Age-related disability in multiple sclerosis.

ObjectivesOver the past few decades, there has been an improvement in the rate of disability progression in multiple sclerosis (MS) patients, and most studies relate this evolvement to the introduction of disease-modifying therapies. However, several other factors have changed over this period, including access to MRI and newer diagnostic criteria. The aim of this study is to investigate changes in the natural course of MS over time in a near-complete and geographically well-defined population from the south-east of Norway.MethodsWe examined disease progression and demographics over two decades and assessed the effect of disease-modifying therapies using linear mixed-effect models.ResultsIn a cohort of 2097 patients, we found a significant improvement in disability as measured by the Expanded Disability Status Scale (EDSS) stratified by age, and the improvement remained significant after adjusting for time on disease-modifying medications, gender and progressive MS at onset. The time from disease onset to EDSS 6 in the total cohort was 29.8 years (95% CI 28.5–31.1) and was significantly longer in patients diagnosed after 2006 compared to patients diagnosed before. There are significant differences between patient demographics, as well as time to EDSS 6, in the near-complete, geographically well-defined population compared to an additional cohort from the capital Oslo and its suburbs.ConclusionThe natural course of MS is improving, but the improvement seen in disease progression has multifaceted explanations. Our study underlines the importance of completeness of data, relevant timeframes and demographics when comparing different MS populations. Studies on incomplete populations should be interpreted with caution.

The study objective was to analyse the costs and quality of life (QOL) of multiple sclerosis (MS) related to disease severity in Sweden as part of a study in nine European countries. Information on demographics, disease, resource utilisation, informal care needs, work capacity and QOL (utility) was collected using a questionnaire that was sent to patients registered with the Swedish organisation of patients with neurological disabilities (Neurologiskt Handikappades Riksförbund). The study used a prevalence-based and cross-sectional approach, and costs were estimated from a societal perspective. A total of 1,339 patients were included in the analysis. Seventy-three percent of patients were female, and the mean age was 53 years (standard deviation [SD], 12 years). The mean Expanded Disability Status Scale (EDSS) score was 5.1 (SD, 2.2); only 29% of patients had mild disease (EDSS score <4), 46% had moderate disease and 25% had severe disease (EDSS score > or =7). Costs were significantly correlated with disease severity, increasing sevenfold from around euro 16.000 at EDSS scores of 0-1 to euro 116.000 at EDSS scores of 8-9. At the same time, utility decreased with worsening disease from 0.825 to 0.047, with a mean established at 0.546 (SD, 0.287). This is significantly lower than utilities for an age- and gender-matched sample of the general population, which would be estimated at 0.80-0.85. Patients with a relapse during the last 3 months had a significant cost increase, of euro 3.080, and a utility loss of 0.088. Costs and utilities are highly correlated with EDSS score, and the mean cost per patient in the sample is thus heavily influenced by the severity distribution in the sample. Compared to European estimates, patients with moderate and severe disease in our sample appear to be overrepresented, and costs can therefore not be directly extrapolated to the overall MS population in Sweden without adjustment. When correcting for estimated actual prevalence and use of disease modifying drugs (DMDs), the total cost of MS in Sweden is estimated at euro 600 million. Compared to an earlier cost study in 1998 that included a similar sample, and adjusting for differential timing and estimated national use of DMDs, costs have increased by approximately 5% between 1998 and 2005.

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

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.

The role of pregnancy in relapsing-remitting MS prognosis: A five-year study.

Gait disability in people with progressive multiple sclerosis (MS) is difficult to quantify using existing clinical tools. This study aims to identify reliable and objective gait-based biomarkers to monitor progressive multiple sclerosis (MS) in clinical settings. During routine clinical visits, 57 people with secondary progressive MS and 24 healthy controls walked for 6 minutes wearing three inertial motion sensors. Fifteen gait measures were computed from the sensor data and tested for between-session reliability, for differences between controls and people with moderate and severe MS disability, and for correlation with Expanded Disability Status Scale (EDSS) scores. The majority of gait measures showed good to excellent between-session reliability when assessed in a subgroup of 23 healthy controls and 25 people with MS. These measures showed that people with MS walked with significantly longer step and stride durations, reduced step and stride regularity, and experienced difficulties in controlling and maintaining a stable walk when compared to controls. These abnormalities significantly increased in people with a higher level of disability and correlated with their EDSS scores. Reliable and objective gait-based biomarkers using wearable sensors have been identified. These biomarkers may allow clinicians to quantify clinically relevant alterations in gait in people with progressive MS within the context of regular clinical visits.

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

ObjectiveOptical coherence tomography (OCT)‐derived measures of the retina correlate with disability and cortical gray matter atrophy in multiple sclerosis (MS); however, whether such measures predict long‐term disability is unknown. We evaluated whether a single OCT and visual function assessment predict the disability status 10 years later.MethodsBetween 2006 and 2008, 172 people with MS underwent Stratus time domain‐OCT imaging [160 with measurement of total macular volume (TMV)] and high and low‐contrast letter acuity (LCLA) testing (n = 150; 87%). All participants had Expanded Disability Status Scale (EDSS) assessments at baseline and at 10‐year follow‐up. We applied generalized linear regression models to assess associations between baseline TMV, peripapillary retinal nerve fiber layer (pRNFL) thickness, and LCLA with 10‐year EDSS scores (linear) and with clinically significant EDSS worsening (binary), adjusting for age, sex, optic neuritis history, and baseline disability status.ResultsIn multivariable models, lower baseline TMV was associated with higher 10‐year EDSS scores (mean increase in EDSS of 0.75 per 1 mm3 loss in TMV (mean difference = 0.75; 95% CI: 0.11–1.39; P = 0.02). In analyses using tertiles, individuals in the lowest tertile of baseline TMV had an average 0.86 higher EDSS scores at 10 years (mean difference = 0.86; 95% CI: 0.23–1.48) and had over 3.5‐fold increased odds of clinically significant EDSS worsening relative to those in the highest tertile of baseline TMV (OR: 3.58; 95% CI: 1.30–9.82; Ptrend = 0.008). pRNFL and LCLA predicted the 10‐year EDSS scores only in univariate models.InterpretationLower baseline TMV measured by OCT significantly predicts higher disability at 10 years, even after accounting for baseline disability status.

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

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.

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.

S: To study the change in disability over 10 years in individual patients constituting the 1991 Olmsted County, MN, multiple sclerosis (MS) prevalence cohort. The authors reassessed this 1991 cohort in 2001. The authors determined the Expanded Disability Status Scale scores (EDSS) for each patient still alive, and within the year prior to death for those who died. The authors analyzed determinants of potential prognostic significance on change in disability. Follow-up information was available for 161 of 162 patients in the 1991 cohort. Only 15% had received immunomodulatory therapy. The mean change in EDSS for the entire cohort over 10 years was 1 point and 20% worsened by >or=2 points. For patients with EDSS <3 in 1991 (n = 66), 83% were ambulatory without a cane 10 years later. For patients with EDSS of 3 through 5 in 1991 (n = 33), 51% required a cane to ambulate (48%) or worse (3%). For patients with EDSS 6 to 7 in 1991 (n = 39), 51% required a wheelchair or worse in 2001. Gait impairment at onset, progressive disease, or longer duration of disease were associated with more worsening of disability (p < 0.002). The 10-year survival was decreased compared with the Minnesota white population for both men and women. Although survival was reduced and 30% of patients progressed to needing a cane or wheelchair or worse over the 10-year follow-up period, most remained stable or minimally progressed. Patients within the EDSS 3.0 through 5.0 range are at moderate risk of developing important gait limitations over the 10-year period. The authors did not identify factors strongly predictive of worsening disability in this study.

To evaluate the clinical and radiological consequences of delayed escalation of therapy in patients with relapsing-remitting multiple sclerosis (RRMS), in whom, despite finding platform therapy ineffective, high-efficacy drugs were introduced with a delay. We performed a single-centre, observational study evaluating patients with RRMS for ineffectiveness of disease-modifying therapies (DMTs). Depending on the time of therapy escalation to high-efficacy drugs, the patients were divided into an early escalation or a late escalation group, both of which were then observed for 48 months. All patients underwent a neurological examination every six months and a brain magnetic resonance imaging (MRI) every 12 months. The primary endpoint was a change in the Expanded Disability Status Scale (EDSS) score during the observation period. The secondary endpoint was the time to 6-month confirmed disability progression (6mCDP). In addition, we analysed the annualised relapse rate and the cumulative number of new Gd+ and T2 lesions on brain MRI. 165 patients were qualified for the analysis. On treatment initiation, mean age was 38 years (± 10.9), and mean EDSS was 1.41 ± 0.38. After 48 months, there was a statistically insignificant decrease in the EDSS score in the early escalation group (-0.17 ± 0.35; p > 0.05), while in the late escalation group there was an increase in the EDSS score. The highest increase was noted in the group in which the escalation was performed with a delay of more than two years (1.2 ± 0.63; p < 0.001), and moreover 80% of patients in this group met the 6mCDP criteria. The median time to 6mCDP was 4.6 years (LESC1) and 4.5 years (LESC2) in the late escalation groups. In the early escalation group, zero subjects met the 6mCDP criteria after 48 months of observation. In everyday practice, the long-term outcomes in patients with RRMS and disease activity, despite DMT being used, are more favourable after early implementation of high-efficacy drugs. Delaying therapy escalation results in the accumulation of permanent disability in patients with RRMS.

Body composition in ambulatory women with multiple sclerosis

To evaluate the efficacy and safety of IFNbeta-1a (Avonex, Biogen, Inc., Cambridge, MA, USA) in patients with relapsing-remitting multiple sclerosis (MS). In this multicenter, open-label, prospective clinical trial, 96 patients with relapsing-remitting MS received IFNbeta-1a 30 mcg intramuscularly once weekly for 2 years. Outcome variables included: change from baseline in mean number of exacerbations, proportion of exacerbation-free patients, and mean Expanded Disability Status Scale (EDSS) scores at Years 1 and 2. IFNbeta-1a significantly (P < 0.0001) reduced exacerbation rate at Years 1 and 2 of treatment. The percentage of exacerbation-free patients was 53% during Year 1 and 33% during Year 2. Mean EDSS scores were 2.96 +/- 1.26 at baseline, 2.89 +/- 1.42 at Year 1, and 3.00 +/- 1.62 at Year 2 (P = 0.116). EDSS scores improved in 35.4%, remained stable in 28.1%, and worsened in 36.5% of patients. IFNbeta-1a treatment was well tolerated. This study confirms and extends the beneficial clinical profile for IFNbeta-1a in relapsing MS.