Factors associated with the progression of disability (EDSS) among MS patients

Mental Disorders in Mexican Patients With Multiple Sclerosis

Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS

Background and Objectives: We aimed to determine the link between brain volumetry results and functional disability calculated using the Expanded Disability Status Scale (EDSS) among multiple sclerosis (MS) patients in relation to the provided treatment (disease-modifying therapies (DMTs)) during a 5-year follow-up period. Materials and Methods: A retrospective cohort study was performed enrolling 66 consecutive patients with a confirmed diagnosis of MS, predominantly females (62% (n = 41)). Relapsing-remitting (RR) MS was noted in 92% (n = 61) of patients, with the rest being patients with secondary progressive (SP) MS. The mean age was 43.3 years (SD 8.3 years). All patients were evaluated clinically using the EDSS and "FreeSurfer© 7.2.0" radiologically during a 5-year follow-up. Results: A significant increase in patient functional disability was noted, calculated using the EDSS during a 5-year follow-up. The baseline EDSS ranged between 1 and 6 with a median of 1.5 (IQR 1.5-2.0), and after 5 years, the EDSS was between 1 and 7, with a median EDSS of 3.0 (IQR 2.4-3.6). Compared with RRMS patients, SPMS patients demonstrated a significant increase in EDSS score during a 5-year period, with a median EDSS of 2.5 in RRMS patients (IQR 2.0-3.3) and 7.0 (IQR 5.0-7.0) among SPMS patients. Significantly lower brain volumetry results in different brain areas were found, including cortical, total grey and white matter, p < 0.05. Statistically significant differences were observed between baseline volumetry results of the hippocampus and the middle anterior part of the corpus callosum and their volumetry results after 5 years, p < 0.001. In this study population, the thalamus did not demonstrate significant changes in volumetry results during follow-up, p > 0.05. The provided treatment (DMTs) did not demonstrate a significant impact on the brain MRI volumetry results during a 5-year follow-up, p > 0.05. Conclusions: Brain MRI volumetry seriously impacts the early detection of brain atrophic changes. In this study, significant relationship between brain magnetic resonance volumetry results and disability progression among MS patients with no important impact of the provided treatment was described. Brain MRI volumetry may aid in the identification of early disease progression among MS patients, as well as enrich the clinical evaluation of MS patients in clinical patient care.

BackgroundFunctional biomarkers able to identify multiple sclerosis (MS) patients at high risk of fast disability progression are lacking. The aim of this study was to evaluate the ability of multimodal (upper and lower limbs motor, visual, lower limbs somatosensory) evoked potentials (EP) to monitor disease course and identify patients exposed to unfavourable evolution.MethodsOne hundred MS patients were assessed with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) at baseline (T0) and about 6 years later (T1). The Spearman correlation (rS) was used to evaluate the relationship between conventional EP scores and clinical findings. Multiple (logistic) regression analysis estimated the predictive value of baseline electrophysiological data for three clinical outcomes: EDSS, annual EDSS progression, and the risk of EDSS worsening.ResultsIn contrast to longitudinal correlations, cross-sectional correlations between the different EP scores and EDSS were all significant (0.33 ≤ rS < 0.67, p < 0.001). Baseline global EP score and EDSS were highly significant predictors (p < 0.0001) of EDSS progression 6 years later. The baseline global EP score was found to be an independent predictor of the EDSS annual progression rate (p < 0.001), and of the risk of disability progression over time (p < 0.005). Based on a ROC curve determination, we defined a Global EP Score cut off point (17/30) to identify patients at high risk of disability progression illustrated by a positive predictive value of 70 %.ConclusionThis study provides a proof of the concept that electrophysiology could be added to MRI and used as another complementary prognostic tool in MS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0608-1) contains supplementary material, which is available to authorized users.

To study the relationship between retinal nerve fiber layer (RNFL) thickness and brain atrophy using magnetic resonance imaging (MRI) with bicaudate ratio (BCR) in patients with multiple sclerosis (MS) with different levels of disease severity. We also assessed whether RNFL thickness correlated with Expanded Disability Status Scale (EDSS) score. The participants consisted of 88 patients with MS and 59 age- and sex-matched healthy control subjects. Eleven patients had clinically isolated syndrome (CIS), 68 patients had relapsing-remitting MS (RR-MS), and 9 patients had secondary progressive MS. Patients and controls were evaluated using optical coherence tomography (OCT, Cirrus) and scanning laser polarimetry with variable corneal compensation (GDx VCC). Patients underwent the same brain MRI scanning protocol. Disability was evaluated according to the EDSS. The BCR was calculated by dividing the minimum intercaudate distance by brain width along the same level. The BCR was higher in patients with MS (0.12 ± 0.03) than in controls (0.08 ± 0.009) (P < 0.001). OCT average RNFL thickness in patients with MS was significantly lower (84.51 ± 14.27 μm) than in control subjects (98.44 ± 6.83 μm). BCR was correlated with OCT average RNFL thickness (r = -0.48, P = 0.002) in patients with MS without optic neuritis. Significant correlations were found between average RNFL thickness and EDSS (r = -0.43, P = 0.003). Additionally, there were correlations between BCR with GDx parameters in patients with MS without optic neuritis. This study shows that RNFL thickness correlates with BCR and with MS subtypes. Additionally, our study indicates that OCT is better suited for MS assessment than GDx. We conclude that the damage of retinal axons appears related to brain damage in patients with MS.

Characteristics of COVID-19 disease in multiple sclerosis patients

Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients. Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results. Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration &gt; 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0. Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.

The effects of the MTHFR 677C>T (rs1801133) genetic variant on susceptibility and disability worsening in multiple sclerosis patients are mediated by homocysteine

Discontinuation of disease modifying therapies is associated with disability progression regardless of prior stable disease and age

Background:In multiple sclerosis (MS), an increase in whole-brain lesion volume (LV) on MRI can be observed even in the absence of newly demarcated focal lesions or clinical relapses. However, it is unknown whether the presence of increasing LV alone is enough to justify changes in the therapeutic regimen. At this point, blood-based biomarkers may aid to identify patients at risk for progression.Objective:To determine the prognostic value of blood-based biomarkers (serum neurofilament (sNfL) and serum glial fibrillary acidic protein (sGFAP)) on disability progression in MS patients without newly demarcated lesions or clinical relapses.Design:Longitudinal cohort study.Methods:In total, out of 291 MS patients who were retrospectively screened for this study, 171 patients underwent a detailed clinical and MRI assessment and were finally included in the analysis: 100 patients with increasing LV (mean baseline Expanded Disability Status Scale (EDSS) = 1.5) and 71 with stable LV over 2 years (mean baseline EDSS = 1.0). Baseline blood-based measures (sNfL and sGFAP) and MRI metrics (total T2-weighted LV, gray matter (GM) volume) were acquired. EDSS worsening served as a clinical outcome measure and was determined through a 2-year follow-up. Receiver operator characteristic analyses were conducted to determine the predictive discriminative power of both blood-based biomarkers. Multivariate logistic regressions were performed to identify independent risk factors for EDSS progression in both cohorts.Results:MS patients with increasing LV had lower GM volume (p = 0.0109, q = 0.0490) and worse EDSS scores (p = 0.0065, q = 0.0650) at clinical follow-up compared to patients with stable LV. Patients with increasing LV and EDSS progression had significantly higher sNfL (p = 0.0049, q = 0.0196), but not sGFAP (p = 0.7425, q = 0.9900) levels. In the logistic regression model, sNfL levels remained an independent risk factor for EDSS progression in patients with increasing LV (odds ratio = 1.344, 95% confidence interval: 1.038–1.739, p = 0.025), but not in patients with stable LV. Finally, in patients with increasing LV, sNfL levels, but not sGFAP levels, discriminated progressive from non-progressive MS patients upon clinical follow-up (area under the curve = 0.67, p = 0.004; q = 0.016).Conclusion:sNfL enhances the prediction of disease progression in MS patients with merely increasing LV on MRI but no new T2 lesions or other signs of inflammatory activity. These findings may support treatment decisions in seemingly stable patients.

Background: Multiple sclerosis (MS) is known as chronic inflammatory causes demyelination and results in neurodegenerative disease in central nervous system (CNS), which is known with progressive disability. MS is accepted and is a multifactorial disorder that is a result of genetic and environmental factors interaction. The set of genes coding for MHC (major histocompatibility complex) molecules exert the effect on disease development. HLA-A*03 (HLA-A3) is one of HLA class I alleles, which is associated with MS. Objectives: Our goal is to survey the frequency of this allele in MS patients from the Khuzestan province. Methods: HLA-A*03 alleles association was investigated in 200 MS patients in the province of Khuzestan then compared with 195 healthy controls. HLA-typing was performed by polymerase chain reaction (PCR) amplification with SSP-PCR method. Results: Frequency of HLA-A*03 was significant among MS patients (47% vs. 26%, P < 0.001). There was no significant correlation among this allele and sex, course of disease, initial symptoms, and expanded disability status scale (EDSS). Conclusions: Our findings suggested that HLA-A*03 allele has a significant association with MS, which is in line with other studies, and also confirmed that the presence of this allele could increase the risk of MS. Furthermore, positive association between the HLA-A*03 allele and the Arab population in the province of Khuzestan was found. CIS patients followed up for three years demonstrated that all patients were converted to RRMS.

PND10 The Disability Progression of Multiple Sclerosis Progressive Course: A Markov MODEL Approach

This study investigates the application of texture analysis methods on brain T2-white matter lesions detected with magnetic resonance imaging (MRI) for the prognosis of future disability in subjects diagnosed with clinical isolated syndrome (CIS) of multiple sclerosis (MS). Brain lesions and normal appearing white matter (NAWM) from 38 symptomatic untreated subjects diagnosed with CIS as well as normal white matter (NWM) from 20 healthy volunteers, were manually segmented, by an experienced MS neurologist, on transverse T2-weighted images obtained from serial brain MR imaging scans (0 and 6-12 months). Additional clinical information in the form of the Expanded Disability Status Scale (EDSS), a scale from 0 to 10, which provides a way of quantifying disability in MS and monitoring the changes over time in the level of disability, were also provided. Shape and most importantly different texture features including GLCM and laws were then extracted for all above regions, after image intensity normalization. The findings showed that: (i) there were significant differences for the texture futures extracted between the NAWM and lesions at 0 month and between NAWM and lesions at 6-12 months. However, no significant differences were found for all texture features extracted when comparing lesions temporally at 0 and 6-12 months with the exception of contrast (gray level difference statistics-GLDS) and difference entropy (spatial gray level dependence matrix-SGLDM); (ii) significant differences were found between NWM and NAWM for most of the texture features investigated in this study; (iii) there were significant differences found for the lesion texture features at 0 month for those with EDSS≤2 versus those with EDSS>2 (mean, median, inverse difference moment and sum average) and for the lesion texture features at 6-12 months with EDSS>2 and EDSS≤2 for the texture features (mean, median, entropy and sum average). It should be noted that whilst there were no differences in entropy at time 0 between the two groups, significant change was observed at 6-12 months, relating the corresponding features to the follow-up and disability (EDSS) progression. For the NAWM, significant differences were found between 0 month and 6-12 months with EDSS≤2 (contrast, inverse difference moment), for 6-12 months for EDSS>2 and 0 month with EDSS>2 (difference entropy) and for 6-12 months for EDSS>2 and EDSS≤2 (sum average); (iv) there was no significant difference for NAWM and the lesion texture features (for both 0 and 6-12 months) for subjects with no change in EDSS score versus subjects with increased EDSS score from 2 to 5 years. The findings of this study provide evidence that texture features of T2 MRI brain white matter lesions may have an additional potential role in the clinical evaluation of MRI images in MS and perhaps may provide some prognostic evidence in relation to future disability of patients. However, a larger scale study is needed to establish the application in clinical practice and for computing shape and texture features that may provide information for better and earlier differentiation between normal brain tissue and MS lesions.

<h3>Objective:</h3> To use Rasch analysis to create a linear, validated scale of patient-reported outcomes to measure disability in multiple sclerosis (MS). <h3>Background:</h3> Measuring disability progression in MS is vital to patient management and clinical research. The gold-standard in MS is the Expanded Disability Status Scale (EDSS). However, it has significant limitations. Patient-reported outcomes (PROs) are a promising additional measurement of MS disability progression. Data on validity are lacking. We aim to create a linear, validated scale measuring MS disability by analyzing patient responses to a preliminary PRO using Rasch analysis. We compare our findings to the EDSS and MS functional composite (MSFC). <h3>Design/Methods:</h3> Participants aged 18 – 65 with all MS subtypes are recruited from the Atlanta VA and Emory MS Clinics. A preliminary questionnaire with 140 questions, EDSS, and MSFC are administered. Participants complete a post-visit questionnaire within 7 days for test-retest reliability. Rasch analysis will be performed on questionnaire data and items will be removed based on fit. Correlational analyses with EDSS and MSFC are performed. We will recruit 250 participants. <h3>Results:</h3> 44 participants have completed the preliminary questionnaire. The mean (SD) age is 50.1 (10.2) with 68.2% females and 31.8% males. 54.6% of participants self-identified as black, 43.2% white and 2.3% mixed. 50% receive anti-CD20 therapy. Median EDSS score is 3.75 with a range of 1.0–7.0 and mean MSFC score is −1.75 (2.7). Total questionnaire score correlated moderately with EDSS (r=0.69) and less with MSFC (r=−0.34). Test-retest reliability studies strongly correlate (n=27, r= 0.95). Rasch analysis data will follow. <h3>Conclusions:</h3> Our sample represents a wide range of demographics, disability, and treatments and is similar to published MS cohorts. Preliminary analysis demonstrated good construct validity compared to EDSS and reliable test-retest. This linear scale may aid in monitoring disability progression in MS patients. <b>Disclosure:</b> Ms. Azad has nothing to disclose. Dr. Tarr has nothing to disclose. Dr. Fournier has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Journals. The institution of Dr. Fournier has received research support from Veterans Affairs. The institution of Dr. Fournier has received research support from Department of Defense. The institution of Dr. Fournier has received research support from Amylyx. The institution of Dr. Fournier has received research support from Biogen. The institution of Dr. Fournier has received research support from MT Pharma. The institution of Dr. Tyor has received research support from NIH. The institution of Dr. Tyor has received research support from VHA. The institution of Dr. Tyor has received research support from NIH. The institution of Dr. Tyor has received research support from VHA. The institution of Dr. Tyor has received research support from NIH.

Disability improvement in the first case treated by Natalizumab in Libya