How similar are commonly combined criteria for EDSS progression in multiple sclerosis?

Introduction Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke’s EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy’s Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment. Methods From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change]/1.0 for baseline EDSS 5/5.5 and patients with EDSS change]/0.5 for baseline EDSS]/6.0. We compared changes in GNDS sum score and in MSFC score between both groups. Results In the group with baseline EDSS]/6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS 5/5.5. The difference in change was 1.00 (95% confidence interval (CI): / 0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC. Conclusion Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS / 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS 5/5.5.

Download Full-text

A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years

Clocks & Sleep ◽

10.3390/clockssleep3030023 ◽

2021 ◽

Vol 3 (3) ◽

pp. 366-376

Author(s):

Lorenzo Tonetti ◽

Federico Camilli ◽

Sara Giovagnoli ◽

Vincenzo Natale ◽

Alessandra Lugaresi

Keyword(s):

Multiple Sclerosis ◽

Motor Activity ◽

Activity Pattern ◽

Activity Patterns ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Edss Score ◽

Activity Prognosis

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.

Download Full-text

Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

Journal of International Medical Research ◽

10.1177/0300060518783083 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3970-3978 ◽

Cited By ~ 4

Author(s):

Shujun Guo ◽

Qingqing Chen ◽

Xiaoli Liang ◽

Mimi Mu ◽

Jing He ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Peripheral Blood ◽

Plasma Cells ◽

Serum Levels ◽

Memory B Cells ◽

Healthy Controls ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

Download Full-text

PATIENT-REPORTED OUTCOMES AND DISABILITY IN MULTIPLE SCLEROSIS

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.127 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.32-e4

Author(s):

Neil Scolding ◽

Hongwei Wang ◽

Yan Liu ◽

Lawrence Steinman

Keyword(s):

Multiple Sclerosis ◽

Patient Reported Outcomes ◽

Short Form ◽

Minimum Important Difference ◽

Point Change ◽

Clinical Difference ◽

Sf 36 ◽

Patient Reported ◽

Edss Score ◽

Multiple Sclerosis Patients

In the 2-year, phase 3 CARE-MS II study (NCT00548405), alemtuzumab demonstrated superior clinical and patient-reported outcomes (PROs) over subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis patients who had inadequate efficacy response to prior therapy. To further evaluate the relationship between PROs and disability, Short-Form 36-Item (SF-36) survey physical component summary (PCS) and mental component summary (MCS), and Functional Assessment of Multiple Sclerosis (FAMS) scores were analysed against Expanded Disability Status Scale (EDSS) outcomes, adjusted for baseline characteristics and randomisation arm. A 1.0-point difference in baseline EDSS score was associated with 2.0-point PCS, 0.8-point MCS, and 4.0-point FAMS worsening over 12 months (all P<0.001). A 1.0-point annualised EDSS score worsening corresponded to a 2.2-point PCS, 1.6-point MCS, and 6.0-point FAMS worsening (all P<0.001). For baseline EDSS score <4.0, 1.0-point annualised worsening was associated with 7.2-point FAMS and 2.0-point MCS worsening (both P<0.001). For baseline EDSS score ≥4.0, 1.0-point worsening corresponded to worsening on FAMS (2.4 points; P=0.04), but not MCS (P=0.82). Given that a half-point EDSS change is considered the minimum reliably measurable clinical difference, a 1.0-point change in SF-36 PCS and MCS or 3.0-point change in FAMS may represent a minimum important difference in PRO for multiple sclerosis patients.

Download Full-text

Brain Function Assessment of Patients with Multiple Sclerosis in the Expanded Disability Status Scale

International Journal of MS Care ◽

10.7224/1537-2073.2018-084 ◽

2020 ◽

Vol 22 (1) ◽

pp. 31-35

Author(s):

Ricardo N. Alonso ◽

Maria B. Eizaguirre ◽

Berenice Silva ◽

Maria C. Pita ◽

Cecilia Yastremiz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Function ◽

Cognitive Assessment ◽

Functional System ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Before And After ◽

Survey Results ◽

Edss Score ◽

The Brain

Abstract Background: There is no consensus regarding assessment of the brain function functional system (FS) of the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS). We sought to describe brain function FS assessment criteria used by Argentinian neurologists and, based on the results, propose redefined brain function FS criteria. Methods: A structured survey was conducted of 113 Argentinian neurologists. Considering the survey results, we decided to redefine the brain function FS scoring using the Brief International Cognitive Assessment for MS (BICAMS) battery. For 120 adult patients with MS we calculated the EDSS score without brain function FS (basal EDSS) and compared it with the EDSS score after adding the modified brain function FS (modified EDSS). Results: Of the 93 neurologists analyzed, 14% reported that they did not assess brain function FS, 35% reported that they assessed it through a nonstructured interview, and the remainder used other tools. Significant differences were found in EDSS scores before and after the inclusion of BICAMS (P < .001). Redefining the brain function FS, 15% of patients modified their basal EDSS score, as did 20% of those with a score of 4.0 or less. Conclusions: The survey results show the importance of unifying the brain function FS scoring criteria in calculating the EDSS score. While allowing more consistent brain function FS scoring, including the modified brain function FS led to a change in EDSS score in many patients, particularly in the lower range of EDSS scores. Considering the relevance of the EDSS for monitoring patients with MS and for decision making, it is imperative to further validate the modified brain function FS scoring.

Download Full-text

Improved relapse recovery in paediatric compared to adult multiple sclerosis

Brain ◽

10.1093/brain/awaa199 ◽

2020 ◽

Vol 143 (9) ◽

pp. 2733-2741

Author(s):

Tanuja Chitnis ◽

Greg Aaen ◽

Anita Belman ◽

Leslie Benson ◽

Mark Gorman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Functional System ◽

Progressive Multiple Sclerosis ◽

Age Related ◽

Younger Age ◽

Disability Status ◽

The Us ◽

The Difference ◽

Effect Of Age

Abstract Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.

Download Full-text

Effects of Fatigue on Balance and Mobility in Subjects with Multiple Sclerosis: A Brief Report

ISRN Neurology ◽

10.5402/2012/316097 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 6

Author(s):

Elisa Gervasoni ◽

Davide Cattaneo ◽

Angelo Montesano ◽

Johanna Jonsdottir

Keyword(s):

Multiple Sclerosis ◽

Berg Balance Scale ◽

Balance Performance ◽

Before And After ◽

Increase Risk ◽

Risk Of Falls ◽

Edss Score ◽

The Difference ◽

Dynamic Gait Index ◽

Dynamic Gait

Purpose. People with Multiple Sclerosis (PwMS) tent to have increased levels of fatigue which can impact on their balance and increase risk of falls. However, the relationship between fatigue and balance is poorly understood. The aim of the present study was to assess if an experimentally induced fatigue had an immediate effect on balance. Methods. 37 inpatients with multiple sclerosis were recruited; the mean age (standard deviation) was 48.7 (9.6) years. The average onset of the pathology was 15.3 (9.8) years before the start of the study. The median (1°–3° quartile) Expanded Disability Status Scale (EDSS) score was 5.5 (4.5–6.0). Before and after a fatiguing treadmill, session, subjects were assessed with the Berg Balance Scale and Dynamic Gait Index. Results. After the treadmill, no statistically significant differences were found in balance before and after a treadmill session (monopodalic stance: before 5.3s (10.3) and after 7.7s (13.9); walk with horizontal head turns: before 11.6 (6.9) seconds and after 11.3 (7.7)). There was no correlation between the EDSS score and the difference in balance skills before and after treadmill. Conclusion. After treadmil PwMS were mentally and physically fatigued; however, their balance performance did not change, indicating no increase in risk of falling with fatigue.

Download Full-text

APOE genotypes and disease severity in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458502ms787oa ◽

2002 ◽

Vol 8 (2) ◽

pp. 98-103 ◽

Cited By ~ 35

Author(s):

T Masterman ◽

Z Zhang ◽

D Hellgren ◽

H Salter ◽

M Anvret ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Onset ◽

Membrane Repair ◽

Genome Wide ◽

Disability Status ◽

Unfavorable Clinical Outcome ◽

Edss Score ◽

E4 Allele ◽

Apoe Genotypes ◽

Chromosome 19Q13

Apolipoprotein E (apoE) is involved in the transport of lipids necessary for membrane repair and is encoded by a gene on chromosome 19q13, a region positive for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE e4 allele confers susceptibility to both familial and sporadic Alzheimer’s disease (AD). Carriage of e4 is associated with defective dendritic remodeling in AD, and with unfavorable clinical outcome in head trauma and cerebrovascular disease. According to the results of previous studies, APOE e4 does not increase the risk of developing MS, but it may influence disease progression and ultimate disability. From a total cohort of over 900 MS patients, we compared APOE e2-4 genotypes in, roughly, the cohort’s least disabled and most disabled septiles. ‘Benign MS’ (n=124) was defined as an Expanded Disability Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease duration, and ‘severe MS’ (n=140) as the attainment of an EDSS score of 6.0 within 8 years of disease onset. We found no significant differences in genotype or phenotype frequencies between the benign-MS and severe-MS septiles; however, the risk conferred by e4 rose progressively upon comparison of carriage rates in more narrowly defined anti-podal quantiles.

Download Full-text

Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study

Multiple Sclerosis Journal ◽

10.1177/1352458507078400 ◽

2007 ◽

Vol 13 (9) ◽

pp. 1107-1117 ◽

Cited By ~ 64

Author(s):

D. Pöhlau ◽

H. Przuntek ◽

M. Sailer ◽

F. Bethke ◽

J. Koehler ◽

...

Keyword(s):

Multiple Sclerosis ◽

Placebo Group ◽

Relapse Rate ◽

Fine Motor ◽

Ivig Treatment ◽

Ivig Infusion ◽

Progression Of Disease ◽

Secondary Endpoints ◽

Edss Score ◽

The Difference

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS ( n = 34) and SPMS ( n = 197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group ( P = 0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks ( P = 0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group ( P = 0.028). The difference was significant in PPMS ( P = 0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance ( P = 0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS. Multiple Sclerosis 2007; 13: 1107—1117. http://msj.sagepub.com

Download Full-text

Epilepsy in multiple sclerosis

Neurology ◽

10.1212/wnl.0000000000004740 ◽

2017 ◽

Vol 89 (24) ◽

pp. 2462-2468 ◽

Cited By ~ 22

Author(s):

Joachim Burman ◽

Johan Zelano

Keyword(s):

Multiple Sclerosis ◽

Clinical Features ◽

Cumulative Incidence ◽

Progressive Disease ◽

Disease Duration ◽

Population Based ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Relapsing Remitting ◽

Edss Score

Objective:To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.Methods:All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.Results:The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).Conclusions:Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

Download Full-text

Some Aspects of Balance Disorder in Patients with Multiple Sclerosis

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2008.3003 ◽

2008 ◽

Vol 8 (1) ◽

pp. 80-85 ◽

Cited By ~ 3

Author(s):

Adnan Burina ◽

Osman Sinanović ◽

Dževdet Smajlović ◽

Mirjana Vidović ◽

Fuad Brkić

Keyword(s):

Multiple Sclerosis ◽

Auditory Evoked Potentials ◽

Pathological Finding ◽

Initial Symptom ◽

Disability Status ◽

Balance Disorder ◽

Edss Score ◽

Interpeak Latency ◽

Mri Changes ◽

The Brain

The aim of this study was to analyze: frequency of balance disorder (vertigo and disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP) and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis (MS) patients with balance disorder, relation of patients disability status to balance disorder and relation of the changes in MRI of the brainstem to AEP abnormalities. It was analyzed 60 patients with relapsing-remitting form of MS. Two groups of patients were made consecutively under Expanded Disability Status Scale score (EDSS): A (EDSS <4,5) and B (EDSS >5,0). The study was retrospective-prospective. After the neurological exam AEP and MRI of the brain have been done. Balance disorder has been verified as initial symptom in 29 (48,4%) and out of them disequilibrium experienced 24 (83,4%) patients. During the relapses balance disorder experienced 48 (80%) patients and in 37 (77,1%) it was disequilibrium. Among them 33 (68,7%) were with lower EDSS (<4,5) and 15 (31,3%) with higher EDSS score (>5). There is no correlation between disability status and vertigo which means that vertigo is not more frequent in more disabled patients and vice-versa. The AEP were pathological in 57 (95%) patients. Of all 29 patients with vertigo AEP were pathological in 28 (96,5%) while in 31 patients without vertigo pathological AEP were in 29 (93,5%) but it is not statistical significant. The most frequent characteristic of AEP changes were prolonged inter-peak latency III-V waves (48 patients or 80%). The plaque in brainstem visualized by MRI was found in 41 (71,8%) of patients (38 or 92,6% of them had pathological AEP and in three patients AEP were normal). In group of patients with pathological AEP, 38 (66,6%) of them had plaque in brainstem. In other three patients with normal AEP it was visualized plaque in brainstem. In the group of 29 patients with balance disorder, 20 (68,9%) had plaque in brainstem as well as 21 (67,7%) out of 31 patients without balance disorder had plaque in the brainstem. This difference is not statistical significant. It is concluded that the vertigo (including disequilibrium) is relatively often (48,4%) initial symptom of MS. Vertigo is not more frequent in patients with higher EDSS score and vice-versa. Pathological AEP are frequent neurophysiologic finding in both (95%) patients with (96,5%) and without (93,5%) vertigo. The most often pathological characteristic of AEP are prolonged interpeak latency of III-V waves (78,5%), as well as abnormalities of V and than IV wave. MS plaques in brainstem visualized by MRI technique are frequent in both groups of patients with and without pathological finding of the AEP.

Download Full-text