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

2021 ◽  
pp. 1-10
Author(s):  
Antonio Barreiro-González ◽  
Maria T. Sanz ◽  
Sara Carratalà-Boscà ◽  
Francisco Pérez-Miralles ◽  
Carmen Alcalá ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Cervical Spinal Cord ◽  
Brain Lesion ◽  
Scale Model ◽  
Lesion Volume ◽  
Expanded Disability Status Scale ◽  
Software Analysis ◽  
Disability Status ◽  
Disease Modifying

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> EDSS values correlated with patient’s age (<i>r</i> = 0.543, <i>p</i> = 0.001), SC volume (<i>r</i> = −0.301, <i>p</i> = 0.034), and ganglion cell layer (GCL, <i>r</i> = −0.354, <i>p</i> = 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 <i>R</i><sup>2</sup> = 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. <b><i>Conclusions:</i></b> 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.

scholarly journals Tick-borne encephalitis vaccination in multiple sclerosis

2020 ◽  
Vol 7 (2) ◽  
pp. e664
Author(s):  
Alexander Winkelmann ◽  
Christoph Metze ◽  
Silvius Frimmel ◽  
Emil C. Reisinger ◽  
Uwe K. Zettl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Geometric Mean ◽  
Expanded Disability Status Scale ◽  
Vaccine Response ◽  
Link Type ◽  
Tick Borne Encephalitis ◽  
Disability Status ◽  
Disease Modifying ◽  
Relapse Rates

ObjectiveTo assess the changes in disease activity after tick-borne encephalitis (TBE) vaccination in patients with multiple sclerosis (MS) on a variety of disease-modifying drugs and to assess the immunogenicity, safety, and clinical tolerability of the vaccine in this patient group.MethodsWe conducted a prospective, multicenter, nonrandomized observational study. We enrolled 20 patients with MS receiving TBE vaccination who had been on disease-modifying treatment (DMT) for at least 6 months. Serum samples were obtained before and after 4 weeks of vaccination to determine the specific TBE antibody response. MS disease activity (Expanded Disability Status Scale and relapse rates) was evaluated for 1 year after immunization. Local and systemic adverse events were registered.ResultsIn 20 subjects with TBE vaccination, the annualized relapse rate decreased from 0.65 in the year before vaccination to 0.21 in the following year. Expanded Disability Status Scale remained stable during the 2-year period before vaccination and 1 year after vaccination (range: 1.50–1.97). The geometric mean titer (GMT) increased from 169 Vienna units per milliliter (VIEU/mL) to 719 VIEU/mL 4 weeks after vaccination (p = 0.001), and 77.8% had protective antibody titers after vaccination. In 9 patients treated with beta interferons, GMT increased from 181 VIEU/mL to 690 VIEU/mL (p = 0.018). Three subjects treated with glatiramer acetate developed a 2- to 9.6-fold increase. Patients treated with fingolimod developed the lowest increase in antibody titer.ConclusionTBE vaccination showed good tolerability and was safe in patients with MS. MS disease activity was not increased, and annualized relapse rates decreased after vaccination. Vaccine response differs according to the underlying DMT.Trial registrationClinicalTrials.gov, clinicaltrials.gov, Identifier: NCT02275741.

scholarly journals Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

2019 ◽  
Vol 26 (11) ◽  
pp. 1381-1391 ◽  
Author(s):  
Iris Dekker ◽  
Madeleine H Sombekke ◽  
Lisanne J Balk ◽  
Bastiaan Moraal ◽  
Jeroen JG Geurts ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Odds Ratio ◽  
Expanded Disability Status Scale ◽  
Simultaneous Presence ◽  
Disability Progression ◽  
Spinal Cord Lesions ◽  
Disability Status ◽  
Lesion Analysis

Objective: The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors of disability progression in multiple sclerosis (MS). Methods: We selected 153 MS patients from the longitudinal Amsterdam MS cohort. Lesion analysis was performed at baseline and year 2. Disability progression after 6 and 11 years was measured using the Expanded Disability Status Scale (EDSS) and EDSS-plus (including 25-foot walk and 9-hole peg test). Patients with spinal cord or infratentorial lesions were compared for the risk of 6- and 11-year disability progression to patients without spinal cord or infratentorial lesions, respectively. Subsequently, patients with lesions on both locations were compared to patients with only spinal cord or only infratentorial lesions. Results: Baseline spinal cord lesions show a higher risk of 6-year EDSS progression (odds ratio (OR): 3.6, p = 0.007) and EDSS-plus progression (OR: 2.5, p = 0.028) and 11-year EDSS progression (OR: 2.8, p = 0.047). Patients with both infratentorial and spinal cord lesions did not have a higher risk of 6-year disability progression than patients with only infratentorial or only spinal cord lesions. Conclusion: The presence of early spinal cord lesions seems to be a dominant risk factor of disability progression. Simultaneous presence of early infratentorial and spinal cord lesions did not undisputedly predict disability progression.

scholarly journals Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2089-2105 ◽  
Author(s):  
Anne Kerbrat ◽  
Charley Gros ◽  
Atef Badji ◽  
Elise Bannier ◽  
Francesca Galassi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Volume Fraction ◽  
Lesion Volume ◽  
Corticospinal Tracts ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Brain ◽  
Lesion Frequency

Abstract Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P &lt; 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P &lt; 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P &lt; 0.0001), brainstem (r = 0.45, P &lt; 0.0001) and spinal cord (r = 0.57, P &lt; 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

scholarly journals Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2276-2287 ◽  
Author(s):  
Wallace J Brownlee ◽  
Dan R Altmann ◽  
Ferran Prados ◽  
Katherine A Miszkiel ◽  
Arman Eshaghi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Spinal Cord Lesions ◽  
Secondary Progressive ◽  
Disability Status ◽  
Serial Addition

Abstract The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after ∼15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0–10); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P < 0.01) and spinal cord lesions (odds ratio 4.71, P < 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (β = 1.32, P < 0.01) and spinal cord lesions (β = 1.53, P < 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (β = − 0.79, P < 0.01) and Symbol Digit Modalities Test (β = −0.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.

scholarly journals COVID-19 is associated with multiple sclerosis exacerbations that are prevented by disease modifying therapies

2021 ◽  
Author(s):  
Afagh Garjani ◽  
Rodden M Middleton ◽  
Rachael Hunter ◽  
Katherine A Tuite-Dalton ◽  
Alasdair Coles ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cohort Study ◽  
Expanded Disability Status Scale ◽  
Community Based ◽  
Web Based ◽  
The United Kingdom ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Disease Modifying ◽  
The Impact

ABSTRACTBackgroundInfections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS.MethodsThe COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms.ResultsFifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection.ConclusionCOVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.

scholarly journals Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis

2018 ◽  
Vol 12 (01) ◽  
pp. 144-148 ◽  
Author(s):  
Lucas Senra Correa Carvalho ◽  
Osvaldo José Moreira Nascimento ◽  
Luciane Lacerda Franco Rocha Rodrigues ◽  
Andre Palma Da Cunha Matta
Keyword(s):  
Multiple Sclerosis ◽  
Temporomandibular Disorders ◽  
Control Group ◽  
Expanded Disability Status Scale ◽  
Exact Test ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Scale Scores ◽  
Axis I ◽  
Relapsing Remitting Multiple Sclerosis

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

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

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.

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