Expanded Disability Status Scale Values Research Articles

Claims-based algorithm to estimate the Expanded Disability Status Scale for multiple sclerosis in a German health insurance fund: a validation study using patient medical records.

The Expanded Disability Status Scale (EDSS) quantifies disability and measures disease progression in multiple sclerosis (MS), however is not available in administrative claims databases. To develop a claims-based algorithm for deriving EDSS and validate it against a clinical dataset capturing true EDSS values from medical records. We built a unique linked dataset combining claims data from the German AOK PLUS sickness fund and medical records from the Multiple Sclerosis Management System 3D (MSDS3D). Data were deterministically linked based on insurance numbers. We used 69 MS-related diagnostic indicators recorded with ICD-10-GM codes within 3 months before and after recorded true EDSS measures to estimate a claims-based EDSS proxy (pEDSS). Predictive performance of the pEDSS was assessed as an eight-fold (EDSS 1.0-7.0, ≥8.0), three-fold (EDSS 1.0-3.0, 4.0-5.0, ≥6.0), and binary classifier (EDSS <6.0, ≥6.0). For each classifier, predictive performance measures were determined, and overall performance was summarized using a macro F1-score. Finally, we implemented the algorithm to determine pEDSS among an overall cohort of patients with MS in AOK PLUS, who were alive and insured 12 months prior to and after index diagnosis. We recruited 100 people with MS insured by AOK PLUS who had ≥1 EDSS measure in MSDS3D between 01/10/2015 and 30/06/2019 (620 measurements overall). Patients had a mean rescaled EDSS of 3.2 and pEDSS of 3.0. The pEDSS deviated from the true EDSS by 1.2 points, resulting in a mean squared error of prediction of 2.6. For the eight-fold classifier, the macro F1-score of 0.25 indicated low overall predictive performance. Broader severity groupings were better performing, with the three-fold and binary classifiers for severe disability achieving a F1-score of 0.68 and 0.84, respectively. In the overall AOK PLUS cohort (3,756 patients, 71.9% female, mean 51.9 years), older patients, patients with progressive forms of MS and those with higher comorbidity burden showed higher pEDSS. Generally, EDSS was underestimated by the algorithm as mild-to-moderate symptoms were poorly captured in claims across all functional systems. While the proxy-based approach using claims data may not allow for granular description of MS disability, broader severity groupings show good predictive performance.

Metabolomics of Cerebrospinal Fluid Amino and Fatty Acids in Early Stages of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

Is breastfeeding in MS harmful or not? An answer from real-world Czech data.

The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS. To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status. Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy. We also compared these parameters between breastfeeding patients not using a DMT and non-breastfeeding patients who resumed DMT within 3 months after delivery. EDSS, ARR, and CDW were collected at 12, 24, and 36 months after delivery. A total of 1681 pregnancies that ended in delivery were analyzed from 2013 through 2020. Change in ARR and EDSS values and 6-months CDW did not significantly differ between the analyzed groups. Compared with non-breastfeeding women who resumed DMT early after delivery, breastfeeding women with MS did not experience worse clinical outcomes even without initiating a DMT. Breastfeeding in Czech women with MS did not negatively affect the disease course and can be supported. Patients with MS can be treated with certain DMTs alongside breastfeeding and there is no need to stop breastfeeding, if the patient is clinically stable.

Cognitive Processing Speed Predicts Disability Milestones in Multiple Sclerosis (P5-3.014)

Cognitive Processing Speed Predicts Disability Milestones in Multiple Sclerosis (P5-3.014)

Progression of Relapsing-Remitting Multiple Sclerosis despite the new era of treatments

Objective. The present study aims to evaluate the conditions associated with the progression of Multiple Sclerosis (MS) and patients' dysfunctions. Methods. We perform a retrospective longitudinal analytical observational study in 46 patients with MS from a polyclinic at Rio de Janeiro, Brazil. We used the Expanded Disability Status Scale (EDSS) to rank the patients according to their disability and establish correlation with risk factors, treatment and time of disease. Results. Of 46 patients, 69.6% were female and 67.4% were white. Patients with fewer functional systems affected at the beginning of the disease had a longer time for disease progression, according to EDSS. Low efficacy drugs led to a high rate of discontinuation of the treatment. Patients who used a continuously treatment took longer to reach higher EDSS values ​​than those who discontinued treatment. Conclusion. Despite the control of MS with high effective drugs, there is still some disability for the patient. The factors that influenced the progression of the disability were: multiple symptoms at the beginning of the disease, more than 30 years old at the beginning of the MS, delay in diagnosis and initiation of treatment, among others.

004 Physical activity monitoring to assess disability progression in multiple sclerosis

To monitor multiple sclerosis (MS) disability, scales like the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) are commonly used. Both rely on a single clinical assess- ment in time which may not reflect the patient’s performance in their living environment. They also require training and are time consuming. The SenseWear armband incorporates a triaxial accelerometer sensitive to upper and lower limb motion. A proprietary algorithm computes several physical activity variables, such as total energy expenditure, physical activity duration, metabolic equivalents (METs) and average daily steps. Here we assess the SenseWear armband for its ability to monitor disease progression, alongside the EDSS and MSFC. Progressive MS patients (n=50) wore the device for one week, every 6 months for2.5 years. MSFC and EDSS were performed at the end of each week. The armband was agreeable and easy to use. Patients showed progression across all three disability measures (p&lt;0.01). Baseline physical activity, EDSS and MSFC values correlated well between each other. The change in the three measures with time correlated poorly, suggesting that they measure functional aspects which have different pro- gression trajectories. In summary, physical activity monitoring is a user-friendly and ecological method to measure MS disability progression.c.stuart@soton.ac.uk

Availability of Fibrinogen/Albumin ratio in MS attack

Background/AimMultiple sclerosis (MS) is a chronic central nervous system inflammatory disease. Fibrinogen/Albumin ratio (FAR) has been studied as an inflammatory marker in the past, and its significant relationship with inflammation has been shown. In our study, we examined serum levels of albumin, fibrinogen and FAR in patients presenting with MS attack. We investigated its usability in the diagnosis and management of MS attacks. Materials and methodsThis retrospective study included 40 patients admitted to hospital with MS attack and 40 control patients. All patients’ demographics, medical history, the mean Expanded Disability Status Scale (EDSS), imaging findings and laboratory tests were extracted from medical records. Patients’ fibrinogen, albumin levels were recorded in the blood tests performed before steroid administration, and FAR values were calculated. The patients’ and controls’ results were compared. ResultsFibrinogen and FAR values were significantly higher in the patient group (p<0.001 in both). There was no difference between the patient and control groups in terms of albumin (p = 0,16). No significant relationship was found between parameters such as EDSS, disease duration, smoking status and FAR value (p>0.05 in all). ConclusionSerum fibrinogen and FAR levels in the patients presenting with an attack were significantly higher than the control group. FAR value did not vary with disease duration and EDSS score. Based on this information, FAR may be a useful indicator for MS attack regardless of EDSS and disease duration.

How patients with multiple sclerosis acquire disability.

Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins and the extent to which multiple sclerosis therapies delay disability accumulation.Using the Novartis-Oxford multiple sclerosis (NO.MS) data pool spanning all multiple sclerosis phenotypes and paediatric multiple sclerosis, we evaluated ∼200 000 Expanded Disability Status Scale (EDSS) transitions from >27 000 patients with ≤15 years follow-up. We analysed three datasets: (i) A full analysis dataset containing all observational and randomized controlled clinical trials in which disability and relapses were assessed (n = 27 328); (ii) all phase 3 clinical trials (n = 8346); and (iii) all placebo-controlled phase 3 clinical trials (n = 4970). We determined the relative importance of RAW and PIRA, investigated the role of relapses on all-cause disability worsening using Andersen-Gill models and observed the impact of the mechanism of worsening and disease-modifying therapies on the time to reach milestone disability levels using time continuous Markov models.PIRA started early in the disease process, occurred in all phenotypes and became the principal driver of disability accumulation in the progressive phase of the disease. Relapses significantly increased the hazard of all-cause disability worsening events; following a year in which relapses occurred (versus a year without relapses), the hazard increased by 31–48% (all P < 0.001). Pre-existing disability and older age were the principal risk factors for incomplete relapse recovery. For placebo-treated patients with minimal disability (EDSS 1), it took 8.95 years until increased limitation in walking ability (EDSS 4) and 18.48 years to require walking assistance (EDSS 6). Treating patients with disease-modifying therapies delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and 3.09 years (2.60, 3.72), respectively. In patients with relapsing-remitting multiple sclerosis, those who worsened exclusively due to RAW events took a similar length of time to reach milestone EDSS values compared with those with PIRA events; the fastest transitions were observed in patients with PIRA and superimposed relapses.Our data confirm that relapses contribute to the accumulation of disability, primarily early in multiple sclerosis. PIRA begins in relapsing-remitting multiple sclerosis and becomes the dominant driver of disability accumulation as the disease evolves. Pre-existing disability and older age are the principal risk factors for further disability accumulation. The use of disease-modifying therapies delays disability accrual by years, with the potential to gain time being highest in the earliest stages of multiple sclerosis.

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

Introduction: We aimed to develop and validate an Expanded Disability Status Scale (EDSS) model through clinical, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) measures. Methods: Sixty-four multiple sclerosis (MS) patients underwent peripapillary retinal nerve fiber layer and segmented macular layers evaluation through OCT (Spectralis, Heidelberg Engineering). Brain parenchymal fraction was quantified through Freesurfer, while cervical spinal cord (SC) volume was assessed manually guided by Spinal Cord Toolbox software analysis. EDSS, neuroradiological, and OCT assessment were carried out within 3 months. OCT parameters were calculated as the average of both nonoptic neuritis (ON) eyes, and in case the patient had previous ON, the value of the fellow non-ON eye was taken. Brain lesion volume, sex, age, disease duration, and history of disease-modifying treatment (1st or 2nd line disease-modifying treatments) were tested as covariables of the EDSS score. Results: EDSS values correlated with patient’s age (r = 0.543, p = 0.001), SC volume (r = −0.301, p = 0.034), and ganglion cell layer (GCL, r = −0.354, p = 0.012). Using these correlations, an ordinal regression model to express probability of diverse EDSS scores were designed, the highest of which was the most probable (Nagelkerke R2 = 43.3%). Using EDSS cutoff point of 4.0 in a dichotomous model, compared to a cutoff of 2.0, permits the inclusion of GCL as a disability predictor, in addition to age and SC. Conclusions: MS disability measured through EDSS is an age-dependent magnitude that is partly conditioned by SC and GCL. Further studies assessing paraclinical disability predictors are needed.

Double immune reconstitution therapy: Cladribine after alemtuzumab in the treatment of multiple sclerosis.

Alemtuzumab, a monoclonal anti-CD52 antibody, and cladribine, a purine nucleoside analogue, are used for the treatment of highly active relapsing-remitting multiple sclerosis (MS). Both are administered as two short yearly courses but possess the ability to induce long-term remission, labeling them as immune reconstitution therapies. Although disease activity after alemtuzumab administration is rare, there are a small number of people with MS who will experience disease activity despite repeated alemtuzumab treatment. We report on six patients with MS who experienced disease activity after alemtuzumab and were subsequently treated with cladribine and followed up for up to 2years. None of the patients experienced relapses during the follow-up period and in all patients Expanded Disability Status Scale values remained unchanged. All patients had lymphopenia at one time point. In patients 1 and 2, at the nadir, the lymphopenia was grade 1, in patient 3 it was grade 2 and in patients 5 and 6 it was grade 3. No infections or malignancies were recorded during the follow-up. This report provides a framework for treating people with MS with sequential immune reconstitution therapies.

Oxidative stress activity of fingolimod in multiple sclerosis

ObjectiveMultiple sclerosis (MS) is a demyelinating chronic inflammatory disease of the central nervous system (CNS). Recent studies have shown that oxidative stress plays an important role in MS pathogenesis. This study aimed to investigate the relationship between total oxidative stress (TOS) and total antioxidant capacity (TAC), which were reported to be effective in the pathogenesis of MS, and therapeutic efficacy of fingolimod used in the treatment of MS. Materials and methodsSerum TOS and total TAC levels of 25 patients with relapsing-remitting MS (RRMS) were measured before fingolimod treatment was initiated and in the third month of treatment and compared with those of 40 healthy individuals. Measurement of TOS activity was performed with TOS Assay Kit (Rel Assay Diagnostics, Turkey). Measurement of TAC activity was also performed with TAC Assay Kit (Rel Assay Diagnostics, Turkey). ResultsA statistically significant increase was observed in the TOS levels measured before fingolimod treatment in the patient group compared to the control group. The TOS levels measured in the third month of the treatment were found to decrease significantly compared to the pre-treatment TOS levels. An increase was observed in TAC levels after the treatment; however, no significant difference was found between the groups in terms of TAC levels. There was a positive correlation between the pre- and post-treatment Expanded Disability Status Scale (EDSS) scores and TOS values whereas no significant correlation was observed between the pre- and post-treatment EDSS scores and TAC values. ConclusionThe present study has revealed that fingolimod reduced oxidative stress. There was a positive correlation between the pre- and post-treatment EDSS and TOS values, which confirmed that there was a close correlation between the MS and oxidative stress. There are some limitations in this study. The small number of patients and the short follow-up times can be listed among these limitations. Our study does not contain a definitive answer to what is the mechanism of increased TOS in MS patients and how fingolimod reduces TOS levels. More detailed studies are needed on this subject.

Clinical Significance of Diffusion-weighted Magnetic Resonance Imaging on Treatment Efficacy in MS Patients With Acute Attacks.

Introduction:Despite various imaging methods, the accurate diagnosis of numerous neurodegenerative diseases remains controversial. Using advanced imaging techniques, like diffusion-weighted imaging, can help the early detection of Multiple Sclerosis (MS) and evaluation of the treatment efficacy in these patients.Methods:In total, 24 MS patients with acute attack and 30 healthy subjects were considered in our study. Region of Interest (ROI) was defined for acute and chronic plaques and Normal-Appearing White Matter (NAWM) in the patients’ group. In the normal group, ROI only was mapped in the white matter in the same regions of the patient. All MS patients were receiving Methylprednisolone for 3 to 5 days. The rate of clinical disability in these patients was also evaluated based on the Expanded Disability Status Scale (EDSS) index. Finally evaluate changes of ADC values of plaques and NAWM before and after treatment.Results:The Apparent Diffusion Coefficient (ADC) values of acute plaques, the ADC values of NAWM, the number of enhancement in T1w, and EDSS values suggested a significant difference after treatment compared to before treatment. However, the ADC values of chronic plaques revealed no significant difference after treatment. There was a significant positive correlation between the difference in EDSS values before and after treatment.Conclusion:The study results demonstrated that using diffusion technique and ADC values analysis is a proper non-invasive method for MS diagnosis and evaluating treatment efficacy in these patients.HighlightsThe obtained results suggested that the mean ADC for acute plaques and normal white matter significantly decreased after methylprednisolone treatment.Our study indicated a strong correlation between variations in EDSS, the mean ADC for acute plaques, and normal white matter.The collected results indicated that the number of enhanced plaques decreased after treatment. Besides, there was a positive correlation between its variations and EDSS.Plain Language SummaryMultiple Sclerosis (MS) is a common inflammatory disorder of the central nervous system that could result in physical and mental disabilities in patients. Disease progression usually manifests as a series of attacks. Although there is no proven cure for MS, different treatment strategies aim to modify the cause of the disease, manage its symptoms, and prevent and postpone disability. The most common therapy in acute attacks is using corticosteroid drugs. In addition to the treatment, evaluating the success rate of treatment was also challenging. Historically, clinical assessments method (e.g. EDSS) have been used as the baseline for measuring the therapy’s efficiency. Several supplementary methods, including imaging techniques, are introduced to address this issue. Conventional MRI imaging with injection has been widely accepted to assess the treatment. However, because of the modest sensitivity of conventional MRI to detect subtle pathological changes, there is a poor correlation between its findings and patients’ disability. This study moved from conventional MRI to advanced techniques, such as DWI and its quantitative index named ADC value. This technique can provide information about microstructural changes in MS patients. This method does not require injection, so there are no probable adverse effects and lower scan time. This study emphasizes changes in ADC value and EDSS before and after treatment with methylprednisolone. Our results suggested s that ADC values and EDSS after treatment are significantly different from their typical values. ADC values can be used as a biomarker to evaluate treatment efficiency, yet it is not objective enough to use it alone. So, the combination of DWI imaging with conventional methods might be beneficial in assessing treatment efficiency in MS patients.

Prediction of disease progression and outcomes in multiple sclerosis with machine learning

Multiple Sclerosis is a chronic inflammatory disease, affecting the Central Nervous System and leading to irreversible neurological damage, such as long term functional impairment and disability. It has no cure and the symptoms vary widely, depending on the affected regions, amount of damage, and the ability to activate compensatory mechanisms, which constitutes a challenge to evaluate and predict its course. Additionally, relapsing-remitting patients can evolve its course into a secondary progressive, characterized by a slow progression of disability independent of relapses. With clinical information from Multiple Sclerosis patients, we developed a machine learning exploration framework concerning this disease evolution, more specifically to obtain three predictions: one on conversion to secondary progressive course and two on disease severity with rapid accumulation of disability, concerning the 6th and 10th years of progression. For the first case, the best results were obtained within two years: AUC=0.86pm 0.07, sensitivity=0.76pm 0.14 and specificity=0.77pm 0.05; and for the second, the best results were obtained for the 6th year of progression, also within two years: AUC=0.89pm 0.03, sensitivity=0.84pm 0.11, and specificity=0.81pm 0.05. The Expanded Disability Status Scale value, the majority of functional systems, affected functions during relapses, and age at onset were described as the most predictive features. These results demonstrate the possibility of predicting Multiple Sclerosis progression by using machine learning, which may help to understand this disease’s dynamics and thus, advise physicians on medication intake.

Experience with cladribine tablets for highly active multiple sclerosis in everyday clinical practice

Cladribine tablets are a new drug for the immune reconstitution therapy of highly active multiple sclerosis (HAMS). After discussing the characteristics of action of the drug in clinical trials, the authors give their own experience of its use in the Moscow Multiple Sclerosis Center.Objective: to assess their own experience with cladribine tablets in the treatment of HAMS patients in everyday clinical practice.Patients and methods: In 2018–2020, a total of 14 patients with HAMS and an average exacerbation frequency of 2.42 per year (34 exacerbations) received a full cycle of cladribine therapy. The patients independently purchased the drug for individual indications. Prior to starting therapy and every subsequent 6 months, all the patients underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain, cervical and thoracic spine, and chest X-ray, Expanded Disability Status Scale (EDSS) scoring, clinical blood analysis, lymphocyte subpopulation estimation, biochemical blood analysis. The levels of leukocytes, lymphocytes, and lymphocyte subpopulations were estimated after one- and two-year cladribine tablet therapy cycles.Results and discussion. During a two-year cladribine tablet therapy cycle, there were only 2 exacerbations (0.1 per year); the EDSS values stabilized, while they slightly decreased; according to MRI, the number of foci declined substantially from 78 (an average of 3.12 per image) before treatment to 6 (an average of 0.2 per image) after 2 years of treatment. No serious adverse events were recorded in patients taking cladribine tablets. By the end of the first year of treatment, the level of lymphocytes returned to normal in all the patients. The similar picture was noted after the second cycle of therapy. More than two-thirds of patients showed a decline in CD19+ B lymphocytes. An anti-B-cell effect was recorded even in patients who had normal absolute lymphocyte counts, as shown by clinical blood analysis. The findings demonstrated the efficacy and safety of cladribine tablets in patients with HAMS.Conclusion. Cladribine tablets are a highly effective treatment for HAMS.

Effectiveness and Adverse Events of Use of Natalizumab in a Brazilian Cohort of Patients With Multiple Sclerosis

PurposeNatalizumab (NTZ) is a monoclonal antibody with confirmed efficacy in white populations with recurrent-remitting multiple sclerosis (RRMS); there are few studies, however, in mixed-race populations. Real-world studies of NTZ are needed to better understand the drug's effectiveness. This study evaluated the effectiveness and adverse events of NTZ in a cohort of Brazilian patients with MS, as well as the impact of clinical and demographic factors on patient response to treatment. MethodsThis multicenter, Brazilian observational study was conducted from January 2011 until December 2016 and included patients with RRMS (McDonald criteria 2005 and 2010) aged ≥18 years treated with NTZ for at least 3 months. Demographic, clinical, and radiologic data were obtained from medical records and during follow-up visits. The primary outcomes investigated were the absolute number of relapses and annualized rate of relapses, change in Expanded Disability Status Scale value, and presence of new lesions on magnetic resonance imaging after starting NTZ treatment; the occurrence and type of adverse events were also analyzed. In addition, the impact of demographic and clinical prognostic factors and radiologic activity on the effectiveness of NTZ was measured. Descriptive and univariate statistical analyses used a significance level of P < 0.05. ResultsThe study enrolled 56 patients; 64% were women, and 36% were of African descent. There was a significant reduction in the mean absolute number (P = 0.001) and in the annualized rate (P = 0.001) of relapses and in the radiologic activity of the disease (P = 0.001). Furthermore, 71% of patients showed no increase in Expanded Disability Status Scale score after 1 year of treatment. The effectiveness of NTZ was not associated with the presence of clinical and demographic prognostic factors, and the most frequent adverse events during the use of NTZ were gastrointestinal symptoms; there were no cases of progressive multifocal leukoencephalopathy. ImplicationsAccording to patients' reports and clinicians’ observations regarding clinical and radiologic benefits and tolerability to adverse events, the use of NTZ was favorable in this Brazilian MS cohort, regardless of the presence of unfavorable prognostic factors.

PREDICTION OF MULTIPLE SCLEROSIS COURSE: RESULTS OF PROSPECTIVE STUDY

Background: The course of multiple sclerosis is variable and unpredictable. Despite considerable efforts and research over the decades, one of the major challenges for both neurologists and patients is still to determine the prognosis of multiple sclerosis as well as the factors and markers affecting its progression. Prospective studies can partially contribute to assessment of the factors predetermining the prognosis of the course of multiple sclerosis.&#x0D; Objective: To evaluate the factors affecting the course of multiple sclerosis according to a 5-year prospective dynamic observation.&#x0D; Materials and methods: 175 patients with multiple sclerosis were examined over a 5-year follow-up period. The methodology employed was as follows: statistical analysis by using Microsoft Excel for Windows and SPSS; standard descriptive statistics; calculation of Pearson's chi-square for categorical analysis; single-factor analysis of variance. The magnitude and directivity of the correlation dependence were estimated using the Spearman non-parametric correlation coefficient.&#x0D; Results: 175 patients with multiple sclerosis (123 women and 52 men) were examined over a 5-year follow-up period. Mean age of patients at the onset of multiple sclerosis was 28.46 ± 9.13 years; mean age at the time of diagnosis of the disease was 31.77 ± 9.28 years; the mean length of the disease was 15.48 ± 7.69 years prior the start of the observation. At the time of the patients’ status assessment in 2013, the Expanded Disability Status Scale value was 3.83 ± 1.68 scores and 4.21 ± 1.83 scores in 5 years. The degree of functional disability according to the Expanded Disability Status Scale baseline was statistically significant (p = 0.02). A single-factor analysis of variance showed that sex (p &lt;0.007) was of the highest significance for the degree of difference by the Expanded Disability Status Scale.&#x0D; Conclusions: According to results obtained, we can suggest the most influential factor for a patient's disability due to multiple sclerosis is sex. Men may develop multiple sclerosis at younger age, the disease in men progresses faster, thus, the degree of functional disability is higher compared with women.

Time between expanded disability status scale (EDSS) scores

BackgroundAlthough the expanded disability status scale (EDSS) is the most commonly used measure of disability for multiple sclerosis, measurement of disability accumulation is complex due to the unequal steps of the scale. ObjectiveTo estimate the time between EDSS scores in a large MS cohort from a single center and determine the impact of functional system scores on EDSS transitions. Methods31,394 clinical visits with EDSS scores from 2054 subjects in the CLIMB longitudinal cohort study were included in our analysis. The time to each EDSS score and the time between each EDSS score were calculated using the nonparametric maximum likelihood estimate for interval censored data. For each initial EDSS value, the association between functional status scores and subsequent EDSS value was assessed using a mixed effects linear regression model, and the association with time to EDSS increase was assessed using a Cox proportional hazards model. ResultsThe median time until EDSS 2, 3, 4, 5 and 6 in all subjects were 4.8, 15.1, 28.2, 31.2, and 32.4 years, respectively. The time intervals showed that the disability accumulation intervals from EDSS 4 to 6 were much shorter than the accumulation intervals from EDSS 0 to 3 or from EDSS 6 to 8. For EDSS of 1 or 1.5, pyramidal, cerebellar, sensory, bowel-bladder and mental system scores were associated with higher subsequent EDSS values. For higher EDSS values, only pyramidal and bowel-bladder scores maintained the association. ConclusionsTime between specific EDSS levels varies considerably. Certain functional system scores have greater predictive power for future EDSS-related disability despite same present EDSS level. These findings will assist in adaptation of the EDSS as an outcome measure to assess MS-related disability in clinical trials.

Determination of the levels of fatigue, pain, functional independence and quality of life in people with multiple sclerosis (MS) compared to non-MS individuals: use of standard psychometric tests on a small number of subjects

Aim: Using standard psychometric tests to determine the level of fatigue, pain, functional independence and quality of life in people with multiple sclerosis (MS) compared to non-MS people on a small number of subjects, and establish the correlation between fatigue and pain with perceived quality of life related to fatigue, pain, emotional and physical functioning. Patients and Methods: A group of people with MS (N = 17), predominantly female gender, 21-70 years old, EDSS (Expanded Disability Status Scale) values from 0.0 to 8.0 without relapse and corticosteroid therapy for the past 4 weeks and without severe chronic illnesses, was subjected to the following tests: Barthel Index, Functional Independence Measure, Visual Analogue Scale, Modified Fatigue Impact Scale and Medical Outcomes Study 36-Item Short-Form Health Survey. The control group (N = 17) without severe acute and chronic illnesses was also subjected to the same tests. Results: Statistically significant differences between the groups (P <0.05 - P <0.001) and statistically significant (P <0.05) correlation between fatigue level and perceived quality of life related to fatigue and the absence of link between pain level and perceived quality of life related to pain. The correlations between fatigue and pain level and the quality of life-related physical functioning has been statistically significant (P <0.05), unlike the correlation with the quality of life associated with emotional functioning. Conclusion: The selected combination of psychometric tests showed clear differences in the level of fatigue, pain, functional independence and quality of life in MS patients compared to non-MS people on a small number of subjects and established a correlation between fatigue level with perceived quality of life related to fatigue and also fatigue and pain levels with the quality of life associated with physical functioning.

Association of Prognostic Factors and Immunosuppressive Treatment With Long-term Outcomes in Neurosarcoidosis

Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear. To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS. In this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years). All neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015). The 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months. This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy

ObjectiveTo evaluate the effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder (NMOSD) during pregnancy. MethodsSixteen NMOSD patients who had at least one pregnancy after NMOSD onset were enrolled. The patients were divided into two groups according to whether they received immunosuppressive therapy during pregnancy. The annual relapse rate (ARR) before pregnancy (BP); during the first (DP1), second (DP2), and third trimesters (DP3); first trimester postpartum (PP1); and second trimester postpartum (PP2) were calculated. The Expanded Disability Status Scale (EDSS) was used to evaluate the degree of disability. Pregnancy outcomes were recorded and the children were followed up and their health condition was evaluated. ResultsIn the group taking prednisone alone or in combination with azathioprine as immunosuppressive therapies, there was no difference among ARRs of each period (DP1, DP2, DP3, PP1, PP2) and BP. Compared with EDSS BP, EDSS increased slightly 6months postpartum with no statistical significance (p=0.102). In the group without immunosuppressive therapy, ARR increased during PP1 (p=0.014) and EDSS increased 6months postpartum as compared to BP (p=0.017). Moreover, the added EDSS value was higher in the group without immunosuppressive therapy than in the group with therapy (p=0.038). In 22 pregnancies from 16 patients, 16 pregnancies ended in live births and 6 pregnancies ended in abortions, including 2 spontaneous and 4 induced abortions. None of the children had congenital diseases or malformations. There were no records of abnormal growth among the children during 6months to 12years of follow-up. ConclusionUntreated women showed a propensity for disease relapse in PP1 and increased degree of disability postpartum. Immunosuppressive therapy during pregnancy and postpartum period can reduce the risk of relapse and degree of disability. Immunosuppressive therapy with low-dose prednisone was relatively safe. However, the safety of azathioprine during pregnancy remains unclear and needs future reevaluation.