Cognitive recovery in people with relapsing/remitting multiple sclerosis: A randomized clinical trial on virtual reality-based neurorehabilitation.

BACKGROUND: Multiple sclerosis (MS) can adversely affect several domains of cognitive function, including attention, information processing, memory and learning, executive functions and visuospatial skills. In recent years, technological innovations have proven effective in improving motor and cognitive impairment in neurological patients, including those affected by MS. OBJECTIVE: The study aims to evaluate cognitive outcomes after rehabilitation training with the Virtual Reality rehabilitation system (VRRS) in patients suffering from MS. METHODS: All patients were randomized into either the control group (CG: 15 patients) receiving conventional cognitive rehab or the experimental group (EG) using virtual reality (VR) (15 patients). Both groups underwent the same amount of cognitive training, 3 times a week for 8 weeks. They were submitted to neuropsychological assessment before (T0) and after the rehabilitation treatment (T1). RESULTS: Our data showed that both conventional and VR cognitive rehabilitation approaches improved mood (p < 0.001) and visuospatial skills. However, only in the EG a significant improvement in specific cognitive domains (p < 0.001), including learning ability, short-term verbal memory, lexical access ability, as well as quality of life related to mental states, was found. CONCLUSIONS: The present study demonstrated that VR can be a motivational and effective tool for cognitive recovery in MS patients.

Exercise leads to metabolic changes associated with improved strength and fatigue in people with MS.

OBJECTIVE: The goal of this exploratory study was to evaluate the effects of an exercise intervention - progressive resistance training (PRT) on the metabolome of people with MS (pwMS) and to link these to changes in clinical outcomes. METHODS: 14 pwMS with EDSS <4.0 and 13 age- and sex-matched healthy controls completed a 12-week in-person PRT exercise intervention. Outcome measures included: plasma metabolomics analysis, cardiovascular fitness tests, EDSS, timed 25-foot walk (T25FW), six-minute walk test (6MWT), hip strength, and modified fatigue impact scale (MFIS). We identified changes in the metabolome with PRT intervention in both groups using individual metabolite abundance and weighted correlation network defined metabolite module eigenvalues and then examined correlations in changes in metabolite modules with changes in various clinical outcomes. RESULTS: In both groups PRT intervention improved hip strength, distance walked in 6WMT, speed of walking, while fatigue (MFIS) was improved in pwMS. Fatty acid, phospholipid, and sex steroid metabolism were significantly altered by PRT in pwMS but not in controls. Changes in fatigue (MFIS score) were strongly inversely correlated and hip strength was moderately correlated with change in sex steroid metabolite module in pwMS. A similar relationship was noted between change in dehydroepiandrosterone sulfate abundance (sex steroid metabolite) and fatigue in pwMS. We also noted an inverse correlation between changes in fatty acid metabolism and cardiovascular fitness in pwMS. INTERPRETATION: PRT-induced metabolic changes may underlie improved clinical parameters in pwMS and may warrant investigation as potential therapeutic targets in future studies.

Relationship Between Retinal Layer Thickness and Disability Worsening in Relapsing-Remitting and Progressive Multiple Sclerosis.

BACKGROUND: Data regarding the predictive value of optical coherence tomography (OCT)-derived measures are lacking, especially in progressive multiple sclerosis (PMS). Accordingly, we aimed at investigating whether a single OCT assessment can predict a disability risk in both relapsing-remitting MS (RRMS) and PMS. METHODS: One hundred one patients with RRMS and 79 patients with PMS underwent Spectral-Domain OCT, including intraretinal layer segmentation. All patients had at least 1 Expanded Disability Status Scale (EDSS) measurement during the subsequent follow-up (FU). Differences in terms of OCT metrics and their association with FU disability were assessed by analysis of covariance and linear regression models, respectively. RESULTS: The median FU was 2 years (range 1-5.5 years). The baseline peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell + inner plexiform layer (GCIPL) were thinner in PMS compared with RRMS (P = 0.02 and P = 0.003, respectively). In the RRMS population, multivariable models showed that the GCIPL significantly correlated with FU disability (0.04 increase in the EDSS for each 1-µm decrease in the baseline GCIPL, 95% confidence interval: 0.006-0.08; P = 0.02). The baseline GCIPL was thinner in patients with RRMS with FU-EDSS >4 compared with those with FU-EDSS ≤4, and individuals in the highest baseline GCIPL tertile had a significantly lower FU-EDSS score than those in the middle and lowest tertile (P = 0.01 and P = 0.001, respectively). These findings were not confirmed in analyses restricted to patients with PMS. CONCLUSIONS: Among OCT-derived metrics, GCIPL thickness had the strongest association with short-medium term disability in patients with RRMS. The predictive value of OCT metrics in the longer term will have to be further investigated, especially in PMS.

Computerized cognitive rehabilitation for treatment of cognitive impairment in multiple sclerosis: an explorative study.

In this explorative study, forty-seven patients with relapsing-remitting multiple sclerosis were randomized to a custom 6-week cognitive rehabilitation intervention (n = 23) using the BrainHQTM web-based platform and to a control group condition (n = 24). Cognitive rehabilitation intervention consisted of two 40-minute sessions per week. All patients were tested with the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Stroop Color-Word Test, and the trail making test, while the Beck Depression Inventory - Fast Screen questionnaire was used as a measure of mood and the cognitive reserve index as a measure of cognitive reserve. We used the reliable change index, to calculate clinically meaningful changes of performance, and to discriminate between responders and non-responders of this intervention. Statistically significant improvement of the group receiving treatment was observed mainly on measures of verbal and non-verbal episodic memory and, to a lesser extent, on reading speed, selective attention/response inhibition, and visual attention. Verbal memory and visual attention improvements remained significant after considering the corrected for multiple comparisons level of significance. According to reliable change index scores, 12/23 (52.2%) of patients in the intervention group presented meaningful improvement in at least one measure (Greek Verbal Learning Test: 26%, Brief Visuospatial Memory Test-Revised: 17.4%, Stroop-Words test: 13%). This explorative study provides evidence that, at least in the short term, cognitive rehabilitation may improve the cognitive performance of multiple sclerosis patients.

Effects of aquatic exercises on postural control and hand function in Multiple Sclerosis: Halliwick versus Aquatic Plyometric Exercises: a randomised trial.

OBJECTIVES: Postural control and hand dexterity are significantly impaired in people with multiple sclerosis (pwMS). Aquatic interventions may have additional benefits in the treatment of pwMS. The purpose of this study is to compare the effects of two different aquatic exercises on postural control and hand function. METHODS: Thirty pwMS, relapsing-remitting type were randomly divided into a Halliwick (Hallw) and an Aquatic Plyometric Exercise (APE) group. The Limits of Stability test was used to evaluate postural control using the Biodex Balance System. The Nine-Hole Peg Test was used to evaluate hand dexterity. Both exercise interventions were performed twice a week for 8 weeks, in a pool with a depth of 120 cm and water temperature of 30-31°C. RESULTS: Limits of stability improved significantly in both groups (p<0.05) and Hallw group completed the test in a significantly shorter time (p<0.05). Hand dexterity improved significantly in both groups (p<0.01). Following intergroup analysis, Hallw group showed significantly higher improvement in hand dexterity and overall limits of stability test score (p<0.05). CONCLUSIONS: This study provides evidence that both Halliwick and APE are effective to treat balance and hand dexterity. This paper is the first evidence on APE for pwMS and showed that it is safe and improved trunk control and hand dexterity.

The effect of combined functional training on BDNF, IGF-1, and their association with health-related fitness in the multiple sclerosis women.

OBJECTIVE: Exercise-induced changes in the neurotrophic factors and the physical function are essential for the rehabilitation of the multiple sclerosis (MS) persons. The aim of this study was investigating of effectiveness of the combined functional training (CFT) on brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and their association with health-related fitness in the MS women. DESIGN: Twenty women with relapsing-remitting MS randomly assigned to CFT and control (CON) groups. The CFT consisted of 8 weeks (3 days per week) rhythmic aerobic exercise, TRX suspension training, elastic band training, and bodyweight training. BDNF, IGF-1, and health-related fitness components were assessed before and after the intervention. RESULTS: There was no significant difference in BDNF level between the CFT and the CON group. In contrast, IGF-1, walking speed, and strength of the right- and left-hand was significantly increased in the CFT compared with the CON group. Furthermore, there was a significant and positive correlation between IGF-1 and some fitness components. CONCLUSIONS: The findings indicated that CFT might a useful training mode in the rehabilitation of the MS women. CFT improved IGF-1 level that is a neuroprotective agent in MS. Positive and significant association between IGF-1 and some health-related fitness components indicates of the importance of IGF-1 in the rehabilitation of the MS persons than BDNF.

Efficacy of inpatient personalized multidisciplinary rehabilitation in multiple sclerosis: behavioural and functional imaging results.

BACKGROUND: Although multidisciplinary rehabilitation programs are commonly used in clinical practice for patients with multiple sclerosis (MS), they are currently underexamined. OBJECTIVE: This study aims to investigate the efficacy and underlying brain mechanisms of an inpatient multidisciplinary rehabilitation. METHODS: Twenty-four patients with relapse-onset MS underwent a 4-week personalized inpatient multidisciplinary rehabilitation and three assessment sessions including MRI, clinical, cognitive and motor function evaluation. Twenty-four healthy controls underwent two assessment sessions 4 weeks apart. Test performances were compared using repeated measures ANOVA, Tukey and t tests. A motor sequence learning (MSL) task was presented during fMRI and data were analysed using FSL. RESULTS: Patients had less perceived fatigue, improved walking speed and quality of life following the rehabilitation, which could be maintained at follow-up 4 weeks after rehabilitation. After rehabilitation, differences in accuracy of the MSL task between groups diminished, indicating an improved performance in patients. Improved accuracy went along with changes of brain activity in the left cerebellum and right frontal lobe post-rehabilitation, which could be maintained at follow-up. No changes between sessions were observed in controls. CONCLUSION: Multidisciplinary rehabilitation may improve highly impacting symptoms through more efficient recruitment of brain regions and therefore positively influence MS patients' quality of life.

The Effect of Total Body Resistance Exercise on Mobility, Proprioception, and Muscle Strength of the Knee in People With Multiple Sclerosis.

CONTEXT: Muscle weakness and sensory deficits cause impaired balance and walking abilities that are prerequisites for independent activity of daily living in people with multiple sclerosis (MS). Recent physical exercises tailored to improve the activity of daily living people with MS have focused on the functional training. OBJECTIVE: To investigate the effect of total body resistance exercise suspension training on mobility, proprioception, and muscle strength of the knee in people with MS. DESIGN: Single-blind pretest and posttest control group design. SETTING: Referral Center of Multiple Sclerosis Society. PARTICIPANTS: Thirty-four women with relapsing-remitting MS were participated in this study. The mean (SD) of their age was 36.44 (4.88) years, and the Expanded Disability Status Scale was 2.35 (0.94). The participants were divided into 2 groups: control group (n = 15) and training group (n = 19). INTERVENTION: The training group performed the total body resistance exercise program for 8 weeks, 3 sessions per week. The control group received their usual care and daily activities. Outcomes were measured presessions and postsessions. MAIN OUTCOME MEASURES: Mobility was assessed with Timed Up and Go test, 10-m walk maximum test, 2 minute walk test, and 5-time sit-to-stand test. Knee proprioception absolute error and isometric strength of knee flexor and extensor muscles were measured by using a biodex isokinetic dynamometer. RESULTS: In the training group, mobility (P = .001), maximal voluntary isometric contraction of knee flexor and extensor muscles in both legs (P > .05), and the knee proprioception absolute error in nondominant leg at 60° knee flexion (P = .02) improved significantly compared with the control group. CONCLUSION: Total body resistance exercise is a functional and safe intervention that can improve the mobility and muscles strength of the knee in a short period in people with MS.

Acute effects of whole-body vibration training on neuromuscular performance and mobility in hypoxia and normoxia in persons with multiple sclerosis: A crossover study.

BACKGROUND: Whole-body vibration training (WBVT) has been used in people with relapsing-remitting multiple sclerosis (pwMS), showing improvements in different neuromuscular and mobility variables. However, the acute effects of this training are still unknown. The acute effects of WBVT on neuromuscular performance, mobility and rating of perceived exertion (RPE) were evaluated in 10 pwMS. METHODS: Maximal voluntary isometric contraction (MVIC), central activation ratio (CAR), electromyography (EMG) of the vastus lateralis during isometric knee extension, Timed Up and Go Test (TUG), walking speed and RPE were assessed before and immediately after a session of WBVT (twelve 60-s bout of vibration; frequency 35 Hz; amplitude 4 mm; 1-min rest intervals) in both hypoxic and normoxic conditions. RESULTS: EMG 0-100, 0-200 ms and peak EMG resulted in significant differences (p < 0.05) between normoxic and hypoxic sessions. The EMG activity tended to decrease in all phases after the hypoxic session, indicating possible influence of hypoxia on neuromuscular performance. No changes were found in CAR, MVIC, TUG and walking speed in both conditions. CONCLUSION: Based on our results, as well as those obtained by other studies that have used WBVT with other populations, more studies with a higher sample and lower dose of vibration exposure should be conducted in pwMS.

Efficacy of the Spanish modified Story Memory Technique in Mexicans with multiple sclerosis: A pilot randomized controlled trial.

BACKGROUND: Memory impairments commonly afflict individuals with MS. While evidence-based cognitive rehabilitation treatments are available in English, the lack of such interventions in Spanish is an important barrier to care for Hispanics with MS. There is class I evidence that the modified Story Memory Technique (mSMT) improves learning in English. This intervention has been translated and adapted into Spanish. OBJECTIVE: To examine the preliminary efficacy of the Spanish mSMT to improve learning in Mexicans with MS. METHODS: Twenty individuals with relapsing-remitting MS were randomized to treatment (n = 10) or placebo control (n = 10) groups. The Spanish mSMT is a 10-session intervention that teaches imagery and context to facilitate learning. The control condition was matched to the treatment condition in treatment duration, and stimulus content and presentation. Participants completed baseline and post-treatment neuropsychological assessments. RESULTS: Individuals who received the Spanish mSMT showed significant improvements in learning and life satisfaction relative to the control group. Also observed were a near-moderate effect size on perceived memory complaints and a moderate-to-large effect size on the family's perception of the patient's competency. CONCLUSIONS: The Spanish mSMT showed preliminary efficacy in improving learning deficits in Mexicans with MS, and such improvements may extend to other domains.

Effects of a Game-Based Virtual Reality Video Capture Training Program Plus Occupational Therapy on Manual Dexterity in Patients with Multiple Sclerosis: A Randomized Controlled Trial.

Neurorehabilitation is a fundamental aspect in the treatment approach for multiple sclerosis (MS), in which new technologies have gained popularity, especially the use of virtual reality (VR). The aim of this paper is to analyze an occupational therapy (OT) intervention compared with OT + VR (OT + VR) on the manual dexterity of patients with MS. 26 MS subjects were initially recruited from an MS patient association and randomized into two groups. The OT group received 20 conventional OT sessions distributed in two sessions per week. The OT + VR group received 20 sessions of VR interventions, twice weekly and lasting 30 minutes, consisting of VR games accessed via the online web page motiongamingconsole.com, in addition to the conventional OT sessions. Pre- and postintervention assessments were based on the Purdue Pegboard Test, the Jebsen-Taylor Hand Function Test, and the Grooved Pegboard Test. Clinical improvements were found regarding the precision of movements, the execution times, and the efficiency of certain functional tasks in the Purdue Pegboard Test and Jebsen-Taylor Hand Function Test tests in the OT + VR group. Although significant differences were not found in the manual dexterity between the OT and OT + VR groups, improvements were found regarding the precision and effectiveness of certain functional tasks.

Functional connectivity in multiple sclerosis after robotic rehabilitative treatment: A case report.

RATIONALE: Multiple sclerosis (MS) is an inflammatory demyelinating disease of central nervous system and it is associated with an impaired motor function status. The efficacy of rehabilitation in promoting functional recovery and increasing quality of life in MS patients has been demonstrated. PATIENT CONCERNS: A 47-year-old woman was diagnosed with relapsing-remitting multiple sclerosis (RRMS) in November 2014 because of left upper limb hypoesthesia and weakness with difficulty in hand manipulation skills (there was a 1-point Expanded Disability Status Scale (EDSS) progression, i.e., 2.5 vs 1.5). Magnetic resonance image (MRI) showed a new frontal right cortical high-signal-intensity lesion. DIAGNOSIS: Neurological and MRI examination were suggestive of MS diagnosis. INTERVENTIONS: Patient was treated with robotic rehabilitation and evaluated by a Glove Analyzer for fMRI system (GAF). Functional MRI (fMRI) was acquired before and at the end of rehabilitative treatment performed with robotic device (Armeo-power). OUTCOMES: At the end of the rehabilitation program, most of the behavioral parameters, GAF and fMRI evaluation, showed a significative improvement. Moreover, fMRI showed a significantly increased functional activation within the sensory-motor network in the active, motor task. LESSONS: Our findings suggest a possible restorative effect of robotics on brain networks. Moreover, we may argue that GAF may be a valuable tool in assessing functional recovery after upper limb rehabilitation, especially of associated to fMRI examination.

Influence of different rehabilitative aerobic exercise programs on (anti-) inflammatory immune signalling, cognitive and functional capacity in persons with MS - study protocol of a randomized controlled trial.

BACKGROUND: Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS. METHODS: A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0-6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their maximum heart rate (HRmax) followed by active breaks of unloaded pedalling (60% HRmax) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HRmax. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T0) and after (T3) the 3-week exercise intervention program. Blood samples of T0 will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T1) and three hours (T2) after the first exercise session of each group. DISCUSSION: This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov ( NCT03652519 ; 29 August 2018).

A feasibility study of working memory training for individuals with paediatric-onset multiple sclerosis.

Objective: To investigate the feasibility and experiences of paediatric-onset multiple sclerosis (MS) patients completing a working memory training programme. Methods: Nine paediatric-onset MS patients (mean age 19.3 ± 4.1 years) identified as having attention and/or working memory difficulties underwent a five-week (five days/week) internet-based working memory training programme (Cogmed™); weekly coaching was provided. Measures of adherence and tolerance were used to establish the feasibility of implementing computerised cognitive training. Qualitative experiences reported by the patients were analysed and factors that may modulate the effects of training were explored. Results: Six of the nine enrolled patients completed the programme within the recommended time, and all individuals, with the exception of one, were considered to tolerate the training well. Eight of the nine participants acknowledged that training was helpful in one or more ways. All but one participant reported improvements in working memory, although evidence for improvement on objective neuropsychological testing was limited. Lower normalised brain volume emerged as a potentially important variable in predicting extent of improvement on the training programme. Conclusion: Selected paediatric-onset MS patients can tolerate and complete an intensive cognitive rehabilitation programme. Future investigation of moderators of training effects and the stability of the findings over time is needed.

Lower Aerobic Endurance Linked to History of Depression in Multiple Sclerosis: Preliminary Observations.

BACKGROUND: Despite the demonstrated benefits of exercise in multiple sclerosis (MS), this population shows low rates of physical activity. Understanding barriers to exercise in persons with MS is important. The current study examined the relationship between lifetime history of depression, current depressive symptoms, and aerobic endurance in persons with relapsing-remitting MS to determine whether depression might be one such barrier. METHODS: Thirty-one participants with relapsing-remitting MS self-reported current depressive symptoms and history of depression. Aerobic endurance was assessed via 2-Minute Step Test. RESULTS: Linear regression demonstrated that lifetime history of depression predicted lower aerobic fitness whereas current depressive symptoms did not. CONCLUSIONS: Findings suggest a possible role of lifetime depression as a barrier to exercise in MS and highlight the importance of effective treatment of depression in this population to reduce its potential impact on exercise adherence.

Efficacy of group cognitive rehabilitation therapy in multiple sclerosis.

OBJECTIVE: Cognitive impairment occurs in 40%-65% of patients with multiple sclerosis (MS). Several techniques for cognitive rehabilitation (CR) in these patients have been evaluated; however, the results have been controversial. In this study, we investigated the efficacy of group compensatory CR in patients with MS-related cognitive impairment. MATERIALS AND METHODS: Thirty-four female patients with diagnosed relapsing-remitting MS and evidence of impaired cognitive function were included and randomized to intervention (n = 17) and control (n = 17) groups. CR intervention consisted of eight 2-hour sessions of comprehensive group CR over a 4-week period that focused on improvement of memory, attention, and executive function. As placebo, the control group received the same number of non-therapeutic group sessions. Assessment of cognitive function was performed before intervention (pretest), at the end of intervention (post-test), and 3 months later (follow-up). RESULTS: The study population included 34 patients with a mean age of 35.5 years. Statistical comparison of memory assessments at 3-month follow-up showed significantly higher scores in the CR group than in the control group (93.33 vs 86.40 for Addenbrooke's Cognitive Examination test and 16.58 vs 12.00 for visual memory, 19.32 vs 14.05 for verbal memory, and 51.28 vs 44.41 for general scores on the Memory Functioning Questionnaire test, respectively). Wisconsin card sorting test score comparison showed significantly lower total time consumption in the CR group than in the control group (308.1 vs 340.8 seconds, respectively). Behavior rating inventory of executive function-adult scores in all four subtests were significantly higher in the CR group than in the control group (40.25 vs 55.4 for behavioral regulation index, 51.16 vs 68.6 for metacognition index, and 97.41 vs 124.00 for global executive composite, respectively). Attention was the only domain in which we did not observe any significant variation between groups in terms of post-test and follow-up scores. CONCLUSION: This study supports the efficacy of group CR in the improvement of cognitive function in patients with MS.

Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis.

BACKGROUND: Suppressors of cytokine signaling (SOCS) and brain-derived neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors for MS pathogenesis. The impact of exercise on these factors is yet to be fully elucidated in patients with MS. OBJECTIVE: The primary aim of this study is to investigate the effect of 8-week combined exercise training on serum concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the effects of combined exercise training on balance, functional exercise capacity, and fatigue in patients with MS. METHODS: Serum SOCS1, SOCS3, and BDNF levels were assessed in 36 MS patients and 18 healthy individuals. In addition, balance, functional exercise capacity, and fatigue were assessed in the patients with MS. The patients were randomly divided into the combined exercise group (MS-EX, n:18) and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise training. RESULTS: The serum SOCS1, SOCS3, and BDNF levels were similar in the MS patients and healthy control (HC). In MS-EX, the serum BDNF level, balance, functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but serum SOCS3, BDNF, balance and functional exercise capacity did not change (p>0.05). CONCLUSIONS: In summary, the combined exercise training improved BDNF, and physical performance in patients with MS. But, future studies are needed to clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise on SOCS.

Pulse Width Does Not Influence the Gains Achieved With Neuromuscular Electrical Stimulation in People With Multiple Sclerosis: Double-Blind, Randomized Trial.

BACKGROUND: Multiple sclerosis (MS) eventually compromises the walking ability of most individuals burdened with the disease. Treatment with neuromuscular electrical stimulation (NMES) can restore some functional abilities in persons with MS, but its effectiveness may depend on stimulus-pulse duration. OBJECTIVE: To compare the effects of a 6-week intervention with narrow- or wide-pulse NMES on walking performance, neuromuscular function, and disability status of persons with relapsing-remitting MS. METHODS: Individuals with MS (52.6 ± 7.4 years) were randomly assigned to either the narrow-pulse (n = 13) or wide-pulse (n = 14) group. The NMES intervention was performed on the dorsiflexor and plantar flexor muscles of both legs (10 minutes each muscle, 4 s on and 12 s off) at a tolerable level for 18 sessions across 6 weeks. Outcomes were obtained before (week 0) and after (week 7) the intervention and 4 weeks later (week 11). RESULTS: There was no influence of stimulus-pulse duration on the outcomes ( P > .05); thus, the data were collapsed across groups. The NMES intervention improved ( P < .05) gait speed and walking endurance, dorsiflexor strength in the more-affected leg, plantar flexor strength in the less-affected leg, force control for plantar flexors in the less-affected leg, and self-reported levels of fatigue and walking limitations. CONCLUSION: There was no influence of stimulus-pulse duration on the primary outcomes (gait speed and walking endurance). The 6-week NMES intervention applied to the lower leg muscles of persons with mild to moderate levels of disability can improve their walking performance and provide some symptom relief.

Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

PURPOSE: The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. METHOD: A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. RESULTS: The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). CONCLUSIONS: The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study was a 24-week randomised controlled cross-over trial, including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did not differ between groups. PBVC tended to differ between groups and higher absolute cortical thickness values were observed in 19 of 74 investigated cortical regions after PRT. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups for four areas: anterior cingulate gyrus, temporal pole, orbital sulcus and inferior temporal sulcus. CONCLUSION: PRT seem to induce an increase in cortical thickness, indicating that PRT have a neuroprotective or even neuroregenerative effect in relapsing-remitting MS.