Lower 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.

Diffusion tensor imaging metrics as natural markers of multiple sclerosis-induced brain disorders with a low Expanded Disability Status Scale score

Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1–3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics.

Multifractal organization of EEG signals in multiple sclerosis

Quantifying the complex/multifractal organization of the brain signals is crucial to fully understanding the brain processes and structure. In this contribution, we performed the multifractal analysis of the electroencephalographic (EEG) data obtained from a controlled multiple sclerosis (MS) study, focusing on the correlation between the degree of multifractality, disease duration, and disability level. Our results reveal a significant correspondence between the complexity of the time series and multiple sclerosis development, quantified respectively by scaling exponents and the Expanded Disability Status Scale (EDSS). Namely, for some brain regions, a well-developed multifractality and little persistence of the time series were identified in patients with a high level of disability, whereas the control group and patients with low EDSS were characterized by persistence and monofractality of the signals. The analysis of the cross-correlations between EEG signals supported these results, with the most significant differences identified for patients with EDSS >1 and the combined group of patients with EDSS ≤1 and controls. No association between the multifractality and disease duration was observed, indicating that the multifractal organization of the data is a hallmark of developing the disease. The observed complexity/multifractality of EEG signals is hypothetically a result of neuronal compensation – i.e., of optimizing neural processes in the presence of structural brain degeneration. The presented study is highly relevant due to the multifractal formalism used to quantify complexity and due to scarce resting-state EEG evidence for cortical reorganization associated with compensation.

Late-onset multiple sclerosis: disability trajectories in relapsing-remitting patients of the Italian MS Registry.

Generally infrequent, multiple sclerosis (MS) with late onset (LOMS) is characterized by an onset over the age of 50 and a mainly progressive course, while relapsing-remitting (RR) forms are less frequently observed and explored. This study aimed to characterize a large cohort of MS patients with RRMS at onset to assess the baseline factors related to the worst disability trajectories and explore the role of LOMS. The data were extracted from the Italian MS Register (IMSR). Disability trajectories, defined using at least two and up to twenty expanded disability status scale (EDSS) assessments annually performed, were implemented using group-based trajectory models (GBTMs) to identify different groups with the same trajectories over time. MS profiles were explored using multinomial logistic regression. A total of 16,159 RR patients [1012 (6.26%) presented with LOMS] were analyzed. The GBTM identified four disability trajectories. The group with the most severe EDSS trend included 12.3% of the patients with a mean EDSS score > 4, which increased over time and exceeded 6 score. The group with medium severity EDSS trend comprised 21.9% of the patients and showed a change in EDSS > 3 scores over time. The largest group with 50.8% of patients reported a constant EDSS of 2 score. Finally, the benign group comprised 14.9% of the patients with a low and constant EDSS of 1 score over time. The probability of being in the worst groups increased if the patient was male; had LOMS or experienced brainstem, spinal, or supratentorial symptoms. Four MS severity profiles among RRMS patients in the IMSR have been reported, with LOMS being associated with a rapid worsening of EDSS scores. These findings have important implications for recognizing and managing how older age, aging, and age-related factors interact with MS and its evolution.

Characteristics of aseptic meningitis-like attack-an underestimated phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease.

Aseptic meningitis was recently reported and recognized as a novel phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD). However, the frequency and clinical features of this specific subtype remain unclear. We reported sixteen MOG-AD cases with aseptic meningitis from June 2018 to June 2022. Moreover, systematic literature of 17 reported cases was conducted. Upon reviewing the records of 91 patients diagnosed with MOG-AD in our center, we identified 16 patients (17.6%; 9 men and 7 women) with aseptic meningitis-like MOG-AD. The median age at onset was 23.5 ± 15.7 years. The common clinical presentations were fever (87.5%), headache (75.0%) and seizure (18.8%). Most patients had leukocytosis (62.5%) and a significantly elevated neutrophil-lymphocyte ratio (NLR, ≥3.0). Cerebrospinal fluid showed elevated intracranial hypertension (43.8%), elevated leukocytes (100%) and protein (56.3%). Negative brain magnetic resonance images were observed in 6 patients and only meningeal enhancement was observed in 8 patients at first. Almost all patients had a prolonged fever (over 2 weeks) and ineffectual antibiotic treatment. All patients experienced an effective response to immunotherapy. The majority had a benign course (low Expanded Disability Status Scale score and relapsing rate). Five patients (31.3%) progressed and four patients (25.0%) experienced recurrence. Aseptic meningitis-like MOG-AD of 17 cases reported in previous studies showed similar clinical features to our cases. Aseptic meningitis could be an initial or isolated manifestation of MOG-AD. It is an underestimated phenotype of MOG-AD.

Multidimensional frailty and its association with quality of life and disability: A cross-sectional study in people with multiple sclerosis

BackgroundPeople with multiple sclerosis (pwMS) have a high risk of frailty. We aim to evaluate frailty using the Tilburg frailty indicator (TFI), a multidimensional self-reported questionnaire, and to explore its relationship with autonomy, quality of life (QoL), and disability. MethodsAll the patients with MS enrolled completed TFI (frail when TFI score ≥ 5 points), the Groningen Activities Restriction Scale to evaluate autonomy, and the Multiple Sclerosis Impact Scale-29 to evaluate QoL. We collected the Expanded Disability Status Scale (EDSS) score, age and gender. Data were analysed using descriptive analyses, hierarchical multiple regression, and ANCOVA. ResultsA total of 208 pwMS (mean age 44 years, SD=11; 75% women; 89.4% relapsing-remitting) were enrolled. The mean TFI total score was 5.7 points (SD=3.0; range 0–14), with the 62.5% of participants exhibiting frailty. After controlling for age and gender, the EDSS score was associated with the total (β=0.469; R2=0.255; p<0.001) and the physical (β=0.571; R2=0.349; p<0.001) frailty score, with an explained variance of 25.5% and 34.9%, respectively. No relationships between the EDSS and psychological and social frailty domains were detected. The proportion of frail patients with EDSS ≥ 6.0, EDSS within 3.5–5.5, and EDSS ≤ 3.0 was 91.7%, 83.3%, and 66.0%, respectively. Frail patients exhibited higher autonomy impairment (p = 0.017) and worse QoL (p<0.001). DiscussionWe found a high frequency of frail patients with MS. Frailty is more common in patients with higher disability, but it affects also those with low EDSS. In people with MS frailty could be influenced by factors other than disability.

Premorbid Sociodemographic Status and Multiple Sclerosis Outcomes in a Universal Health Care Context

Multiple sclerosis (MS) severity may be informed by premorbid sociodemographic factors. To determine whether premorbid education, income, and marital status are associated with future MS disability and symptom severity, independent of treatment, in a universal health care context. This nationwide observational cohort study examined data from the Swedish MS Registry linked to national population registries from 2000 to 2020. Participants included people with MS onset from 2005 to 2015 and of working age (aged 23 to 59 years) 1 year and 5 years preceding disease onset. Income quartile, educational attainment, and marital status measured at 1 and 5 years preceding disease onset. Repeated measures of Expanded Disability Status Scale (EDSS) scores and patient-reported Multiple Sclerosis Impact Scale (MSIS-29) scores. Models were adjusted for age, sex, relapses, disease duration, and treatment exposure. Secondary analyses further adjusted for comorbidity. All analyses were stratified by disease course (relapse onset and progressive onset). There were 4557 patients (mean [SD] age, 37.5 [9.3] years; 3136 [68.8%] female, 4195 [92.1%] relapse-onset MS) with sociodemographic data from 1-year preonset of MS. In relapse-onset MS, higher premorbid income and education correlated with lower disability (EDSS, -0.16 [95% CI, -0.12 to -0.20] points) per income quartile; EDSS, -0.47 [95% CI, -0.59 to -0.35] points if tertiary educated), physical symptoms (MSIS-29 physical subscore, -14% [95% CI, -11% to -18%] per income quartile; MSIS-29 physical subscore, -43% [95% CI, -35% to -50%] if tertiary educated), and psychological symptoms (MSIS-29 psychological subscore, -12% [95% CI, -9% to -16%] per income quartile; MSIS-29 psychological subscore, -25% [95% CI, -17% to -33%] if tertiary educated). Marital separation was associated with adverse outcomes (EDSS, 0.34 [95% CI, 0.18 to 0.51]; MSIS-29 physical subscore, 35% [95% CI, 12% to 62%]; MSIS-29 psychological subscore, 25% [95% CI, 8% to 46%]). In progressive-onset MS, higher income correlated with lower EDSS (-0.30 [95% CI, -0.48 to -0.11] points per income quartile) whereas education correlated with lower physical (-34% [95% CI, -53% to -7%]) and psychological symptoms (-33% [95% CI, -54% to -1%]). Estimates for 5-years preonset were comparable with 1-year preonset, as were the comorbidity-adjusted findings. In this cohort study of working-age adults with MS, premorbid income, education, and marital status correlated with disability and symptom severity in relapse-onset and progressive-onset MS, independent of treatment. These findings suggest that socioeconomic status may reflect both structural and individual determinants of health in MS.

Google Maps Timeline: An open-access digital tool to monitor walking abilities in people with multiple sclerosis.

Gait impairment is common in multiple sclerosis (MS), but difficult to evaluate in clinical practice. In this proof-of-concept observational study, we compared walking ability recorded by Google Maps Timeline to conventional clinical measures in people with MS. We used open-access Google Maps Timeline to record the total number of days with walking activity, walking distance, walking time, and walking speed. Each Google Maps Timeline variable was included in a different stepwise linear regression model including all conventional clinical variables. We included nine people with MS (age 43.1 ± 6.6 years; females 55.6%; disease duration 12.7 ± 3.1 years; median Expanded Disability Status Scale 3.0 (range 1.0-5.5)). Higher percentage of days with recorded walking was associated with lower Fatigue Severity Scale (p = 0.01), and higher MS Walking Scale (p = 0.04). Longer average daily walking distance was associated with shorter Timed-25 Foot Walking Test (p = 0.02), lower Expanded Disability Status Scale (p = 0.01), and higher Euro-Quality of Life (p = 0.04). Longer average daily walking time was associated with shorter Timed-25 Foot Walking Test (p = 0.03). Higher walking speed was associated with lower Fatigue Severity Scale (p = 0.04). Google Maps Timeline parameters provide actual estimates of daily walking activities in MS.

Association between clinic-level quality of care and patient-level outcomes in multiple sclerosis

Background: Multiple sclerosis (MS) quality of care guidelines are consensus-based. The effectiveness of the recommendations is unknown. Objective: To determine whether clinic-level quality of care affects clinical and patient-reported outcomes. Methods: This nationwide observational cohort study included patients with adult-onset MS in the Swedish MS registry with disease onset 2005–2015. Clinic-level quality of care was measured by four indicators: visit density, magnetic resonance imaging (MRI) density, mean time to commencement of disease-modifying therapy, and data completeness. Outcomes were Expanded Disability Status Scale (EDSS) and patient-reported symptoms measured by the Multiple Sclerosis Impact Scale (MSIS-29). Analyses were adjusted for individual patient characteristics and disease-modifying therapy exposure. Results: In relapsing MS, all quality indicators benefitted EDSS and physical symptoms. Faster treatment, frequent visits, and higher data completeness benefitted psychological symptoms. After controlling for all indicators and individual treatment exposures, faster treatment remained independently associated with lower EDSS (−0.06, 95% confidence interval (CI): −0.01, −0.10) and more frequent visits were associated with milder physical symptoms (MSIS-29 physical score: −16.2%, 95% CI: −1.8%, −29.5%). Clinic-level quality of care did not affect any outcomes in progressive-onset disease. Conclusion: Certain quality of care indicators correlated to disability and patient-reported outcomes in relapse-onset but not progressive-onset disease. Future guidelines should consider recommendations specific to disease course.

ADC restriction is not associated with clinical response to plasma exchange following a cerebral attack of multiple sclerosis.

MS is the most common CNS inflammatory demyelinating disease. Plasma exchange (PLEX) has well-demonstrated efficacy in acute corticosteroid-refractory attacks of demyelination but identifying the factors that predict favorable PLEX response remains elusive. We aimed to determine if apparent diffusion coefficient (ADC) restriction on brain MRI predicts clinical response to PLEX in individuals with an acute cerebral attack of MS. Retrospective chart review of individuals with a cerebral attack of MS who underwent PLEX at Mayo Clinic. We identified 34 individuals who fulfilled the inclusion criteria.Twenty-seven (79%) responded to plasma exchange, with 16/34 (47%) having moderate and 11/34 (32%) marked improvement. Twenty-three (68%) people had ADC restriction on brain MRI prior to PLEX. ADC restriction did not predict response (p=0.51). Several other pre-PLEX factors, including sex, Expanded Disability Status Scale (EDSS) at initial attack, time to PLEX, and concurrent spinal cord attack, also failed to predict response. Plasma-exchange responders had less disability at 6-month follow-up compared to non-responders (median EDSS 2.5 (range 1.0-10.0) vs. 7.5 (5.5-10.0), p<0.001). Acute cerebral attacks of MS have a high rate of plasma exchange response resulting in a lower EDSS at 6-months. ADC restriction does not predict response to plasma exchange.

Correlation of brain segmental volume changes with clinical parameters: a longitudinal study in multiple sclerosis patients

To measure the cranial volume differences from 15 different parts in the follow-up of relapsing-remitting multiple sclerosis (RRMS) patients and correlate them with clinical parameters. Forty-seven patients with RRMS were included in the study. Patients were grouped into two categories; low Expanded Disability Status Scale (EDSS) (< 3; group 1), and moderate-high EDSS (≥ 3; group 2). Patients were evaluated with Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MOCA), Symbol Digit Modalities Test (SDMT), Fatigue Severity Scale (FSS), and calculated Annualized Relapse Rate (ARR) scores. Magnetic resonance imaging (MRI) was performed with a 1.5T MRI device (Magnetom AERA, Siemens, Erlangen, Germany) twice in a 1-year period. Volumetric analysis was performed by a free, automated, online MRI brain volumetry software. The differences in volumetric values between the two MRI scans were calculated and correlated with the demographic and clinical parameters of the patients. The number of attacks, disease duration, BDI, and FSS scores were higher in group 2; SDMT was higher in group 1. As expected, volumetric analyses have shown volume loss in total cerebral white matter in follow-up patients (p < 0.001). In addition, putaminal volume loss was related to a higher number of attacks. Besides, a negative relation between FSS with total amygdala volumes, a link between atrophy of globus pallidus and ARR, and BDI scores was found with the aid of network analysis. Apart from a visual demonstration of volume loss, cranial MRI with volumetric analysis has a great potential for revealing covert links between segmental volume changes and clinical parameters.

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis.

Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS. We collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31-0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with -0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001). The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy. This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.

Clinical Profile and the Extent of Disability in Multiple Sclerosis Patients in Madinah, Saudi Arabia.

Objectives: The objective is to study the demographics and clinical characteristics of Saudi multiple sclerosis (MS) patients in Madinah, Saudi Arabia, and assess their extent of disability using the Expanded Disability Status Scale (EDSS).Methods: This hospital-based study intended to address the population of all MS-diagnosed patients registered between 2018 and 2021 in the Neurology Department of King Fahad Hospital in the Madinah region. Data were gathered from medical records and by interviewing participants in the Neurology Clinic. The chi-square test and linear and logistic regression were applied to draw inferences.Results: A total of 195 MS-diagnosed patients were included in the analysis. Of these, 72.3% were female. The mean age of the total sample was 34.9±9.2 years, and 7.7% reported a positive family history. Of all patients, 17.9% (n=35) had comorbidities. The mean age at diagnosis was 29.3±8.2 years. The majority (85.6%) were diagnosed with relapsing-remitting multiple sclerosis (RRMS); 77.9% had an EDSS score between 0.0 and 1.5, showing little or no disability. A statistical significance existed between EDSS and the current age of the patients (p=0.004), age at onset (p=0.007), type of MS (p=0.000), presence of muscle weakness (p=0.044), bladder or bowel difficulties at onset (p=0.043), and the duration of MS (p=0.000). Of the patients, 23.6% were not using disease-modifying therapy (DMT). The most commonly used drug was interferon beta 1-b.Conclusion: A lower EDSS was associated with younger age, diagnosis at a younger age, RRMS, duration less than five years, and lower body mass index (BMI). To increase the generalizability of findings, a national MS registry system and further prospective analytical epidemiological research studies are recommended.

Preferences for Disease-Modifying Therapies in Argentina: Cross-Sectional Conjoint Analysis of Patients and Neurologists

ObjectivesThe objective of this study was to determine by a conjoint analysis the preferences for a range of disease-modifying treatment attributes in patients with multiple sclerosis (MS) and treating neurologists. MethodsThis was a cross-sectional study throughout Argentina between August 2020 and February 2021. Participating patients were adults with relapsing-remitting MS, who had received a long-term specific disease-modifying treatment for at least the past 3 months and their treating neurologist. Patients and neurologist were sampled from the Argentinean MS patient registry (RelevarEM). We applied the methodology of conjoint analysis. Patient preferences for hypothetical treatment were collected from the overall sample and from stratified subgroups according to the expanded disability status scale (EDSS) score. An ordinary least squares regression model was used to estimate parameters. ResultsA total of 275 patients from 25 centers (31 principal investigators) were included, mean age was 43.2 ± 10.9 years, 59.6% were female, and mean EDSS was 3.1 ± 2. For the entire sample, we observed that patients had higher preferences for treatments with lower side effect risks (28.7 relative preference [RP]), lower frequency of administration (21.4 RP), and higher impact on relapses (19.6 RP). Patients with a higher EDSS give significantly greater importance to a less frequent administration regime and the oral route than patients with a lower EDSS (23.5 RP vs 20.1 [P =.02] and 17.1 vs 15.3 [P =.03], respectively). For neurologists, the most important attribute was to prevent disease progression (RP 29.3). ConclusionOur study contributes to the understanding of treatment selection preferences from the perspectives of both patient and neurologists.

Peripartum disease activity in moderately and severely disabled women with multiple sclerosis.

BackgroundThe effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities.ObjectiveTo quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3.MethodsWe performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening.ResultsThere were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS.ConclusionsModerately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.

Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study.

Disability accrual in multiple sclerosis may occur as relapse-associated worsening or progression independent of relapse activity. The role of progression independent of relapse activity in early multiple sclerosis is yet to be established. The objective of this multicentre, observational, retrospective cohort study was to investigate the contribution of relapse-associated worsening and progression independent of relapse activity to confirmed disability accumulation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, assessed within one year from onset and with follow-up ≥5 years (n = 5169). Data were extracted from the Italian Multiple Sclerosis Register. Confirmed disability accumulation was defined by an increase in Expanded Disability Status Scale score confirmed at 6 months, and classified per temporal association with relapses. Factors associated with progression independent of relapse activity and relapse-associated worsening were assessed using multivariable Cox regression models. Over a follow-up period of 11.5 ± 5.5 years, progression independent of relapse activity occurred in 1427 (27.6%) and relapse-associated worsening in 922 (17.8%) patients. Progression independent of relapse activity was associated with older age at baseline [hazard ratio (HR) = 1.19; 95% confidence interval (CI) 1.13-1.25, P < 0.001], having a relapsing-remitting course at baseline (HR = 1.44; 95% CI 1.28-1.61, P < 0.001), longer disease duration at baseline (HR = 1.56; 95% CI 1.28-1.90, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.92; 95% CI 0.88-0.96, P < 0.001) and lower number of relapses before the event (HR = 0.76; 95% CI 0.73-0.80, P < 0.001). Relapse-associated worsening was associated with younger age at baseline (HR = 0.87; 95% CI 0.81-0.93, P < 0.001), having a relapsing-remitting course at baseline (HR = 1.55; 95% CI 1.35-1.79, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.94; 95% CI 0.89-0.99, P = 0.017) and a higher number of relapses before the event (HR = 1.04; 95% CI 1.01-1.07, P < 0.001). Longer exposure to disease-modifying drugs was associated with a lower risk of both progression independent of relapse activity and relapse-associated worsening (P < 0.001). This study provides evidence that in an early relapsing-onset multiple sclerosis cohort, progression independent of relapse activity was an important contributor to confirmed disability accumulation. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum, in which age is one of the main determinants of disease phenomenology.

Theory of mind, emotion recognition and emotional reactivity factors in early multiple sclerosis: Results from a South American cohort

Objectives To study different components of social cognition and quality of life in patients with early multiple sclerosis and low Expanded Disability Status Scale and to test the influence of cognitive performance, fatigue and neuropsychiatric symptoms on social cognition performance. Methods Thirty-four patients with relapsing-remitting MS, with ≤2 years of disease duration and scores ≤2 on the EDSS and 30 healthy controls underwent neuropsychological assessment with the Brief Repeatable Neuropsychological Test Battery. Components of social cognition, such as emotion recognition, theory of mind, empathy, and emotional reactivity, were assessed with the Reading the Mind in the Eyes test, the Faux Pas task, the International Affective Imagery System, and the Empathy Quotient. Anxiety, depression, fatigue and quality of life were measured. Results Patients showed significant differences in verbal memory, executive functions and social cognition, especially emotion recognition and ToM. Regarding emotional reactivity, patients showed a positive bias in the interpretation of the valence of neutral images. Conclusions Patients with early MS showed impairments in several components of social cognition independent of cognitive performance, neuropsychiatric symptoms and fatigue. Social cognition deficits may be present in MS even in the early stages.

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.

Maternal education has significant influence on progression in multiple sclerosis

ObjectiveThe identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life. MethodsA total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients’ age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18. ResultsHigh maternal level of education at patients’ age 16 was significantly associated with less pronounced disease progression measured by MSSS (β-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (β-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not. ConclusionThis study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life.

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019. This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits. A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up. Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.