Retinal measurements predict 10‐year disability in multiple sclerosis

Background: Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research. Objective: To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner. Methods: Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician. EDSS and tele-EDSS scores were compared. Results: Overall, 41 adults participated (mean (standard deviation (SD)) age: 47.0 years (11.6); median EDSS: 2 (range: 0–7)); 37 required no in-home assistance for the tele-EDSS evaluation (e.g. help positioning camera). Mean difference between EDSS and tele-EDSS was 0.34 (95% confidence interval (CI): 0.07–0.61). For 88% of evaluations, tele-EDSS and EDSS scores were within 1 point (similar to reported in-person inter-rater differences). Unweighted kappa for agreement within 0.5 point was 0.72. Correlation for individual functional systems (FS) ranged from modest (vision: 0.37) to high (bowel/bladder: 0.79). Overall correlation between EDSS and tele-EDSS was 0.89 (p < 0.0001); and 0.98 (p < 0.0001) at EDSS range: 4–7. Conclusion: In this proof of principle study, disability evaluation in mild to moderate MS is feasible using telemedicine without an aide at the patient’s location.

In a retrospective multicentre cohort study, we explored the association between brain atrophy and multiple sclerosis (MS) disability using different MRI scanners and protocols at multiple sites. Relapse-onset MS patients were included if they had two clinical MRIs 12 months apart and ≥2 Expanded Disability Status Scale (EDSS) scores. Percentage brain volume change (PBVC), percentage grey matter change (PGMC), fluid-attenuated inversion recovery (FLAIR) lesion volume change, whole brain volume (BV), grey matter volume (GMV), FLAIR lesion volume and T1 hypointense lesion volume were assessed by icobrain. Disability was measured by EDSS scores and 6-month confirmed disability progression (CDP). Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. 93% of patients were on treatment and mean PBVC was -0.26% (±0.52). During the median follow-up of 2.8 years from the second MRI, median EDSS change was 0.0 and 12% patients experienced 6-month CDP. Cross-sectional BV and GMV at the later MRI showed a trend for association with CDP (HR 0.99; 95% CI 0.98 to 1.00; p=0.06). Only BV at the later MRI was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (β -0.001, SE 0.0003, p=0.02). There was no association between longitudinal PBVC or PGMC and CDP or EDSS (p>0.05). In this highly treated MS cohort with low disability accrual, only cross-sectional BV showed an association with future EDSS scores, while no MRI metric predicted 6-month CDP. These findings highlight the limitations of current clinical MRI measures in predicting disability worsening in real-world settings.

Disability measurement in Multiple Sclerosis patients 55 years and older: What is the Expanded Disability Status Scale really telling clinicians?

Multiple sclerosis (MS)-related disability in Hispanic people with MS is associated with inequities in social determinants of health (SDOH) as measured by composite indices of areal-level census data. Studies of individual-level measures of SDOH are lacking. This study examined the separate and joint effects of person-centered SDOH indicators and an area-level composite on MS disability measures. Hispanic people diagnosed with MS (≤5 years) who had SDOH and Social Deprivation Index (SDI) based on 2015-2019 American Community Survey estimates were included. At study entry, data on MS disability outcomes were collected: Expanded Disability Status Scale (EDSS) score, Symbol Digit Modality Test (SDMT) score, Hauser Ambulation Index (HA index), and 25-Foot Walk Time (25FWT). Principal component analysis was used to identify person-centered SDOH factors, mapped across a socioecological model. Multivariable regression modeling measured separate and joint effects of SDOH principal components (PCs) and SDI on outcome measures. Of the 170 participants with MS, most were women (71.9%) and had a mean age at first symptom of 34.01 (SD ±11.24) years and at diagnosis of 36.27 (SD ±10.68) years. The top 2 PCs were identified to represent person-centered SDOH related to assimilation and socioeconomic disadvantage in multivariable models. In both separate and joint effect models, both PC1 and PC2 were significantly associated with longer 25FWT (β 0.43, 95% CI 0.04-0.82, and β 0.66, 95% CI 0.28-1.05), higher HA index (β 0.22, 95% CI 0.04-0.41, and β 0.31, 95% CI 0.12-0.51), and higher EDSS score (β 0.39, 95% CI 0.16-0.62, and β 0.36, 95% CI 0.13-0.60). PC1 was also significantly associated with a lower SDMT score (β -4.15, 95% CI -5.60 to -2.69). SDI was significantly associated with lower SDMT score and higher HA index in separate effect models but was not associated with any outcome measure in joint effect models with PCs. Our findings suggest that census-based indicators may underestimate the effect of SDOH on MS outcomes and the person-centered level measures are better markers of disease severity in Hispanic people with MS. Future research and policy change can focus on the amelioration of assimilation barriers and socioeconomic disadvantage because these were strongly associated with MS-related ambulatory and cognitive disability.

This meta-analysis systematically explored predictive factors for the progression of multiple sclerosis (MS). Computerized searches were conducted in Pubmed, OVID, Web of science, Willey Library, and EMbase from inception to August 2023. Patients with MS were divided into the deterioration group, defined as those with an increase in the Expanded Disability Status Scale (EDSS) score of ≥ 1.0 for a baseline EDSS ≤ 5.5 or ≥ 0.5 for a baseline EDSS > 5.5 during the follow-up period, and the non-deterioration group, comprising patients who exhibited no significant changes in EDSS over the same period. This study analyzed the impact of specific predictors, including age at onset, sex (male), smoking status, disease duration, number of relapses, EDSS score, prodromal neurological symptoms, and the use of disease-modifying therapies (DMTs) on MS progression. Of 3647 retrieved, 14 studies were finally included. Meta-analysis showed that sex (male) [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.05-1.26, P < 0.01], smoking [OR = 1.92, 95%CI: 1.41-2.60, P < 0.01], relapses frequency [OR = 1.05, 95%CI: 1.02-1.08, P < 0.01], EDSS score [OR = 1.54, 95%CI: 1.10-2.15, P = 0.01], and DMTs use [OR = 0.38, 95%CI: 0.26-0.55, P < 0.01] significant influenced MS progression, while age at onset, disease duration, and prodromal neurological symptoms were not significant. Sex (male), smoking, a higher number of relapses, EDSS score, and DMTs are predictors of MS deterioration. Hence, particular attention should be given to these risk factors when assessing MS deterioration.

Objective: Identify relapsing multiple sclerosis (RMS) patients with aggressive disease characterized by rapid disability progression. Background Criteria for identifying RMS patients with aggressive disease, which would be useful for clinical decision making and trial design, are currently unavailable. Design/Methods: The Multiple Sclerosis Collaborative Research Group (MSCRG) study was a phase 3, double-blind, placebo-controlled trial of intramuscular interferon beta-1a (IM IFNβ-1a) in patients with RMS. Patients received IM IFNβ-1a 30 μg or placebo once weekly for up to 2 years. Patients were required to have a baseline Expanded Disability Status Scale (EDSS) score of 1.0–3.5. Patients with a ≥2.0-point increase in EDSS score resulting in a score ≥4.0 by study end were considered to have aggressive RMS. The risk of a poor long-term outcome, defined as an EDSS score ≥8.0 at 8 years of follow-up, was calculated as an odds ratio from a logistic regression model comparing patients with and without aggressive RMS. Results: Few patients (n=39) had EDSS ≥4.0 over 2 years. Only 25 patients met the criteria for aggressive RMS. Among these patients, mean disease duration was 5.1±3.85 years, mean baseline age was 37.2±6.35 years, and mean baseline EDSS was 2.8±0.74. More patients in the placebo group (22%) than in the IM IFNβ-1a group (7%) met the criteria for aggressive RMS at 2 years ( P =0.0072). Thirteen patients reached the EDSS milestone of 8.0 (severe disability) by the end of the 8-year follow-up. The odds ratio for attaining severe disability was 31.4 (95% confidence interval, 7.7–127.8; P Conclusions: The proposed definition for aggressive RMS characterized by rapid EDSS progression appeared to be useful in identifying patients at high risk for a more severe long-term disease course with greater accumulation of physical disability. Supported by: Biogen Idec Inc. Disclosure: Dr. Scott has received personal compensation for activities with Novartis, Biogen Idec, Teva Neuroscience, and Genzyme as a consultant or speaker. Dr. Scott has received research support from the Pittsburgh Foundation. Dr. Laforet has received personal compensation for activities with Biogen Idec Inc. as an employee.Dr. Laforet holds stock and/or stock options in Biogen Idec Inc., which sponsored research in which Dr. Laforet was involved as an investigator. Dr. You has received personal compensation for activities with Biogen Idec as an employee.

Determination of disability progression in moderately and highly disabled ambulatory patients with relapsing-remitting multiple sclerosis using the EDSS-Plus: A prospective study in Argentina.

Nine Hole Peg Test asymmetry in refining upper limb assessment in multiple sclerosis

Multiple sclerosis is an autoimmune disorder resulting in progressive neurologic disability. Our aim was to evaluate the associations between diffusional kurtosis imaging-derived metrics for the corticospinal tract and disability in multiple sclerosis. Forty patients with MS underwent brain MR imaging including diffusional kurtosis imaging. After we masked out T2 hyperintense lesions, the fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, mean kurtosis, radial kurtosis, and axial kurtosis were estimated for the corticospinal tract. Disability was quantified by using the Expanded Disability Status Scale at the time of MR imaging and 12 months post-MR imaging. The Pearson correlation coefficient and linear regression analyses were conducted to evaluate the associations between diffusion metrics and disability. Significant correlations were found between the Expanded Disability Status Scale scores during the baseline visit and age (r = 0.47), T2 lesion volume (r = 0.38), corticospinal tract mean diffusivity (r = 0.41), radial diffusivity (r = 0.41), axial diffusivity (r = 0.34), fractional anisotropy (r = -0.36), and radial kurtosis (r = -0.42). Significant correlations were also found between the Expanded Disability Status Scale scores at 12-month follow-up and age (r = 0.38), mean diffusivity (r = 0.45), radial diffusivity (r = 0.41), axial diffusivity (r = 0.45), mean kurtosis (r = -0.42), radial kurtosis (r = -0.56), and axial kurtosis (r = -0.36). Linear regression analyses demonstrated significant associations among radial kurtosis, age, and Expanded Disability Status Scale score during the baseline visit, while radial kurtosis was the only variable associated with Expanded Disability Status Scale score for the 12-month follow-up. Radial kurtosis of the corticospinal tract may have an association with neurologic disability in MS.

To investigate the relationship between myelin density measured by q-space diffusional MRI (q-space myelin map; qMM) in normal-appearing white matter (NAWM) and clinical disability in multiple sclerosis (MS).

BackgroundThe Expanded Disability Status Scale (EDSS) is widely used to rate multiple sclerosis (MS) disability, but lack of disease duration information limits utility in assessing severity. EDSS ranking at specific...

Background: Multiple sclerosis (MS) is a disease which has a variable clinical presentation followed by a variable clinical course. Therefore, accuracy of clinical rating scales to measure disability at initial clinical presentation and during follow-up visits is essential to accurately capture the variability inherent in this disease. This is particularly vital when attempting to identify the efficacy of interventions. Objective: This observational study in veterans with MS compared the Kurtkze Expanded Disability Status Scale (EDSS) and the Total Functional Independence Measure (TFIM) scale as measures of MS-related disability. Methods: We retrospectively reviewed the electronic charts of 76 veterans with MS who are regularly followed in our VA MS clinic. Local Institutional Review Board approval was obtained for the protocol. Data were analyzed using SAS (SAS System for Windows, version 9.2, SAS Institute Inc., Cary, NC, USA). Chi-square and Fisher exact tests were used to assess categorical variables. Kruskal–Wallis tests evaluated the relationships between MS types [relapsing–remitting MS (RR), secondary progressive MS (SP), primary progressive MS (PP) and clinical isolated syndrome (CIS)] and the initial TFIM, EDSS and Impairment Index (II) scores. Results: The EDSS score accurately measured MS-related impairment at initial evaluation and follow-up relative to an II. However, the EDSS score did not change over time, compared to the TFIM suggesting reduced sensitivity of the EDSS for detecting change in MS-related disability over time. Conclusions: This suggests TFIM scale is a more sensitive measure of MS-related disability than EDSS for use in future MS clinical trials.Implications for RehabilitationThis study highlights that given the paucity of scales to which EDSS has been compared, TFIM is a valuable adjunct to EDSS in measuring MS-related disability.TFIM is able to accurately measure the severity of MS-related disability and help provide for services patients with MS-related disability would need.TFIM is an easy to administer and a sensitive scale to measure the change in MS-related disability following interventions.

BackgroundA contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data...

Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NABT MTR histograms. 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NABT after extracting lesions and cerebrospinal fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59). Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001). There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Autologous HSCT for Multiple Sclerosis Should be Done Early in the Course of the Disease