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 December 31, 2010, in 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 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27–0.32), fell to 0.19 (0.14–0.24) in the 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 (odds ratio 0.76 per month [0.60–0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [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). We found that 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 reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications.

To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting. Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10 years of follow-up. Patients were classified into those with confirmed disability progression (CDP) (n = 85) and those without CDP (n = 67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP. The identified patterns generally included structurally or functionally related GM regions. No significant differences were detected at baseline GM volume between the sub-groups. Over the follow-up, patients with CDP experienced a significantly greater rate of GM atrophy within two of the eight patterns, after correction for multiple comparisons (corrected p-values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory. SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10 years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning.

We explored the evolution of brain atrophy in relation to development of confirmed disability progression (CDP) on serial 1.5T magnetic resonance imaging (MRI) scans over a 10-year period in 181 patients with early relapsing–remitting multiple sclerosis (RRMS). At 10-year follow-up, they were divided into those with (100) or without (76) CDP (confirmed after 48 weeks). Changes in whole brain (WB), cortical, gray matter (GM), white matter, and ventricular cerebrospinal fluid (vCSF) volumes were calculated on three-dimensional T1-weighted (3D-T1) scans between all available time points. In multiple sclerosis (MS) patients with CDP compared to those without, the greatest effect size percentage volume change from baseline to follow-up was detected for WB (d = 0.55, −7.5% vs −5.2%, p < 0.001), followed by vCSF (d = 0.51, +41.1% vs +25.7%, p < 0.001), cortical (d = 0.49, −7.7% vs −6.2%, p = 0.001), and GM (d = 0.40, −7.1% vs −5.8%, p = 0.006) volumes. Mixed-effects model analysis, adjusted for age, sex, and treatment change, showed significant interactions between CDP status and percentage changes for WB and vCSF (p < 0.001), cortical (p = 0.02), and GM (p = 0.04) volumes. WB and cortical atrophy, and enlargement of vCSF spaces are associated with development of CDP on serial yearly MRI assessments over a period of 10 years.

Background: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). Objective: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. Methods: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene ( HLA DRB1)*1501, anti-Epstein–Barr virus (EBV) antibodies, and 25-hydroxy vitamin D₃, were also measured. Results: Higher serum NfL (sNfL) levels were associated with higher albumin quotient ( p < 0.001), CSF CD80+ ( p = 0.012), and CD80+ CD19+ ( p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels ( p = 0.0026). Conclusion: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.

Introduction: As neurodegeneration is recognized as a major contributor to disability in multiple sclerosis (MS), brain atrophy quantification could have a high added value in clinical practice to assess treatment efficacy and disease progression, provided that it has a sufficiently low measurement error to draw meaningful conclusions for an individual patient.Method: In this paper, we present an automated longitudinal method based on Jacobian integration for measuring whole‐brain and gray matter atrophy based on anatomical magnetic resonance images (MRI), named MSmetrix. MSmetrix is specifically designed to measure atrophy in patients with MS, by including iterative lesion segmentation and lesion filling based on FLAIR and T1‐weighted MRI scans.Results: MSmetrix is compared with SIENA with respect to test–retest error and consistency, resulting in an average test–retest error on an MS data set of 0.13% (MSmetrix) and 0.17% (SIENA) and a consistency error of 0.07% (MSmetrix) and 0.05% (SIENA). On a healthy subject data set including physiological variability the test–retest is 0.19% (MSmetrix) and 0.31% (SIENA).Conclusion: Therefore, we can conclude that MSmetrix could be of added value in clinical practice for the follow‐up of treatment and disease progression in MS patients.