MS-related Outcomes Research Articles

Evaluating the Impact of Seated Pilates on Functional Outcomes Among Those With Mild, Moderate, and Severe Multiple Sclerosis Impairment: A Pilot Feasibility Trial.

This pilot study assessed the feasibility and functional benefits of a twice-weekly, 12-week, virtual, seated, group-based Pilates program in persons with mild to severe multiple sclerosis (MS). Participants were randomized into either a Pilates-only group or a Pilates group, which also incorporated hip and shoulder-cuff activation exercises. Process, management, and scientific-feasibility metrics were analyzed descriptively. Functional outcomes, physical activity, and MS-related outcomes (impact, fatigue, and quality of life) were measured pre- and postintervention and analyzed using mixed-effects models, analysis of variance, and cluster analysis. Twenty-two participants completed baseline testing. Sixteen completed the intervention and postintervention testing. Collapsed across groups, analyses demonstrated improvements in the Timed 25-Foot Walk (36%), Timed Up-and-Go (13%), and the Berg Balance Scale (10%, statistically significant). Neither between-groups differences nor physical activity or MS outcome changes were significant. Participants reported high satisfaction. Findings suggest thatvirtual, seated Pilates is feasible and may confer balance benefits to individuals with MS.

Long term effects of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea syndrome in multiple sclerosis patients

BackgroundObstructive sleep apnea-hypopnea (OSAH) is common in MS patients and is associated with fatigue. We recently published a randomized, controlled trial (RCT) of active vs sham continuous positive airway pressure (CPAP) treatment in MS patients with fatigue, poor sleep quality, and (OSAH) (Mult Scl J 2022;28:82–92). Our aim was to evaluate the long-term effects of CPAP treatment on fatigue (Fatigue Severity Scale, FSS, primary outcome) and other clinical outcomes in MS patients with OSAH. MethodsFollowing the RCT, participants were offered treatment with CPAP and participation in an open label study. Patients were re-evaluated with RCT outcome measures at least 6 months after completion of the RCT. ResultsTwenty-eight of 34 (82 %) RCT-completers participated in this study a mean of 2.7 years after the RCT. Sixteen (57 %) patients were treated with CPAP (mean use 5.4 ± 1.0 h/night during the 6 months prior to follow-up visit), while the other 12 patients declined CPAP use and received no other OSAH treatments. Baseline clinical characteristics, including MS related disability and sleep outcomes, were not significantly different between CPAP-treated vs non-CPAP treated patients. Patients using CPAP at follow-up (n = 16) demonstrated significant improvements from RCT baseline in FSS (p = 0.005), Fatigue Scale for Motor and Cognitive Functions (p = 0.008, p = 0.012), Pittsburgh Sleep Quality Index (p = 0.016), Center of Epidemiological Studies-Depression Scale (p = 0.05), and Multiple Sclerosis Quality of Life-54 (MSQOL-54) physical and mental component scores (p = 0.012, p = 0.023), but no improvements in Epworth Sleepiness Scale, Pain Visual Analog Scale, or Expanded Disability Status Scale. Patients not using CPAP (n = 12) had no significant improvements in outcome measures. Using a linear mixed model, FSS (p = 0.03), morning fatigue (p = 0.048), and MSQOL-54 physical component score (p = 0.02) improved significantly in CPAP treated patients compared with non-CPAP treated patients from RCT baseline. ConclusionIn this post-RCT open label study, long-term CPAP use was associated with improved fatigue (FSS, our primary outcome) and physical quality of life in MS patients with OSAH.

Health behaviors of people with multiple sclerosis and its associations with MS related outcomes: a German clinical cohort.

Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes. The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical impairment, quality of life (QoL) and cardiovascular comorbidities. A questionnaire was administered at the MS Outpatient Clinic of the University Medical Center Hamburg Eppendorf asking for health behaviors regarding dietary habits assessed with the German adaptation of the validated Spanish short Diet Quality Screener (sDQS), level of physical activity assessed with the Godin Leisure Time Questionnaire (GLTEQ) and tobacco smoking. Participants were asked to report cardiovascular comorbidities using items from the Self-Report Comorbidity Questionnaire for Multiple Sclerosis. Additionally, cardiovascular risk factors like blood pressure, height and weight (to calculate BMI) and waist circumference were measured. MS specific clinical data, e.g., disease course, duration, disability and MS-specific QoL were collected from the clinical database. Descriptive analyses were performed and multivariate regression analyses for complete cases were carried out for each of the three outcome variables including all mentioned modifiable risk factors (dietary behavior, smoking, physical activity and BMI) as independent variables. In this sample of 399 pwMS the mean age was 42 years (SD 12.8) with a mean disease duration since diagnosis of 7.4 years (SD 8.4) and a mean EDSS of 2.8 (SD 1.9). 24% were current smokers, 44% were insufficiently physically active and 54% did not follow a healthy dietary pattern. 49% of this relatively young clinical population was overweight and 27% reported one or more cardiovascular comorbidities. Most modifiable risk factors showed no convincing associations with MS-related disease outcomes in the multiple regression analyses. This clinical cohort of pwMS shows a high prevalence of critical health behaviors and comorbidities and emphasizes the need for monitoring, education and assistance for behavior change in this population.

Effects of aerobic, resistance, and combined exercise training on health-related quality of life in multiple sclerosis: Systematic review and meta-analysis.

Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system that manifests in symptoms that compromise health-related quality of life (HRQOL). HRQOL focuses on a person's overall, subjective evaluation of health status primarily in the physical and mental domains. Exercise training is a form of rehabilitation for managing MS-related outcomes that might influence HRQOL. Reviews on exercise training are available, but we are unaware of a recent comprehensive review and meta-analysis of exercise effects for improving physical and mental domains of HRQOL. This analysis provides an updated review and meta-analysis of randomized controlled trials (RCTs) examining interventions consisting of aerobic, resistance and combined exercise training for improving HRQOL in persons with MS. This systematic review 1) assessed the overall strength of evidence for exercise interventions on HRQOL, 2) evaluated the relative effect of exercise interventions on physical and mental domains of HRQOL, and 3) determined moderators of exercise intervention effects on HRQOL. Seven databases were searched for RCTs evaluating physical and/or mental domains of HRQOL with adults diagnosed with MS and undergoing an intervention of aerobic, resistance or combined exercise training compared with a non-exercise comparator. Data extraction included participant and intervention characteristics, and pre- and post-intervention HRQOL outcome data. Effect sizes (ESs) were calculated as standardized mean differences (SMDs) and a multilevel random-effects model was used to generate an aggregated SMD that compared exercise with non-exercise control conditions. Twelve RCTs met the inclusion criteria and yielded 23 ESs to be analyzed. Participants (N=593; 308 intervention vs. 285 control conditions) had a mean (±standard deviation) age of 42.4 (6.5) years and 80% (18.3%) were female. Results generated a medium effect of exercise for improving overall HRQOL (ES=0.64, p=0.0001) with high heterogeneity (Q11=58.8, I2=86.7%). Exercise training yielded a large effect on the physical domain (k=12, ES=0.82, p<0.0009) and a medium effect on the mental domain (k=11, ES=0.41, p<0.0001). Moderator analyses identified exercise modality, supervision level, intervention delivery and length, HRQOL tool, and number of participants with relapsing-remitting MS as significant influences of ES for HRQOL. Exercise training is clinically effective for improving overall HRQOL in MS and produces greater improvements in the physical domain of HRQOL than the mental domain. The moderator analysis suggests that supervised, aerobic, and group-delivered exercise training of ≥3 months yields the most influence on HRQOL. Such results may have major implications for MS treatment and care.

Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials

Background: A growing number of clinical trials have investigated the role of diet in multiple sclerosis (MS) patients. We systematically reviewed the literature for clinical trials to assess the impact of different kinds of diets on MS-related outcomes. Methods: We searched MEDLINE, EMBASE, and Web of Science for relevant studies published before July 2019. The clinical trials included a defined dietary intervention and MS outcomes, including fatigue, relapse rate (RR), quality of life (QOL), and disability. Results: In the present review, 15 trials on 669 MS patients were included. The 2 plant-based diet trials, 1 was low-fat and the other was low-calorie, included in the review showed a large effect (ES: 0.6 to 0.7) on fatigue compared to the regular diet. The other plant-based diet was a low-protein diet and showed moderate to large effects on disability and RR compared to the Western diet. Moreover, 2 studies showed the clinically meaningful effects of the ketogenic diet (KD) on QOL and disability compared to the regular diet. In addition, 2 studies compared fish oil (FO) to placebo and found a small effect on disability (ES: 0.1 to 0.3). There were 2 studies that evaluated evening primrose oil and hemp seed oil and showed medium to large effect (ES: 0.7 to 1.5) on RR compared to olive oil. Finally, we found 2 studies that showed high flavonoid cocoa had a moderate effect (ES: 0.4) on fatigue and a small effect (ES: 0.04) on QOL compared to low flavonoid cocoa. Conclusion: Plant-based diet is a backbone for dietary recommendations in MS patients although low-fat, low-calorie, and KD diets with the addition of fish oil, vegetable oil, and flavonoids could be helpful.

Fatigue and fluctuations in physical and psychological wellbeing in people with multiple sclerosis: A longitudinal study

BackgroundFatigue is a highly prevalent and disabling symptom of multiple sclerosis (MS). The aetiology remains unclear, potentially resulting from neuroinflammatory or neurodegenerative processes, mood disturbance, MS symptoms including pain, poor sleep, physical decompensation or medication side effects. Cross-sectional associations have been reported between fatigue and markers of physical and psychological health in people with MS. The current study examined if fluctuations in markers of physical and psychological wellbeing were associated with between-person differences in fatigue in MS. MethodsLongitudinal data of up to 7 years was available of 3369 people with MS who were enrolled in the UK MS Register. Participants completed MS impact scale ratings and MS walking scales up to 4 times per year for up to 7 years. Fatigue was assessed at one time point using the Fatigue Severity Scale. Multilevel analyses were conducted to examine the degree of variance in the outcome measures accounted for by fatigue. ResultsFatigue was associated with fluctuations in depression, MS impact, and walking ability, and to a lesser extent with fluctuations in anxiety and perceived health status. Interference of fatigue in participation in social activities and work-related responsibilities and the physical effects of fatigue were most strongly related to MS-related outcomes. ConclusionGiven the strong associations between fatigue and many MS outcomes, fatigue management interventions are likely to impact on different aspects of physical and psychological wellbeing in MS.

Dietary interventions for multiple sclerosis-related outcomes.

Dietary interventions for multiple sclerosis-related outcomes.

The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with neurological disability and brain atrophy in multiple sclerosis

BackgroundSerum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well.Objectives/Aims: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS).MethodsWe identified a large cohort of clinically well-defined patients from our longitudinal database that included MS-related outcomes, disease-modifying therapy, patient-reported outcome (PRO) measures, and quantified cerebral MRI at 1.5 T. We queried hospital records for complete blood counts within 2 months of each clinic visit and excluded those obtained during clinical relapses. Four hundred eighty-three patients, with a mean of 3 longitudinal observations each, were identified who met these criteria. Initial analyses assessed the association between NLR and MLR as the outcomes, and psychological and demographic predictors in univariable and multivariable models controlling for age, gender and treatment. The second set of analyses assessed the association between clinical and MRI outcomes including whole brain atrophy and T2-hyperintense lesion volume, with NLR and MLR as predictors in univariable and multivariable models. All analyses used a mixed effects linear or logistic regression model with repeated measures.ResultsUnadjusted analyses demonstrated significant associations between higher (log-transformed) NLR (but not MLR) and PRO measures including increasing depression (p = 0.01), fatigue (p < 0.01), and decreased physical quality of life (p < 0.01). Higher NLR and MLR strongly predicted increased MS-related disability as assessed by the Expanded Disability Status Scale, independent of all demographic, clinical, treatment-related, and psychosocial variables (p < 0.001). Lastly, higher NLR and MLR significantly discriminated progressive from relapsing status (p ≤ 0.01 for both), and higher MLR correlated with increased whole-brain atrophy (p < 0.05) but not T2 hyperintense lesion volume (p > 0.05) even after controlling for all clinical and demographic covariates. Sensitivity analyses using a subset of untreated patients (N = 146) corroborated these results.ConclusionsElevated NLR and MLR may represent hematopoetic bias toward increased production and pro-inflammatory priming of the myeloid innate immune system (numerator) in conjunction with dysregulated adaptive immune processes (denominator), and consequently reflect a complementary and independent marker for severity of MS-related neurological disability and MRI outcomes.

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression

Background: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing–remitting (RR). Objective: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. Methods: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. Results: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Conclusion: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS.

CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS.

Objective:To assess the relationship between CD56bright natural killer (NK) cells and multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS treated with daclizumab high-yield process (DAC HYP).Methods:Data were from patients enrolled in a 52-week randomized, double-blind, placebo-controlled study of DAC HYP and its extension study. Assessments included relationships of CD56bright NK cell numbers (identified using fluorescence-activated cell sorting) at weeks 4 and 8 with the numbers of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 and the annualized relapse rate.Results:In DAC HYP–treated patients but not placebo-treated patients, the numbers of CD56bright NK cells increased over 52 weeks of treatment, and their numbers at weeks 4 and 8 predicted the number of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 of treatment (p ≤ 0.005 for each comparison). Similar but nonsignificant trends were observed between CD56bright NK cell counts and the annualized relapse rate in DAC HYP–treated patients. DAC HYP–treated patients who showed lower levels of expansion of CD56bright NK cells still developed fewer new or newly enlarging T2-hyperintense lesions than placebo-treated patients during the first year of treatment.Conclusions:CD56bright NK cells appear to mediate some of the treatment-related effects of DAC HYP, but their numbers do not account for the full effect of DAC HYP on MS-related outcomes.

Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis

Adherence to disease-modifying therapies (DMTs) is essential for the reduction of multiple sclerosis (MS) progression and relapse. However, only limited data currently exist on the impact of treatment adherence on MS-related clinical and economic outcomes in the real world setting. To assess the impact of treatment adherence on MS-related hospitalizations (inpatient [INP]), ER visits, MS relapses, and medical costs. Patients with ≥ 1 ICD-9-CM code for MS who received ≥ 1 DMT between July 1, 2004 and June 30, 2008 were identified using the administrative claims database. The first DMT received during the study period was defined as the index treatment and ≥ 6-month preindex and ≥ 12-month postindex continuous health-plan enrollment were required for inclusion. Adherence was assessed using the medication possession ratio (MPR); patients with MPR ≥ 80% were regarded as adherent. Multivariate analyses were used to evaluate the impact of adherence on MS-related outcomes after controlling for baseline demographic and clinical characteristics. In this cohort (n=2446), 59.6% of the patients were adherent to their DMT. Compared with the nonadherent group, adherent patients were significantly less likely to have MS-related INP (odds ratio [OR]: 0.63, 95% confidence interval [CI], 0.47-0.83) and MS relapses (OR: 0.71, 95% CI, 0.59-0.85). No significant difference was found in ER risk between adherent and nonadherent groups (8.4% vs. 10.5%, P=0.068, OR: 0.80, 95% CI: 0.60-1.07). On average, the adherent group incurred lower medical costs than the nonadherent group ($3380, 95% CI, $3046-$3750 vs. $4348, 95% CI, $3828-$4940, P=0.003). Treatment adherence is associated with better clinical and economic outcomes including lower risks for MS-related hospitalization, MS relapse, and less MS-related medical costs. Treatments that require infrequent administrations and have favorable adherence profiles may benefit patients who are unable to adhere to DMT therapies. Such treatments may be important in improving disease outcomes and may be suitable therapeutic candidates for the management of MS.

Cognitive test results in pediatric MS

Heterogeneity in physical and cognitive outcomes is a well-recognized but little understood feature of multiple sclerosis (MS). Such heterogeneity likely reflects the contribution of multiple factors including genetics, physical environment, social environment, comorbid diseases, and health behaviors. Increasingly, race and ethnicity are being studied as possible factors influencing MS-related outcomes.1 In this issue of Neurology ®, Ross et al.2 examined 42 patients with pediatric-onset MS to determine whether race is associated with differences in cognition. Each study participant underwent testing to evaluate global functioning, complex attention, verbal fluency, confrontation naming, and verbal memory. The 20 African American (AA) subjects did not perform as well as the 22 Caucasian American (CA) subjects on tests of complex attention and language. Previous studies of the pediatric MS population showed a high burden of cognitive impairment and difficulties with complex attention and language; the burden of impairment increased with longer disease duration, earlier age at onset, increasing number of relapses, and level of physical disability.3,4 Ross et al. extend earlier findings by focusing on a patient-related characteristic, race, on cognitive impairment rather than on disease-related characteristics such as age …

High frequency of adverse health behaviors in multiple sclerosis

Background Health behaviors influence chronic disease risks in the general population, and may influence health outcomes independently of comorbid diseases. Health behaviors receive less attention in multiple sclerosis (MS) than in the general population. We assessed health behaviors among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the demographic characteristics associated with particular health behaviors. Methods In October 2006, we surveyed NARCOMS participants regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; physical activity using questions from the PEPI study, alcohol use using the AUDIT-C; and height and weight. To determine the independent demographic predictors of health behaviors, we used multivariable logistic regression, either binary or polytomous as appropriate. Results Of 8983 responders, 4867 (54.2%) ever smoked; 1542 (17.3%) currently smoked. On the basis of the AUDIT-C, 1632 (18.2%) were at risk for alcohol abuse or dependence. A quarter of participants were obese (n = 2269), and 2780 (31.3%) were overweight. Fewer than 25% of participants reported moderate or heavy leisure-time physical activity. Generally, lower socioeconomic status was associated with a higher frequency of adverse health behaviors accounting for other demographic factors. With increasing levels of disability, the reported intensity of physical activity was lower, and the frequency of overweight or obesity was higher. Conclusions Patients with MS exhibit frequent adverse health behaviors, increasing the risk of other chronic diseases. Further research is needed to determine how these behaviors influence disability progression, quality of life, and other MS-related outcomes.