Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

Hip kinematics and kinetics in patients with femoroacetabular impingement syndrome before and 1 year after hip arthroscopic surgery. Results from the HAFAI cohort.

INTRODUCTION: Patients with femoroacetabular impingement syndrome (FAIS) experience decreased function. Consequently, earlier studies have evaluated gait biomechanics in these patients, but a larger study evaluating gait biomechanics before and after an intervention standardising gait speed is lacking. We aimed at investigating gait kinematics and kinetics in patients with FAIS compared with pain-free controls before and 1 year after hip arthroscopic surgery. Secondary, we aimed at analysing gait pattern separately for the sexes and to investigate associations between peak kinematics and kinetics and the Copenhagen Hip and Groin Outcome Score (HAGOS). MATERIALS AND METHODS: Sixty patients with FAIS and 30 pain-free controls were tested at a standardised gait speed (1.40 m/s ± 10%). Patients were tested twice: before and 1 year after surgery. Kinematics and kinetics were recorded using infrared high-speed cameras and a force plate. Participants answered HAGOS. RESULTS: The largest difference among groups was that gait differed between males and females. Neither before nor after surgery could we demonstrate large alterations in gait pattern between patients and pain-free controls. Male patients demonstrated associations between peak kinematics and kinetics and HAGOS Sports function. CONCLUSIONS: Gait pattern was only vaguely altered in patients with FAIS compared with pain-free controls before and after surgery when using at standardised gait speed. Hence, analysing gait in patients with FAIS does not seem of major importance. Nevertheless, there was an association between HAGOS Sports function and peak kinematics and kinetics in male patients, implying that there could be a clinical importance.

Time matters: Early-phase multiple sclerosis is accompanied by considerable impairments across multiple domains.

Impairments across multiple domains are a disabling consequence of multiple sclerosis (MS). Originating from preventive medical strategies, the "time matters"-perspective has become a focal point when treating MS. In particular, early detection of physical and cognitive deficits, along with deficits in patient-reported outcomes seems crucial to further optimize both pharmacological and non-pharmacological MS treatment strategies. Therefore, this topical review investigates the level of impairments across multiple domains (physical function, cognitive function, and patient-reported outcomes) in the early stage of MS (⩽5 years since diagnosis, including clinically isolated syndrome (CIS)), when compared to matched healthy controls. Even at early disease stages, studies show impairments corresponding to 8%-34% and small-to-large numerical effect sizes (0.35-2.85) in MS/CIS patients across domains. This evidence call for early screening programs along with early interventions targeting the multiple impaired domains. This further highlights the importance of preventive initiatives preserving and/or restoring physical and cognitive reserve capacity if possible.

No association between femoral or acetabular angles and patient-reported outcomes in patients with femoroacetabular impingement syndrome-results from the HAFAI cohort.

Patients with femoroacetabular impingement syndrome (FAIS) are diagnosed using imaging, but detailed description especially the acetabular shape is lacking and may help give more insight to the pathogenesis of FAIS. Furthermore, associations between patient-reported outcomes (PROs) and the radiological angles might highlight which radiological angles affect outcomes experienced by the patients. Hence, the aims of this study were (i) to describe computer tomography (CT) acquired angles in patients with FAIS and (ii) to investigate the association between radiological angles and the Copenhagen Hip and Groin Outcome Score (HAGOS) in patients with FAIS. Patients scheduled for primary hip arthroscopic surgery for FAIS were included. Based on CT, following angles were measured before and 1 year after surgery; femoral anteversion, alpha, lateral centre edge, acetabular index, anterior sector, posterior sector and acetabular anteversion. All patients completed the HAGOS. Sixty patients (63% females) aged 36 ± 9 were included. One year after surgery, significant alterations in the alpha angle and the acetabular index angle were found. Neither baseline PROs nor changes in PROs were associated with the radiological angles or changes in angles. Since neither changes in CT angles nor baseline scores were associated with HAGOS, the improvements felt by patients must origin from somewhere else. These findings further underlines that morphological changes seen at imaging should not be treated arthroscopically without a patient history of symptoms and clinical findings.

Is diet associated with physical capacity and fatigue in persons with multiple sclerosis? -Results from a pilot study.

BACKGROUND: Diet may have immunomodulatory effects in persons with multiple sclerosis (PwMS) and studies suggest that diet may be considered a complementary treatment to control the progression of the disease. The role of nutrition in MS and related symptoms have been reported by several studies but remains controversial. OBJECTIVE: To explore the association between dietary intake and physical capacity and fatigue in PwMS. METHODS: An explorative cross-sectional pilot study was conducted, in which 23 ambulatory PwMS were enrolled. Dietary intake was assessed using a 4-day food record. Outcome variables included a 6-Minute Walk Test (6MWT), a VO2max test, and self-reported questionnaires assessing fatigue severity (Fatigue Severity Scale, FSS) and impact (Modified Fatigue Impact Scale, MFIS). Associations between variables were determined using simple and multiple regression analyses. RESULTS: In the simple but not the multiple (adjusted for sex and age) regression analyses the carbohydrate intake (% of total energy intake) was positively associated with physical capacity (i.e. the 6MWT and VO2max test), whereas fat intake (% of total energy intake) was inversely associated with physical capacity. In the multiple regression analyses the absolute intake of ω-3 and vitamin D showed trends towards a positive association with the MFIS physical subscale and VO2max, respectively. CONCLUSION: Although not consistent across analyses, these findings suggest that better physical capacity most often is associated with a diet rich in carbohydrates and reduced fat content. Further research and randomized controlled trials are required to fully assess the role and the efficacy of diet quality and content on physical capacity in PwMS.

Plasma brain-derived neurotrophic factor (BDNF) and sphingosine-1-phosphat (S1P) are NOT the main mediators of neuroprotection induced by resistance training in persons with multiple sclerosis-A randomized controlled trial.

Resistance training (RT) has been shown to elicit neuroprotective effects in persons with multiple sclerosis (pwMS). Brain-derived neurotrophic factor (BDNF) and Sphingosine-1-phosphat (S1P) have been put forward as potent mediators of the neuroprotective effects induced by RT. However, while increases have been shown in acute and chronic circulating BDNF levels in pwMS following aerobic exercise alone or in combination with other exercise regimes, no studies have examined this in response to RT. As a novel 'proof-of-concept' approach, we therefore examined the effects of 24 weeks of RT on acute and chronic circulating BDNF and S1P levels in the same pwMS whom our group had previously observed RT-induced neuroprotective effects in (i.e. increased cortical thickness and preservation of whole brain volume). A total of n = 30 relapsing-remitting pwMS were randomized into a training group (TG: 24 weeks of progressive high intensity resistance training, 2 sessions per week; n = 16, age 44[40:51] years, EDSS score 3.0[2.0:3.5] (median[IQR]) or a control group (CG: 24 weeks of habitual lifestyle; n = 14, age 45[37:47] years, EDSS score 3.0[2.5:3.5]). Plasma levels of BDNF and S1P were assessed by ELISA kits before and after the 24-week intervention period. No within- or between group changes were observed in acute or chronic circulating levels of BDNF. A substantial proportion of the participants had S1P levels below the detection limit, yet no within- or between changes were observed in chronic S1P plasma levels in the remaining samples. Thus, the present findings do not support that circulating plasma BDNF or S1P levels are the main mediators of the neuroprotective effects previously reported in the same group of pwMS.

Is hip muscle strength normalised in patients with femoroacetabular impingement syndrome one year after surgery?: Results from the HAFAI cohort.

OBJECTIVES: Little is known about hip function after hip arthroscopic surgery in patients with femoroacetabular impingement syndrome. Hence, the aim of the study was (1) to investigate changes in hip muscle strength from before to one year after hip arthroscopic surgery, (2) to compare patients with a reference group. DESIGN: Cohort study with a cross-sectional comparison. METHODS: Before and after hip arthroscopic surgery, patients underwent hip muscle strength testing of their hip flexors and extensors during concentric, isometric and eccentric contraction in an isokinetic dynamometer. Reference persons with no hip problems underwent tests at a single time point. Participants completed completed the Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaire and physical capacity (stair climbing loaded and unloaded, stepping loaded and unloaded and jumping) tests. RESULTS: After surgery, hip flexion strength improved during all tests (6-13%, p<0.01) and concentric hip extension strength improved (4%, p=0.002). Hip flexion and extension strength was lower for patients than for reference persons (9-13%, p<0.05) one year after surgery. Higher hip extension strength after surgery was associated with better patient reported outcomes. Patients, who were unable to complete at minimum one test of physical capacity, demonstrated significantly weaker hip muscle strength. Compared with their healthy counterparts, female patients were more impaired than male patients. CONCLUSIONS: One year after surgery, patients improved their maximal hip muscle strength. When compared to reference persons, maximal hip muscle strength was still impaired.

Is the impact of fatigue related to walking capacity and perceived ability in persons with multiple sclerosis? A multicenter study.

BACKGROUND: The relationship between fatigue impact and walking capacity and perceived ability in patients with multiple sclerosis (MS) is inconclusive in the existing literature. A better understanding might guide new treatment avenues for fatigue and/or walking capacity in patients with MS. OBJECTIVE: To investigate the relationship between the subjective impact of fatigue and objective walking capacity as well as subjective walking ability in MS patients. METHODS: A cross-sectional multicenter study design was applied. Ambulatory MS patients (n = 189, age: 47.6 ±â€¯10.5 years; gender: 115/74 women/men; Expanded Disability Status Scale (EDSS): 4.1 ±â€¯1.8 [range: 0-6.5]) were tested at 11 sites. Objective tests of walking capacity included short walking tests (Timed 25-Foot Walk (T25FW), 10-Metre Walk Test (10mWT) at usual and fastest speed and the timed up and go (TUG)), and long walking tests (2- and 6-Minute Walk Tests (MWT). Subjective walking ability was tested applying the Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue impact was measured by the self-reported modified fatigue impact scale (MFIS) consisting of a total score (MFIStotal) and three subscales (MFISphysical, MFIScognitive and MFISpsychosocial). Uni- and multivariate regression analysis were performed to evaluate the relation between walking and fatigue impact. RESULTS: MFIStotal was negatively related with long (6MWT, r = -0.14, p = 0.05) and short composite (TUG, r = -0.22, p = 0.003) walking measures. MFISphysical showed a significant albeit weak relationship to walking speed in all walking capacity tests (r = -0.22 to -0.33, p < .0001), which persisted in the multivariate linear regression analysis. Subjective walking ability (MSWS-12) was related to MFIStotal (r = 0.49, p < 0.0001), as well as to all other subscales of MFIS (r = 0.24-0.63, p < 0.001), showing stronger relationships than objective measures of walking. CONCLUSIONS: The physical impact of fatigue is weakly related to objective walking capacity, while general, physical, cognitive and psychosocial fatigue impact are weakly to moderately related to subjective walking ability, when analysed in a large heterogeneous sample of MS patients.

Performed and perceived walking ability in relation to the Expanded Disability Status Scale in persons with multiple sclerosis.

BACKGROUND: The severity of walking impairment in persons with multiple sclerosis (pwMS) at different levels on the expanded disability status scale (EDSS) is unclear. Furthermore, it is unclear if the EDSS is differently related to performed- and perceived walking capacity tests. AIMS: To quantify walking impairment and perceived impact of MS on walking according to EDSS scores and to examine the relations between these parameters in pwMS. METHODS: EDSS was collected by neurologists and walking was assessed by the timed 25ft walk test (T25FWT), two minute walk test (2MWT), six minute walk test (6MWT) and the 12-item MS walking scale (MSWS-12) in 474 PwMS with mild (EDSS 1-4: n=200) to moderate (EDSS 4.5-6.5: n=274) MS. Magnitude of walking impairment was calculated and related to EDSS. RESULTS: Compared to predicted values in healthy controls, walking speed was reduced by 41.5±25.8% in the 6MWT for the total MS group and by 21.8±20.2% and 55.8±19.1% in the mild and moderate MS subgroups, respectively. The EDSS score showed the strongest relationship to the 2MWT and the 6MWT in the total MS group (r=-0.76, p<0.0001), to the MSWS-12 score in the mild MS group (r=0.56, p<0.0001), and to the 2MWT in the moderate MS group (r=-0.50, p<0.0001). CONCLUSION: In pwMS (EDSS scores 1-6.5), walking speed is on average reduced by ~40% when compared to predicted values in healthy controls, and impairments are already present at early disease stages, suggesting early initiation of rehabilitation. The 2MWT and 6MWT show the strongest relationship to EDSS, but the MSWS-12 identify impairments more gradually at low EDSS scores.

Muscle strength and power in persons with multiple sclerosis - A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease in the central nervous system which causes a number of physical symptoms including impairments of muscle mechanical function (muscle strength, muscle power and explosive muscle strength (~rate of force development, RFD)). However, a full overview of the existing knowledge regarding muscle mechanical function in persons with MS (PwMS) is still pending. OBJECTIVES: To systematically review 1) the psychometric properties of isokinetic dynamometry testing in PwMS, and 2) studies comparing muscle mechanical function in PwMS to matched healthy controls (HC). In addition, a meta-analysis will evaluate 3) the effects of progressive resistance training on muscle mechanical function in PwMS. METHODS: A systematic literature search was performed in eight databases. To be included in the review, the study had to 1) enroll participants with a confirmed diagnosis of MS; 2) assess muscle mechanical function 3) had undergone peer-review. The psychometric properties of isokinetic dynamometry were reviewed with respect to validity, reliability, and responsiveness. Comparison of muscle strength between PwMS and HC was performed across contraction velocities, contraction modes and muscle groups, as were the rate of force development. The effects of progressive resistance training on muscle mechanical function were evaluated in a meta-analysis using a random effects model and standardized mean difference (SMD). RESULTS: A total of four, twenty-four, and ten studies were identified for aim 1, 2, and 3, respectively. High Intraclass correlations coefficients (range: 0.87-0.99) for isokinetic dynamometry was reported when assessing knee extensor and knee flexor muscle strength independent of contraction velocity. Compared to match HC, PwMS display impaired muscle strength, power and explosive muscle strength. Muscle strength impairments were most pronounced during maximal moderate to fast dynamic muscle contractions of the lower extremities. Progressive resistance training has a small but significant effect on muscle mechanical function in PwMS (SMD=0.45, 95% CI: 0.18-0.72, p=0.001). CONCLUSIONS: The present review showed that 1) isokinetic dynamometry has a high reliability in PwMS; 2) muscle strength, power and rate of force development is impaired in PwMS compared to HC, and muscle strength impairments are most pronounced during maximal moderate to fast dynamic muscle contractions of the lower extremities; and 3) progressive resistance training can improve muscle mechanical function in PwMS. Future studies should evaluate progressive resistance training designed to optimize maximal moderate to fast dynamic muscle contractions of the lower extremities.

Effect of slow release-Fampridine on muscle strength, rate of force development, functional capacity and cognitive function in an enriched population of MS patients. A randomized, double blind, placebo controlled study.

DESIGN: This study was conducted as a randomized, double blind, placebo-controlled parallel group trial preceded by open label enrichment phase. OBJECTIVES: The objectives of this study were 1) to examine the effect of SR-Fampridine treatment on muscle strength in terms of maximal voluntary contraction (MVC) and rate of force development (RFD) of the lower extremities and 2) to replicate previously published data on the effect of slow release-Fampridine (SR-Fampridine) on the functional capacity of the lower limbs, the upper limb and cognitive function, in persons with multiple sclerosis (pwMS). METHODS: Previously identified responders to SR-Fampridine were randomized to SR- Fampridine or placebo treatment for four weeks. On days 0 and 26-28 participants underwent testing by isokinetic dynamometry, Nine Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Six Spot Step Test (SSST), Timed 25 Foot Walk Test (T25FW) and 5-Times Sit-to-Stand (5-STS). RESULTS: A statistical significant effect of SR-Fampridine on MVC was demonstrated during knee extension, knee flexion and hip flexion of the weakest leg, as well as on RFD during knee extension and knee flexion of the weakest leg. Furthermore, a significant effect of SR-Fampridine on T25FW, SSST and 5-STS was demonstrated. CONCLUSION: Gold standard dynamometry assessment of muscle strength showed improved MVC and RFD in persons with MS treated with SR-Fampridine compared to placebo. Furthermore, previous findings on the effects of SR-Fampridine on functional capacity of the lower limbs were replicated. ClinicalTrials.gov identifier: NCT01656148.

Distribution-based estimates of minimum clinically important difference in cognition, arm function and lower body function after slow release-fampridine treatment of patients with multiple sclerosis.

OBJECTIVE: To provide distribution-based estimates of the minimal clinical important difference (MCID) after slow release fampridine treatment on cognition and functional capacity in people with MS (PwMS). METHOD: MCID values were determined after SR-Fampridine treatment in 105 PwMS. Testing included the Timed 25 Foot Walk (T25FW), the Symbol Digit Modalities Test (SDMT), the Six Spot Step Test (SSST), the 9-Hole-Peg-Test (9-HPT), and the 5-Time-Sit-To-Stand test (5-STS). RESULTS: MCID values: T25FW 17.8% (9.1-17.8), SDMT 17.1% (9.2-17.1), SSST 16.7% (8.5-16.7), 9-HPT 15.3% (0-15.3), and 5-STS 34.6% (16.9-34.6). CONCLUSION: This study presents distribution-based estimates of MCID values for the SSST, the 9-HPT, and the 5-STS and confirms MCID estimates for the T25FW and the SDMT.

Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training.

BACKGROUND AND PURPOSE: Brain derived neurotrophic factor (BDNF) is suggested to play a neuroprotective role in multiple sclerosis (MS). However, the BDNF response to long-term exercise in MS remains unknown. Our objective was to compare resting BDNF profiles of healthy controls (HCs) and persons with relapsing-remitting MS (RRMS) and to investigate the impact of a 24-week exercise intervention on serum BDNF release in MS. METHODS: At baseline, blood BDNF levels were assessed in MS (n = 22, mean Expanded Disability Status Scale 2.6 ± 0.2, mean age 43 ± 2 years) and HCs (n = 19, mean age 47 ± 1 year). Next, persons with MS were randomized to an exercise intervention group (EX, n = 15) or a sedentary control group (SED, n = 7) completing a 24-week randomized controlled trial. In persons with MS, muscle strength, exercise tolerance and body composition were assessed, as compliance measures, at baseline and after 24 weeks. RESULTS: At baseline, the BDNF concentration of persons with RRMS was 21% lower than HCs. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between EX and SED. In particular, within EX BDNF concentrations increased 13.9% ± 8.8%, whereas it decreased 10.5% ± 4.1% within SED. Furthermore, 24 weeks of exercise induced changes in the compliance measures between EX and SED. In addition, within EX muscle strength, exercise tolerance and lean tissue mass improved, whereas these remained stable within SED. CONCLUSION: In conclusion, BDNF concentration of persons with RRMS was lower compared to HCs and increased after 24 weeks of exercise in persons with MS, compared to the non-exercise MS control group.

Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.

Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-ß, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1ß, IL-4, IL-10, IL-17F, IL-23, tumor necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F secretion following resistance exercise was observed in the trained compared with the untrained state. This study suggests little acute and chronic effect of PRT on cytokine levels in IFN-treated PwMS.

Impact of high intensity exercise on muscle morphology in EAE rats.

The impact of high-intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain-derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it remained stable in EAE. BDNF-responses were not affected by EAE or exercise. In conclusion, EAE affected CSA-properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE-animals. However, exercise was not able to prevent muscle fiber atrophy.

Walking capacity and ability are more impaired in progressive compared to relapsing type of multiple sclerosis.

BACKGROUND: Patients with progressive multiple sclerosis (MS) have been attributed greater walking disability than relapsing-remitting MS (RRMS) patients but quantitative data on walking speed and ability are lacking. AIM: To investigate the impact of type of MS on severity of reduced walking ability and capacity taking into account age, sex, height and disease duration. DESIGN: Cross-sectional observational multi-center study SETTING: European MS centers providing either in- or out-patient services, or both. POPULATION: This study included 502 patients: 259, 162 and 81 patients showed RRMS, secondary and primary progressive MS respectively. METHODS: Walking was evaluated by T25FW, six minute walk test and MS-Walking Scale-12. Patient characteristics were compared using a one-way ANOVA, and simple and multivariate regression analysis were applied with the walking measures. RESULTS: In adjusted (sex, age, weight, height and disease duration) analyses, walking impairments were more than 20% greater in progressive types of MS compared to RRMS. There were also indications of greater walking impairment in primary compared to secondary progressive MS patients. CONCLUSION: Clinical walking impairment was larger in progressive compared to relapsing-remitting type of MS. The biological disease mechanism, being degeneration or inflammation, impacts on disability. CLINICAL REHABILITATION IMPACT: Health care professionals must be aware of different severity of walking impairment in progressive compared to relapsing type of MS, and need for intensive treatment. Also, studies must report rehabiltiation effects according to MS type.

The effect of exercise on depressive symptoms in multiple sclerosis based on a meta-analysis and critical review of the literature.

BACKGROUND AND PURPOSE: The purpose of this study was to perform a systematic review of the literature on the effects of exercise on depressive symptoms in patients with multiple sclerosis (MS), as well as to apply meta-analytical procedures to the results. METHODS: A systematic search covering eight databases was conducted. The included studies were randomized controlled trials applied to people with definite MS who completed a structured exercise intervention which were compared to any comparator, including other forms of exercise. The outcomes included a primary measure of depression/depressive symptoms or an instrument with a clearly defined depression subscale. RESULTS: Fifteen randomized controlled trial studies were identified including a total of 331 exercising subjects and 260 controls. The average Physiotherapy Evidence Database (PEDro) score was 5.6 ± 1.3 points. Only one study applied depressive symptoms as the primary outcome. Four studies showed positive effects of exercise on depressive symptoms. An in-depth analysis of the studies revealed that the baseline level of depressive symptoms, patient disability level, choice of depression instrument and exercise intensity may influence the results. The meta-analysis included 12 studies reflecting a total of 476 subjects. The standardized mean difference across studies was g = -0.37, 95% confidence interval (-0.56; -0.17), and the null hypothesis of homogeneity within the sample could not be rejected (Q = 12.05, df = 11, P = 0.36). DISCUSSION: Exercise may be a potential treatment to prevent or reduce depressive symptoms in individuals with MS, but existing studies do not allow solid conclusions. Future well-designed studies evaluating the effects of exercise on depressive symptoms and major depression disorder in MS are highly warranted.

Changes in cognition, arm function and lower body function after slow-release Fampridine treatment.

OBJECTIVE: We aimed to evaluate the effect of slow-release (SR) Fampridine on multiple outcome measures reflecting different domains, and to compare the responsiveness of the Six Spot Step Test (SSST) and the Timed 25 Foot Walk (T25FW). METHODS: For this study 108 participants were included. On day 0 they were tested with the T25FW, the SSST, the 9-Hole Peg Test (9-HPT), the 5 Times Sit-To-Stand test (5-STS) and the Symbol Digit Modalities Test (SDMT). Four weeks of treatment with SR Fampridine 10 mg BID was commenced. Participants were tested again after 26-28 days of treatment. RESULTS: Mean changes observed were: SSST -3.4±6.4 s (p<0.001), T25FW -1.2±3.7 s (p<0.001), 9-HPT -1.2±6.0 s (p<0.001), 5- STS -3.4±7.2 s (p<0.001) and SDMT 1.4±4.8 a.u. (p=0.003). Change on the SSST differed significantly from T25FW (SSST 17.0±19.6% vs. T25FW 11.2±17.1%, p=0.0013). Some 48.6% were found to have a meaningful change on the SSST compared with 25.7% on the T25FW. The response to treatment with SR Fampridine did not correlate with age, sex, Expanded Disability Status Scale and disease duration. CONCLUSION: SR Fampridine treatment has significant effects on different domains including upper and lower body and cognition. Furthermore, the SSST is more responsive to the effect of SR Fampridine than is the T25FW. ClinicalTrials.gov identifier: NCT01656148.

Endurance training is feasible in severely disabled patients with progressive multiple sclerosis.

This study tested whether upper-body endurance training (ET) is feasible and can be performed at sufficient intensity to induce cardiovascular adaptations in severely disabled patients with progressive multiple sclerosis (MS). Eleven progressive MS patients (6.5 ≤ EDSS ≤ 8.0) scheduled for a four-week inpatient rehabilitation program were randomized to a control group (CON, n = 5) that received standard individualized MS rehabilitation or an intervention group (EXE, n = 6) that in addition received 10 sessions of predominantly upper-body ET. One patient dropped out of the EXE group (drop-out rate: 1/6~17%) and no adverse events were recorded. The EXE group completed on average 9.3±0.8 sessions (~96.0±5%). During the ET sessions an average heart rate of 93.9±9.3beats*min(-1) were sustained corresponding to 91.6±6.8% of the maximal pre-intervention heart rate. In the EXE group a trend toward a time*group interaction was seen for VO2peak (p = 0.06). ET is feasible in severely disabled patients with progressive MS and it can probably be performed at sufficient intensity to induce cardiovascular adaptations.

Does multiple sclerosis affect glucose tolerance?

Based on current literature, it is not clear if multiple sclerosis (MS) patients are at increased risk to develop impaired glucose tolerance (IGT). Eighty-one MS patients and 45 healthy controls (HC) performed an oral glucose tolerance test. IGT was defined as a fasting glucose concentration of 6.1-6.9 mmol/l and two-hour post-load glucose of 7.8-11.1 mmol/l. The prevalence of impaired fasting glucose concentrations (17% vs 2%) and IGT (11% vs 0%) was higher in MS patients than HC. Accordingly, the areas under the glucose and insulin curves were higher in MS patients. The current study demonstrates an elevated IGT-prevalence in MS.