Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

2017 ◽  
Vol 48 (3-4) ◽  
pp. 179-187 ◽  
Author(s):  
Francis Guillemin ◽  
Cédric Baumann ◽  
Jonathan Epstein ◽  
Philippe Kerschen ◽  
Teresa Garot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Late Onset ◽  
Disease Onset ◽  
Population Based ◽  
Male Gender ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Short Time

Background: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. Methods: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. Results: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). Conclusions: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

2011 ◽  
Vol 18 (1) ◽  
pp. 45-54 ◽  
Author(s):  
M Cossburn ◽  
G Ingram ◽  
C Hirst ◽  
Y Ben-Shlomo ◽  
TP Pickersgill ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Disease Onset ◽  
Complete Recovery ◽  
Population Based ◽  
Disease Course ◽  
Index Event ◽  
Relapsing Remitting ◽  
Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

scholarly journals Clinical Characteristics and Disability Progression of Early- and Late-Onset Multiple Sclerosis Compared to Adult-Onset Multiple Sclerosis

2020 ◽  
Vol 9 (5) ◽  
pp. 1326 ◽  
Author(s):  
Omid Mirmosayyeb ◽  
Serge Brand ◽  
Mahdi Barzegar ◽  
Alireza Afshari-Safavi ◽  
Nasim Nehzat ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Visual Impairments ◽  
Disease Onset ◽  
Adult Onset ◽  
Disability Progression ◽  
Secondary Progressive ◽  
Spinal Lesions ◽  
Relapsing Remitting ◽  
Sensory Disturbances

Background: Compared to the adult onset of multiple sclerosis (AOMS), both early-onset (EOMS) and late-onset (LOMS) are much less frequent, but are often under- or misdiagnosed. The aims of the present study were: 1. To compare demographic and clinical features of individuals with EOMS, AOMS and LOMS, and 2. To identify predictors for disability progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS). Method: Data were taken from the Isfahan Hakim MS database. Cases were classified as EOMS (MS onset ≤ 18 years), LOMS (MS onset >50 years) and AOMS (MS >18 and ≤ 50 years). Patients’ demographic and clinical (initial symptoms; course of disease; disease patterns from MRI; disease progress) information were gathered and assessed. Kaplan–Meier and Cox proportional hazard regressions were conducted to determine differences between the three groups in the time lapse in conversion from relapsing remitting MS to secondary progressive MS. Results: A total of 2627 MS cases were assessed; of these 127 were EOMS, 84 LOMS and 2416 AOMS. The mean age of those with EOMS was 14.5 years; key symptoms were visual impairments, brain stem dysfunction, sensory disturbances and motor dysfunctions. On average, 24.6 years after disease onset, 14.2% with relapsing remitting MS (RRMS) were diagnosed with secondary progressive MS (SPMS). The key predictor variable was a higher Expanded Disability Status Scale (EDSS) score at disease onset. Compared to individuals with AOMS and LOMS, those with EOMS more often had one or two relapses in the first two years, and more often gadolinium-enhancing brain lesions. For individuals with AOMS, mean age was 29.4 years; key symptoms were sensory disturbances, motor dysfunctions and visual impairments. On average, 20.5 years after disease onset, 15.6% with RRMS progressed to SPMS. The key predictors at disease onset were: a higher EDSS score, younger age, a shorter inter-attack interval and spinal lesions. Compared to individuals with EOMS and LOMS, individuals with AOMS more often had either no or three and more relapses in the first two years. For individuals with LOMS, mean age was 53.8 years; key symptoms were motor dysfunctions, sensory disturbances and visual impairments. On average, 14 years after disease onset, 25.3% with RRMS switched to an SPMS. The key predictors at disease onset were: occurrence of spinal lesions and spinal gadolinium-enhancement. Compared to individuals with EOMS and AOMS, individuals with LOMS more often had no relapses in the first two years, and higher EDSS scores at disease onset and at follow-up. Conclusion: Among a large sample of MS sufferers, cases with early onset and late onset are observable. Individuals with early, adult and late onset MS each display distinct features which should be taken in consideration in their treatment.

scholarly journals Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012084
Author(s):  
Wei Zhen Yeh ◽  
Putu Ayu Widyastuti ◽  
Anneke Van der Walt ◽  
Jim Stankovich ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Dimethyl Fumarate ◽  
Disability Progression ◽  
Third Trimester ◽  
Early Postpartum ◽  
Pregnancy And Postpartum ◽  
Relapsing Remitting ◽  
Effective Option ◽  
Using Data

Objective:To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.Methods:Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.Results:We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.Conclusion:Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors

2016 ◽  
Vol 23 (9) ◽  
pp. 1241-1248 ◽  
Author(s):  
Gabriel Bsteh ◽  
Julia Feige ◽  
Rainer Ehling ◽  
Michael Auer ◽  
Harald Hegen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Activity ◽  
Cox Regression ◽  
Disability Progression ◽  
Hazard Ratios ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Disease Modifying Treatment ◽  
Relapsing Remitting Multiple Sclerosis

Background: Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing–remitting multiple sclerosis (RRMS). Objective: To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making. Methods: We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation. Hazard ratios (HRs) with 95% confidence intervals (CIs) regarding relapse and disability progression after DMT discontinuation were calculated from Cox regression models. Results: Age >45 years at discontinuation (HR = 0.47, CI = 0.23–0.95, p = 0.038), absence of relapses for ⩾4 years on DMT before discontinuation (HR = 0.29, CI = 0.10–0.82, p = 0.020) and absence of contrast enhancing lesions (HR = 0.46, CI = 0.28–0.78, p = 0.004) were independent predictors of absence of relapse after discontinuation. Age >45 years and absence of relapses ⩾4 years on DMT combined had an HR of 0.06 (CI = 0.01–0.44, p < 0.001). Higher Expanded Disability Status Scale (EDSS) at discontinuation, age >45 years and longer disease duration were significantly associated with disability progression after discontinuation. Conclusion: While freedom from further disease activity is generally unpredictable, there is a subset of patients (age ⩾45 years, DMT intake ⩾4 years without evidence of clinical or radiological disease activity) having a high likelihood of remaining relapse-free after DMT discontinuation. However, close clinical monitoring for recurrent disease activity is mandatory after discontinuing treatment.

Progression in familial and nonfamilial MS

2008 ◽  
Vol 14 (3) ◽  
pp. 300-306 ◽  
Author(s):  
Marcus Koch ◽  
Maarten Uyttenboogaart ◽  
Marco Heerings ◽  
Dorothea Heersema ◽  
Jop Mostert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Age At Onset ◽  
Disease Onset ◽  
Genetic Research ◽  
Primary Progressive ◽  
Kaplan Meier ◽  
Younger Age ◽  
Relapsing Remitting ◽  
History Of

Objective To investigate whether the timing of secondary or primary progression is different between patients with familial and nonfamilial multiple sclerosis (MS). Methods Information on the family history of 313 patients with MS was taken from our prospective hospital-based database. We used Kaplan—Meier analyses and Cox regression models to evaluate differences between familial and nonfamilial MS in several endpoint measures. We investigated the risk of developing secondary progression in all patients with a relapsing—remitting disease onset, the length of the relapsing—remitting phase and age at onset of progression in patients with secondary progressive MS and the age at disease onset in patients with primary progressive MS (PPMS). Results Among the primary progressive patients, those with familial MS had a significantly younger age at disease onset than patients with nonfamilial MS (mean 33.04 years versus mean 37.73 years in nonfamilial MS, P = 0.02). There were no significant differences between familial and nonfamilial MS patients in any other investigated measure. Conclusions Familial MS appears related to the time of disease onset in PPMS. Patients with familial PPMS may be an important patient group for future genetic research in MS. Multiple Sclerosis 2008; 14: 300—306. http://msj.sagepub.com

Influence of C C R5 δ32 polymorphism on multiple sclerosis susceptibility and disease course

2004 ◽  
Vol 10 (2) ◽  
pp. 149-152 ◽  
Author(s):  
J A Silversides ◽  
S V Heggarty ◽  
G V McDonnell ◽  
S A Hawkins ◽  
C A Graham
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Disease Onset ◽  
Population Based ◽  
Allelic Association ◽  
Coding Region ◽  
Significant Difference ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Duration Of Disease

The C C R5 chemokine receptor has been implicated in the patho genesis of multiple sclerosis (MS). We carried out an allelic association study using a deletion polymorphism in the coding region of the C C R5 gene in 331 relapsing-remitting (RR) and secondary progressive (SP) MS patients, 108 primary progressive (PP) MS patients and 230 healthy controls. O f the 331 RR and SPMS patients, 172 were recruited from specialist clinics and 159 from a population survey. Disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS) and used to calculate a progression index for each patient (defined as EDSS divided by duration of disease). No significant difference in distribution of the C C R5 d32 allele was observed between the 331 RR/SPMS patients and controls, between the 108 PPMS patients and controls or between the PPMS and RR/SPMS groups. Furthermore, no differences in rate of disease progression were detected between carriers and noncarriers of the d32 allele. In the population-based group of RR/SPMS patients, carriage of the C C R5 d32 polymorphism was associated with a lower age at disease onset (mean age 26.562 versus 31.065 years, P =0.003). However, no significant differences in age of onset were present in the PPMS group or in a second RRMS population. These results suggest that the C C R5 d32 polymorphism is not a major determinant of susceptibility to develop MS in the population under study, and conflict with a previously reported association between C C R5 d32 carriage and a better prognosis.

Factors associated with the risk of secondary progression in multiple sclerosis

2008 ◽  
Vol 14 (6) ◽  
pp. 799-803 ◽  
Author(s):  
M Koch ◽  
M Uyttenboogaart ◽  
A van Harten ◽  
J De Keyser
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Disease Onset ◽  
Hazard Ratio ◽  
Immunomodulatory Drugs ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Natural History Studies ◽  
Relapsing Remitting ◽  
Randomised Controlled

Objective To investigate factors associated with the risk of secondary progression in relapsing-remitting onset multiple sclerosis (MS). Methods We used Kaplan-Meier survival analyses and a multivariable Cox regression model to estimate the influence of the factors: gender, age at disease onset, use of immunomodulatory drugs (IMD), and clinical manifestation at disease onset on the time to secondary progression in a hospital-based cohort of 571 MS patients with a relapsing-remitting onset. Results Gender and onset manifestation had no significant influence on the timing of secondary progression. A higher age at disease onset was associated with a shorter time to secondary progression (multivariable hazard ratio per year increase: 1.02, 95% CI:1.01 - 1.03). The use of IMD was associated with a longer time to secondary progression (multivariable hazard ratio: 0.30, 95% CI: 0.15 - 0.61). Conclusions The inverse relationship between age at disease onset and onset of secondary progression is in keeping with previous natural history studies. The beneficial effect of IMD treatment on the time to secondary progression should be taken as hypothesis-generating rather than as proof of a treatment effect, and needs to be further evaluated in well-designed randomised controlled trials.

Longitudinal disability curves for predicting the course of relapsing-remitting multiple sclerosis

2003 ◽  
Vol 9 (5) ◽  
pp. 486-491 ◽  
Author(s):  
Anat Achiron ◽  
Yoram Barak ◽  
Zeev Rotstein
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Disease Onset ◽  
Disease Process ◽  
Predictive Ability ◽  
Rank Test ◽  
Clinical Impression ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Table Analysis

Background: Multiple sclerosis (MS) is a lifelong disease affecting young adults that ultimately can lead to significant neurological disability. Identifying the rate of progression of disability for an individual patient early in the disease process can influence treatment decisions as well as enable monitoring of the disease overtime. Objective: The aims of the present study were to develop longitudinal disability curves to assess disease progression in patients with relapsing -remitting MS. The construction of these disability curves was based on the mean yearly Expanded Disability Status Scale (EDSS) scores, represented as a major percentile group. To determine their predictive ability, validation of the percentile curves was performed. Methods: Using the Multiple Sclerosis C enter computerized database of 1540 patients’ records, we identified 1317 subjects with a definite MS and a relapsing-remitting disease course. Longitudinal disability curves were constructed for a subgroup of relapsing-remitting patients (n=1001) with consecutive (3-6 months) EDSS assessments for a period of up to 10 years since onset. The constructed disability curves were then validated in an additional subgroup of relapsing - remitting MS patients (n=268) with continuous follow-up visits for a period of 10 years. Results: Statistical procedures using parametric and nonparametric regression procedures were applied to the data in two stages. In the first stage, selected major percentiles were generated for up to 10 years from disease onset with a variety of parametric procedures including moving averages. In the second stage, the empirical percentiles were smoothed to obtain the final disability progression curves. The log-rank test for equality demonstrated a significant adjustment between the initial percentile assignment and disability progression (P B-0.001). Life table analysis demonstrated that the probability of deviating from the initially assigned percentile to a higher percentile over time, representing more severe disability than expected, is in the range of 6.5% for the 50th percentile to 10.4% for the 75th percentile. Conclusion: Longitudinal disability curves can be used in MS to assess individual patient disability, can contribute to the overall clinical impression of disease progression and can add to the evaluation of immunomodulating treatment effects overtime.

scholarly journals Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Katarzyna Kapica-Topczewska ◽  
François Collin ◽  
Joanna Tarasiuk ◽  
Agata Czarnowska ◽  
Monika Chorąży ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Activity ◽  
Brain Mri ◽  
Disability Progression ◽  
Program Monitoring ◽  
Therapeutic Program ◽  
Relapsing Remitting ◽  
Second Year ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.

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