Persons With Multiple Sclerosis Research Articles

Clinical manifestation and perceived symptoms of walking-related performance fatigability in persons with multiple sclerosis.

Fatigue and walking difficulties are common impairments and activity limitations in persons with multiple sclerosis (PwMS). Walking fatigability (WF) can be measured by a Distance Walked Index and is defined as a decline in walking distance of 10% or more during the six-minute walking test (6MWT). However, the clinical manifestation and perceived symptoms related to fatigability are still not well documented. Forty-nine PwMS [Expanded Disability Status Scale (EDSS) ≤6] and 28 healthy controls (HC) performed a 6MWT. The perceived severity of 11 common symptoms was rated on a visual analogue scale of 0-10 before, immediately after, and 10, 20 and 30 minutes after the 6MWT by means of the symptom inventory. Short motor impairment screening tests at baseline together with other descriptive measures were performed. Twenty pwMS were categorized in the WF group and were more disabled (EDSS: 4.16 ± 1.41) than the non-walking fatigability group (n = 29, EDSS: 2.62 ± 1.94). PwMS showed exacerbations of several perceived symptoms in MS, where most symptoms returned to baseline within 10 minutes after the walking test. The WF group showed significantly more muscle weakness and gait impairment, together with balance problems, and experienced an increase in spasticity, pain and dizziness after 6MWT. Our findings showed that perceived severity of symptoms are higher in pwMS presenting WF, and increase temporally after the 6MWT. Future research with quantitative measurement during and after walking is recommended.

Does cognitive training improve attention/working memory in persons with MS? A pilot study using the Cogmed Working Memory Training program

BackgroundCognitive deficits, especially in attention, are common in persons with MS (PwMS) and are associated with clinically meaningful outcomes, such as work disability and lower quality of life (QOL). In this study, we aimed to determine whether Cogmed Working Memory Training (CWMT) improves attention/working memory in PwMS displaying impairment in these domains. MethodsThis single blind, randomized controlled, pilot study compared the effects of CWMT, a five-week evidenced-based computer-assisted training program that is supported by weekly meetings with a coach, to standard medical care (treatment as usual). We recruited PwMS from one MS center (London (ON) Canada), aged 18-64, with an Expanded Disability Status Scale (EDSS) score of ≤ 7.0, and a visual acuity (corrected) of at least 20/70. Potential subjects had to demonstrate impaired attention on at least two of three measures (Paced Auditory Serial Addition Test [PASAT], Symbol Digit Modalities Test [SDMT], and/or DKEFS Color-Word Interference Test); these measures also served as the primary study outcomes. Subjects were randomized to either the CWMT or treatment as usual. Secondary cognitive outcomes included other measures of attention, memory, as well as a self-reported cognitive function measure. Self-reported measures of mood (depression and anxiety), pain, and QOL were also included as other secondary outcomes. Subjects received assessments at baseline, post-treatment, and 6-month follow-up, or an equivalent time period for the treatment as usual group. The two groups were compared at baseline on background measures using independent samples t-tests, Chi-Square tests, and Mann-Whitney U tests. To analyze primary and secondary outcomes, a non-parametric approach was used due the small sample size and that many of our outcomes did not meet assumptions for parametric analyses. Friedman's test was conducted followed by post hoc pairwise comparisons within each group using Wilcoxon Signed-Rank tests with Bonferroni corrected post hoc contrasts, which allowed us to examine for differences between time points. ResultsOf 30 subjects, 15 were assigned to CWMT. Significant training effects were noted in 1 of 3 primary attentional outcomes (DKEFS Color-Word Interference Test), 2 of 3 secondary attentional outcomes (Letter-Number Sequencing, Digit Span), and 1 mood scale (Hospital Anxiety and Depression scale (HADS) - Depression Subscale), ps < .025. No significant changes were observed in the treatment as usual group. ConclusionThis pilot study demonstrates that cognitive training with CWMT has the potential to improve attention/working memory in PwMS, as well as a potential positive effect on mood, in PwMS. Further exploration of this intervention in PwMS with attention/working memory impairment is warranted.

Short-term laboratory and related safety outcomes for the multiple sclerosis oral disease-modifying therapies: an observational study

ABSTRACT Background Real-world safety data for the oral multiple sclerosis (MS) disease-modifying therapies (DMTs), dimethyl fumarate (DMF), fingolimod, and teriflunomide are important. We examined laboratory test abnormalities and adverse health conditions in new users. Methods Linked laboratory and administrative health data were accessed for all persons with MS (PwMS) filling their first oral DMT prescription in two Canadian provinces. PwMS were followed from first prescription fill until discontinuation, death, emigration or study end. Proportions of PwMS, and incidence rates (IR)/100 person-years, were calculated for ≥1 event of elevated alanine aminotransferase (ALT) (>the upper limit of normal [ULN]; all DMTs), liver toxicity (ALT>3xULN; fingolimod); lymphopenia and proteinuria (DMF), and cardiac arrhythmia, hypertension and pneumonia (all DMTs). Results Overall, 1,140 PwMS were followed for up to 2 years. De novo elevated alanine aminotransferase affected 13.2% (DMF), 12.4% (teriflunomide), and 30.0% (fingolimod) of users. Liver toxicity affected 2.8% of fingolimod, lymphopenia 3.1% of DMF, and proteinuria 2.9% of DMF users. The incidences of cardiac arrhythmia, pneumonia and hypertension ranged from <1 to 1.86/100 person-years depending on the DMT. Conclusions The short-term, real-world incidences of abnormal laboratory results or adverse events were consistent with the pivotal clinical trial findings. Longer-term safety data are still needed.

Coping strategies: Seeking personalized care in relapsing-remitting multiple sclerosis. A patient reported measure–coping responses inventory

BackgroundCoping is defined as a set of cognitive and behavioral efforts made to master stressful specific demands. Adaptation to chronic diseases, such as Multiple Sclerosis (MS), depends on the effectiveness of coping.Objective: To assess the psychometric properties of the Coping Responses Inventory (CRI-A) in persons with MS (PwMS), verifying the transferability of the measure, already validated in the Argentine general population, and to describe the types of coping strategies available for PwMS.Methods: 90 PwMS were included.Outcome measures: CRI-A Inventory, Expanded Disability Status Scale (EDSS), Beck Depression Inventory, Fatigue Severity Scale and MS International Quality of Life questionnaire.Results: Descriptive data is as follows: mean age (years): 40.97 ± 12.85; years of education: 13.46 ± 3.93; EDSS: 2.48 ± 1.79; disease evolution (years): 10.76 ± 9.72; depression: 13.92 ± 10.45; fatigue 3.77 ± 1.72. The psychometric properties of the CRI-A Inventory observed in the Argentine general population are present in the MS sample as well, with adequate validity and reliability. The respondents most frequently utilized a problem-focused coping style.Conclusions: Results showed the CRI-A has good transferability properties from the Argentine general population to the MS population.

Anatomical Covariance Analysis: Detection of Disrupted Correlation Network Related to Clinical Trait Fatigue in Multiple Sclerosis: A Pilot Study

Background Fatigue is one of the most distressing symptoms among persons with multiple sclerosis (PwMS). The experience of fatigue is inherently interoceptive, yet no study to date has explicitly investigated the insular cortex (IC) as a primary goal in the experience of fatigue in PwMS. In addition, it is unknown how brain regions such as IC play a role in state or trait fatigue. Objective Assess the involvement of the IC in trait fatigue and state fatigue in PwMS with and without clinical fatigue. Methods Trait and state fatigue, cognitive status, and structural MRI were assessed in 27 PwMS. PwMS were stratified into nonclinical fatigue (nF-MS, FSS ≤ 4.0) (n = 10) and clinical fatigue (F-MS, FSS ≥ 5.0) (n = 10). Voxel-based morphometry analysis (VBM) for the whole sample (n = 20) and for the two groups was performed. Anatomical covariance analysis (ACA) analysis was conducted by selecting different volumes included in the corticostriatal network (CoStN) and analyzing interhemispheric correlations between those volumes to explore the state of the CoStN in both groups. Results In the VBM analysis, when considering the whole sample of PwMS, higher levels of trait fatigue were negatively associated with grey matter (GM) volume in the left dorsal anterior insula (dAI) (rho = −0.647; p = 0.002; R2 = 0.369). When comparing nF-MS versus F-MS, significant differences were found in the left dAI, where the F-MS group showed less GM volume in the left dAI. In the ACA analysis, the F-MS group showed fewer significant interhemispheric correlations in comparison with the Low-FSS group. Conclusions The present results provide support to the interoceptive component of self-reported fatigue and suggest that changes in the relationship between the different anatomical regions involved in the CoStN are present even in nonclinical trait fatigue. Those changes might be responsible for the experience of trait fatigue in PwMS. Future studies with larger samples and multimodal MRI acquisitions should be considered to fully understand the changes in the CoStN and the specific role of the IC in trait fatigue.

Validation of the French version of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS)

BackgroundThe Minimal Assessment of Cognitive Function in Multiple sclerosis (MACFIMS) is an internationally recognised battery of neuropsychological tests for patients with multiple sclerosis (MS). ObjectivesTo establish regression-based norms for the MACFIMS in French-speaking healthy subjects (HS) and validate its use in persons with multiple sclerosis (PwMS). Methods136 PwMS, including 43 with relapsing-remitting MS, 46 with secondary progressive MS and 45 with primary progressive MS, as well as 276 HS were enrolled. Regression-based norms and validity were established for the seven tests of the MACIMS: the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), the French learning test (FLT) a French-adapted memory test (or the California Verbal Learning Test (CVLT) at re-testing), the Judgment of Line Orientation Test (JLO), the ‘épreuve de classement de cartes de Champagne’ (ECCC), a French adaptation of the DKEF-sorting test, the Brief Visuospatial Memory Test (BVMT-R) and the Controlled Oral Word Association Test (COWAT). ResultsRegression-based norms of MACFIMS tests were established in the HS population. The MACFIMS battery was able to identify cognitive impairment (CI) (at least two abnormal tests in different domains) in 32.7% of PwMS. The domains with more frequent impairment were (in descending order): learning followed by IPS, delayed memory, verbal fluency and working memory. ConclusionThis study established the regression-based norms for French subjects of the French adaptation of the MACFIMS and its validity in PwMS.

Among Persons With Multiple Sclerosis (MS), Objective Sleep, Psychological Functioning, and Higher Physical Activity Scores Remained Stable Over 2 Years-Results From a Small Study Under Naturalistic Conditions.

Background: Persons with multiple sclerosis (PwMS) are at increased risk to report poor sleep patterns and lower physical activity indices. To date, data on longitudinal objectively sleep assessment is missing. In the present study, we investigated the pattern of objective sleep and subjective physical activity indices over a period of 13.5 months, under naturalistic conditions.Method: 13.5 months after their first assessment, a total of 16 PwMS (mean age = 49.13 median EDSS score: 5; 11 females) were reassessed on their objective sleep via portable sleep-electroencephalogram (EEG-) devices, along with their subjective sleep patterns (symptoms of insomnia, restless legs syndrome (RLS), and sleep-disordered breathing), physical activity indices, psychological functioning (symptoms of depression, fatigue, daytime sleepiness), and MS-related information (fatigue, EDSS; disease-modifying treatments). While the baseline assessment was performed in a rehabilitation center, the follow-up assessment took place at participants' naturalistic and familiar setting.Results: Statistically, symptoms of depression and fatigue, subjective sleep, and physical activity levels did neither increase, nor decrease over time, although descriptively, both moderate and vigorous physical activity levels decreased, and fatigue and subjective insomnia increased. Time awake after sleep onset statistically significantly decreased, while light sleep duration increased by trend.Conclusions: Among a smaller sample of PwMS, objective sleep in their naturalistic setting remained fairly stable over a mean time lapse of 13.5 months after clinic discharge. Physical activity levels descriptively decreased. The present results are of clinical and practical importance for treatment counseling: PwMS can be reassured that their sleep quality does not deteriorate, once they have left a rehabilitation center. Further, they should be encouraged to keeping their physical activity levels as stable as possible.

Blood pressure changes during alemtuzumab infusion for multiple sclerosis patients.

Blood pressure (BP) changes during alemtuzumab infusions are poorly understood. The aim of this study was to examine BP changes during alemtuzumab infusions in persons with multiple sclerosis (PwMS). This was a retrospective cohort review of systolic (S) and diastolic (D) BP in PwMS receiving alemtuzumab. Thirty-one patients were identified; 22 (64.5%) were women. Mean age and disease duration were 35.2±7.1 and 9.2±5.4years, respectively. There was no history of hypertension or vascular events. Mean baseline SBP was 119.8±15.1mmHg, 118.8±14.3mmHg and 106.5±6.1mmHg whilst mean DBP was 75.3±9.2mmHg, 74.1±12.4mmHg and 69.2±4.3mmHg at doses 1, 6 and 9, respectively. During the first cycle, SBP increased by 19.2±9.4mmHg, with comparable percentage increases over the five infusions (16%, 22%, 17%, 11%, 13%, respectively). DBP increased by 6.2±3.8mmHg with similar percentage increases over the five infusions (8.4%, 11.5%, 5.5%, 7%, 3%). For the second cycle, SBP increased by 16.9±3.2mmHg, with similar increases over the 3days (12%, 15%, 17%). DBP increased by 5.4±4.2mmHg (11%, 9%, 12.8%). The third cycle demonstrated increased mean and percentage of SBP and DBP by 8.9±2.3mmHg (10%, 70%, 11.8%) and 4.2±1.9mmHg (3%, 2%, 6.5%), respectively. Collectively, for 31 patients, in the first cycle, mean SBP increased from 119.8±15.1mmHg to 138.8±13mmHg (p˂0.001), whilst mean DBP increased from 74.5±9.2mmHg to 79.2±9.1mmHg (p=0.007). Overall, 17 (54.8%) patients had increasing BP by ≥20% and nine (29%) had increasing BP by ≥20mmHg from baseline. This demonstrates significant increases in BP during alemtuzumab infusions in PwMS.

Impaired consolidation of visuomotor adaptation in patients with multiple sclerosis

Apart from inflammation and neurodegeneration, the individual clinical course of multiple sclerosis (MS) might be determined by differential adaptive capacities of the central nervous system. It has been postulated that the retention of adaptive training effects may be impaired in persons with MS (PwMS). To investigate motor adaptation and consolidation capacities of people with MS in a visual motor adaptation task (VAT). A total of 23 PwMS (Expanded Disability Status Scale (EDSS) score<6) and 20 matched healthy controls were recruited. All participants completed three sessions of a VAT where a clockwise rotation angle of 30° was introduced as perturbation during the active learning part of the paradigm. The training session (T0 ) was repeated after 24h (T1 ) and 72h (T2 ). Directional errors and parameters of adaptation and retention were evaluated. PwMS showed similar adaptation and online learning abilities as controls. However, the retention ratio was significantly lower in patients compared to controls at T1 (p=0.036) and T2 (p=0.039). There was no significant correlation between the overall adaptation or retention ratio and the EDSS score, respectively. Our findings indicate intact adaptation, but limited consolidation, in patients with mild-to-moderate MS. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which it can influence clinical outcomes.

Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses

Background: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. Objective: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. Methods: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. Results: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. Conclusion: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.

The effects of aging and disease duration on cognition in multiple sclerosis

ObjectivesMultiple sclerosis (MS) is a disease of the central nervous system that can interfere with cognitive functions. The purpose of this study is to document the impact of MS, aging and disease duration on cognitive functioning as both life expectancy and incidence of the disease among persons with MS (PwMS) aged 50 years and over (late-onset MS) are increasing in the last two decades. MethodsExhaustive neuropsychological evaluation was performed in 84 PwMS (30 young, 30 elderly adult-onset, 25 elderly late-onset) and 50 control participants (25 young, 24 elderly). ANCOVAs and hierarchical linear regressions were used to meet the objectives. ResultsInteraction effects were found between age and presence of MS on higher executive function and information processing speed/working memory. After controlling for confounding variables (fatigue, quality of life, depression, MS course, comorbidity), results demonstrated an important role of age on all cognitive functions but only a trend of disease duration on information processing speed/working memory. ConclusionDecline in higher executive functions and information processing speed/working memory in aging is accentuated by the presence of MS, but the impact of age and MS on memory are independent. Age appears to be the variable having the most important role on cognition.

Gait Characteristics Harvested During a Smartphone-Based Self-Administered 2-Minute Walk Test in People with Multiple Sclerosis: Test-Retest Reliability and Minimum Detectable Change.

The measurement of gait characteristics during a self-administered 2-minute walk test (2MWT), in persons with multiple sclerosis (PwMS), using a single body-worn device, has the potential to provide high-density longitudinal information on disease progression, beyond what is currently measured in the clinician-administered 2MWT. The purpose of this study is to determine the test-retest reliability, standard error of measurement (SEM) and minimum detectable change (MDC) of features calculated on gait characteristics, harvested during a self-administered 2MWT in a home environment, in 51 PwMS and 11 healthy control (HC) subjects over 24 weeks, using a single waist-worn inertial sensor-based smartphone. Excellent, or good to excellent test-retest reliability were observed in 58 of the 92 temporal, spatial and spatiotemporal gait features in PwMS. However, these were less reliable for HCs. Low SEM% and MDC% values were observed for most of the distribution measures for all gait characteristics for PwMS and HCs. This study demonstrates the inter-session test-retest reliability and provides an indication of clinically important change estimates, for interpreting the outcomes of gait characteristics measured using a body-worn smartphone, during a self-administered 2MWT. This system thus provides a reliable measure of gait characteristics in PwMS, supporting its application for the longitudinal assessment of gait deficits in this population.

What (more) can verbal fluency tell us about multiple sclerosis?

Clinical symptoms of multiple sclerosis (MS) are variable and may include cognitive impairment, which can be assessed with the verbal fluency test (VFT). This test is evaluated by counting words spoken during a 2-min period, which is not a functional approach. The objectives of this observational study were to: (1) determine new parameters that reflect communication and cognitive functions in persons with multiple sclerosis (PwMS) considering the evaluation of real-time word production in the VFT; (2) compare the results with those of a control group; and (3) evaluate the impact of including errors. A phonological fluency test ("letter P") and a semantic fluency test ("animals") were used. The real-time word production was recorded. The main variables studied were the total number of words, first word delay, moment of inflection of the curve corresponding to the change in the cognitive process, speed of word production before inflection, and maximum delay between 2 consecutive words. These variables were studied by taking into account or not errors. We included 68 PwMS and 33 healthy controls. VFT results were impaired in PwMS. The total number of words, first word delay, speed before inflection, and maximum delay were relevant to the study of phonologic fluency. For studying semantic fluency, the total number of words, first word delay, speed before inflection, and inflection time of the curve seemed relevant. Taking into account errors was significant only for total number of words. Taking into account errors in evaluating real-time word production in PwMS is of interest only for the total number of words performed but has no impact on the variables studied. These variables should be used to quantitatively evaluate verbal fluency with the objective of evaluating functionally relevant parameters (communication).

Advanced characterization of static postural control dysfunction in persons with multiple sclerosis and associated neural mechanisms

BackgroundMultiple sclerosis (MS) is an autoimmune-based chronic inflammatory disease characterized by the neurodegeneration of the central nervous system and produces postural dysfunction. Quiet or static standing is a complex task carried out through afferent sensory inputs and efferent postural corrective outputs. Currently the mechanisms underlying these outputs remain largely unknown. Research questionAssess the relationship between multi-dimensional measures of postural control and microstructural integrity of the cortical sensorimotor pathway (CSP) in persons with MS (PwMS) and neurotypical adults. MethodsPostural control performance was assessed by both overall and directional time-to-boundary measures across four manipulated sensory stance conditions (eyes open/closed; stance firm/foam) in twenty-nine neurotypical and twenty-seven PwMS. These postural outcomes were evaluated with mixed-model repeated measures analysis of variance across group (MS and control) and stance condition. Postural performance was also correlated with magnetic resonance imaging diffusion tensor-derived measures of microstructural integrity of the CSP. ResultsPwMS displayed significantly (p = 0.026) worse anterior-posterior postural control compared to their neurotypical counterparts across sensory testing conditions and poorer CSP microstructural integrity in comparison to neurotypical adults (p = 0.008). Additionally, PwMS displayed a significant association (2D (rho = -0.384, p = 0.048), AP (rho = -0.355, p = 0.035), and ML (rho = -0.365, p = 0.030) between integrity of the CSP and postural control performance during proprioceptive-based balance, such that those with worse cortical structure had poorer balance control. SignificanceThis is the first study to establish connections between the microstructural integrity of the CSP and multi-dimensional postural control performance. Results indicate that a reduction in the CSP microstructural integrity is associated with poorer postural control in PwMS. These outcomes identify neural underpinnings of postural control dysfunction in PwMS and provide new avenues for evaluating the efficacy of postural rehabilitation strategies in PwMS that express proprioceptive-based postural deficits.

Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis.

Background: Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects.Objective: To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS).Methods: 36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms.Results: Relaxation was differentially linked to heart rate in both groups (t = 2.20, p = 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t = 1.99, p = 0.045) although this link differed weakly between groups (t = 1.62, p = 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t = −5.55, pfamily−wise−error(FWE)corrected = 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t = −4.89, pFWE = 0.039).Conclusion: PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS.

Acceptability and outcomes of an individualized exergaming telePT program for veterans with multiple sclerosis: a pilot study

BackgroundPhysical rehabilitation services are an important component of treatment for persons with multiple sclerosis (PwMS) to improve and maintain physical mobility. However, PwMS often have significant barriers to outpatient physical therapy (PT) services including mobility deficits and lack of transportation. The integration of exercise gaming (exergaming) and telehealth into clinical PT practices may overcome these barriers. The overarching purpose of this pilot study was to evaluate the acceptability and effects of an individualized telePT intervention using exergaming.MethodsTen individuals with multiple sclerosis (MS) completed a 12-week exergaming (Jintronix®) telerehabilitation intervention. In order to measure the acceptability of the telerehabilitation intervention, adherence was measured through the tablet-based rehabilitation software and each participant completed a satisfaction questionnaire. Clinical outcome measures were assessed at baseline and post-intervention. To evaluate the efficacy of this intervention, the following measures of physical function and fatigue were included; the Short Physical Performance Battery (SPPB), 25-Foot Walk (25FW), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale-12 (MSWS), and the 2-Minute Walk Test (2MWT). Clinical outcomes were analyzed using the Sign test and Wilcoxon signed rank test. All other data were evaluated using descriptive statistics.ResultsAfter the intervention, participants demonstrated significant improvements in ambulation speed during the 25FW (p = 0.04) and ambulation distance during the 2MWT (p = 0.002). Statistically significant increases of SPPB total score (p = .04) and sub-scores were also found. Participants did not demonstrate significant changes in the MFIS (p = 0.31) or MSWS-12 (p = 0.06) after the intervention. Participants had a 58.3% adherence rate during the intervention and performed their exercise program an average of 2.5 times per week. All participants reported that they were either ‘satisfied or ‘very satisfied’ with their telerehabilitation experience, would use telerehabilitation again, and would recommend telerehabilitation to others.ConclusionThis individualized telerehabilitation intervention which integrates exergaming and clinical video teleconferencing is acceptable to patients and may offer a viable alternative to traditional PT for PwMS.Trial registrationNCT03655431, retrospectively registered on August 31st, 2018.

Social support in multiple sclerosis: Associations with quality of life, depression, and anxiety

ObjectiveSocial support plays a role in the well-being of persons with multiple sclerosis (PwMS). The aims of this study were to compare social support in PwMS with relapsing versus progressive disease, examine the relationships with patient reported outcomes (PROs), and investigate social support longitudinally. MethodsFor this study, we have performed an analysis of data routinely collected from subjects enrolled in the CLIMB at the Partners MS Center. Subjects (n = 789) completed measures of social support, quality of life (QOL), depression, and anxiety. Relapsing and progressive PwMS were compared using a two sample t-test, and linear regression was used to adjust for other variables. Correlations between social support and PROs were assessed using partial Pearson's correlation coefficient. A random intercept and slope model with a linear trend with time estimated the change over time. ResultsSubjects with relapsing MS reported higher overall social support than subjects with progressive disease (difference in means = −6.7; 95% CI: −10.3, −3.1) as well as higher levels of 3 of the 4 dimensions of social support measured. These differences remained after adjusting for age and gender only, but were attenuated adjusting for age, gender, and depression (adjusted difference in means = −1.2; 95% CI: −5.0, 2.6). Higher overall social support was associated with higher QOL (r = 0.16–0.27), lower depression (r = −0.36), and lower state (r = −0.27) and trait (r = −0.29) anxiety. Social support was mostly stable over time. ConclusionSocial support was associated with QOL, depression, and anxiety in PwMS.

High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple sclerosis during inpatient rehabilitation

In persons with multiple sclerosis (PwMS), the neutrophil-to-lymphocyte ratio (NLR) is associated with disability status, symptomatology and disease activity. High-intensity interval training (HIIT) improves many symptoms in PwMS and may positively influence disease progression. Here, we present results from a randomized controlled trial during inpatient rehabilitation on immediate (single bout) and training (3-week intervention) effects of HIIT versus moderate continuous training on NLR and related cellular inflammation markers. Only HIIT reduced the NLR over the 3-week intervention period. These training effects might be due to repetitive inflammatory states with compensatory anti-inflammatory counterbalancing after each HIIT session.

Diagnosis of depression in multiple sclerosis is predicted by frontal-parietal white matter tract disruption.

Persons with multiple sclerosis (PwMS) are at an elevated risk of depression. Decreased Conscientiousness may affect patient outcomes in PwMS. Low Conscientiousness has a strong correlation with depression. Previous work has also reported that white matter (WM) tract disruption in frontal-parietal networks explains reduced Conscientiousness in PwMS. We hypothesized that Conscientiousness-associated WM tract disruption predicts new-onset depression over 5years in PwMS and evaluated this by assessing the predictive power of mean Conscientiousness associated frontal-parietal network (CFPN) disruption in PwMS for clinically diagnosed depression over 5years. This longitudinal retrospective analysis included 53 PwMS who were not previously diagnosed as depressed. All participants underwent structural MRI. Medical records were reviewed to evaluate diagnosis of depression for these patients over 5years. WM tract damage between pairs of gray matter regions in the CFPN was measured using diffusion imaging. The relationship between CFPN disruption and depression was analyzed using logistic regression. Participants with MS had a mean age of 46.0years (SD = 11.2). 22.6% (n = 12) acquired a diagnosis of clinical depression over the 5-year period. Baseline disruption in the CFPN was a significant predictor (ROC AUC = 61.8%). of new-onset clinical depression, accounting for age, sex, lateral ventricular volume, disease modifying treatment, and lesion volume. Baseline CFPN disruption is associated with progression to clinical depression over 5years in PwMS. Development of new WM pathology within this network may be a risk factor for depression.

Detrended fluctuation analysis of gait dynamics when entraining to music and metronomes at different tempi in persons with multiple sclerosis

In persons with multiple sclerosis (PwMS), synchronizing walking to auditory stimuli such as to music and metronomes have been shown to be feasible, and positive clinical effects have been reported on step frequency and perception of fatigue. Yet, the dynamic interaction during the process of synchronization, such as the coupling of the steps to the beat intervals in music and metronomes, and at different tempi remain unknown. Understanding these interactions are clinically relevant, as it reflects the pattern of step intervals over time, known as gait dynamics. 28 PwMS and 29 healthy controls were instructed to walk to music and metronomes at 6 tempi (0–10% in increments of 2%). Detrended fluctuation analysis was applied to calculate the fractal statistical properties of the gait time-series to quantify gait dynamics by the outcome measure alpha. The results showed no group differences, but significantly higher alpha when walking to music compared to metronomes, and when walking to both stimuli at tempi + 8, + 10% compared to lower tempi. These observations suggest that the precision and adaptation gain differ during the coupling of the steps to beats in music compared to metronomes (continuous compared to discrete auditory structures) and at different tempi (different inter-beat-intervals).