Multiple Sclerosis Impact Scale Research Articles

Translation, cross-cultural adaptation, and validation of the Greek version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19

Introduction Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) explores optimally impact of MS on sexual activity/satisfaction/intimacy. Aim The present study aims to provide the only validation of the Greek Version of MSISQ-19, and compare results to validation studies in other languages. Methods The original/English version of the MSISQ-19 was translated into Greek according to standardized guidelines, while validity/reliability, correlations with other scales and sexual dysfunction prevalence were tested. Subjects were requested to complete all questionnaires and MSISQ-19, being re-tested three weeks later. Construct-validity of the Greek version of the MSISQ-19 was confirmed with principal-component-analysis. Bartlett’s test assessed correlation-adequacy between items. Pearson’s correlation explored internal-construct-validity between subscales and overall score, and external–construct-validity with disease-status variables, cognitive testing and patient-reported outcomes regarding fatigue, depression/anxiety, MS impact, and quality of life. Results 201 PwMS (130 female). Mean age was 39.3 ± 11.8 years with median disease-duration 11.7 ± 7.9 years. 79.1% RRMS, PPMS (10.4%) and SPMS (10.4%). Cronbach’s alpha coefficient was 0.949. MSISQ-19 correlations between items were large. Significant associations of sexual dysfunction were identified with age (rho = 0.392, p < 0.01), years of education (rho=–0.199, p = 0.006), the Expanded Disability Status Scale (rho = 0.518, p < 0.01) and MS duration (rho = 0.354, p < 0.01). Correlations were disclosed with the Brief International Cognitive Assessment for MS (rho=-0.247, p < 0.05), Modified Fatigue Impact Scale (rho = 0.374, p < 0.05), Depression Anxiety Stress Scale (rho = 0.375, p < 0.05), Multiple Sclerosis Impact Scale (rho = 0.442, p < 0.05), and EuroQoL-five-dimensional instrument (rho = 0.375, p < 0.05). Internal consistency of the Greek version of the MSISQ-19 was confirmed with Cronbach’s alpha. Test-retest reliability (31 PwMS) was excellent with intraclass-correlation-coefficients > 0.90. Conclusion Besides Greek MSISQ-19 satisfactory validity/reliability/reproducibility and being first to include cognitive-testing, authors estimated sexual-dysfunction prevalence affecting half PwMS. HIGHLIGHTS This study provides the only validation of the Greek Version of the MSISQ-19. The latter was found with satisfactory validity, reliability and reproducibility. 50% of the Greek PwMS sample was found to be afflicted with sexual dysfunction. This is also the first validation study to examine associations with cognitive testing. Sexual function is still an underestimated functionality parameter upon examination.

Association between early treatment of multiple sclerosis and patient-reported outcomes: a nationwide observational cohort study

BackgroundTiming of disease-modifying therapy affects clinical disability in multiple sclerosis, but it is not known whether patient reported outcomes are also affected. This study investigates the relationship between treatment timing...

The Patient Health Questionnaire (PHQ-9) as a tool to screen for depression in people with multiple sclerosis: a cross-sectional validation study

Background:Depression has a point prevalence of 25% and lifetime prevalence of 50% in people with multiple sclerosis (pwMS). Due to accessibility and brevity, the 9-item Patient Health Questionnaire (PHQ-9) may be a useful tool in clinical practice for screening and monitoring of depressive symptoms in people with MS (pwMS).Methods:The objective of this study was to evaluate the reliability, validity and acceptability of the PHQ-9 as a screening tool for depressive symptoms in pwMS. PwMS completed online questionnaires at 3 time-points over 4-weeks. The PHQ-9, Multiple Sclerosis Impact Scale (MSIS-29), Centre for Disease Control Health-Related Quality of Life Measure (CDC-HQOL-4) and clinical history.Results:103 participants completed the PHQ-9 at three time points, 43% were categorised as depressed on at least one response. The PHQ-9 exhibited high internal reliability (Cronbach’s α = 0.89), and test-re-test agreement (ICC 0.89, 95% CI 0.85–0.91). Convergent validity was indicated through positive correlation with the mental health items on the MSIS-29 (r = 0.46 and r = 0.50) and CDC-HQOL-4 (r = 0.79 and r = 0.73) at both assessment points. Positive correlations between the PHQ-9 and the MSIS-29 (r = 0.86 and r = 0.84) and CDC-HQOL-4 (r = 0.55 and r = 0.37) physical symptom sub-scores did not indicate divergent validity. 93% of ratings evaluated the PHQ-9 as “Very” or “Completely” acceptable.Conclusion:The PHQ-9 is a reliable and valid measure of depressive symptoms in people with MS. Given its accessibility, ease of administration, and acceptability, we recommend the PHQ-9 as a tool to screen for depressive symptoms in people with MS.

Psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12)

Purpose Walking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients’ quality of life. The study objective was to determine the psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12) among pwMS in Croatia and to examine the association between MSWS-12 and Depression, Anxiety, and Stress Scale-21 (DASS-21), and Multiple Sclerosis Impact Scale-29 (MSIS-29). Materials and methods A cross-sectional study included a sample of pwMS (N = 148). Psychometric properties were examined by estimating the validity and reliability of the MSWS-12. The predictive validity of MSWS-12 and demographic and disease-related factors were assessed by a hierarchical regression model using MSIS-29 and DASS-21 as criterion variables. Results Scale reliability was good for the MSWS-12 scale, expressed by Cronbach’s alpha coefficient (α = 0.98). Correlations between MSWS-12 and DASS-21 (0.20–0.27) and between MSWS-12 and MSIS-29 subscales (0.47–0.83) provided initial support for the convergent validity. Factor analysis demonstrated the unidimensional structure of the MSWS-12. Conclusions The Croatian version of the MSWS-12 is a reliable, valid, and clinically useful tool for assessing walking impairments in pwMS. Implications for rehabilitation Walking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients’ quality of life. Multiple Sclerosis Walking Scale (MSWS-12) is a measure of the disease’s impact on walking abilities from the patient’s perspective. MSWS-12 is a reliable scale for assessing walking speed, endurance, and gait quality in multiple sclerosis and is validated in several languages (Korean, Italian, Brazilian, and Persian). The Croatian version of the MSWS-12 is a reliable, predictive, and valid tool for screening walking impairments in pwMS.

Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide.

Background: A poor patient adherence often limits the real-world effectiveness of an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). In the present study, we aimed to map patient preferences, attitudes toward treatment, and quality of life to identify the predictors of non-adherence to teriflunomide. Methods: This was a single-arm, non-interventional, multicenter study (Czech Act 378/2007 Coll.) consisting of three visits: the first at treatment initiation (teriflunomide 14 mg), and then after 3 and 9 months of therapy. We enrolled both DMT-naïve and patients who had undergone a DMT diagnosed with a clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). The functional status and MS activity were estimated using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR); the quality of life via the Multiple Sclerosis Impact Scale (MSIS-29); the medication adherence with the Morisky Medication Adherence Scale (MMAS-8); the confidence in the ability to take medications by the Self-Efficacy for Appropriate Medication Score (SEAMS); and the attitude to the therapy via the Beliefs about Medicines Questionnaire (BMQ). After nine months of therapy, we predicted the adherence to teriflunomide (MMAS-8) by fitting a multivariate ordinal logistic model with EDSS changes, gender, previous DMT, MSIS-29, BMQ, and SEAMS as the explanatory variables. Results: Between 2018 and 2019, 114 patients were enrolled at 10 sites in the Czech Republic. The mean age was 41.2 years, 64.8% were diagnosed with a CIS, 52.4% were DMT-naïve, and 98.1% of patients preferred an oral administration at the baseline. The mean EDSS baseline was 1.97 and remained constant during the 9 months of therapy. The ARR baseline was 0.72 and dropped to 0.19 and 0.15 after 3 and 9 months, respectively. Despite a more than 4-fold higher ARR baseline, the treatment-naïve patients achieved an ARR at 9 months comparable with those previously treated. There were ten non-serious adverse reactions. After nine months of teriflunomide therapy, 63.3%, 21.2%, and 15.4% of patients had a high, medium, and low adherence, respectively, as per the MMAS-8; 100% of patients preferred an oral administration. The SEAMS score (odds ratio (OR) = 0.91; p = 0.013) and previous DMT (OR = 4.28; p = 0.005) were the only significant predictors of non-adherence. The disability, the quality of life, and beliefs about medicines had no measurable effect on adherence. Conclusion: After nine months of teriflunomide therapy, both the disability and quality of life remained stable; the relapse rate significantly decreased, 63.3% of patients had a high adherence, and 100% of patients preferred an oral administration. A low adherence was associated with previous DMT experiences and a low self-efficacy for the appropriate medication (i.e., the confidence in one’s ability to take medication correctly).

Association between brain volume and disability over time in multiple sclerosis.

Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability status scale (EDSS), SDMT, and MSIS-29, and whether MRI-clinical associations vary with age. We acquired MRI and clinical data from a real-world Swedish MS cohort. FreeSurfer and SPM Lesion Segmentation Tool were used to obtain brain parenchymal, cortical and subcortical grey matter, thalamic and white matter fractions as well as T1- and T2-lesion volumes. Mixed-effects and rolling regression models were used in the statistical analyses. We included 989 persons with MS followed for a median of 9.3 (EDSS), 10.1 (SDMT), and 9.3 (MSIS-29) years, respectively. In a cross-sectional analysis, the strength of the associations of the MRI metrics with the EDSS and MSIS-29 was found to drastically increase after 40-50 years of age. Low baseline regional grey matter fractions were associated with longitudinal increase of EDSS and physical MSIS-29 scores and decrease in SDMT scores and these atrophy measures were stronger predictors than the lesion volumes. The strength of MRI-clinical associations increase with age. Grey matter volume fractions are stronger predictors of long-term disability measures than lesion volumes.

Satisfaction with alemtuzumab in relapsing multiple sclerosis patients: Results from the real-world PRO-ACT study.

Patient-reported outcomes are increasingly used in the management of patients with multiple sclerosis to understand the patient's perspective of disease and treatment. These measures provide insights into important factors including treatment satisfaction, physical and psychological function, and quality of life. To present results from the real-world PRO-ACT study in patients with multiple sclerosis who switched to alemtuzumab from another disease-modifying therapy. This 24-month, prospective, multicenter, observational study had a primary endpoint of change in overall satisfaction, measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Secondary endpoints included the Multiple Sclerosis Impact Scale-29 (MSIS-29), Modified Fatigue Impact Scale-5 (MFIS-5), and the Patient-Determined Disease Steps (PDDS). Safety was monitored with adverse events (AEs). Of 199 enrolled patients, improvements were observed in mean TSQM scores for overall satisfaction (baseline, 50.3; year 2, + 13.2; p < 0.0001), effectiveness (49.3 and + 12.2; p < 0.0001), and side effects (77.6 and + 4.5; p = 0.04). Improvements were also observed in MSIS-29 physical (52.4 and -6.0; p < 0.0001), MSIS-29 psychological (53.4 and -7.0; p = 0.0003), and MFIS-5 (12.8 and -1.7; p < 0.0001). Most (95.0%) patients experienced ≥ 1 AE (88.4% mild, 67.8% moderate). The primary endpoint was met; the safety of alemtuzumab was consistent with pivotal studies.

The MSIS-29 and SF-36 as outcomes in secondary progressive MS trials

Background: Patient-reported outcome measures (PROMs) are often used in clinical research, but little is known about their performance as longitudinal outcomes. Methods: We used data from ASCEND, a large SPMS trial (n = 889), to investigate changes on the Short Form Health Survey 36 (SF-36 v2) and the Multiple Sclerosis Impact Scale (MSIS-29) over 2 years of follow-up. Results: PROM scores changed little over the 2 years of follow-up. In contrast to physical disability measures, there was no consistent trend in PROM change: significant worsening occurred about as often as improvement. Using a 6-month confirmation reduced the number of both worsening and improvement events without altering their relative balance. There was no clear difference in worsening events in groups based on population characteristics, nor was there a noticeable effect using different thresholds for clinically significant change. Conclusion: We found little consistent change in MSIS-29 and SF-36 over 2 years of follow-up in people with SPMS. Our findings show a disconnect between disability worsening and PROM change in this population. Our findings raise caution about the use of these PROMs as primary outcome measures in SPMS trials and call for a critical reappraisal of the longitudinal use of these measures in SPMS trials.

Comparison of spouse and patient personality change judgments following MS onset

ABSTRACT Objectives This is the first study to estimate the prevalence and predictors of spouse and patient perceptions of global/overall personality change (PC) in patients with multiple sclerosis (MS). Methods 69 clinic patients and their spouses completed parallel measures of perceived PC and semantic differential scales measuring pre-MS and current specific behaviours. We correlated perceived personality changes with the following measures of perceived physical, cognitive, emotional, and social functioning: MS Impact Scale, MS Neuropsychological Questionnaire, Beck Depression Inventory-FastScreen; Hospital Anxiety and Depression Scale; Family Questionnaire, McMaster Assessment Device; and Social Provisions Scale. Results Spouses and patients reported comparable levels of substantial change. Both associated PC with patient distress, perceived cognitive impairment, spouse distress, and poorer family functioning. Spouse, but not patient, PC ratings predicted severity of physical symptoms and social support. Principal component analysis of semantic differential ratings yielded a Compassionate Empathy component correlating with PC within spouse, but not patient, data. Conclusions These partially overlapping potential triggers for spouse and patient PC judgments raise questions about the extent they overlap with clinicians’ criteria for PC, since spouses did not link impulsivity with PC. It is also suggested that the initial focus of treatment of PC should focus on partner-agreed changes.

Real-World Assessment of Quality of Life in Patients with Relapsing Remitting Multiple Sclerosis Treated with Teriflunomide for Two Years: Patient-Reported Outcomes from the AURELIO Study in Greece.

IntroductionMultiple sclerosis (MS) is a highly heterogeneous inflammatory disease of the central nervous system. Patient-reported outcomes (PROs) in a real-world clinical setting can provide detailed information about MS from the patient's perspective. PROs were used here to assess quality of life (QoL), treatment satisfaction, clinical efficacy, and safety outcomes in a Greek cohort of relapsing remitting MS (RRMS) patients treated with oral teriflunomide (14 mg/day).MethodsAURELIO was a 2-year, prospective, observational study whose QoL primary endpoint was assessed with the Multiple Sclerosis Impact Scale (MSIS-29). Secondary endpoints included analyses of Patient Determined Disease Steps (PDDS), Treatment Satisfaction Questionnaire for Medication (TSQM), Expanded Disability Status Scale (EDSS), annualized relapse rate (ARR), adherence, and safety outcomes.ResultsAURELIO enrolled 282 patients (62.8% female; mean age 44.8 [SD ± 11] years; EDSS 2.0 [SD ± 1.6]; 44.6% treatment-naïve), with 212 patients (75%) remaining on treatment at study end. MSIS-29 total scores remained stable, while the MSIS-29 psychological scale showed significant improvement (p = 0.0015) at 2 years vs. baseline. TSQM scores at 2 years showed significant improvements in effectiveness (+ 6.6, p = 0.0001), convenience (+ 1.9, p = 0.0256), and global satisfaction (+ 8.1, p = 0.0001) vs. baseline. Disease progression was stable as indicated by non-significant changes in PDDS and EDSS vs. baseline. The ARR was low at 0.065, with a slightly higher ARR in previously treated (0.070) vs. naïve patients (0.058). Adherence was high at > 90%. Overall, 91 patients (32.3%) in the study reported a total of 215 safety events (32 serious, of which 21 were classified as mild–moderate). No new safety signals were observed.ConclusionsThese data highlight the importance of PROs to facilitate personalized treatment strategies in MS. In line with other teriflunomide studies, AURELIO showed stable QoL, efficacy and safety outcomes, and good treatment satisfaction both in treatment-naïve and previously treated patients in this Greek cohort of patients with RRMS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00384-2.

A crossover pilot trial of the feasibility, acceptability, and effectiveness of LoveYourBrain Yoga for community-dwelling adults with multiple sclerosis

Background and purposeAmong people with multiple sclerosis (MS), yoga has potential to improve fatigue and other symptoms that undermine quality of life. The aim of this study was to assess the feasibility, acceptability, and effectiveness of LoveYourBrain Yoga, a six-week yoga with psychoeducation program, on fatigue and other health-related outcomes among people with MS in a rural, community-based setting in the United States. MethodsThis non-randomized 2x2 crossover pilot trial compared LoveYourBrain Yoga to a control among 15 people with MS. People were eligible if they were adults with MS (EDSS score ≤6), English-speaking, and ambulatory. Paired t-tests and Wilcoxon signed rank sum analyses assessed mean differences in PROMIS-FatigueMS, Multiple Sclerosis Impact Scale, Symbol Digit Modalities Test, NIH Neuro-QoL measures, and Liverpool Self-Efficacy scale. We assessed feasibility using recruitment and retention rates, mean attendance, fidelity, and acceptability using satisfaction measures. ResultsSignificant improvements in fatigue (MD -4.34, SD 5.26, p = 0.012), positive affect and wellbeing (MD 2.76, SD 3.99, p = 0.028), and anxiety (MD -4.42, SD 5.36, p = 0.012) were found after LoveYourBrain Yoga compared to the control. Participants reported high satisfaction (M 9.5, SD 1.4) and a majority (92.3%) reported ‘Definitely, yes’ to recommending it to a friend or family. ConclusionLoveYourBrain Yoga is feasible and acceptable when implemented in a rural, community-based setting for people with MS. It may improve a range of MS symptoms and offer a means for acquiring new skills for stress reduction, anxiety management, and overall wellbeing.

Nintendo Switch Joy-Cons' Infrared Motion Camera Sensor for Training Manual Dexterity in People with Multiple Sclerosis: A Randomized Controlled Trial.

Background: The Nintendo Switch® (NS) is the ninth video game console developed by Nintendo®. Joy-Cons® are the primary game controllers for the NS® video game console, and they have an infrared motion camera sensor that allows capturing the patient’s hands without the need to place sensors or devices on the body. The primary aim of the present study was to evaluate the effects of the NS®, combined with a conventional intervention, for improving upper limb (UL) grip muscle strength, coordination, speed of movements, fine and gross dexterity, functionality, quality of life, and executive function in multiple sclerosis (MS) patients. Furthermore, we sought to assess satisfaction and compliance levels. Methods: A single-blinded, randomized clinical trial was conducted. The sample was randomized into two groups: an experimental group who received treatment based on Dr Kawashima’s Brain Training® for the NS® (20 min) plus conventional rehabilitation (40 min), and a control group who received the same conventional rehabilitation (60 min) for the ULs. Both groups received two 60 min sessions per week over an eight-week period. Grip strength, the Box and Blocks Test (BBT), the Nine Hole Peg Test (NHPT), the QuickDASH, the Multiple Sclerosis Impact Scale (MSIS-29), the Trail Making Test (TMT), and the Stroop Color and Word Test (SCWT) were used pre- and post-treatment. Side effects and attendance rates were also recorded. Results: Intragroup analysis showed significant improvements for the experimental group in the post-treatment assessments for grip strength in the more affected side (p = 0.033), the BBT for the more (p = 0.030) and the less affected side (p = 0.022), the TMT (A section) (p = 0.012), and the QuickDASH (p = 0.017). No differences were observed for the control group in intragroup analysis, but they were observed in the NHPT for the more affected side (p = 0.012). The intergroup analysis did not show differences between both groups. Conclusions: Our results show that an eight-week experimental protocol, after using Dr Kawashima’s Brain Training® and the right-side Joy-Con controller for the NS®, combined with a conventional intervention, showed improvements in grip strength, coordination, fine and gross motor function, executive functions, and upper limb functionality in the experimental group. However, no differences were observed when both groups were compared in the intergroup analysis. The addition of Brain Training® for the NS® for the upper limb rehabilitation did not show side effects and was rated with a high satisfaction and excellent compliance in people with MS. Trial registration: This randomized controlled trial has been registered at ClinicalTrials Identifier: NCT04171908, November 2019.

Comparative Effectiveness of 4 Exercise Interventions Followed by 2 Years of Exercise Maintenance in Multiple Sclerosis: A Randomized Controlled Trial

ObjectiveTo determine the effects of exergaming (EXE) on quality of life (QOL), motor, and clinical symptoms in multiple sclerosis (MS). We compared the effects of EXE, balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group on clinical and motor symptoms and quality of life (QOL) in people with MS (PwMS) and determined the effects of subsequent maintenance programs for 2 years in a hospital setting. DesignA randomized controlled trial, using before-after test design. SettingUniversity hospital setting. ParticipantsOf 82 outpatients with MS, 70 were randomized (N=70), and 68 completed the study. InterventionsThe initial high-intensity and high-frequency interventions consisted of 25 one-hour sessions over 5 weeks. After the 5-week-long initial intervention, the 2-year-long maintenance programs followed, consisting of 3 sessions per week, each for 1 hour. Main Outcome MeasuresThe primary outcome: Multiple Sclerosis Impact Scale (MSIS-29). Secondary outcomes: Measures 5 aspects of health-related QOL (EuroQol 5-Dimension questionnaire), Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), Tinetti Assessment Tool (TAT), and static BAL (center of pressure). ResultsMSIS-29 improved most in EXE (11 points), BAL (6), and CYC (6) (all P<.05). QOL improved most in EXE (3 points), CYC, and BAL (2) (all P<.05). TAT and BBS improved significantly (P<.05) but similarly (P>.05) in EXE, BAL, and CYC. 6MWT improved most in EXE (57m), BAL (32m), and CYC (19m) (all P<.001). Standing sway did not change. Maintenance programs further increased the initial exercise-induced gains, robustly in EXE. ConclusionsA total of 25 sessions of EXE, BAL, CYC, and PNF, in this order, improved clinical and motor symptoms and QOL, and subsequent 2-year-long thrice weekly maintenance programs further slowed symptom worsening and improved QOL. EXE was the most and PNF was the least effective to improve clinical symptoms, motor function, and QOL in PwMS.

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective: An Observational Cross-Sectional Study.

IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients’ perspective and its relationship with other disease factors.MethodsAn observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman’s correlation and multivariate linear regression analysis.ResultsSeventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5–4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29.ConclusionFatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions.

Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission.

ObjectiveTo investigate the association of pain with plasma C5a levels and other related inflammatory cytokines in neuromyelitis optica spectrum disorders (NMOSD) patients during remission.Participants and MethodsNMOSD patients (n = 87) and healthy controls (HC; n = 44) were consecutively recruited between January 2017 and April 2018. Plasma complement 5 (C5), C5a, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β levels were detected. Visual Analogue Scale (VAS), ID pain scale, 24-item Hamilton Depression Scale (HAMD), Multiple Sclerosis Impact Scale (MSIS-29), and Kurtzke Expanded Disability Status Scale (EDSS) were used to evaluate the degree and types of pain, the existence of depression and anxiety, and the life quality and disability status of patients. Binary logistic regression equation was used to assess the association of pain with plasma C5a levels.ResultsAmong the 87 NMOSD patients, 40 complained of pain that in 67.5% (27/40) of cases had a neuropathic component (ID pain ≥2). Plasma C5a, IL-6, TNF-α, and IL-1β levels were significantly elevated in NMOSD patients than in HC. Plasma C5 levels were negatively correlated with the time from sampling to the last relapse or disease onset. NMOSD patients with pain had higher plasma C5a levels, and they suffered from a higher disability, more anxiety, and worse life quality compared to those patients without pain. In NMOSD patients with pain, there were not significant differences between plasma levels of C5, C5a, IL-6, TNF-α, or IL-1β, regardless of neuropathic pain or not. Binary logistic regression showed that the OR of plasma C5a level was 1.002, with gender and EDSS score were identified as independent factors associated with pain in NMOSD.ConclusionNMOSD patients during remission had elevated C5a and related inflammatory cytokines levels in peripheral blood. Elevated C5a may have a unique role in the pathogenesis of pain in NMOSD patients.

Objectively assessed physiological, physical, and cognitive function along with patient-reported outcomes during the first 2 years of Alemtuzumab treatment in multiple sclerosis: a prospective observational study.

In persons with multiple sclerosis (pwMS), little evidence exist on the effects of Alemtuzumab on physiological, physical, and cognitive function along with patient-reported outcomes, despite these domains are being rated as highly important. Therefore, our purpose was to perform a prospective observational study to examine these outlined outcomes during the first two years of Alemtuzumab treatment in pwMS. In n = 17 relapsing-remitting pwMS, physiological function [body composition; bone mineral content; muscle strength; aerobic capacity], physical function [6-min walk test (6MWT, primary outcome); timed 25 ft walk test (T25FWT); six spot step test (SSST); 9-step stair ascend (9SSA); timed up and go test (TUG); 5 × sit to stand test (5STS)], cognitive function [selective reminding test (SRT); symbol digit modalities test (SDMT)], and patient-reported outcomes [multiple sclerosis impact scale-29 (MSIS29); 12-item multiple sclerosis walking scale (MSWS12); modified fatigue impact scale (MFIS); hospital anxiety and depression scale (HADS)] were assessed prior to Alemtuzumab treatment initiation as well as 3, 6, 12, and 24months into the treatment. Improvements were observed at 24-month follow-up in T25FWT (+ 8%), SSST (+ 10%), SDMT (+ 5.2 points, 53% improved more than the clinical cut-off score) and SRT, whereas the primary outcome 6MWT, and all other remaining outcomes, remained stable throughout the Alemtuzumab treatment period. The present findings suggest that Alemtuzumab treatment in relapsing-remitting pwMS can improve certain domains of physical function (short distance walking) and cognitive function (processing speed, memory), and furthermore stabilize physiological and physical function along with patient-reported outcomes. Registered at clinicaltrials.gov: NCT03806387.

Combining a supervised and home-based task-oriented circuit training improves walking endurance in patients with multiple sclerosis. The MS_TOCT randomized-controlled trial

BackgroundBalance and mobility impairments are widespread in patients with Multiple Sclerosis (PwMS), even at an early stage. They can contribute to disability, physical deconditioning and reduced quality of life. Task-oriented is a training modality that may promote walking abilities and conditioning. However, the effects usually are short-lasting and exercising at home can have several barriers. This randomized controlled trial aimed to test the effectiveness of the combination of a 2-weeks in-person, supervised task-oriented circuit training (TOCT), followed by a 12-weeks home-based task-oriented program with monthly in-person visits. Methods36 PwMS with EDSS 4–5.5 and unassisted walking have been randomly assigned to 10 supervised TOCT sessions over two weeks (Phase 1) followed by a 12-weeks home-based task-oriented program (Phase 2) or a delayed-treatment group. At the end of Phase 2, the delayed-treatment group (usual care) received the same TOCT protocol. Phase 1 was composed of six gait-based workstations and treadmill training, whereas Phase 2 was based on progressive task-oriented tasks practice at home with monthly visits to adjust activities levels. Six Minute Walk Test (6MWT), Timed 25-foot walk test (T25FW), Timed Up and Go test (TUG), Dynamic Gait Index (DGI), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale – 12 (MSWS-12), Multiple Sclerosis Impact Scale–29 (MSIS-29) and resting muscle oxygen consumption (rmVO2) were assessed as outcome measures at baseline, after Phase 1 and after Phase 2. Retention was tested on the whole sample at a 12-weeks follow-up. ResultsThe entire sample completed the 2-weeks TOCT, whereas adherence was good for the 12-weeks home-based task-oriented program (6.2/10). The mean repetitions and level of difficulty of each task significantly increased after every timepoint. A superiority of task-oriented program was verified for 6MWT (F, 2,88 = 7.80; p<0.001) on usual care after the 12-weeks home-based program. Moreover, between-group differences were highlighted at the same point, even for T25FW, TUG and MSWS-12. RmVO2 and fatigue were significantly improved only in the experimental group. Positive effects on 6MWT were retained 12 weeks after the end of the protocol (p<0.001) in the whole sample. ConclusionsThe combination of a supervised and self-managed task-oriented program enhances walking endurance with positive effects on walking ability, fatigue and resting muscle oxygen consumption in PwMS with unassisted walking. These preliminary results reflected how this intervention was effective for impairment and activity improvements; moreover, it was cardiorespiratory stressful and possibly reduced deconditioning.

Results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection for multiple sclerosis relapse that did not adequately respond to corticosteroids.

IntroductionAbout 20%–35% of multiple sclerosis (MS) patients fail to respond to high‐dose corticosteroids during a relapse. Repository corticotropin injection (RCI, Acthar® Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and pituitary peptides that has anti‐inflammatory and immunomodulatory effects.AimsThe study objective was to determine the efficacy and safety of RCI in patients with MS relapse that inadequately responded to corticosteroids. This was a multicenter, double‐blind, placebo‐controlled study. Nonresponders to high‐dose corticosteroids were randomized to receive RCI (80 U) or placebo daily for 14 days. Assessments included improvements on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS‐29), Clinical Global Impression of Improvement (CGI‐I), and adverse events (AEs).ResultsEighteen patients received RCI, and 17 received placebo. A greater proportion of EDSS responders was observed in the RCI group at Day 7, 21, and 42 compared with the placebo group. Qualitative CGI‐I showed that more patients receiving RCI were much improved or very much improved than with placebo. No meaningful differences were observed between treatment groups for MSIS‐29. No serious AEs or deaths were reported.ConclusionRCI is safe and effective for MS relapse patients who do not respond to high‐dose corticosteroids.

Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients.

Cognitive impairment is a common complaint in people with multiple sclerosis (pwMS). The study objective was to determine the psychometric properties of the letter digit substitution test (LDST) that measures information processing speed and to investigate the impact of relevant predictors of LDST achievement in pwMS. The design was cross-sectional. The study included 87 pwMS and 154 control subjects. The validity of LDST was examined, and a hierarchical regression model was used to explore relevant predictors of LDST success. The LDST had excellent construct validity, as expressed by differences between pwMS and control subjects. Convergent validity of the LDST was supported by a significant moderate correlation with the expanded disability status scale (EDSS) (ρ = −0.36; p < 0.05) and a significantly strong correlation with the multiple sclerosis impact scale (MSIS-29) physical subscale (r = −0.64; p < 0.01). The LDTS score well differentiated the pwMS considering age, education, EDSS, disease duration, comorbidity, and medication therapy. Using the LDST as a criterion variable in pwMS results showed consistent evidence for the age, education, and EDSS impact on LDST performance. The best cut-off score of ≤35 discriminated the control and MS group. LDST proved to be a valid test for assessing information processing speed in pwMS.

Quantifying the impact of upper limb tremor on the quality of life of people with multiple sclerosis: a comparison between the QUEST and MSIS-29 scales

BackgroundUpper limb tremor is common in people with multiple sclerosis (pwMS) and can affect day to day function, impacting on their tremor related quality of life (tremor-QOL). The Quality of Life in Essential Tremor Questionnaire (QUEST) is a tremor-QOL scale, however it has not been validated for use in pwMS. This is in contrast to the Multiple Sclerosis Impact Scale (MSIS-29), a MS health related QOL (MS-QOL) scale validated in pwMS. The aim of this study was to quantify tremor-QOL in pwMS using both the QUEST and MSIS-29 and establish the convergent validity of the QUEST scale with the MSIS-29. MethodsData were derived from an existing registered clinical trial studying the efficacy of Botox (onabotulinumtoxinA) compared to placebo in pwMS-related upper limb tremor (ACTRN12617000379314). We determined MS-related disability (Expanded Disability status scale score (EDSS)), tremor severity (Bain and Findley Clinical Tremor Rating Scale (Bain)), cerebellar function (Scale for the Assessment and rating of Ataxia (SARA)), and upper limb manual dexterity (9 Hole Peg Test (9-HPT)). The QUEST and MSIS-29 were used to quantify tremor-QOL and MS-QOL respectively. Convergent validity was investigated by examining the correlation between QUEST and MSIS-29, and the pattern of correlation of the two scales compared to the EDSS, SARA, BAIN and 9-HPT. ResultsOur cohort of 57 patients (16 male; 41 female), mean age of 47.6, had moderate MS-related disability with median EDSS score of 5 (IQR = 3.5). Median Bain score was 8, indicating mild tremor severity, which corresponded to mild to moderately poor tremor-QOL given mean Quest Summary Index (QSI) of 45.7. QSI correlated to tremor severity as measured by Bain total score (rs(55) = 0.339, p < 0.01), manual dexterity as measured by 9-HPT (rs(55) = 0.304, p < 0.05), and MS disease activity measured by EDSS (rs(55) = 0.347, p < 0.01). MSIS-29 also showed correlations to EDSS, and 9-HPT, but did not correlate to Bain total score. There was a strong relationship between QSI and MSIS-29 in pwMS (r(55) = 0.709, p < 0.01). ConclusionIn this cross-sectional study, we found that both the MS-QOL and tremor-QOL of pwMS with upper limb tremor was reduced. We were also the first to demonstrate that tremor-QOL in pwMS with upper limb tremor can be measured using the QUEST, which may be better suited for use in pwMS affected by arm-tremor than the MSIS-29. There is a lack of literature to specifically address tremor-QOL in pwMS, and more research is warranted.