Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

2021 ◽  
pp. 135245852110530
Author(s):  
Susana Otero-Romero ◽  
Pere Carbonell-Mirabent ◽  
Luciana Midaglia ◽  
María Zuluaga ◽  
Ingrid Galán ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prospective Cohort ◽  
Cox Regression ◽  
Clinically Isolated Syndrome ◽  
Sensitivity Analyses ◽  
Oligoclonal Bands ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
T2 Lesions ◽  
Disease Modifying Treatment

Objective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

2015 ◽  
Vol 21 (8) ◽  
pp. 1013-1024 ◽  
Author(s):  
J Kuhle ◽  
G Disanto ◽  
R Dobson ◽  
R Adiutori ◽  
L Bianchi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Nuclear Antigen ◽  
Oligoclonal Bands ◽  
Serum Samples ◽  
T2 Lesions ◽  
Definite Multiple Sclerosis ◽  
Epstein Barr ◽  
Csf Oligoclonal Bands

Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

scholarly journals High neurofilament levels are associated with clinically definite multiple sclerosis in children and adults with clinically isolated syndrome

2018 ◽  
Vol 25 (7) ◽  
pp. 958-967 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Yu Yi M Wong ◽  
Julia Y Mescheriakova ◽  
E Daniëlle van Pelt ◽  
Tessel F Runia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Predictive Value ◽  
Cox Regression ◽  
Geometric Mean ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Course ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis

Background: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. Objective: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. Methods: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62.8 months (standard deviation (SD) ±38.7 months) and 43.8 months (SD ±27.1 months) in children). Thirty control patients were also included. Lumbar puncture was done within 6 months after onset of symptoms. NfL was determined in CSF using enzyme-linked immunosorbent assay (ELISA). COX regression analyses were used to calculate hazard ratios (HR) for clinically definite multiple sclerosis (CDMS) diagnosis. Results: After adjustments for age, oligoclonal bands (OCB), and asymptomatic T2 lesions on baseline magnetic resonance imaging (MRI), increased NfL levels in both paediatric and adult CIS patients were associated with a shorter time to CDMS diagnosis (children HR = 3.7; p = 0.007, adults HR = 2.1; p = 0.032). For CIS patients with a future CDMS diagnosis, children showed higher NfL levels than adults (geometric mean 4888 vs 2156 pg/mL; p = 0.007). Conclusion: CSF NfL levels are associated with CDMS diagnosis in children and adults with CIS. This makes NfL a promising predictive marker for disease course with potential value in clinical practice.

scholarly journals Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1507-e1516 ◽  
Author(s):  
María I. Zuluaga ◽  
Susana Otero-Romero ◽  
Alex Rovira ◽  
Santiago Perez-Hoyos ◽  
Georgina Arrambide ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Time Dependent ◽  
Sensitivity Analyses ◽  
Age At Menarche ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Propensity Score Model ◽  
Before And After

ObjectiveTo investigate the effect of menarche, pregnancies, and breastfeeding on the risk of developing multiple sclerosis (MS) and disability accrual using a multivariate approach based on a large prospective cohort of patients with clinically isolated syndrome (CIS).MethodsA cross-sectional survey of the reproductive information of female participants in a CIS cohort was performed. We examined the relationship of age at menarche with the risk of clinically definite MS (CDMS), McDonald 2010 MS, and Expanded Disability Status Scale (EDSS) 3.0 and 6.0. The effect of pregnancy (before and after CIS) and breastfeeding in the risk of CDMS, McDonald 2010 MS, and EDSS 3.0 was also examined. Univariate and multivariate analyses were performed and findings were confirmed using sensitivity analyses and a propensity score model.ResultsThe data of 501 female participants were collected. Age at menarche did not correlate with age at CIS and was not associated with the risk of CDMS or EDSS 3.0 or 6.0. Pregnancy before CIS was protective for CDMS in the univariate analysis, but the effect was lost in the multivariate model and did not modify the risk of EDSS 3.0. Pregnancy after CIS was protective for both outcomes in univariate and multivariate analyses when pregnancy was considered a baseline variable, but the protective effect disappeared when analyzed as a time-dependent event. Breastfeeding did not modify the risk for the 3 outcomes.ConclusionsThese results demonstrate that menarche, pregnancies, and breastfeeding did not substantially modify the risk of CDMS or disability accrual using a multivariable and time-dependent approach.

scholarly journals Integrative biochemical, proteomics, and metabolomics cerebrospinal fluid biomarkers predict clinical conversion to multiple sclerosis

2021 ◽  
Author(s):  
Fay Probert ◽  
Tianrong Yeo ◽  
Yifan Zhou ◽  
Megan Sealey ◽  
Siddharth Arora ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Predictive Accuracy ◽  
Personalised Medicine ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Protein Biomarkers ◽  
Glucose Levels ◽  
Prognostic Accuracy ◽  
New Biomarkers

Abstract Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalised medicine approach. We sought to identify biomarkers from biochemical, metabolic, and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism, and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis.

Early predictors of multiple sclerosis after a typical clinically isolated syndrome

2014 ◽  
Vol 20 (13) ◽  
pp. 1721-1726 ◽  
Author(s):  
Aurélie Ruet ◽  
Georgina Arrambide ◽  
Bruno Brochet ◽  
Cristina Auger ◽  
Eva Simon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
High Specificity ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Mcdonald Criteria ◽  
Early Predictors ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri ◽  
Periventricular Lesions

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions. Objective: The purpose of this study was to evaluate the 2010 McDonald criteria performance and to assess other PFs in patients without dissemination in space (DIS). Methods: Patients with clinically isolated syndrome (CIS) underwent baseline MRI and OB determination with clinical and radiological follow-up. Adjusted hazard ratios (aHRs) for clinically definite MS were estimated for DIS, dissemination in time (DIT), and DIS+DIT. Diagnostic properties at two years were calculated. In cases without DIS, combinations of ≥2 PFs were assessed. Results: A total of 652 patients were recruited; aHRs were 3.8 (2.5–5.8) for DIS, 4.2 (1.9–9.2) for DIT, and 8.6 (5.4–13.8) for DIS+DIT. Sensitivities were 69.6%, 42.3%, and 36.4%, and specificities were 67.3%, 87.9%, and 90.2%, respectively. In patients without DIS, aHRs varied between 2.7–5.5 and specificities ranged from 73.5–89.7% for PF combinations. Conclusion: The high specificity of the 2010 McDonald criteria is confirmed. In patients without DIS, PF combinations could be helpful in identifying those at risk for MS.

Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis

2011 ◽  
Vol 18 (3) ◽  
pp. 322-328 ◽  
Author(s):  
CM Dalton ◽  
B Bodini ◽  
RS Samson ◽  
M Battaglini ◽  
LK Fisniku ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spatial Distribution ◽  
Brain Lesion ◽  
Multiple Linear Regression Model ◽  
Clinically Isolated Syndrome ◽  
Optic Radiation ◽  
Lesion Location ◽  
T2 Lesions ◽  
Significant Difference ◽  
T1 And T2

Background/Objectives: The objective of this study was to investigate associations between the spatial distribution of brain lesions and clinical outcomes in a cohort of people followed up 20 years after presentation with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated from 74 people who underwent magnetic resonance imaging (MRI) and clinical assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics were used to compare LPMs between the following groups: clinically definite (CD) MS and those who remained with CIS, with an abnormal MRI; people with MS and an Expanded Disability Status Scale (EDSS) ≤3 and >3; people with relapsing–remitting (RR) and secondary progressive (SP) MS. The probability of each voxel being lesional was analysed adjusting for age and gender using a multiple linear regression model. Results: People with CDMS were significantly more likely than those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions in the corona radiata, optic radiation, and splenium of the corpus callosum (periventricularly) and T2 lesions in the right fronto-occipital fasciculus. People with MS EDSS >3, compared with those with EDSS ≤3, were more likely to have optic radiation and left internal capsule T2 lesions. No significant difference in lesion distribution was noted between RRMS and SPMS. Conclusion: This work demonstrates that lesion location characteristics are associated with CDMS and disability after long-term follow-up following a CIS. The lack of lesion spatial distribution differences between RRMS and SPMS suggests focal pathology affects similar regions in both subgroups.

scholarly journals Factors for Lower Walking Speed in Persons with Multiple Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Leandro Alberto Calazans Nogueira ◽  
Luciano Teixeira dos Santos ◽  
Pollyane Galinari Sabino ◽  
Regina Maria Papais Alvarenga ◽  
Luiz Claudio Santos Thuler
Keyword(s):  
Physical Activity ◽  
Multiple Sclerosis ◽  
Physical Activity Level ◽  
Walking Speed ◽  
Motor Planning ◽  
Activity Level ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Balance Confidence ◽  
Significant Difference

Objective. The purpose of this study was to analyze factors related to lower walking speed in persons with multiple sclerosis (PwMS).Methods. A cross-sectional survey was conducted. The study participants were 120 consecutive PwMS, who were able to walk, even with device assistance. Demographic and clinical data were collected. Walking speed was measured in 10 m walk test. Possible factors were assessed: disability, fatigue, visual functioning, balance confidence, physical activity level, walking impact, cognitive interference, and motor planning. A forward linear multiple regression analysis examined the correlation with lower speed.Results. Lower walking speed was observed in 85% of the patients. Fatigue (41%), recurrent falls (30%), and balance problems were also present, even with mild disability (averageEDSS=2.68). A good level of physical activity was noted in most of the subjects. Dual-task procedure revealed 11.58% of walking speed reduction. Many participants (69.57%) imagined greater walking speed than motor execution (mean ≥ 28.42%). Physical activity level was the only characteristic that demonstrated no significant difference between the groups (lower versus normal walking speed). Many mobility measures were correlated with walking speed; however, disability, balance confidence, and motor planning were the most significant.Conclusions. Disability, balance confidence, and motor planning were correlated with lower walking speed.

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