Median EDSS Score Research Articles

Associations between fatigue impact and physical and neurobehavioural factors: An exploration in people with progressive multiple sclerosis

BackgroundFatigue is common in people with multiple sclerosis (MS). Understanding the relationship between fatigue, physical and neurobehavioural factors is important to inform future research and practice. Few studies explore this explicitly in people with progressive MS (pwPMS). ObjectiveTo explore relationships between self-reported fatigue, physical and neurobehavioural measures in a large, international progressive MS sample of cognitively impaired people recruited to the CogEx trial. MethodsBaseline assessments of fatigue (Modified Fatigue Impact Scale; MFIS), aerobic capacity (VO2peak), time in moderate-vigorous physical activity (MVPA; accelerometery over seven-days), walking performance (6-minute walk test; 6MWT), self-reported walking difficulty (MS Walking Scale; MSWS-12), anxiety and depression (Hospital Anxiety and Depression Scale; HADS and Beck Depression Inventory-II; BDI-II), and disease impact (MS Impact Scale-29, MSIS-29) were assessed. Participants were categorised as fatigued (MFISTotal >=38) or non-fatigued (MFISTotal ≤38). Statistical AnalysisDifferences in individuals categorised as fatigued or non-fatigued were assessed (t-tests, chi square). Pearson's correlation and partial correlations (adjusted for EDSS score, country, sex, and depressive symptoms) determined associations with MFISTotal, MFISPhysical, MFISCognitive and MFISPsychosocial, and the other measures. Multivariable logistic regression evaluated the independent association of fatigue (categorised MFISTotal) with physical and neurobehavioural measures. ResultsThe sample comprised 308 pwPMS (62 % female, 27 % primary progressive, 73 % secondary progressive), mean age 52.5 ± 7.2 yrs, median EDSS score 6.0 (4.5–6.5), mean MFISTotal 44.1 ± 17.1, with 67.2 % categorised as fatigued. Fatigued participants walked shorter distances (6MWT, p = 0.043), had worse MSWS-12 scores (p < 0.001), and lower average % in MVPA (p = 0.026). The magnitude of associations was mostly weak between MFISTotal and physical measures (r = 0.13 to 0.18), apart from the MSWS-12 where it was strong (r = 0.51). The magnitude of correlations were strong between the MFISTotal and neurobehavioural measures of anxiety (r = 0.56), depression (r = 0.59), and measures of disease impact (MSIS-physical r = 0.67; MSIS-mental r = 0.71). This pattern was broadly similar for the MSIF subscales. The multivariable model indicated a five-point increase in MSWS-12 was associated with a 14 % increase in the odds of being fatigued (OR [95 %CI]: 1.14 [1.07–1.22], p < 0.0001) ConclusionManagement of fatigue should consider both physical and neurobehavioural factors, in cognitively impaired persons with progressive MS.

Beneficial therapeutic plasma exchange response in the treatment of severe relapses in patients with multiple sclerosis.

Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020. This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved. Our study in a large cohort of MS patients confirmed that PLEX is effective.

Comparison of patient-reported outcomes of physical activity and accelerometry in people with multiple sclerosis and ambulatory impairment: A cross-sectional study

BackgroundAccelerometers and patient-reported outcomes (PRO) are used to assess physical activity (PA) in people with multiple sclerosis (pwMS). So far it is unknown, however, whether these assessments represent mobility limitations in pwMS with mild and moderate to severe disability alike. The primary aim of the study was to assess the correlation between accelerometry and International Physical Activity Questionnaire (IPAQ) scores in pwMS with different degrees of ambulatory impairment. Taken its frequent use into account, the Godin Leisure Time Exercise Questionnaire (GLTEQ) was investigated as additional PRO. MethodsIn a prospective cohort of pwMS, correlational analyses were performed between the number of daily steps, time spent in light, moderate to vigorous PA (MVPA) and time spent sitting as assessed using accelerometry (ActiGraph®-GT3X), and the respective IPAQ and GLTEQ scores. Additionally, associations of PA with disease-specific characteristics, aerobic capacity (VO2peak), walking assessments (Timed 25-Foot Walk, T25FW; 2-Minute Walk Test, 2MWT) and walking perception (Multiple Sclerosis Walking Scale-12; MSWS-12) were explored. Patient subgroups with mild (Expanded Disability Status Scale; EDSS score <4.0) and moderate to severe disability (EDSS ≥4.0) were analysed for the impact of ambulatory impairment on PA. Multiple linear regression was used to determine predictors of PA. ResultsA total of 56 pwMS completed the study, with a mean (standard deviation, SD) age of 48.4 (10.3) years, disease duration of 14.8 (9.6) years and median (interquartile range) EDSS score of 3.5 (2.0 – 4.4). Moderate to weak correlations were found between daily step count and IPAQ total metabolic equivalent (MET) minutes/week (p < 0.001; r = 0.506), MVPA MET-minutes/week (p < 0.01; r = 0.479) and walking MET-minutes/week (p < 0.05; r = 0.372) in the total cohort. Time spent sitting was inversely correlated with total MET-minutes/week and MVPA MET-minutes/week (p < 0.05; r = -0.358 and r = -0.365). Subgroup analysis revealed, that daily step count was significantly correlated with total MET-minutes/week, MVPA MET-minutes/week and walking MET-minutes/week (p < 0.01, r = 0.569; p < 0.01, r = 0.531 and p < 0.05, r = 0.480, respectively) in the “mild disability” subgroup only, whereas time spent sitting was inversely correlated with total MET-minutes/week (p < 0.05; r = -0.582) in the “moderate to severe disability” subgroup. There was no association between objectively assessed PA and GLTEQ scores in any group. In the total cohort, moderate to weak correlations were found between daily step count and walking assessments (T25FW: p < 0.01, ρ = -0.508; 2MWT: p < 0.01, ρ=0.463) and MSWS-12 (p < 0.001; ρ = -0.609). Moderate to weak correlations were also observed between VO2peak and walking assessments (T25FW: p < 0.01; ρ = -0.516; 2MWT: p < 0.01, ρ=0.480). Multiple linear regression analysis identified disability and VO2peak as predictors of PA (p = 0.045; β=0.25 and p < 0.001; β=0.49). ConclusionSignificant associations of objective PA measurements using accelerometry with IPAQ were found only in pwMS with “mild disability”. In pwMS with “moderate to severe disability”, IPAQ did not reflect the objectively assessed amount of PA. In our cohort, GLTEQ showed no association with objectively assessed PA. Thus, an MS-specific self-reported questionnaire for assessing PA is warranted.

Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Clinical and demographic characteristics of patients with NMOSD: a longitudinal retrospective analysis of a Slovak cohort of 63 patients.

Neuromyelitis optica spectrum disorders (NMOSD) are autoantibody-mediated inflammatory diseases of the central nervous system predominantly targeting optic nerves and the spinal cord. Two distinct phenotypes are recognized based on the presence of serum aquaporin-4 (AQP4-IgG) antibodies. However, contrasting clinical course patterns have been identified between AQP4-IgG-positive and AQP4-IgG-negative patients. This study aimed to present demographic and clinical characteristics of patients with NMOSD in Slovakia and to evaluate the significance of differences between AQP4-IgG-seropositive and AQP4-IgG-seronegative patients. We performed a longitudinal multi-centric retrospective study and analysed the clinical and demographic characteristics of a cohort of 63 Slovak NMOSD patients. Eighty-six percent of patients were women, and ninety-four patients were Caucasian.The median age at diagnosis was 37years. The most frequent initial manifestations were optic neuritis (47.6% of patients) and transverse myelitis (39.7% of patients).The median EDSS score deteriorated from the initial 3.0to 4.0 at the last follow-up. Sixty-eight percent of patients were AQP4-IgG positive; 10% of patients were MOG-IgG positive;27% of patients had no NMOSD-specific antibodies detected. There was a higher prevalence of autoimmune thyroiditis among AQP4-IgG-positive patients (25.6%) compared to AQP4-IgG-negative patients (0%) (p = 0.01). This study provides a detailed overview of the clinical and demographic characteristics of NMOSD based on a retrospective analysis of a Slovak cohort of 63 NMOSD patients and extends information provided by similar recently published studies. The most important finding is that there is a high prevalence of autoimmune thyroiditis among AQP4-IgG-negative patients (25%).

Evaluation of the correlation between thalamic area and cognitive functions in patients with early-stage relapsing-remitting multiple sclerosis

Background: The aim of this study is to investigate the presence of cognitive dysfunction and deep gray matter involvement in the early-stages of Relapsing-Remitting Multiple Sclerosis(RRMS) disease and examine the relationship between them.&#x0D; Materials and Methods: Thirty-four patients and 23 healthy individuals were included in the study. Patients diagnosed with RRMS according to the Revised 2010 and 2017 McDonald criteria, aged between 18-50, were enrolled in the study. The control group consisted of 23 healthy individuals with normal neurological examination, cranial magnetic resonance imaging(MRI), and cognitive functions. All participants underwent a neuropsychological test battery that covers memory, executive functions, language, and visuospatial domains, and the results of these tests were compared among the study groups. The data on MRI parameters, including the areas of the thalamus and corpus callosum as well as the width of the third ventricle, were compared among the study groups. Finally, the relationship between neuropsychological test results and MRI parameters was investigated in patients with early-stage RRMS.&#x0D; Results: The mean duration of the disease for MS patients was 3.53 years, and their median EDSS score was 2. It was observed that memory, executive functions, and fine motor skills were affected in early-stage RRMS patients. This impairment correlated with a decrease in the thalamus and corpus callosum areas and an increase in the third ventricle width.&#x0D; Conclusion: The MRI parameters defined as biomarkers for potential cognitive impairments in RRMS have critical importance in predicting the prognosis of the disease and taking early measures against future cognitive dysfunction.

Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic.

Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort.

Real-World Effectiveness of Ocrelizumab in a Multi-Centre Pediatric-Onset Multiple Sclerosis (POMS) Cohort in the United Kingdom (S31.007)

<h3>Objective:</h3> The aim of this study was to evaluate the efficacy and safety of ocrelizumab treatment for pediatric-onset Multiple Sclerosis (POMS) in a real-world clinical setting. <h3>Background:</h3> There is a growing consensus favouring earlier use of highly effective disease modifying therapies (DMTs) in POMS. <h3>Design/Methods:</h3> We conducted a prospective study including consecutive POMS (&lt;18 years) from three UK tertiary paediatric neurosciences centers who received ocrelizumab. <h3>Results:</h3> We included a total of 60 POMS patients; 49 female (81.7%), 41 non-white (68.3%), median age 14.6 yrs (IQR 13.3, 15.5). Median follow-up period was 1.0 yr (range, 0.1–2.6). Forty-three patients (71.7%) had ocrelizumab as their first DMT. The median number of relapses per patient pre-treatment was 2 (range 1–5). Two patients relapsed within one month of starting ocrelizumab and 1 patient had an optic neuritis 6-months post ocrelizumab initiation. During the follow-up period, a median of 2 (range 1–5) repeated MRI scans were performed (total scans, n=140). Forty out of 43 (93.0%) patients achieved no evidence of disease activity (NEDA-3) at 12-months follow-up; two patients had one new brain lesion each at 6-months and a different patient had a relapse (optic neuritis) without new brain lesions at 6-months post treatment. Median EDSS score remained stable during follow-up; 1.0 at baseline and follow-up (p=0.21). In addition, there was no change in cognitive measures at follow-up; baseline SDMT mean score 46 vs follow-up SDMT mean score 48 (p=0.39). The most common adverse events reported were infusion-related-reactions (33/60, 55%), all of which were grade 1 or 2. Serious adverse events were recorded in one patient with enterovirus meningitis, who made a full recovery. <h3>Conclusions:</h3> This study confirms that ocrelizumab, which is proven efficacious for adults with MS, is also effective in POMS with a comparable safety profile. Assessment for long-term efficacy and safety is ongoing. <b>Disclosure:</b> Dr. Abdel-Mannan has nothing to disclose. Arman Eshaghi has nothing to disclose. Dr. Champsas has nothing to disclose. Kshitij Mankad has nothing to disclose. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Brownlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. Dr. Rossor has nothing to disclose. Sukhvir Wright has nothing to disclose. Dr. Wassmer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Wassmer has received research support from Birmingham Children’s Hospital Charity Research Foundation. The institution of Cheryl Hemingway has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. The institution of Cheryl Hemingway has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. The institution of Cheryl Hemingway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Cheryl Hemingway has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Cheryl Hemingway has received research support from Medical research Committee. Ming Lim has nothing to disclose. Prof. Ciccarelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Ciccarelli has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Prof. Ciccarelli has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEUROLOGY Journal. Dr. Hacohen has nothing to disclose.

Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) Add-On Therapy to a Standard Treatment in Individuals with Multiple Sclerosis and Concomitant Symptoms of Depression-Results from a Randomized Clinical Trial and Pilot Study.

Compared to the general population, persons with multiple sclerosis (MS) are at increased risk of suffering from major depressive disorder (MDD). Repetitive Transcranial Magnetic Stimulation (rTMS) was used successfully to treat individuals with MDD. Here, we conducted a randomized clinical trial and pilot study, and tested the effectiveness of rTMS adjuvant to a standard pharmacological treatment among persons with MS, compared to a sham condition. A total of 40 persons with MS (mean age: 32 years; 42.5% females; median EDSS score: 4) and with moderate to severe symptoms of depression were randomly assigned to the rTMS or to the rTMS sham condition, always as adjuvant intervention to the standard treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI). rTMS consisted of 10 sessions each of 37.5 min; the sham condition was identical to the active condition except for the absence of rTMS stimuli. At the beginning and two weeks after the end of the study, participants reported on their fatigue, while experts rated the severity of participants' depressive symptoms (Montgomery-Asberg Depression Rating Scale; MADRS), cognitive performance (Montreal Cognitive Assessment; MoCA), and degree of disability (Expanded Disability Status Scale; EDSS). Data were analyzed per intent-to-treat. Scores for depression, fatigue, and EDSS declined significantly over time (large effect sizes), but more so in the rTMS condition than in the sham condition (large effect sizes for the time by group-interactions). Compared to the sham condition, scores for depression were significantly lower in the rTMS condition. Scores for cognition improved over time in both study conditions (large effect size). Compared to a sham condition, adjuvant rTMS to a standard pharmacological treatment ameliorated typical MS-related symptoms (depression; fatigue; EDSS scores). Results from this pilot study suggested that rTMS might be routinely applied in persons with MS displaying symptoms of depression and fatigue.

Change in Insomnia and Depressive Symptoms During COVID-19: A Prospective Longitudinal Study of Iranian Women with Multiple Sclerosis

ABSTRACT Background There is some evidence that sleep patterns and psychological health have worsened in the general population as a result of the COVID-19-pandemic. Persons with multiple sclerosis (MS) represent a particularly vulnerable population for COVID-19 infections and effects of restrictions. The present study investigated whether insomnia and depressive symptoms, as well as other MS-related symptoms (i.e. fatigue and paresthesia), changed from before to during the COVID-19-pandemic among persons with diagnosed MS. Method A sample of 90 Iranian females with MS (mean age; 37.62 years; median EDSS score: 2.5) completed a series of self-rating scales at two time points: Nine months before the COVID-19 outbreak in May 2019 (baseline) and then again during the COVID-19 pandemic in May 2020 (study end). Self-rating questionnaires covered sociodemographic and disease-related information, insomnia, depressive symptoms, fatigue, and paresthesia. Results Depressive symptoms increased over time with a significant p-value and medium effect size. Symptoms of insomnia increased over time (significant p-value, but small effect size), while no significant changes were observed in fatigue and paresthesia (very small effect sizes). The only predictor for insomnia during the COVID-19 pandemic was insomnia before the COVID-19 pandemic; the only predictor for depressive symptoms during the COVID-19 pandemic was insomnia before the COVID-19 pandemic. Conclusions Overall, the COVID-19 pandemic and its related social restrictions had significant effects on symptoms of depression and insomnia in this sample of Iranian women with MS, but had no effect on fatigue and paresthesia.

Discontinuation of disease-modifying therapy in MS patients over 60 years old and its impact on relapse rate and disease progression

Background / AimsThe benefit of disease-modifying therapy (DMT) is unclear for older patients with multiple sclerosis (MS), namely those who have not experienced clinical disease activity for a prolonged time. We aimed to compare baseline differences and clinical outcomes between DMT discontinuers and continuers in a cohort of MS patients older than 60 years. MethodsRetrospective, observational study identifying MS patients aged over 60 years, stable on DMT> 24 months. Additional inclusion criteria were a previous diagnosis of relapsing MS and a minimum follow-up period of 24 months. Differences between groups (continuers/discontinuers) were assessed. For risk of relapse and of confirmed disability worsening at follow up, a time to outcome survival model was constructed using Cox proportional hazards regression, testing for possible risk predictors. ResultsThirty-five patients were included (68.6% female), with a mean age at diagnosis of 42.1 ( ± 9.5) years and a median EDSS score of 3 (IQR 2) at the age of 60 years (baseline). Thirteen patients discontinued DMT after baseline, in a mean follow-up time of 77.1 months ( ± 40.2). No differences were found between DMT continuers vs discontinuers. DMT discontinuation did not predict risk to relapse (HR 0.38, 95%CI 0.04–3.80, p = 0.408) or disability worsening at follow-up (HR 0.83, 95%CI 0.31–2.22, p = 0.712). MRI gadolinium-enhancing lesions and EDSS score > 3 at baseline were found to be independent predictors of risk to relapse and disability worsening at follow-up, respectively. ConclusionDMT discontinuation did not seem to influence clinical outcome, equating with the perceived limited effect of continued immunomodulation on older stable and/or progressive patients.

Delayed cognitive processing and treatment status quo bias in early-stage multiple sclerosis

BackgroundThe evolving therapeutic landscape requires more participation of patients with relapsing remitting multiple sclerosis (RRMS) in treatment decisions. The aim of this study was to assess the association between patient's self-perception, cognitive impairment and behavioral factors in treatment choices in a cohort of patients at an early stage of RRMS. MethodsWe conducted a multicenter, non-interventional study including adult patients with a diagnosis of RRMS, a disease duration ≤18 months and receiving care at one of the 21 participating MS centers from across Spain. We used patient-reported measures to gather information on fatigue, mood, quality of life, and perception of severity of their MS. Functional metrics (Expanded Disability Status Scale [EDSS], cognitive function by the Symbol Digit Modalities Test [SDMT], 25-foot walk test) and clinical and radiological data were provided by the treating neurologist. The primary outcome of the study was status quo (SQ) bias, defined as participant's tendency to continue taking a previously selected but inferior treatment when intensification was warranted. SQ bias was assessed based on participants treatment preference in six simulated RRMS case scenarios with evidence of clinical relapses and radiological disease progression. ResultsOf 189 participants who met the inclusion criteria, 188 (99.5%) fully completed the study. The mean age was 36.6 ± 9.5 years, 70.7% female, mean disease duration: 1.2 ± 0.8 years, median EDSS score: 1.0 [IQR=0.0–2.0]). Overall, 43.1% patients (n = 81/188) had an abnormal SDMT (≤49 correct answers). SQ bias was observed in at least one case scenario in 72.3% (137/188). Participant's perception of their MS severity was associated with higher SQ bias (β coeff 0.042; 95% CI 0.0074–0.076) among those with delayed cognitive processing. Higher baseline EDSS and number of T2 lesions were predictors of delayed processing speed (OR EDSS=1.57, 95% CI: 1.11–2.21, p = 0.011; OR T2 lesions=1.50, 95% CI: 1.11–2.03, p<0.01). Bayesian multilevel model accounting for clustering showed that delayed cognitive processing (exp coeff 1.06; 95% CI 1.04–1.09) and MS symptoms severity (exp coeff 1.28; 95% CI 1.22–1.33) were associated with SQ bias. ConclusionOver 40% of patients in earlier stages of RRMS experience delays in cognitive processing that might affect their decision-making ability. Our findings suggest that patients' self-perception of disease severity combined with a delay in cognitive processing would affect treatment choices leading to status quo bias early in the course of their disease.

Symptom-Level Disability Status Assessed with an Electronic Unsupervised Patient-Reported Expanded Disability Status Scale (ePR-EDSS) in Multiple Sclerosis Patients-The Example of Croatia.

The present study aimed to apply an electronic, unsupervised patient-reported Expanded Disability Status Scale (ePR-EDSS) to investigate disability severity in people with multiple sclerosis (pwMS) as a case study in Croatia in 2021, including demographic and comorbidity characteristics and multiple sclerosis (MS) disease-related factors. The cross-sectional study was conducted as an online survey from 4 October 2021 to 31 December 2021. Symptom-level disability status was assessed with ePR-EDSS for MS capturing MS-related disability across the spectrum of severity.The study enrolled 147 pwMS patients, of which 84% were women. The mean age ± standard deviation in the sample was 41.1 ± 11.3, and the mean disease duration was 8.5 ± 7.4 years, with a median EDSS score of 3.0 (range, 0–8). The distribution of the participants according to clinical forms of MS was as follows: 71% had relapsing-remitting MS, 13% had primary progressive MS, 4% had secondary progressive PMS, and 12% did not provide information on their MS type. Twenty-nine point two percent (29.2%) of the participants had comorbidities in addition to MS. EDSS scores indicate significant differences with regard to age (t = −3.51, p < 0.001), gender (χ2 = 8.04, p < 0.01), and immunomodulatory drug use (χ2 = 5.89, p < 0.05). An ePR-EDSS analysis of disability symptoms showed a significant difference in symptoms with regard to strength, sensation, coordination, vision, fatigue, mobility, and overall wellness among MS types. Participants with PPMS and SPMS were older on average, had higher EDSS, and had more pronounced symptoms of disability measured with ePR-EDSS compared to those with RRMS. Application of ePR-EDSS shows it to be a reliable eHealth tool for clinical assessment of pwMS disability status, and future studies should correlate it with standard self-report scales capturing MS symptoms such as fatigue, depression, anxiety, and stress.

The disease course of multiple sclerosis before and during COVID-19 pandemic: A retrospective five-year study

IntroductionCOVID-19 pandemic is thought to influence the natural history of immune disorders, yet the knowledge on its effect on multiple sclerosis (MS) is unknown and not fully understood for which we conducted this retrospective study. Methods and materialsWe included all patients with MS seen in King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia, between January 2017 and October 20201. We determined clinical and radiological evidence of disease activities in all patients by the end of the study period, and we compared the disease patterns before and during the pandemic. We also identified patients with COVID-19 since March 2020, who had at least 3 months of follow-up following the infection. ResultsWe studied 301 patients; 216 (72%) were women, the mean age was 38 years (range; 16, 73 years), the mean disease duration was 10 years (range; 1, 36 years), and the median EDSS score was 0.5 (range; 0, 8). RRMS accounted for most of the cases (270 patients). MS disease activities were 25% less prevalent during the pandemic compared to the preceding 3 years (26 vs. 51%, respectively, p < 0.01). Bivariate analysis showed significant higher disease activities in patients younger than 35 years (73 vs 27%), on DMT (68 vs 32%), and complaint to therapy (69 vs 31%). Multiple logistic regression analysis showed that the likelihood of MS disease activities were 3 times more during the pre-pandemic era (adjusted OR = 3.1, p value < 0.05, 95% CI; 1.4, 7.1). Thirty patients (10%) were infected with COVID-19. All patients reported mild symptoms, and none required hospitalization. COVID-19 was prevalent among younger patients with RRMS, with low EDSS scores, irrespective of DMTs they received. COVID-19 infection was not associated with clinical relapses or MRI changes. Disease activities were dependent on DMT use and not COVID-19 status. Multivariate analyses also confirmed no effect of COVID-19 on disease activities (p = 0.3 and 0.4, for clinical and MRI changes, respectively). ConclusionsMS disease activities did not increase during the pandemic, yet the apparent decrease in the disease activities is probably due to under reporting and not a real decrease in disease activities because of the pandemic. The COVID-19 infection in our MS patients showed a benign disease course, yet standard precautions to reduce the risk of COVID-19 transmission should be applied accordingly.

Red cell distribution width as a predictor of disability in relapsing-remitting multiple sclerosis

BackgroundRed blood cell distribution width (RDW) reflects the variability of circulating red blood cells. The relationship between multiple sclerosis (MS) and RDW is not well studied. The main objective of this work was to compare baseline RDW to EDSS at 5 years of diagnosis and verify if RDW predicts worse disability.MethodsWe conduct a retrospective observational study of relapsing-remitting MS (RRMS) patients followed in the Neuroimmunology Clinic that had at least one measuring of RDW at baseline.ResultsWe included 82 patients with RRMS meeting inclusion criteria, 73,2% female with a mean age of 33,56 years old. Median EDSS score at baseline was 1.5.9,8% patients had new T2 lesions in MRI at 5 years and 4,9% showed lesions capturing contrast at 5 years. Regarding DMT, 75,6% were treated with interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate, and 21,9% were under fingolimod, natalizumab, rituximab, and cladribine, and the remaining 2,4% were without treatment at 5 years.A multiple linear regression model confirmed increased disability (EDSS at 5 years) for patients undergoing second-line treatment (β=0,86;p=,003) and higher RDW at baseline (β=0,47;p=,007). Presenting RDW results for quartiles, it was statistically significant for quartile 4 [13,5;16,4[(β=0,74;p=,039), suggesting that a very increased RDW at baseline is strongly associated with higher EDSS at 5 years.ConclusionHigher RDW at baseline was correlated with a worse disability at 5 years in RRMS patients. Furthermore, RDW equal to or higher than 13,5% may be useful in identifying patients that will have a worse disability at 5 years.

Prevalence, severity, outcomes, and risk factors of COVID-19 in multiple sclerosis: An observational study in the Middle East

A cross-sectional hospital records-based study was conducted to evaluate the prevalence, severity, outcomes, and identify demographic and clinical risk factors of coronavirus disease (COVID-19) in patients with MS. The study was conducted at multiple clinics in Oman, Kuwait, and the United Arab Emirates (UAE) from March 2020 to February 2021. The association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes of COVID-19 illness were evaluated using odds ratio. A total of 134 MS patients with COVID-19 (prevalence rate of 3.7%) having a median age of 35.5 years were analyzed in the study. A majority (126 [94.0%]) of patients had mild COVID-19 illness and 122 (91.0%) made a full recovery, while 1 (0.7%) patient died. The median EDSS score reported in the study was low (1.0). Univariate regression analysis showed high EDSS scores, progressive MS disease, and use of anti-CD20 therapy such as rituximab as risk factors for moderate to severe COVID-19 requiring hospitalization. Comorbidities were associated with a higher risk of non-recovery from COVID-19 in both univariate and multivariate analyses. Age, sex, smoking history, and duration of MS did not show a significant association with severity or adverse COVID-19 disease outcome. Identification of risk factors can aid in improving the treatment and monitoring of pwMS and COVID-19.

Prevalence study of multiple sclerosis in the Spanish province of Zamora

IntroductionWe conducted a prevalence study of multiple sclerosis (MS) in the Spanish province of Zamora. MethodsWe conducted a retrospective cohort study of data on patients with multiple sclerosis under follow-up at the neurology outpatient clinic at Hospital de Zamora as of 6 June 2021. We studied demographic (sex, age) and clinical variables (form of disease, duration, expanded disability status scale [EDSS] score, progression index [EDSS/years duration], and treatment). ResultsAs of 6 June 2021, the prevalence of MS was 98.8 cases/100000 population (95% confidence interval [CI], 91.3–106.3), and the mean incidence for the last 10 years was 3.5 cases/100000 person-years (95% CI, 2.1–4.9). The age-standardised prevalence (calculated using the 2013 European Standard Population) was 102.4 (95% CI, 83.5–121.3), and incidence was 4.6 (95% CI, 0.5–8.7).Out of the 168 patients in our cohort, 119 (70.8%) were women. The mean age (standard deviation) in our sample was 46.5 (13.1) (95% CI, 45.5–47.5) years, and the mean disease duration was 12.6 (9.0) (95% CI, 11.8–13.4) years, with a median EDSS score of 2.0 (range, 0–8.5). A total of 129 (78.7%) patients were receiving treatment, of which 84 (51.2%) were receiving a moderate-efficacy drug and 42 (25.6%) were receiving a high-efficacy drug. Among patients not receiving treatment, this was mostly due to their personal decision, long disease duration, and/or clinical stability. ConclusionsThe prevalence of multiple sclerosis in the Spanish province of Zamora is intermediate-high and is in line with the mean for Spain.

Simplified stance limb kinetics patterns revealed during gait initiation in early stage of multiple sclerosis

BackgroundAlthough patients with an early stage of Multiple Sclerosis (MS) commonly complain about balance and gait impairments, their troubles remain misunderstood. The objective was to compare body kinematics and lower limb kinetics during gait initiation between patients with MS with an EDSS score ≤ 4 and healthy participants. MethodsSixteen patients with MS with a median EDSS score of 2.5 [0–4] and disease duration of 7.4 ± 4.2 years, as well as 16 healthy participants were included, and 3-D motion analysis was performed during gait initiation to calculate spatiotemporal, kinematic and kinetic parameters. FindingsThe center of pressure position at the beginning of the gait initiation was more anterior (p = 0.02) in patients with MS than healthy participants. The kinetic parameters of the stance limb were highly affected in patients with MS compared to healthy participants during gait initiation. The net muscular moments for each joint were significantly different during the anticipatory postural adjustment phase with smoother variations for patients with MS compared to healthy participants. InterpretationEarly stage MS strongly affects the motor modulation of stance limb kinetics during the anticipatory postural adjustment of gait initiation, without alteration of the execution phase. The net muscular moments are sensitive in detecting unobservable balance impairments and can be used to assess disease progression at the early stage. These results suggest that early rehabilitation programs aimed at improving motor modulation and flexibility in gait initiation should be implemented.

Long-Term Disease Stability Assessed by the Expanded Disability Status Scale in Patients Treated with Cladribine Tablets 3.5mg/kg for Relapsing Multiple Sclerosis: An Exploratory Post Hoc Analysis of the CLARITY and CLARITY Extension Studies.

IntroductionIn the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study, cladribine tablets significantly reduced relapse rates and improved findings on magnetic resonance imaging versus placebo in patients with relapsing multiple sclerosis. In the CLARITY Extension study, treatment with cladribine tablets for 2 years followed by placebo for 2 years produced similar clinical benefits to 4 years of cladribine tablets. The objective of this exploratory post hoc analysis was to evaluate long-term disease stability (assessed by the Expanded Disability Status Scale [EDSS] score) after treatment with cladribine tablets.MethodsPatients enrolled into CLARITY Extension who were previously randomized to cladribine tablets 3.5 mg/kg in the CLARITY study were included in this post hoc analysis. Two treatment groups were investigated—patients randomized to cladribine tablets 3.5 mg/kg in CLARITY and thereafter randomized to placebo in CLARITY Extension (the CP3.5 group) or to cladribine tablets 3.5 mg/kg in CLARITY Extension (the CC7 group). In each treatment group, EDSS scores at 6-month intervals, EDSS score improvement/worsening each year, and time to 3- and 6-month confirmed EDSS progression were assessed from CLARITY baseline over 5 years of follow-up (including a variable bridging interval between studies). All analyses are descriptive, and no statistical comparisons were performed for between-treatment group differences.ResultsThe median (95% confidence interval [CI]) EDSS score for patients in the CP3.5 group at 5 years was 2.5 (2.0–3.5) compared with 3.0 (2.5–3.5) at baseline. In the CC7 group, median EDSS score (95% CI) at 5 years was 2.0 (2.0–3.0) compared with 2.5 (2.5–3.0) at baseline. During year 5 for the CP3.5 group, and based on changes in minimum score each year, EDSS score stability was observed in 53.9% of patients, improvement in 21.3%, and worsening in 24.7%. In the CC7 group, EDSS score remained stable in 66.1%, improved in 18.1%, and worsened in 15.8% of patients. Over 70% of patients in both treatment groups did not show 3- or 6-month confirmed EDSS progression at 5 years from CLARITY baseline.ConclusionsThese findings confirm long-term beneficial effects on disability afforded by either the recommended dose of cladribine tablets over 4 years (cumulative dose, 3.5 mg/kg) or a higher cumulative dose.Trial RegistrationClinicalTrials.gov NCT00213135 (CLARITY); NCT00641537 (CLARITY Extension).

A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years.

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.