Higher Expanded Disability Status Scale Research Articles

Atherosclerosis and multiple sclerosis: An overview on the prevalence of risk factors

BackgroundAtherosclerosis is the leading cause of ischemic heart disease and coronary artery disease. The process of atherosclerosis develops over a period of years and is mainly immune-mediated. Data regarding the prevalence of vascular disease and atherosclerosis among people with multiple sclerosis (pwMS) is inconsistent, therefore, we aimed to provide an overview of the prevalence of atherosclerotic risk factors in pwMS. MethodsThis is a cross-sectional study over a period of one year among pwMS visiting the Isfahan MS center. Study data have been extracted using participants’ files and a checklist that was completed by the observers. Only people with relapsing-remitting (RRMS) and secondary progressive (SPMS) forms of MS were included in the study. Participants with primary progressive (PPMS) disease are only described and have been excluded from analyses. ResultsOf the 396 pwMS (343 with RRMS and 53 with SPMS), in descending order, the reported risk factors were tobacco smoking (18.4%), dyslipidemia (10%), hypertension (8.8%), and diabetes mellitus (4.5%). In people with RRMS, 17.4% were smokers, 9.9% had dyslipidemia, 8.1% had hypertension, and 4.3% had diabetes mellitus. In SPMS patients 24.5% reported a history of smoking, 13.2% had hypertension, 9.4% had dyslipidemia, and 3.7% had diabetes mellitus. Smoking was insignificantly associated with higher expanded disability status scale (Z: 1.70, p-value = 0.090). Male sex (RR [95%CI]: 1.628 [1.172, 2.261], p-value = 0.004) and increasing age (RR [95%CI]: 1.024 [1.008, 1.040], p-value = 0.003) were associated with a higher number of risk factors. ConclusionThe highest observed atherosclerosis risk factor among pwMS was smoking. Diabetes mellitus was the least reported risk factor in our population as a whole. Overall, and in participants with RRMS, dyslipidemia and hypertension were the second and third most commonly reported risk factors, however, hypertension exceeded dyslipidemia in participants with SPMS. Male sex and increasing age were associated with a higher number of atherosclerosis risk factors.

Predictors of disability in a cohort with neuromyelitis optica spectrum

Disability in neuromyelitis optica spectrum disorder (NMOSD) is common and can be severe. To determine factors associated with increased disability in NMOSD. Observational, analytical, ambispective study in a cohort of patients with NMOSD between January 2015 and July 2021, using a secondary source to review variables and the expanded disability status scale (EDSS) after onset and a primary source, with a telephone survey for the final EDSS and missing data. Major disability was defined as occurring when the EDSS score was = 6. The analysis was performed by means of logistic regression with SPSS 25®. A total of 125 patients were analysed. The average age at onset was 41 (standard deviation: 14) years, with a female-to-male ratio of 8:1. Of the total sample, 87% (109) were positive for anti-aquaporin antibodies. Optic neuritis (44.8%) and transverse myelitis (39.2%) were the most frequent clinical manifestations at onset. Altogether 71.2% of patients received acute treatment at their first relapse. Mean chronic treatment initiation was 12 months (interquartile range: 3-60) and 44% had difficulties with immunosuppression compliance. Of the total number of patients, 80.8% had relapses and 44% had a final EDSS score = 6. The median baseline-to-final EDSS score was 1 (interquartile range: 0-3), often towards disability accumulation. An association was found between a relapsing course (odds ratio = 3.73; p = 0.011) and a high baseline EDSS (odds ratio = 1.54; p = 0.0001) with increased disability. In the multivariate analysis, with a higher baseline EDSS and a relapsing course disability was 1.6 and 5.3 times more likely to occur, respectively. Disease relapses and high EDSS after the first episode are predictors of disability in NMOSD.

Does pandemic change the ocrelizumab therapy approach? Yes. - Single center ocrelizumab experience.

We know that treatment algorithms have changed in Multiple Sclerosis (MS) practice during the pandemic. In this study, we aimed to investigate whether there was a change in the patient population for ocrelizumab (OCR) treatment during the pandemic period, the treatment compliance of the patients, and the course of the Coronavirus Disease-19 (COVID-19) disease in the patients who received OCR. Our study was designed as a survey study. A questionnaire was sent to the patients assessing whether they had COVID-19 infection, whether they received treatments regularly before and after the pandemic, vaccination status and duration of OCR treatment. Demographic characteristics of the patients, treatments they used before, MS type, Expanded Disability Status Scale (EDSS) scores were determined from the database. Each group of OCR started before pandemic and OCR started after pandemic were compared. We included into the study 86 patients who started OCR before pandemic period and 75 patients who started OCR after the pandemic. Demographic features were similar. EDSS scores were higher in the group that started OCR treatment before the pandemic (p<0.0001). The patients who started OCR treatment before the pandemic had more disruptions than which started during the pandemic (p<0.0001). No correlation was found between the duration of OCR treatment and COVID-19 infection (p=0.940). We observed that the patients who had severe COVID-19 infection had received OCR therapy for a longer period. This retrospective study concluded that the OCR treatment approach in our center had changed during the pandemic period. OCR therapy was started in patients with less disability. The possible reasons for this situation include the proven relationship between high EDSS and serious COVID-19 infection, and that the patients who have higher EDSS score had troubles in reaching health institutions during the pandemic. The result that patients with severe COVID-19 infection received OCR treatment for a longer period necessitates more evidence-based research to investigate the relationship between treatment duration and disease severity.

Leptomeningeal enhancement in multiple sclerosis and other neurological diseases: A systematic review and Meta-Analysis

BackgroundThe lack of systematic evidence on leptomeningeal enhancement (LME) on MRI in neurological diseases, including multiple sclerosis (MS), hampers its interpretation in clinical routine and research settings. PurposeTo perform a systematic review and meta-analysis of MRI LME in MS and other neurological diseases. Materials and MethodsIn a comprehensive literature search in Medline, Scopus, and Embase, out of 2292 publications, 459 records assessing LME in neurological diseases were eligible for qualitative synthesis. Of these, 135 were included in a random-effects model meta-analysis with subgroup analyses for MS. ResultsOf eligible publications, 161 investigated LME in neoplastic neurological (n = 2392), 91 in neuroinfectious (n = 1890), and 75 in primary neuroinflammatory diseases (n = 4038). The LME-proportions for these disease classes were 0.47 [95%-CI: 0.37–0.57], 0.59 [95%-CI: 0.47–0.69], and 0.26 [95%-CI: 0.20–0.35], respectively. In a subgroup analysis comprising 1605 MS cases, LME proportion was 0.30 [95%-CI 0.21–0.42] with lower proportions in relapsing-remitting (0.19 [95%-CI 0.13–0.27]) compared to progressive MS (0.39 [95%-CI 0.30–0.49], p = 0.002) and higher proportions in studies imaging at 7 T (0.79 [95%-CI 0.64–0.89]) compared to lower field strengths (0.21 [95%-CI 0.15–0.29], p < 0.001). LME in MS was associated with longer disease duration (mean difference 2.2 years [95%-CI 0.2–4.2], p = 0.03), higher Expanded Disability Status Scale (mean difference 0.6 points [95%-CI 0.2–1.0], p = 0.006), higher T1 (mean difference 1.6 ml [95%-CI 0.1–3.0], p = 0.04) and T2 lesion load (mean difference 5.9 ml [95%-CI 3.2–8.6], p < 0.001), and lower cortical volume (mean difference −21.3 ml [95%-CI −34.7–-7.9], p = 0.002). ConclusionsOur study provides high-grade evidence for the substantial presence of LME in MS and a comprehensive panel of other neurological diseases. Our data could facilitate differential diagnosis of LME in clinical settings. Additionally, our meta-analysis corroborates that LME is associated with key clinical and imaging features of MS.PROSPERO No: CRD42021235026.

Acute disseminated encephalomyelitis in children and adolescents - 20-year single-center experience in Serbia

Introduction/Objective. Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disease of the central nervous system in pediatric patients. We aimed to evaluate the clinical profile of children with ADEM and to discern prognostic factors for disease outcome. Methods. A 20-year retrospective?prospective study was conducted in a cohort with the diagnosis of ADEM. Results. The study included 36 patients, with range of follow-up period of 6?120 months (median of 26 months). Prior infection was reported in 72.2% of the patients. In the clinical presentation of the disease, motor deficit was most common (81.1%), followed by ataxia (77.8%). More than a third of patients had back and limb pain or abdominal visceral pain, which highly correlated with MRI findings of myelitis. Abnormal brain CT findings were evident in 22.2% of the patients, and this was associated with higher Expanded Disability Status Scale (EDSS) and quicker progression of the disease. Median EDSS was 0 at the most recent follow-up visit, in all the patients. EDSS 0?2.5 was verified in 29 (80.6%) of the patients, while three (8.3%) patients scored 7?9.5 at the last visit. Two patients had a lethal outcome. Conclusions. ADEM is a serious disease in pediatric patients, but with a good prognosis, which is illustrated by the fact that 80.6% of our patients had a complete or almost complete recovery.

Impact of Ramadan fasting on disease activity in patients with multiple sclerosis: a multicenter study

ABSTRACT Background The safety of Ramadan fasting for Muslim patients suffering from multiple sclerosis (MS) is still a matter of debate. This work aimed to study the clinical course of MS during Ramadan fasting and to clarify the predictors of relapses and symptoms exacerbation. Methods This retrospective study included 153 Muslim patients with MS. Data related to the disease course before Ramadan were obtained from patients' files, whereas data related to the disease activity during Ramadan, were collected from patients over the two months following Ramadan. Results Patients with MS who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant longer disease duration compared to those who did not experience (P < 0.001, <0.001, 0.01 respectively). Also, patients who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant higher expanded disability status scale (EDSS) compared to those who did not experience (P <0.001, <0.001,0.01, respectively). The occurrence of relapses, exacerbation of symptoms and development of new symptoms during Ramadan, were significantly higher in patients who experienced relapses in the preceding year compared to those who did not (P= 0.002, 0.002, 0.01, respectively). Binary logistic regression revealed that each score elevation of EDSS increased the odds of relapse during Ramadan by 1.02 (P-value = 0.04). Also, each month's increase in disease duration increased the odds of relapse during Ramadan by 1.87 (P-value = 0.046). Conclusion High EDSS and long disease duration are independent predictors of relapse during Ramadan.

Restless legs syndrome and related factors in people with multiple sclerosis in Turkey

ABSTRACT Objective Restless legs syndrome is one of the most reported sleep disorders in multiple sclerosis (MS). The study aims to investigate the possible factors related to the occurrence and severity of restless legs syndrome in persons with MS (pwMS) comparing with healthy controls. Methods This is a case-control study that included 447 pwMS and 57 healthy controls. Demographic and clinical data such as gender, age, duration of education, body mass index, marital status, disease duration, and MS type were recorded. Neurological disability was assessed by the Expanded Disability Status Scale. The Restless Legs Syndrome Rating Scale was used to assess the severity of restless legs syndrome. Results The prevalence of restless legs syndrome in pwMS was 133 (29.8%) and 3 (4.9%) in healthy controls (p < 0.001). There was no significant difference between the groups in terms of gender, body mass index, and MS type (p > 0.05). Patients with restless legs syndrome have more advanced age, longer disease duration, and higher Expanded Disability Status Scale scores than patients without restless legs syndrome (p < 0.05). The correlation between restless legs syndrome severity and age, Expanded Disability Status Scale score, disease duration was not statistically significant (p > 0.05). Conclusions This study has shown that the presence of restless legs syndrome is high in persons with MS compared to healthy controls. Advanced age, disease duration, and higher disability level could be related to the increased rate of restless legs syndrome in persons with MS, especially those with high-frequency symptoms.

Information processing speed as a prognostic marker of physical impairment and progression in patients with multiple sclerosis

BackgroundPrediction of disability progression in patients with MS (pwMS) is challenging. So far, scarce evidence exists suggesting knowledge about how cognitive performance may potentially improve prediction of physical impairment and disability progression in MS. Therefore, we wanted to assess the prognostic value of cognitive performance regarding physical impairment and disability progression in pwMS. Methods85 patients (64% female; 60% relapse-remitting MS; mean age=36.78 ± 9.63 years) underwent clinical, neuropsychological (Brief Repeatable Battery for Neuropsychological Test (BRB-N)) and brain MRI (T1-weighted and T2-weighted FLAIR images) assessment at baseline and after an average of 7 years (SD=3.75) at follow-up. We assessed physical impairment and annualized disability progression (disability progression divided by follow-up duration) using the Expanded Disability Status Scale (EDSS). To compare patients with no or mild physical impairment (EDSS≤2.5) and patients with moderate to severe physical impairment (EDSS≥3.0), we used an EDSS score ≥3.0 as cut-off. Silent progression was defined by an EDSS worsening of at least 0.5 in the absence of relapses and inflammation in relapsing-remitting MS. ResultsIn hierarchical regression models (method “STEPWISE”, forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R²=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R²=0.257, β=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p<0.001) and silent progression (m=-2.19, SD=1.01, p=0.038). ConclusionPerformance in information processing speed might help to identify patients at risk for physical impairment. Therefore, neuropsychological assessment should be integrated in clinical standard care to support disease management in pwMS.

Performance of Activities of daily living in people with multiple sclerosis

ObjectiveMultiple sclerosis (MS) may result in activity and participation limitations, including the performance of activities of daily living (ADL). This study aims at systematically investigate ADL performance by using Assessment of Motor and Process Skills (AMPS) in people with MS (PwMS) of all disease types and within the Kurtzke Expanded Disability Status Scale (EDSS) range from 1.0 – 8.0. MethodsEight multiple sclerosis (MS) centres participated in data collection of a consecutive sample of PwMS. Participants were referred for assessment to occupational therapy (OT) by treating physician or recruited from neurology department in each hospital and assessed by EDSS and AMPS. The AMPS is an observational, criterion referenced ADL assessment, providing values for a person's ADL performance in terms of motor and process skills. Criterion referenced cut-off scores were established at 2.0 for motor skills and at 1.0 for process skills and both values above the cut-off score indicate competent (independent, safe, efficient and effortless) ADL performance. Process skills refer to the act of carrying out a series of actions and is summarized in terms of efficiency, like initiating without pauses, continuing actions through to completion, performing actions in logical order (sequences), choosing, and completing the task as planned (heeds). ResultsTwo hundred and ten PwMS were recruited (48 +/- 13 years of age, 145 women/65 men, average disease duration was 11.8 +/- 9.6 years, average EDSS was 4.8+/-1.8). Average motor skills score was 1.01+/- 1.12 (indicating need for assistance with evidence of increased clumsiness/physical effort) and average process skills score was 1.02 +/- 0.66 (risk zone, questionable efficiency and more likely to need assistance). Overall, motor skills and process skills decreased with increasing EDSS score. No need for assistance in motor skills was indicated in subjects with lower EDSS scores (1.0 – 2.5). In higher EDSS group (≥4.5), 57% of subjects needed assistance in motor skills and 27% in process skills. The competency in process skills was either questionable or reduced within all EDSS scores. However, 33–38% of subjects with higher EDSS scores (6.0–8.5) showed competent performance in process skills. Overall correlation between motor and process scores was moderate (r = 0.56, p<0.0001), but no significant relationships between motor and process skills were found in the lower EDSS (1–2.5) and high EDSS scores (8–8.5). Further, EDSS and disease type were significant predictors, explaining 52.7% of motor skills and 22.3% of process skills performance. ConclusionProblems in ADL performance were found in EDSS categories 1.0 to 8.0 and in all disease types, therefore it is advisable to screen all PwMS for ADL deficits and provide relevant rehabilitation interventions.

Assessment of cognitive functions in patients with multiple sclerosis

BackgroundAbout 40–70% of patients with multiple sclerosis (MS) develop cognitive impairment (CI) throughout their life. We aim to study the influence of MS on cognitive changes. This is a case–control study of fifty patients with MS who met the revised 2017 Mc Donald Criteria and fifty age- and sex-matched healthy subjects. The Expanded Disability Status Scale (EDSS) was used to assess the degree of disability, and the Montreal Cognitive Assessment (MoCA) scoring system was used to assess cognitive function.ResultsMS patients show low total MoCA score than the controls. Total MoCA scores were lower in patients with CI versus those with intact cognition. CI was higher in those with a longer duration of illness and a high EDSS. MoCA was positively correlated with education level but negatively with EDSS and disease duration.ConclusionMoCA scale has optimal psychometric properties for routine clinical use in patients with MS, even in those with mild functional disability. The longer the disease duration and the higher the EDSS, the lower the MoCA score and the higher the education level, the higher the MoCA score. As for the profile of cognitive dysfunction in patients with MS, the domains most frequently failed by the patients were memory, attention, visuospatial learning, and language.

Cerebrospinal fluid markers in incident pediatric-onset multiple sclerosis: a nationwide study

To investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset < 18 years) and adult-onset (AoMS), and whether these markers are associated with clinical outcomes among PoMS. Prospective nationwide registry study of incident MS, including persons with a CSF sample < 3 years post-MS onset. We compared CSF oligoclonal band (OCB) status, immunoglobulin G (IgG) index levels, and mononuclear cell count between PoMS and AoMS. Within the PoMS cohort we analyzed the association between CSF markers, relapse rate and Expanded Disability Status Scale (EDSS) score, using negative binomial regression and generalized estimating equations, respectively. The cohort consisted of 130 PoMS and 3228 AoMS cases. The PoMS group had higher odds of OCB-positivity (odds ratio: 2.70; 95% CI 1.21–7.67). None of the CSF markers were associated with relapse rate in the PoMS cohort; however, OCB-positivity was associated with higher EDSS scores. This study suggested that PoMS more commonly display CSF evidence for intrathecal IgG production than AoMS. Further, we found evidence of a relationship between OCB-positivity and subsequent disability, suggesting that they could play a role in the prognostication of MS in children.

Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p&lt;0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p &lt;0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

Association of peripapillary hyper-reflective ovoid masslike structures and disease duration in primary progressive multiple sclerosis.

Peripapillary hyper-reflective ovoid masslike structures (PHOMS) are a novel finding during retinal optical coherence tomography in patients with multiple sclerosis (MS). To date, there are no data on the occurrence of PHOMS in early MS. The aim of this study was to investigate the frequency of PHOMS in patients with first diagnosed early relapsing-remitting MS (RRMS) and to search for associations of PHOMS with disease patterns in different MS subtypes. This was a cross-sectional analysis in two different cohorts: cohort 1, consisting of early RRMS patients (n=349); cohort 2, consisting of patients with primary progressive MS (PPMS) (n=66) and RRMS (n=65). Peripapillary hyper-reflective ovoid masslike structures were detected in 18.3% of patients with early RRMS. The occurrence of PHOMS was not associated with age, disease duration and disability. Investigating clinical patterns and the occurrence of PHOMS (cohort 2), an association of PHOMS with higher Expanded Disability Status Scale measures (PHOMS 4.9, 3.7-6.1; no PHOMS 3.5, 3.0-5.3; p=0.03) and longer disease durations (PHOMS 6.5years, 1.9-11.0; no PHOMS 1.0years, 0.0-4.0, p=0.0007) was found in patients with PPMS but not RRMS. After p value adjustment, the disease duration appeared to be more relevant (β=0.16, p=0.06). Peripapillary hyper-reflective ovoid masslike structures were found in 18% of patients with early MS. The presence of PHOMS might be associated with disease progression only in PPMS but not RRMS, suggesting that PHOMS might be embedded in neurodegenerative processes.

Alemtuzumab in a Large Real-Life Cohort: Interim Baseline Data of the TREAT-MS Study.

The non-interventional long-Term study foR obsErvAtion of Treatment with alemtuzumab in active relapsing–remitting MS (TREAT-MS) study collects the so far largest real-life cohort regarding utilization, long-term effectiveness, and safety of alemtuzumab, a humanized monoclonal antibody directed against the cell surface glycoprotein CD52, in adult patients with active relapsing–remitting multiple sclerosis (RRMS). An interim analysis of baseline parameters at inclusion of a non-interventional real-world study about alemtuzumab in Germany including previous multiple sclerosis (MS) medication utilization, MS activity, severity, and duration, as well as comorbidities was performed. Of the 883 patients, 71.6% were women. Mean age was 35.7 ± 9.2 years, time since first MS symptoms (=disease duration) is 8.0 ± 6.8 years, and Expanded Disability Status Scale (EDSS) is 2.7 ± 1.8 points (range, 0.0–7.5 points). The number of relapses in the 12 and 24 months prior to inclusion were 1.6 ± 1.2 and 2.2 ± 1.8, respectively. Of the patients, 14.4% were treatment naive, while for the majority, a wide spectrum of MS disease-modifying treatments (DMTs) and treatment sequences were documented. Overall, interferon beta (IFN-beta) was reported most frequently (52.4%), followed by fingolimod (35.2%), natalizumab (34.9%), and glatiramer acetate (28.9%). Patients with longer disease duration and higher EDSS had a higher number of previous DMTs. Compared to the pivotal phase 2/3 studies, RRMS patients starting alemtuzumab treatment had a longer disease duration in real-world conditions. There was variety of different treatment sequences before the final switch to alemtuzumab. In the future, linking these treatment sequences or other baseline characteristics with effectiveness and safety outcomes might be useful to support treatment decisions. Registered at Paul-Ehrlich-Institut under NIS 281.

MSCopilot: New smartphone-based digital biomarkers correlate with Expanded Disability Status Scale scores in people with Multiple Sclerosis

BackgroundA previous clinical study showed the high specificity, sensitivity and reliability of MSCopilot, a software medical device designed by Ad Scientiam for the self-assessment of people with Multiple Sclerosis (PwMS), compared to the traditional Multiple Sclerosis Functional Composite (MSFC). We conducted further analyses to assess MSCopilot's performance with respect to the Expanded Disability Status Scale (EDSS). MethodsThe data of 116 PwMS were analysed. We studied the correlations between MSCopilot scores and the EDSS, and their ability to distinguish PwMS with high and low EDSS through a study of the distribution of the digital test scores as well as logistic regression models. The same analyses were performed using the MSFC tests. ResultsMSCopilot composite scores were as highly correlated to the EDSS (|r| = 0.65, p < 0.01) as their MSFC counterparts, confirming the known correlation of the MSFC with the EDSS. In a linear regression framework, the Walking digital tests have good explanatory power, especially for PwMS with EDSS > 3.5 (R²adj=0.47). The mean values of each MSCopilot subscore were significantly different between patients with an EDSS > 3.5 and others (p < 0.05), which could not be proved for the MSFC Cognition tests. MSCopilot4 was the best model to predict an EDSS score > 3.5 (AUC = 0.92). ConclusionThese analyses confirm the reliability of MSCopilot and show interesting correlations with the EDSS (similar results obtained with the MSFC). MSCopilot was able to highlight nuances in the different stages of MS the MSFC could not capture.

A Greek Validation Study of the Multiple Sclerosis Work Difficulties Questionnaire-23.

The Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) is a self-report instrument developed to assess barriers faced by People with Multiple Sclerosis (PwMS) in the workplace. The aim of this study was to explore the psychometric properties of the Greek version of the MSWDQ-23. The study sample consisted of 196 PwMS, all currently working in part- or full-time jobs. Participants underwent clinical examination and cognitive screening with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and completed self-report measures of fatigue, psychological functioning, and quality of life, along with the MSWDQ-23 questionnaire. Confirmatory Factor Analysis (CFA) was performed, and goodness-of-fit measures were used to evaluate construct validity. Convergent validity was checked by correlating MSWDQ-23 scores with study measures. Cronbach’s alpha value was produced to assess internal consistency. CFA yielded a model with a fair fit confirming the three-factor structure of the instrument. Higher work difficulties were associated with higher Expanded Disability Status Scale (EDSS) scores, poorer cognitive function, more fatigue, stress, anxiety, and depression, and poorer health status, supporting the convergent validity of MSWDQ-23. Internal consistency (Cronbach’s alpha = 0.94) and test–retest reliability (ICC = 0.996, 95%, CI = 0.990–0.998) were excellent. The Greek MSWDQ-23 can be considered a valid patient-reported outcome measure and can be used in interventions aiming to improve the vocational status of PwMS.

P 24. Dysphagia in NMOSD and MOGAD: Swallowing endoscopy as a surrogate of brain involvement?

Background. Neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) are demyelinating disorders that typically affect the optic nerves and the spinal cord. However, recent studies have demonstrated various forms of brain involvement indicating encephalitic syndromes, which consequently are included in the diagnostic criteria for both. Swallowing is processed in a distributed brain-network and is therefore disturbed in many neurological diseases. Objective. The aim of this study was to investigate the occurrence of oropharyngeal dysphagia in NMOSD and MOGAD and to further assess the value of flexible endoscopic evaluation of swallowing (FEES) as a surrogate parameter of brain involvement. Methods. 13 Patients with NMOSD and MOGAD (mean age 54.2 ± 18.6 years, men: 13) who received FEES during clinical routine were retrospectively reviewed: Their extent of oropharyngeal dysphagia was rated using an ordinal dysphagia severity scale. FEES-results were compared to a control group of healthy individuals. Dysphagia severity was correlated with the presence of clinical and radiological signs of brain involvement, the Expanded Disability Status Scale (EDSS) and the occurrence of pneumonia. Results. Oropharyngeal dysphagia was present in 8/13 patients, including 6 patients without other clinical indication of brain involvement. Clinical or subclinical swallowing impairment was significantly more severe in patients with NMOSD and MOGAD compared to the healthy individuals ( p = 0.009) and correlated with clinical signs of brain involvement ( p = 0.019), higher EDSS ( p = 0.006) and pneumonia ( p = 0.019). Conclusion. Oropharyngeal dysphagia can occur in NMOSD and MOGAD and might be associated with pneumonia and disability. FEES may help to detect subclinical brain involvement.

Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening

Background: The influence of pregnancy on long-term disability in multiple sclerosis (MS) is still controversial. Objective: To assess the risk of long-term disability worsening after pregnancy in MS women as compared with a propensity-score (PS) matched group of MS women without pregnancy. Methods: In the setting of the Italian Pregnancy Dataset, MS patients with (pregnancy group (PG)) and without pregnancy (control group (CG)) were recruited. Time to disability worsening on the Expanded Disability Status Scale (EDSS) was assessed through a multivariable Cox regression model. Results: The PS-matching retained 230 PG and 102 CG patients. After a follow-up of 6.5 +/- 3.1 years, disability worsening occurred in 87 (26.2%) women. In the multivariable analysis, disability worsening was associated with pregnancy in women with relapses in the year before conception (adjusted hazard ratio (aHR) = 1.74; 95% confidence interval (CI) 1.06–2.84; p = 0.027), higher EDSS (aHR = 1.39; 95% CI 1.12–1.74; p = 0.003), younger age (aHR = 0.95; 95% CI 0.91–0.99; p = 0.022) and shorter DMD exposure over the follow-up (p < 0.008). Conclusion: Pregnancy in MS women with relapses in the year before conception increases the risk of long-term disability worsening. Our findings underscore the importance of counselling in MS women facing a pregnancy that should be planned after a period of clinical stability, favouring treatment optimization in patients with recent disease activity.

Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

BackgroundAnti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy. MethodsIn this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR). Data were collected from medical charts and the DMSR. We assessed occurrence of severe infections (requiring hospitalization), varicella zoster virus (VZV), major comorbidities and routine laboratory values for lymphocytes, IgG and IgM. ResultsA total of 447 patients ever treated with anti-CD20 antibody therapy were identified; of these 416 with 649 patient years of follow-up were still under therapy. In this group, seven patients had VZV infections, and 16 patients had been hospitalized with infections during up to three years of follow-up on anti-CD20 therapy. Comorbidity was recorded in 80 patients. The risk of severe infection was associated with comorbidities, higher age, longer duration of treatment, and higher Expanded Disability Status Scale (EDSS) scores. In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections. Serum concentrations of IgG and IgM decreased with increasing duration of therapy but were not associated with risk of severe infections. Patients with VZV infection had lower lymphocyte counts and lower serum concentrations of IgM. In multivariable analyses only lymphocyte counts were independently associated with risk of VZV infection. ConclusionsIn this retrospective study of patients treated with anti-CD20 antibodies, the risk of infections requiring hospitalization was independently associated with comorbidities, duration of treatment, and higher EDSS scores. Risk of VZV infection was independently associated with lymphopenia. Future studies investigating strategies for mitigating risk of infection in patients treated with anti-CD20 antibodies are warranted, especially for older patients, patients with higher levels of disability and for patients with a longer duration of treatment.

Gut Microbiome in Progressive Multiple Sclerosis.

This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease. We sequenced the microbiota from healthy controls and relapsing-remitting MS (RRMS) and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including Expanded Disability Status Scale (EDSS), quality of life, and brain magnetic resonance imaging lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis (EAE). Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17-producing γδ T cells. Whereas some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome. ANN NEUROL 2021;89:1195-1211.