Clinical correlation between disease progression and central vein sign in pediatric onset multiple sclerosis: A binational study.

BACKGROUND: The central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered. OBJECTIVES: To investigate the appearance of CVS and its correlation with POMS disease progression. METHODS: One hundred fifty-six POMS from two MS centers in Israel and Czech Republic MS centers were followed for five years. Patient assessment was performed by the Expanded Disability Status Scale (EDSS) and Annual Relapse Rate (ARR). Patients in whom at least 40 % of brain MRI lesions had CVS ("rule of 40") were determined as CVS-positive. RESULTS: The total group of POMS consisted of 96 CVS-negative (61.5 %), aged 14.6 ± 1.9 years, EDSS 2.0, 75 % Interquartile Range (IQR) 1.0-3.0, disease duration (DD) 6.28 ± 0.38 years, and 60 CVS-positive (38.5 %), aged 15.1 ± 0.3 years, EDSS 2.0, IQR 1.5-3.0, DD 5.62 ± 0.13 years, were analyzed. After a three and five-year follow-up, the CVS-positive patients had higher EDSS scores than those who were CVS-negative, 2.0, IQR 1.0-2.5, vs 1.0, IQR 1.0-2.0, (p = 0.009) and 2.0, IQR 1.0-3.25 vs 1.0, IQR 1.0-2.0, (p = 0.0003), respectively. Patients with CVS-positive POMS were characterized by a significantly higher ARR (0.78 ± 0.08 vs 0.57 ± 0.04, p = 0.002). These results were confirmed in subgroups of Disease Modifying Treatments (DMT) untreated and treated patients. CONCLUSION: CVS-positive POMS is characterized by higher disability progression than CVS-negative, indicating the importance of CVS in disease pathogenesis.

The association of fear of falling and falls with sedentary behavior in people with multiple sclerosis.

OBJECTIVE: Sedentary behavior, falls, and fear of falling (FoF) are specific concerns for people with MS (pwMS). Considering the relatively high incidence and potential linkage, it is surprising that this triple relationship has as yet not been extensively investigated in pwMS. Thus, the present study aimed to examine the correlates of sedentary behavior with FoF and falls in pwMS. METHODS: Fifty pwMS, 30 women, were admitted to this cross-sectional study. Primary outcome measures included physical activity and sedentary behavior metrics measured by accelerometry, fall status, and FoF. Additional measures included mobility clinical tests, cognition, perceived fatigue, depression, and anxiety. The sample was divided into two subgroups according to the daily Metabolic Equivalent of Task (MET) rate scores; <1.5 was defined as sedentary, ≥1.5 were defined as non-sedentary. Multivariate analysis of variance and linear regression analyses assessed the relationships by using an alpha of 0.05. RESULTS: Sixty-four percent of the sample were classified as sedentary. The sedentary subgroup reported more FoF than the non-sedentary subgroup (32.5 (S·D. = 11.3) vs. 29.9 (S.D. = 9.5); however, no differences were found in fall status between the subgroups. No differences were found for depression, anxiety, cognition, and perceived fatigue between the subgroups. Furthermore, according to the linear regression analysis, FoF explained 23.9% of the variance pertaining to the daily MET rate when controlling for age, gender, disease duration, and disability. CONCLUSIONS: Clinicians are encouraged to incorporate the issue of FoF during standard management, which may represent an opportunity to improve care and reduce sedentary behavior in pwMS.

Attention Deficit/Hyperactivity Disorder in Children with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological autoimmune disease; pediatric-onset multiple sclerosis (POMS) represents 5% to 10% of total MS population. Children with POMS may experience attention difficulties due to the disease's impact on the central nervous system. However, little is known regarding Attention Deficit Hyperactivity Disorder (ADHD) in POMS, and its relation to cognitive performance. METHODS: A retrospective case review was conducted using medical records of 66 children and adolescent patients diagnosed with POMS between 2012 and 2021 in a MS center of a tertiary medical center. All patients had undergone routine clinical neurological examinations and had been assessed for a diagnosis of ADHD by a department pediatric neurologist. In addition, sociodemographic data, disease-related variables, and cognitive performance were collected. RESULTS: Of the 66 patients, 31 (47%) had a diagnosis of ADHD; 29 (44%) had cognitive impairment. Moreover, we identified four different profiles of POMS: those with only ADHD (17, 26%); only cognitive impairment (15, 23%), ADHD and cognitive impairment (14, 21%), and only POMS (20, 30%). A significant difference in disease duration was found among the four profiles [F(3,65) = 8.17, p < .001, η² = 0.29], indicating that patients with ADHD and cognitive impairment were characterized by longer disease duration. CONCLUSIONS: ADHD may be prominently involved in POMS, even during the early stages of the disease and early diagnosis is crucial in order to provide appropriate interventions and support.

Range of motion abnormalities in the lower limb joints during gait in youth with multiple sclerosis.

BACKGROUND: The major objective of this study was to examine whether differences occur in the joint angles of the major lower limb joints while walking in youth with multiple sclerosis (YwMS) compared to age-gender-matched healthy youngsters. METHODS: Gait analysis was collected using a six-camera Cartesian Optoelectronic Dynamic Anthropometer (CODA) 3D motion analysis system. To determine the gait normality in the YwMS group, we compared our results to reference gait data from normal youngsters. Gait data was divided according to gender and age subgroups (8-14, 15-18 years old). RESULTS: The total sample included 26 YwMS (12 girls, 14 boys), 11 in the 8-14 age subgroup, and 15 in the 15-18 age subgroup. The mean expanded disability status scale score was 1.3 (S.D=1.0), indicating minimal disability. The total range of hip motion was significantly less in the YwMS group aged 15-18 (both genders) compared with the normative values. Additionally, the maximum flexion in the knee joint during gait was significantly less in boys in the 15 to 18 age subgroup (p<0.001). No differences were found in the hip and knee joint angles in the 8-14 age subgroup. CONCLUSIONS: YwMS experience modifications in their gait pattern compared with age-gender-matched healthy youngsters. The MS teenagers demonstrated less range of movement in the hip joints and walked slower at a decreased pace than the healthy teenagers. By tracking gait patterns, healthcare providers can identify subtle changes that might facilitate timely interventions to prevent further mobility impairment in this young population.

Between-Day Reliability of the Gait Characteristics and Their Changes During the 6-Minute Walking Test in People With Multiple Sclerosis.

BACKGROUND: Gait characteristics and their changes during the 6-minute walking test (6MWT) in people with multiple sclerosis (pwMS) have been described in the literature, which one may refer to as walking fatigability in the body function level of the International Classification of Functioning, Disability, and Health. However, whether these metrics are reliable is unknown. OBJECTIVE: To investigate the between-day reliability of the gait characteristics and their changes in pwMS and healthy controls (HCs). METHODS: Forty-nine pwMS (EDSS 4.82 ± 1.22 and 54.7 ± 9.36 years) and 23 HCs (50.6 ± 6.1 years) performed the 6MWT, as fast as possible but safely while wearing Inertial Measurement Units. Gait characteristics were measured in the pace, rhythm, variability, asymmetry, kinematics, coordination, and postural control domains and were obtained in intervals of 1 minute during the 6MWT. In addition, gait characteristics change in the last minute compared with the first minute were calculated for all gait variables using a fatigability index (ie, distance walking index). The intraclass correlation coefficient (ICC), Bland-Altman Plots, and Standard error of measurement were applied to investigate reliability. RESULTS: Reliability of gait characteristics, minute-by-minute, and for their changes (ie, using the fatigability index) ranged from poor to excellent (pwMS: ICC 0.46-0.96; HC: ICC 0.09-0.97 and pwMS: ICC 0-0.72; HC: ICC 0-0.77, respectively). CONCLUSION: Besides coordination, at least 1 variable of each gait domain showed an ICC of moderate or good reliability for gait characteristics changes in both pwMS and HC. These metrics can be incorporated into future clinical trials and research on walking fatigability.Clinical Trial Registration: NCT05412043.

The MoXFo initiative - study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis.

BACKGROUND: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. OBJECTIVES: This paper outlines the work of the 'Study design and methodology' group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients. METHODS: The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs). RESULTS: Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework. CONCLUSION: We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.

Correction: Application of eccentric training in various clinical populations: Protocol for a multi-centered pilot and feasibility study in people with low back pain and people with multiple sclerosis.

[This corrects the article DOI: 10.1371/journal.pone.0270875.].

An Immersive Virtual Kitchen Training System for People with Multiple Sclerosis: A Development and Validation Study.

Rehabilitation via virtual reality (VR) training tools allows repetitive, intensive, and task-specific practice in a controlled and safe environment. Our goal was to develop and validate a novel immersive VR system based on the practice of real-life activities in a kitchen environment in people with multiple sclerosis (pwMS) with upper-limb dysfunction. The novel immersive VR kitchen application includes several tasks, i.e., tidying up the kitchen, preparing a hamburger and soup meal, and dish washing. Following the development phase, the system was tested for an 8-week intervention period on a small sample of pwMS suffering from upper-limb dysfunction. The Suitability Evaluation Questionnaire for VR systems served as the primary outcome. The scores for enjoyment, sense of comfort with the system, feelings of success and control, realism, easy-to-understand instructions, assists in rehabilitation therapy, were between 4.0 and 4.6, indicating a high satisfaction. The scores for eye discomfort, dizziness, nausea, and disorientation during practice were between 2.8 and 1.3, indicating a low-to-moderate interference of the system. The virtual kitchen training system is feasible and safe for upper-limb training in pwMS and paves the way for future RCTs to examine the benefits of the system compared with standard care, thus improving the functionality of the upper limbs in pwMS.

Prefrontal hemodynamics during forward and backward walking, with and without a cognitive task, in people with multiple sclerosis.

BACKGROUND: Hemodynamics in the prefrontal cortex (PFC) while walking forward and backward, with and without an additional cognitive task (motor single-task [ST] and motor cognitive dual-task [DT]) have not been studied in people with multiple sclerosis (pwMS). AIM: To investigate the PFC hemodynamics during forward and as well as backward walking, with and without a cognitive task, in pwMS and healthy controls. DESIGN: Observational case-control study. SETTING: Sheba Multiple Sclerosis Center, Tel-Hashomer, Israel. POPULATION: Eighteen pwMS (36.1±11.7 years, 66.6% female) and 17 healthy controls (37.5±13.8 years, 76.5% female). METHODS: Each subject completed four walking trials: ST forward walking, DT forward walking, ST backward walking, DT backward walking. PFC activity for all trials was recorded using functional near-infrared spectroscopy (fNIRS). The PFC was subdivided in the frontal eye field (FEF), frontopolar cortex (FPC) and the dorsolateral PFC (DLPFC). RESULTS: The relative oxygenated hemoglobin (HbO) concentration was higher during the DT forward walking in all PFC subareas compared with the ST forward walking for both groups. The relative HbO concentration was higher during ST backward walking compared with ST forward walking in pwMS (DLPFC, FEF) and the healthy controls (FEF, FPC), specifically during the initial part of the trial. CONCLUSIONS: ST backward walking and DT forward walking impact the hemodynamics at the PFC, although, the difference between pwMS and healthy adults requires further clarification. Future RCT's are encouraged to examine the impact of an intervention program based on DT forward and backward walking on PFC activity in pwMS. CLINICAL REHABILITATION IMPACT: Backward walking increases activity in the PFC region in pwMS. Similarly, when performing a cognitive task while walking forward.

Changes in physiotherapy services and use of technology for people with multiple sclerosis during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has led to reorganization or reduction of neurorehabilitation services for people with multiple sclerosis (PwMS). The aim of this study was to explore the changes in the organizational framework and technology usage in physiotherapy services for PwMS during the COVID-19 pandemic. METHODS: This international cross-sectional survey study was designed, developed, and disseminated by RIMS European Network for Best Practice and Research in Multiple Sclerosis Rehabilitation. Physiotherapists from nine countries (Australia, Belgium, Czech Republic, Ireland, Israel, Italy, Norway, Spain, Turkey) who provided physiotherapy services to PwMS, were invited to complete an online survey to compare physiotherapy delivery to PwMS prior to and during the pandemic period. RESULTS: The survey was completed by 215 physiotherapists. Accessibility, the average number, length and perceived effectiveness of physiotherapy sessions provided to PwMS were significantly reduced during the COVID-19 pandemic (p=0.001). Physiotherapists increased the advice of mobile apps, recorded videos for rehabilitation and exercise websites during the pandemic (p<0.001) while the use of telerehabilitation and virtual reality technology did not change. CONCLUSION: There was of a reduction in the number, duration and perceived effectiveness of rehabilitation sessions for people with multiple sclerosis during the COVID-19 pandemic while use of remote technologies for physiotherapy did not change. To ensure the continuity of physiotherapy for PwMS with complex healthcare needs also during pandemics, the provision of guidelines and training in telehealth technologies in professional education becomes crucial.

A Thematic Survey on the Reporting Quality of Randomized Controlled Trials in Rehabilitation: The Case of Multiple Sclerosis.

BACKGROUND AND PURPOSE: Optimal reporting is a critical element of scholarly communications. Several initiatives, such as the EQUATOR checklists, have raised authors' awareness about the importance of adequate research reports. On these premises, we aimed at appraising the reporting quality of published randomized controlled trials (RCTs) dealing with rehabilitation interventions. Given the breadth of such literature, we focused on rehabilitation for multiple sclerosis (MS), which was taken as a model of a challenging condition for all the rehabilitation professionals.A thematic methodological survey was performed to critically examine rehabilitative RCTs published in the last 2 decades in MS populations according to 3 main reporting themes: (1) basic methodological and statistical aspects; (2) reproducibility and responsiveness of measurements; and (3) clinical meaningfulness of the change. SUMMARY OF KEY POINTS: Of the initial 526 RCTs retrieved, 370 satisfied the inclusion criteria and were included in the analysis. The survey revealed several sources of weakness affecting all the predefined themes: among these, 25.7% of the studies complemented the P values with the confidence interval of the change; 46.8% reported the effect size of the observed differences; 40.0% conducted power analyses to establish the sample size; 4.3% performed retest procedures to determine the outcomes' reproducibility and responsiveness; and 5.9% appraised the observed differences against thresholds for clinically meaningful change, for example, the minimal important change. RECOMMENDATIONS FOR CLINICAL PRACTICE: The RCTs dealing with MS rehabilitation still suffer from incomplete reporting. Adherence to evidence-based checklists and attention to measurement issues and their impact on data interpretation can improve study design and reporting in order to truly advance the field of rehabilitation in people with MS.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A424 ).

Physical Activity in Multiple Sclerosis: Meeting the Guidelines at the Time of the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Regular physical activity (PA) helps to reduce the severity of physical and mental symptoms and improves quality of life in people with multiple sclerosis (PwMS). Based on current evidence and expert opinion, the recent multiple sclerosis guidelines recommend at least 150 minutes/week of PA. This study presents the results of a survey analyzing whether and how PwMS met the guidelines before and during the pandemic. METHODS: We developed and disseminated an international online survey between December 2020 and July 2021, investigating changes in self-reported PA type, duration, frequency, and intensity due to the COVID-19 outbreak in PwMS with differing disability levels. RESULTS: Among respondents (n = 3810), 3725 were eligible. The proportion of those who conducted at least one activity decreased with increasing disability level at both time points (pre and during). Overall 60% of respondents met the guidelines before the pandemic (mild: 64.43%; moderate: 51.53%; severe: 39.34%; χ 2(2) = 109.13, P < 0.01); a reduction of approximately 10% occurred during the pandemic in all disability groups (mild: 54.76%; moderate: 42.47%; severe: 29.48%; χ 2(2) = 109.67, P < 0.01). Respondents with higher disability participated more in physical therapy and less in walking, cycling, and running at both time points. Most respondents reported practicing PA at a moderate intensity at both time points; frequency and duration of sessions decreased as disability level increased. DISCUSSION AND CONCLUSIONS: The percentage of those meeting the guidelines reduced with increasing disability level and during the pandemic. PA type and intensity varied widely across the disability categories. Interventions accounting for disability level are required to enable more PwMS to reap the benefits of PA.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A415 ).

Energy expenditure and perceived effort during uphill and downhill walking in people with multiple sclerosis.

BACKGROUND: Walking on different slopes is a common daily activity for many ambulatory people with multiple sclerosis (pwMS) AIM: Investigate energy expenditure measures of walking on level, uphill and downhill slopes in pwMS. DESIGN: Observational case-control study. SETTING: Sheba Multiple Sclerosis Center, Tel-Hashomer, Israel. POPULATION: Eighteen pwMS; 10 women and 8 men, aged 39.7 (SD=6.8), mean EDSS was 2.9 (SD=1.2) and 23 healthy adults; 8 women and 15 men, aged 37.1 (S.D.=5.3). METHODS: Energy expenditure values were obtained via a metabolic device during four conditions: sitting, comfortable walking, uphill and downhill walking. Each walking trial, obtained on a treadmill, lasted 6-min and were separated by10-min recovery intervals. RESULTS: For both pwMS and healthy controls, the O2 rate and O2 cost was higher during uphill walking compared to level walking and lower during downhill walking compared with level walking. O2 rate and net O2 cost during uphill walking was lower in pwMS compared with the healthy controls. The most demanding effort was during uphill walking, with pwMS rating it more demanding compared with the healthy controls. CONCLUSIONS: Perceived effort of walking on different slopes is not consistent with changes in the energy expenditure values in pwMS. CLINICAL REHABILITATION IMPACT: pwMS describe the effort of walking on different slopes higher than normal, regardless of the energy expenditure values.

Application of eccentric training in various clinical populations: Protocol for a multi-centered pilot and feasibility study in people with low back pain and people with multiple sclerosis.

Physical activity and exercise are effective approaches in prevention and therapy of multiple diseases. Although the specific characteristics of lengthening contractions have the potential to be beneficial in many clinical conditions, eccentric training is not commonly used in clinical populations with metabolic, orthopaedic, or neurologic conditions. The purpose of this pilot study is to investigate the feasibility, functional benefits, and systemic responses of an eccentric exercise program focused on the trunk and lower extremities in people with low back pain (LBP) and multiple sclerosis (MS). A six-week eccentric training program with three weekly sessions is performed by people with LBP and MS. The program consists of ten exercises addressing strength of the trunk and lower extremities. The study follows a four-group design (N = 12 per group) in two study centers (Israel and Germany): three groups perform the eccentric training program: A) control group (healthy, asymptomatic); B) people with LBP; C) people with MS; group D (people with MS) receives standard care physiotherapy. Baseline measurements are conducted before first training, post-measurement takes place after the last session both comprise blood sampling, self-reported questionnaires, mobility, balance, and strength testing. The feasibility of the eccentric training program will be evaluated using quantitative and qualitative measures related to the study process, compliance and adherence, safety, and overall program assessment. For preliminary assessment of potential intervention effects, surrogate parameters related to mobility, postural control, muscle strength and systemic effects are assessed. The presented study will add knowledge regarding safety, feasibility, and initial effects of eccentric training in people with orthopaedic and neurological conditions. The simple exercises, that are easily modifiable in complexity and intensity, are likely beneficial to other populations. Thus, multiple applications and implementation pathways for the herein presented training program are conceivable. Trial registration: DRKS00020483 (DRKS, German Clinical Trials Register; 24th January 2020 -retrospectively registered; https://www.drks.de/DRKS00020483).

Patient-Reported Outcome Measures for Assessing Dual-Task Performance in Daily Life: A Review of Current Instruments, Use, and Measurement Properties.

The patient perspective of dual-task (DT) impairment in real life is unclear. This review aimed (i) to identify patient-reported outcome measures (PROMs) on DT and evaluate their measurement properties and (ii) to investigate the usage of PROMs for the evaluation of DT difficulties. A systematic literature search was conducted using PubMed and Web of Science from inception to March 2022. Methodological quality was evaluated using the COSMIN checklist. Six studies examined the measurement properties of DT PROMs. Nine studies used DT PROMs as the outcome measure. Five PROMs were identified, including the Divided Attention Questionnaire (DAQ), Dual-Task-Impact on Daily-life Activities Questionnaire (DIDA-Q), a Questionnaire by Cock et al. (QOC), Dual-Tasking Questionnaire (DTQ), and Dual-Task Screening-List (DTSL). Fourteen measurement properties were documented: five (35.7%) rated quality as "sufficient", six (42.8%) "insufficient", and three (21.4%) "indeterminate". The quality of evidence for each measurement property ranged from very low to high. While DT performance is investigated in many populations, the use of PROMs is still limited, although five instruments are available. Currently, due to insufficient data, it is not possible to recommend a specific DT PROM in a specific population. An exception is DIDA-Q, which has the highest quality of measurement properties in people with multiple sclerosis.

The Design, Development, and Testing of a Virtual Reality Device for Upper Limb Training in People With Multiple Sclerosis: Single-Center Feasibility Study.

BACKGROUND: Multiple sclerosis (MS) is a common nontraumatic, neurological, disabling disease that often presents with upper limb dysfunction. Exercise training has resulted in improvement for patients; however, there can be a lack of compliance due to access because of location and lack of MS experts. Virtual reality (VR) is a promising technology that can offer exercise therapy/rehabilitation at a distance. This type of remote training can be motivational and effective for patients with MS and can improve range of motion and muscle strength for those with upper limb dysfunction. OBJECTIVE: The aim of this study is to evaluate the safety and feasibility of the XRHealth software and the Oculus Rift Station for patients with MS with upper limb motor dysfunction. METHODS: A single-center, prospective, feasibility study was conducted with patients with MS who had upper limb motor dysfunction. Patients participated in a single 45-minute digital environment session with VR and completed a questionnaire about the quality of the training and fatigability. The clinician also completed a questionnaire to evaluate the suitability and safety of the training. RESULTS: Overall, 30 patients were enrolled between the ages of 20 and 81 years. Patients reported that the training sessions within the digital environment were helpful, challenging, fun, and simple to understand, and that they would be willing to repeat the sessions again. The physical therapist that oversaw the patients reported that the training was suitable for 87% (n=26) of the patients. Anticipated adverse events were fatigue, temporary dizziness, and temporary nausea. The operator complications included that the cable of the head-mounted display interrupted the training (n=2, 7%) and fatigue that caused cessation of the VR training session (n=2, 7%). No serious adverse events were reported. CONCLUSIONS: These preliminary results demonstrated that the use of the XRHealth software and Oculus Rift Station platform is feasible, safe, and engaging for patients, and has the potential to improve the functionality of the upper limbs in patients with MS. This study provides support for future studies of implementing a series of training sessions with virtual reality in a home-based environment.

Motoric cognitive risk syndrome in people with multiple sclerosis: prevalence and correlations with disease-related factors.

Background: The motoric cognitive risk (MCR) syndrome, defined as the coexistence of slow gait and subjective cognitive complaints, has as yet not been researched in people with multiple sclerosis (pwMS). Objective: To examine the prevalence of the MCR syndrome in pwMS and its association with disability, disease duration, perceived fatigue, and fear of falling. Methods: The study comprised 618 pwMS [43.7 (SD = 12.6) years, 61.7% females]. Gait speed was measured by the GAITRite™ electronic walkway (CIR Systems, Inc. Haverton, PA, USA). Cognitive status was defined according to the global cognitive score computed by the NeuroTrax™ cognitive battery (NeuroTrax Corporation, Medina, NY, USA). The sample was divided into four main groups: 'normal', 'cognitively impaired', 'gait impaired' or 'MCR'. Perceived fatigue was assessed by the Modified Fatigue Impact Scale; fear of falling by the Falls Efficacy Scale International. Results: Sixty-three (10.2%) patients were diagnosed with MCR. The percentage of subjects categorized as MCR was 26.0% in severely disabled pwMS compared with 10.9%, 6.0%, and 4.6% in moderately, mildly and very mildly disabled pwMS, respectively. Subjects in the MCR group presented with elevated fatigue compared with patients classified as normal [49.7 (SD = 23.3) vs 26.5 (SD = 19.2), p < 0.001]. Fear of falling was significantly higher in the MCR and gait impairment groups compared with the cognitively impaired and normal groups. Conclusions: The current study corroborates the presence of MCR in pwMS. Nevertheless, future longitudinal research is warranted to better understand its application.

Is BDNF related to spatial-temporal gait parameters in people with multiple sclerosis? An observational study.

BACKGROUND: It has been suggested that the protein Brain-derived Neurotrophic Factor (BDNF) plays a neuroprotective role in people with multiple sclerosis (pwMS). Also, BDNF seems to play a role in cognition performance. In the same line, gait in pwMS requires a higher cognitive resource, mainly during complex walking. Thus, maybe BDNF could be related to gait in pwMS. OBJECTIVE: To investigate the relationship between BDNF and gait spatial-temporal parameters during unobstructed and obstructed conditions and the Timed Up and Go (TUG) in pwMS and healthy controls (HC). METHODS: The study included 20 pwMS (11F/9M, 33.1±7.5 years, Expanded Disability Status Scale- EDSS 2.2±1.2) and 18 HC (13F/5M, 35.5±5.9 years). Both groups performed 20 gait attempts in two conditions: unobstructed walking (10 trials) and avoiding an obstacle. The obstacle was 15 cm in height and made of foam material. The BDNF serum concentration was collected with participants in fasting and completed before the clinical, gait, and mobility assessments. Clinical variables included the Symbol Digit Modality Test (SDMT), the Fatigue Severity Scale (FSS), and the International Physical Activity Questionnaire (IPAQ- short version). Associations between BDNF and spatial-temporal gait parameters, clinical variables, and TUG were determined by Pearson/Spearman correlations with Bonferroni's correction being applied (p<0.0013). Gait was compared by a two-way, repeated-measures ANOVA (group and condition) to characterize our cohort. RESULTS: Reduced BDNF was observed for pwMS (41.66±4.45 ng/ml) in comparison with HC (61.67±7.07, p<0.001). However, although some correlations presented a moderate correlation between BDNF with gait variables, the correlations didn't reach a significant p-value after Bonferroni's correction. Lastly, pwMS presented shorter step length and slower step velocity for both gait conditions, with more evidence for obstacle conditions. Only pwMS changed gait behavior from unobstructed walking to obstacle avoidance conditions (i.e., reduced step length and velocity and increased step duration). CONCLUSION: BDNF is not related to either clinical (i.e., EDSS, SDMT, FSS, or IPAQ) or gait parameters in pwMS and HC, even in a condition involving higher cognitive demand. These results may suggest that BDNF does not play a role in these parameters' performance.

Impact of the COVID-19 Pandemic on Physical Activity and Associated Technology Use in Persons With Multiple Sclerosis: An International RIMS-SIG Mobility Survey Study.

OBJECTIVE: To investigate the impact of the COVID-19 pandemic on physical activity in persons with multiple sclerosis (PwMS). DESIGN: Multicenter international online survey study. SETTING: The survey was conducted within 11 participating countries. Each country launched the survey using online platforms from May to July 2021. PARTICIPANTS: This was an electronic survey study targeting PwMS (N=3725). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The survey ascertained physical activity performance and its intensity, the nature of the activities conducted, and the use of technology to support home-based physical activity before and during the pandemic. RESULTS: A total of 3725 respondents completed the survey. Prepandemic, the majority (83%) of respondents reported being physically active, and this decreased to 75% during the pandemic. This change was significant for moderate- and high-intensity activity (P<.0001). Activities carried out in physiotherapy centers, gyms, or pools decreased the most. Walking was the most frequently performed activity prepandemic (27%) and increased during the pandemic (33%). A total of 24% of those inactive during the pandemic had no intention of changing their physical activity behavior post pandemic. A total of 58% of the respondents did not use technology to support physical activity during the pandemic. Of those who did use technology, wearables were most used (24%). Of those currently nonactive (25%) expressed a preference for an in-person format to conduct physical activity post pandemic. CONCLUSIONS: Physical activity performance, especially activities at moderate and high intensities, decreased during the pandemic in PwMS compared with prepandemic. Walking and using wearables gained popularity as ways to stay active. As we move toward an endemic COVID-19, a call for action to develop interventions focused on walking programs with specific emphasis on increasing physical activity of PwMS is proposed.