progressively reduced. In seven out of twelve studies RAGT was provided in a multimodal rehabilitation program or in combination with standard physical therapy. There is level 2 evidence that RAGT has positive impact in PwMS, reaching the minimally clinically importance difference in Berg Balance Scale, six-minute walking test and gait speed., Conclusions: In available RCT, RAGT is mostly provided with exoskeleton devices and improves balance and gait outcomes in a clinically meaningful way. Considering several advantages in terms of safety, motor assistance and intensity of training provided, RAGT should be promoted for PwMS with severe disability in a multimodal rehabilitation context as an opportunity to maximize recovery.

Introduction: Persons with MS (PwMS) have markedly reduced push-off and toe-clearance during gait compared to healthy subjects (HS). These deficits may result from alterations in neuromotor control at the ankle. To optimize rehabilitation interventions for PwMS, a crucial step is to evaluate if and how altered neuromotor control, as represented by muscle synergies, improves with rehabilitation. In this study we investigated changes in ankle motor control and associated biomechanical parameters during gait in PwMS, occurring with increase in speed after gait rehabilitation. Methods: 3D motion and EMG data were collected while 11 PwMS (age 50.3 + 11.1; EDSS 5.2 + 1.2) walked overground at self-selected speed before (T0) and after 20 sessions (T1) of intensive treadmill training. Muscle synergies were extracted using non-negative matrix factorization. Gait parameters were computed according to the LAMB protocol. Pearson's correlation coefficient was used to evaluate the similarity of motor modules between PwMS and HS. To assess differences in distal module activations representing neuromotor control at the ankle [Forward Propulsion (FPM) and Ground Clearance modules (GCM)], each module's activation timing was integrated over 100% of the gait cycle and the activation percentage index (API) was computed in six phases. Ten age matched HS provided two separate speed-matched normative datasets for T0 and T1. For speed independent comparison for the PwMs Z scores were calculated for all their gait variables. Results: In PwMS velocity increased significantly from T0 to T1 (0.74-0.90 m/s, p < 0.05). The activation profiles (API) of FPM and GCM of PwMS improved in pre-swing ( p < 0.05): FPM (Mean [95% CI] [%]: T0: 12.5 [5.7-19.3] vs. T1: 9.0 [2.7-15.3]); GCM (T0: 26.7 [18.2-35.3] vs. T1: 24.5 [18.2-30.7]). This was associated with an increase in toe clearance (80.3 to 103.6 mm, p < 0.05) and a higher ankle power peak in pre-swing (1.53-1.93 W/kg, p < 0.05). Conclusion: Increased gait speed of PwMS after intensive gait training was consistent with improvements in spatio-temporal gait parameters. The most important finding of this study was the re-organization of distal leg modules related to neurophysiological changes induced by rehabilitation. This was associated with an improved ankle performance., (Copyright © 2020 Jonsdottir, Lencioni, Gervasoni, Crippa, Anastasi, Carpinella, Rovaris, Cattaneo and Ferrarin.)

Objective: To validate the Fullerton Advanced Balance (FAB) scale for high-functioning non-disabled people with multiple sclerosis (PwMS)., Design: Cross-sectional study., Participants: A convenience sample of early-diagnosed PwMS (N = 82; Expanded Disability Status Scale score ≤ 2.5) with disease duration ≤ 5 years and a control group of healthy volunteers (N = 45)., Main Outcome Measures: FAB scale, Timed Up and Go test (TUG), 6 Min Walk Test (6MWT) and 25 Foot Walk Test (25FWT)., Results: Six of the ten original FAB scale items were selected to represent a unidimensional construct. Only one factor with eigenvalues > 1.0 (1.90) was found. The new version of the scale reported a Cronbach alpha value of 0.65, and it was also statistically significantly correlated with TUG (r = -0.48). The new six-item scale, dubbed the FAB-short scale (FAB-s), discriminated between healthy volunteers and PwMS; moreover, both the FAB-s and the TUG test discriminated between the two PwMS subgroups: EDSS=0-1.5 (no disability) and EDSS=2-2.5 (minimal disability)., Conclusions: FAB-s is a unidimensional clinical tool for assessing balance. The scale is a promising instrument for detecting subtle changes in balance performance in high-functioning PwMS., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Poor dynamic balance, such as poor walking stability, is a hallmark of multiple sclerosis. Instrumental measures of local dynamic stability (LDS, e.g. short-term Lyapunov's exponents, sLyEs) are genuine measures of walking stability and increasingly used as dynamic balance indicators. The current work aims to investigate if people with multiple sclerosis (PWMS) with no clinical evidence of gait impairment suffer poor LDS of gait. Eighty PWMS with minimal impairment (EDSS ≤2.5) and twenty controls completed the Six-Minute Walk Test (6MWT) at their maximum speed, wearing inertial sensors. sLyEs were calculated from trunk vertical, mediolateral and anteroposterior (sLyE AP ) acceleration. PWMS also completed a full clinical assessment including gait, balance and fatigue. Gait speed was lower in PWMS than controls (-15%), while sLyEs were larger in PWMS (+12%), even when adjusting for the different gait speed. High sLyE AP was associated with low gait speed, high impact of disease (including high fatigue) and poor balance, the three variables returned by a principal component analysis of the dataset of clinical measures. PWMS suffer poor LDS of gait, as indicated by large sLyEs. The association between high sLyE AP and poor balance supports the validity of sLyE AP as a dynamic balance measure. The inverse relationship between sLyE AP and gait speed is in line with the view that good balance is decisive for high gait speed. Finally, these findings are in line with the vicious circle linking poor balance and fatigue in PWMS, with fatigue worsening balance and poor balance leading to fatigue.

Background: Heart Rate Recovery (HRR) after a physical exercise has been poorly investigated in people with multiple sclerosis (PwMS)., Objective: To evaluate the kinetics of HRR and its autonomic modulation in PwMS and to elucidate the interplay between HRR and subjective fatigue., Methods: ECG was digitally acquired during rest (5 min), submaximal exercise (4 min at 10 W of upper limb cycling) and recovery (3 min) in 17 PwMS (EDSS: 5.9 ± 1.2, mean±standard deviation) and 17 healthy control (HC) subjects. Short-term (first 30 s) and long-term (up to180 s) validated indices of HRR were calculated. The time course of the parasympathetic index of heart rate variability RMSSD (Root Mean Square of Successive Differences) was computed every 30 s of recovery. Subjective fatigue was evaluated by the Borg scale applied to breathing and upper limbs., Results: In comparison with HC, the short-term HRR indices were significantly slower (P < 0.05) in PwMS, whereas the long-term ones did not. The time course of RMSSD was significantly different in PwMS (P < 0.05). HRR and HRV indexes did not correlate with fatigue perception and baseline HRV values., Conclusion: The cardiac parasympathetic reactivation from a submaximal exercise was blunted in PwMS, thereby slowing the short-term phase of HRR. This may contribute to the higher cardiovascular risk in PwMS, but the mechanism needs further investigation. The parasympathetic impairment during post-exercise HR reactivation cannot be predicted by baseline HRV values and may therefore be revealed only by an appropriate provocative low-intensity physical test., (Copyright © 2020 Elsevier B.V. All rights reserved.)