Expanded Disability Status Scale Research Articles

Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

Long-term clinical outcomes in patients with CIS treated with interferon beta-1b: results from the 15-year follow up of the BENEFIT trial.

Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Initial Treatment (BENEFIT) randomized, parallel group trial. In BENEFIT patients were assigned to "early" IFNB-1b treatment or placebo ("delayed" treatment). After 2years or conversion to clinically definite multiple sclerosis (CDMS), all patients were offered IFNB-1b and were reassessed 15years later. Of 468 patients, 261 (55.8%) were enrolled into BENEFIT 15 (161 [55.1%] from the early, 100 [56.8%] from the delayed treatment arm). In the full BENEFIT analysis set, risk of conversion to CDMS remained lower in the early treatment group ( - 30.5%; hazard ratio 0.695 [95% CI, 0.547-0.883]; p = 0.0029) with a 15.7% lower risk of relapse than in the delayed treatment group (p = 0.1008). Overall, 25 patients (9.6%; 9.9% early, 9.0% delayed) converted to secondary progressive multiple sclerosis. Disability remained low and stable with no significant difference between groups in Expanded Disability Status Scale score or MRI metrics. Paced Auditory Serial Addition Task-3 scores were better in the early treatment group (p = 0.0036 for treatment effect over 15years). 66.3% of patients were still employed at Year 15 versus 74.7% at baseline. In conclusion, results 15years from initial randomization support long-term benefits of early treatment with IFNB-1b.

Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS). Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.5-point EDSS decrease), and safety outcomes until initiation of a subsequent DMT. The EDSS was re-baselined at 30 days from ALEM start (BL EDSS). Eighty-seven ALEM-treated patients (median age: 32 years, 72% female, 14% treatment-naïve) were followed for a median of 55 (interquartile range 31-68) months. We found significant reductions in the ARR from 1.16 before ALEM to 0.15 throughout Years 1-9 (p < 0.001). Subsequent DMTs were initiated in 19 patients (22%, 74% anti-CD20 monoclonal antibodies). At Year 5 (n = 53), more patients achieved CDI (58%, 95% confidence interval (CI) 45%-71%) than had experienced PIRA (14%, CI 7.5%-24%), and 58% remained relapse-free. Shorter MS duration (p < 0.001, hazard ratio (HR) 0.86 (CI 0.80-0.93)) and no previous high-efficacy treatment (p < 0.001, HR 5.16 (CI 2.66-10.0)) were the best predictors of CDI, while PIRA was associated with a higher number of previous DMTs (p = 0.04, HR 3.06, CI 1.05-8.89). We found no new safety signals. ALEM had long-lasting beneficial effects on the ARR and disability improvement, especially when initiated early in the course of the disease. Only a subset of patients received subsequent DMTs.

The telephone-based application of the modified fatigue impact scale in individuals with multiple sclerosis: An investigation of measurement properties

BackgroundFatigue is one of the most common symptoms reported by individuals with multiple sclerosis and it contributes to the reduction of the functionality. Therefore, it is important to assess the impact of fatigue on daily living of individuals with multiple sclerosis. The Modified Fatigue Impact Scale (MFIS) is an instrument to assess the perception of the impact of fatigue. However, there have been no investigations about the measurement properties of this instrument administered over the telephone for individuals with multiple sclerosis. ObjectivesTo verify the concurrent validity, the test-retest reliability, the standard error of measurement (SEM) and the minimal detectable change (MDC) of the MFIS applied over the telephone to assess the perception of the impact of fatigue of individuals with multiple sclerosis. MethodsThe MFIS, composed of 21 items covering three domains: physical, cognitive and psychosocial, was applied at three different moments with an interval of 5–7 days. To establish the concurrent criterion validity, the face-to-face application and the first evaluation by telephone were used. The two telephone assessments were used to assess the test-retest reliability The intraclass correlation coefficient (ICC) with 95 % confidence interval (CI) and the Bland-Altman method were used. The standard error of measurement (SEM) and the MDC was calculated according to reliability results. ResultsThirty individuals (40.83 ± 10.61, 60 % female) were included. The median score on the Expanded Disability Status Scale was 2.00 (±4.00). The majority of participants experienced fatigue (n = 17; 56.67 %). A significant and high magnitude correlation (0.70 ≤ ICC ≤ 0.87, p < 0.001) was found in the investigation of concurrent criterion validity. The Bland-Altman method showed a mean difference between 0.70 to 2.17 points between face-to-face and telephone-based application of the MFIS. For test-retest reliability, a significant and very high magnitude correlation (0.91 ≤ ICC ≤ 0.97, p < 0.001) was found. The Bland-Altman method showed a mean difference between -0.03 and -0.77 points between two telephone-based applications. The SEM and the MDC were 0.71 and 1.97 points. ConclusionThe telephone-based application of the MFIS to assess the perceived impact of fatigue in individuals with multiple sclerosis demonstrated adequate measurement properties, and may be a valuable tool to assess patients in clinical practice.

Suicidal ideation in people with multiple sclerosis and its association with coping self-efficacy

BackgroundChronic neurological disease such as multiple sclerosis (MS), is a significant risk factor for psychological distress, which can result in suicidal behaviour. Suicidal ideation (SI) is considered a harbinger of suicide-related mortality. However, so far, little is known about the role of protective factors against SI in MS. ObjectiveThis study aims to assess the association between coping self-efficacy and SI when controlled for sociodemographic variables, clinical variables, sleep-related problems, and depression. MethodsThe study sample consisted of 162 people with MS, was predominantly female (75.9 %), the mean age was 40.9 ± 11.4 years, the mean disease duration was 11.7 ± 7.1 years, and the mean functional disability score was 3.55 ± 1.1. We used the Coping Self-Efficacy scale (CSE), the General Health Questionnaire-28 (GHQ-28), the Expanded Disability Status Scale (EDSS), the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), and the Multidimensional Fatigue Inventory (MFI). Multiple linear regressions were utilized to statistically analyse the data. ResultsAll assessed coping self-efficacy dimensions were significantly associated with SI in MS when controlled for sociodemographic variables, clinical variables, sleep-related problems, and depression. Furthermore, all assessed coping self-efficacy dimensions were able to alleviate the negative association between income, depression and SI. ConclusionPeople with MS may significantly benefit from psychological support aimed at promoting coping self-efficacy and utilization of various coping strategies. Problem-focused coping, coping focused on getting support, and coping focused on stopping unpleasant thoughts and feelings seem to have comparable associations with SI, and thus interventions aimed at empowering any of these dimensions may be beneficial in diminishing the severity of SI.

Motor function in multiple sclerosis assessed by navigated transcranial magnetic stimulation mapping.

Impaired motor function is a major cause of disability in multiple sclerosis (MS), involving various neuroplasticity processes typically assessed by neuroimaging. This study aimed to determine whether navigated transcranial magnetic stimulation (nTMS) could also provide biomarkers of motor cortex plasticity in patients with MS (pwMS). nTMS motor mapping was performed for hand and leg muscles bilaterally. nTMS variables included the amplitude and latency of motor evoked potentials (MEPs), corticospinal excitability measures, and the size of cortical motor maps (CMMs). Clinical assessment included disability (Expanded Disability Status Scale, EDSS), strength (MRC scale, pinch and grip), and dexterity (9-hole Pegboard Test). nTMS motor mapping was performed in 68 pwMS. PwMS with high disability (EDSS ≥ 3) had enlarged CMMs with less dense distribution of MEPs and various MEP parameter changes compared to pwMS with low disability (EDSS < 3). Patients with progressive MS had also various MEP parameter changes compared to pwMS with relapsing remitting form. MRC score correlated positively with MEP amplitude and negatively with MEP latency, pinch strength correlated negatively with CMM volume and dexterity with MEP latency. This is the first study to perform 4-limb cortical motor mapping in pwMS using a dedicated nTMS procedure. By quantifying the cortical surface representation of a given muscle and the variability of MEP within this representation, nTMS can provide new biomarkers of motor function impairment in pwMS. Our study opens perspectives for the use of nTMS as an objective method for assessing pwMS disability in clinical practice.

Serum neurofilament light chain and glial fibrillary acidic protein for predicting response to apheresis in steroid-refractory multiple sclerosis relapses.

The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated. We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635-0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903-0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965-2.069, p = 0.076). Analysis of the sNfL-to-sGFAP ratio showed an OR of 1.924 (95% CI = 1.073-3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. Lower sGFAP levels, a higher sNfL-to-sGFAP ratio, and younger age are associated with a favourable apheresis outcome.

Cortical Lesions as an Early Hallmark of Multiple Sclerosis: Visualization by 7 T MRI

Objectives Compelling evidence indicates a significant involvement of cortical lesions in the progressive phase of multiple sclerosis (MS), significantly contributing to late-stage disability. Despite the promise of ultra-high-field magnetic resonance imaging (MRI) in detecting cortical lesions, current evidence falls short in providing insights into the existence of such lesions during the early stages of MS or their underlying cause. This study delineated, at the early stage of MS, (1) the prevalence and spatial distribution of cortical lesions identified by 7 T MRI, (2) their relationship with white matter lesions, and (3) their clinical implications. Materials and Methods Twenty individuals with early-stage relapsing-remitting MS (disease duration &lt;1 year) underwent a 7 T MRI session involving T1-weighted MP2RAGE, T2*-weighted multiGRE, and T2-weighted FLAIR sequences for cortical and white matter segmentation. Disability assessments included the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite, and an extensive evaluation of cognitive function. Results Cortical lesions were detected in 15 of 20 patients (75%). MP2RAGE revealed a total of 190 intracortical lesions (median, 4 lesions/case [range, 0–44]) and 216 leukocortical lesions (median, 2 lesions/case [range, 0–75]). Although the number of white matter lesions correlated with the total number of leukocortical lesions (r = 0.91, P &lt; 0.001), no correlation was observed between the number of white matter or leukocortical lesions and the number of intracortical lesions. Furthermore, the number of leukocortical lesions but not intracortical or white-matter lesions was significantly correlated with cognitive impairment (r = 0.63, P = 0.04, corrected for multiple comparisons). Conclusions This study highlights the notable prevalence of cortical lesions at the early stage of MS identified by 7 T MRI. There may be a potential divergence in the underlying pathophysiological mechanisms driving distinct lesion types, notably between intracortical lesions and white matter/leukocortical lesions. Moreover, during the early disease phase, leukocortical lesions more effectively accounted for cognitive deficits.

Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis

Abstract Cortical lesions are common in multiple sclerosis and are associated with with disability and progressive disease. We asked whether cortical lesions continue to form in people with stable white matter lesions and whether the association of cortical lesions with worsening disability relates to pre-existing or new cortical lesions. 50 adults with multiple sclerosis and no new white matter lesions in the year prior to enrollment (33 relapsing-remitting, 17 progressive) and a comparison group of 9 adults who had formed at least one new white matter lesion in the year prior to enrollment (active relapsing-remitting) were evaluated annually with 7 tesla brain MRI and 3 tesla brain and spine MRI for 2 years, with clinical assessments for 3 years. Cortical lesions and paramagnetic rim lesions were identified on 7 tesla images. Seven total cortical lesions formed in 3/30 individuals in the stable relapsing-remitting group (median 0, range 0-5), four total cortical lesions formed in 4/17 individuals in the progressive group (median 0, range 0-1), and 16 cortical lesions formed in 5/9 individuals in the active relapsing-remitting group (median 1, range 0-10, stable relapsing-remitting vs progressive vs active relapsing-remitting P=0.006). New cortical lesions were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Individuals with at least 3 paramagnetic rim lesions had a greater increase in cortical lesion volume over time (median 16µl, range -61-215 vs median 1µl, range -24-184, P=0.007), but change in lesion volume was not associated with disability change. Baseline cortical lesion volume was higher in people with worsening disability (median 1010µl, range 13-9888 vs median 267µl, range 0-3539, P=0.001, adjusted for age and sex) and in individuals with relapsing-remitting multiple sclerosis who subsequently transitioned to secondary progressive multiple sclerosis (median 2183µl, range 270-9888 vs median 321µl, range 0-6392 in those who remained relapsing-remitting, P=0.01, adjusted for age and sex). Baseline white matter lesion volume was not associated with worsening disability or transition from relapsing-remitting to secondary progressive multiple sclerosis. Cortical lesion formation is rare in people with stable white matter lesions, even in those with worsening disability. Cortical but not white matter lesion burden predicts disability worsening, suggesting that disability progression is related to long-term effects of cortical lesions that form early in disease, rather than to ongoing cortical lesion formation.

Clinical correlation between disease progression and central vein sign in pediatric onset multiple sclerosis: A binational study

BackgroundThe central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered. ObjectivesTo investigate the appearance of CVS and its correlation with POMS disease progression. MethodsOne hundred fifty-six POMS from two MS centers in Israel and Czech Republic MS centers were followed for five years. Patient assessment was performed by the Expanded Disability Status Scale (EDSS) and Annual Relapse Rate (ARR). Patients in whom at least 40% of brain MRI lesions had CVS (“rule of 40”) were determined as CVS-positive. ResultsThe total group of POMS consisted of 96 CVS-negative (61.5%), aged 14.6 ± 1.9 years, EDSS 2.0, 75% Interquartile Range (IQR) 1.0-3.0, disease duration (DD) 6.28 ± 0.38 years, and 60 CVS-positive (38.5%), aged 15.1 ± 0.3 years, EDSS 2.0, IQR 1.5-3.0, DD 5.62 ± 0.13 years, were analyzed. After a three and five-year follow-up, the CVS-positive patients had higher EDSS scores than those who were CVS-negative, 2.0, IQR 1.0-2.5, vs 1.0, IQR 1.0-2.0, (p=0.009) and 2.0, IQR 1.0-3.25 vs 1.0, IQR 1.0-2.0, (p=0.0003), respectively. Patients with CVS-positive POMS were characterized by a significantly higher ARR (0.78 ± 0.08 vs 0.57 ± 0.04, p=0.002). These results were confirmed in subgroups of Disease Modifying Treatments (DMT) untreated and treated patients. ConclusionCVS-positive POMS is characterized by higher disability progression than CVS-negative, indicating the importance of CVS in disease pathogenesis.

Reliability and validity of the 4-meter walk test in patients with multiple sclerosis

BackgroundWalking speed is considered a vital sign of health and better functional outcomes. It is important to assess walking speed both for disease monitoring and before starting rehabilitation. The aim of this study was to examine the reliability, validity, minimal detectable change, and the ideal cutoff time for differentiating patients with multiple sclerosis (PwMS) who fall from PwMS who do not. MethodsThis study included 43 PwMS (26 female and 17 male) and 36 healthy controls (23 female and 13 male). The 4-meter walk test (4-MWT) was conducted with the 10-meter walk test (10-MWT), timed up and go (TUG) test, dynamic gait index (DGI), timed 25-foot walk (T25-FW), multiple sclerosis walking scale-12 (MSWS-12), and the expanded disability status scale (EDSS). ResultsExcellent test-retest reliability (ICC = 0.971) was found for the 4-MWT. The SEM value was 0.38 and MDC value was 1.05. The correlations with 4-MWT, 10-MWT, TUG, DGI, T25-FW, MSWS-12, and EDSS were found to be statistically significant (p < 0.001). PwMS had longer 4-MWT times than healthy controls, and PwMS fallers had longer 4-MWT times than non-fallers with PwMS (r between 0.668 and -0.858; p<0.05 for all). In order to distinguish fallers from non-fallers with PwMS, a 4-MWT cutoff time of 4.14 s was shown to be optimal. ConclusionThe 4-MWT was found to be valid and reliable for PwMS. It is concluded that the 4-MWT is a feasible assessment method for clinical and methodological studies of PwMS with mild to moderate disability.

Exploring the Relationship between Disability Status, Depression, and Quality of Life in Individuals with Multiple Sclerosis

Introduction: Depression and the presence of a disability emerge as noteworthy predictors of the quality of life (QoL) in patients with multiple sclerosis (MS). In this article, we explore the relationship between disability status, depression, and quality of life in individuals with multiple sclerosis. Methods: A total of 150 patients participated in this cross-sectional study. A Persian translation of the Multiple Sclerosis Quality of Life-54 questionnaire was utilized to assess their health-related quality of life (QoL), while the patients' disability levels were measured using the Expanded Disability Status Scale. Additionally, we assessed patients' depression levels using the 21-item BDI-II scale. The questionnaire data were analyzed using SPSS version 25. Results: A total of 150 MS patients participated in the study, with a mean age of 33.4 years (SD = 3.1). The majority were female (n = 71.2%). The mean EDSS score was 3.7 (SD = 1.8). In the correlation analysis, we found that EDSS scores were not significantly correlated with mental QoL (r = -0.180, p = 0.109), but were significantly correlated with lower physical QoL (r = -0.393, p 0.001). Depression scores were significantly correlated with mental QoL (r = -0.776, P 0.001) and physical QoL (r = -0. 726, P 0.001). The results reveal that both EDSS and Beck scores significantly affect mental and physical health, explaining 62% and 60% of their variances, respectively. Conclusion: Our findings indicate a significant relationship between physical quality of life and EDSS scores in MS patients. Higher EDSS scores consistently corresponded to more significant physical impact, as evidenced by higher impact ratings. Conversely, there was no clear association between EDSS scores and mental quality of life. Furthermore, increased depression levels were linked to reduced levels of both mental and physical well-being. These results emphasize the intricate interplay between the physical aspects of quality of life and their implications for the progression and severity of MS in patients.

FUNCTIONAL ELECTRICAL STIMULATION COMBINED WITH VOLUNTARY CYCLING ACCENTUATES VO2 RESPONSE IN PEOPLE WITH ADVANCED MULTIPLE SCLEROSIS: A PILOT STUDY

INTRODUCTION &amp; AIMS Lower limb muscle weakness and reduced balance due to disease progression in multiple sclerosis (MS) may make robust aerobic exercise difficult. Functional electrical stimulation (FES) cycling combined with voluntary cycling may allow people with advanced MS to enhance the intensity of aerobic exercise. The aim of this study was to investigate the cardiorespiratory, power, and participant perceptions during acute bouts of FES cycling, voluntary cycling, and FES cycling combined with voluntary cycling (FES assist cycling). METHODS Participants with advanced MS (Expanded Disability Status Scale [EDSS] ≥ 6.0) undertook three exercise trials on a leg cycle ergometer. Trial 1: 30 minutes of FES cycling; Trial 2: two 10-minute bouts of voluntary cycling separated by 10 minutes rest; and Trial 3: a combination of trials 1 and 2 (FES assist cycling). Outcome measures included VO2, cycle power output, heart rate, exertion, and post-exercise perceptions of fatigue. RESULTS Ten people with advanced MS participated (9 female; age 52.4±9.98 y; EDSS 7.1±0.6). Average VO2 during the 30-minute trials was significantly higher for FES assist cycling compared to voluntary cycling (429.7 ± 111.0 vs 388.5 ± 101.0 mL/min, 95% CI 23.4 to 113.0 mL/min, p=0.01), with a large effect size (Hedges’ g=1.04). Participants reported similar perceptions of exertion at the end of each trial (p=0.14). There was no difference in self-reported fatigue at the end of each trial (p=0.21). CONCLUSION This study found FES assist cycling produced significantly higher VO2 values than voluntary cycling, although the clinical significance of these differences is unknown. Participants performed FES assist cycling at a self-reported levels of exertion consistent with moderate to vigorous intensity, however it was considered light-intensity exercise when expressed by METS. FES assist cycling was no more fatiguing post-exercise than the other modes.

THE EFFECTS OF HYBRID FUNCTIONAL ELECTRICAL STIMULATION INTERVAL TRAINING ON AEROBIC FITNESS AND FATIGUE IN PEOPLE WITH ADVANCED MULTIPLE SCLEROSIS

INTRODUCTION &amp; AIMS Improving aerobic fitness in people with multiple sclerosis (MS) can reduce fatigue, and lower the risk of cardiovascular disease. Aerobic training can be challenging due to paresis, access to suitable equipment and fatigue. The aim was to investigate whether functional electrical stimulation (FES) cycling combined with arm crank interval exercise (hybrid FES interval training) is feasible for people with advanced MS, and its effects on aerobic fitness and fatigue. METHODS Hybrid FES interval training was performed 2 d/wk for 12 weeks. Each session consisted of 40 minutes of continuous FES cycling with arm crank intervals of 30 seconds work/30 seconds rest added concurrently for 20 minutes. The intensity target was a minimum of 60% of arm crank power and ‘hard’ measured by rate of perceived exertion (RPE) on a scale of 6-20. Feasibility was measured by attendance, compliance to intensity and time targets, adverse events, and drop outs. Aerobic fitness was assessed by an arm crank maximal test. Fatigue was measured via the Modified Fatigue Impact Scale (MFIS). RESULTS Seven participants (6 female; age 57.1±7.8y; Expanded Disability Status Scale 7.1±0.8) with advanced MS attended 80±10.4% of the scheduled sessions and there were no adverse events or drop outs. Average RPE at the end of each training session was 15±2, representing vigorous intensity exercise. Aerobic fitness did not change pre- to post-intervention [14.2±5.7 to 14.78±6.0 mL/kg/min (p=0.43)]. There was a trend towards a reduction in the MFIS score pre- to post-intervention [31.0±10.4 to 21.7±11.4 (p=0.10)]. CONCLUSION Hybrid FES interval training is feasible for people with advanced MS who need exercise equipment appropriate for their condition, and can represent vigorous intensity exercise. The positive findings support the need for future randomized control trials that can assess the aerobic fitness changes and associated health benefits of hybrid FES interval training.

Investigating the effects of 25-hydroxyvitamin D3 on clinical outcomes in multiple sclerosis patients: A randomized, double-blind clinical trial- a pilot study

BackgroundThe primary objective of this clinical trial was to assess whether administrating oral calcifediol (25(OH)D3) could enhance the clinical outcomes of patients diagnosed with multiple sclerosis. MethodsThis clinical trial was designed as a randomized, double-blind, two-arm study, with 25 participants receiving daily 50μg of calcifediol and 25 people receiving daily 50μg of cholecalciferol. The primary outcomes were serum levels of 25(OH)D3, number of relapses, changes in Kurtzke Expanded Disability Status Scale (EDSS), the 25-foot walk, and cognitive function. ResultsAt the end of the trial, delta serum concentrations of 25(OH)D3 were 85.32±40.94 ng/ml in the calcifediol group compared to 13.72±11.56 ng/ml in the cholecalciferol group; 84% of the calcifediol group and none of the cholecalciferol group had circulating 25(OH)D3 concentrations exceeding 70ng/ml. While both groups showed an overall trend towards improved cognitive function at the end of the study, the calcifediol group exhibited greater improvements in most cognitive tests. However, the trial had no significant beneficial effects on MS relapse, EDSS score, quality of life, or fatigue in either group, the calcifediol or cholecalciferol. ConclusionsThe trial shows that calcifediol is more effective in rapidly increasing 25(OH)D3 levels in MS patients compared to cholecalciferol when administrated at a similar dosage.

Concomitant autoimmunity and risk of multiple sclerosis disability worsening

BackgroundFew studies have examined the effect of concomitant autoimmune diseases on multiple sclerosis (MS) disability worsening. We set out to examine whether concomitant Crohn's Disease (CD), Ulcerative Colitis (UC), or Type 1 Diabetes (T1D) affect MS disability worsening in a nationwide cohort of MS patients as defined by reaching expanded disability scale status (EDSS) scores 3.0, 4.0 and 6.0. MethodsPatients with MS onset between January 2004 and January 2019 were identified from the Swedish MS registry and the Swedish National Patient Register. Kaplan-Meier analysis was used to estimate the median time to reach sustained disability milestones. Adjusted Cox proportional hazard regression models were used to calculate the risk of reaching disability milestones among persons with and without CD, UC, or T1D. ResultsOut of 8972 persons with MS, 88 (1.0%) had T1D, 47 (0.8%) had UC, and 78 (0.9%) had CD. There was a significantly higher risk of disability progression, for persons with MS and T1D for reaching EDSS 6.0, hazard ratio (HR) = 2.21 (95% confidence interval (CI) =1.48 -3.31) and persons with MS and comorbid CD for reaching EDSS 3.0, HR=2.30 (95%CI=1.74-3.04) and 4.0, HR=1.59 (95%CI=1.09-2.32), and persons with MS and comorbid UC for reaching EDSS 3.0 HR=1.57 (95%CI=1.15-2.14). As defined by Charlson's comorbidity index, the co-existence of other co-morbidities conferred a significant increase in the risk of reaching all endpoints, with HR ranging from 1.23 to 1.62. ConclusionComorbidity is associated with a significantly increased risk of reaching disability end-points, and T1D, CD, and UC increase the risk further. Thus, there appears to be a need for increased vigilance of comorbidites in persons with MS in order to optimise the long-term outcome of MS

Whole spinal transverse myelitis in neuromyelitis optica spectrum disorder

Background: Spinal cord is one of the prominent targets of autoimmune mechanisms in Neuromyelitis Optica Spectrum Disorder (NMOSD). Rarely, NMOSD causes damage to the entire length of the spinal cord, from cervical segments to conus medullaris, which has not been characterized in the existing literature.Material and method: We reviewed medical records, demographic information, and magnetic resonance imaging (MRI) sequences of 174 NMOSD patients from January 2011 to January 2023 who were admitted to Isfahan Multiple Sclerosis center to find patients with whole spinal transverse myelitis (TM).Results: Whole spinal TM was present in five patients (2.9%). Three patients were seropositive for Aquaporin-4 (AQP4) antibody; Myelin Oligodendrocyte Glycoprotein antibody (MOG IgG) tested negative for all of them. Lower limb weakness was the most frequent clinical complaint. Two patients presented with optic neuritis; One patient reported having episodes of nausea and vomiting. These patients, overall, yielded a higher expanded disability status scale (EDSS) score than the other NMOSD patients.Conclusion: Whole spinal TM is a rare finding in NMOSD, which is strongly associated with a higher severity and a worse outcome of the disease. The role of anti-AQP4 antibodies in the extent of myelitis in NMOSD has yet to be investigated.

Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Integration of the expanded disability status scale with ambulation, visual and cognitive tests.

The Expanded Disability Status Scale (EDSS) is usually calculated through a neurological examination with self-reported performance. This may lead to incorrect assessment of Functional System scores (FSs). Aim of our study was to estimate the difference between EDSS obtained during routine visits, or after specific tests. We enrolled 670 MS patients that underwent a regular neurology consultation, and visual evaluation using optotype tables, ambulation evaluation with a rodometer, and cognitive assessment with the Brief International Cognitive assessment for MS (BICAMS). We calculated a new integrated EDSS (iEDSS) using the refined values of the FS and compared it to the standard EDSS. Visual, cerebral and ambulation FSs were significantly higher compared with the self-reported counterpart [+ 1.169 (95%CI 1.077, 1.262; p < 0.001), + 0.727 (95%CI 0.653, 0.801; p < 0.001) and + 0.822 (95%CI 0.705, 0.939; p < 0.001), respectively]. Mean iEDSS was higher than EDSS (+ 0.642; p < 0.001). Visual acuity tests worsened the EDSS in 31% of cases, cognitive tests in 10%, ambulation measurement in 35%, all three measurements in 59% of cases. Objective measurement of FSs results in a more accurate EDSS score in almost two-thirds of cases. This could lead to a more thorough evaluation of patients in the transition or progressive phase.