Background:
Infections are discussed as risk factor for multiple sclerosis (MS) development and relapses. This may lead to decreased vaccination frequency in newly diagnosed patients.
Objective:
The ...aim of this study was to evaluate the relation of MS diagnosis to subsequent vaccination frequency.
Methods:
Based on German ambulatory claims data from 2005 to 2019, regression models were used to assess the relation of MS diagnosis (n = 12,270) to vaccination. A cohort of patients with MS was compared to control cohorts with Crohn’s disease, psoriasis, and without these autoimmune diseases (total n = 198,126) in the 5 years after and before diagnosis.
Results:
Patients with MS were less likely to be vaccinated compared to persons without the autoimmune diseases 5 years after diagnosis (odds ratio = 0.91, p < 0.001). Exceptions were vaccinations against influenza (1.29, p < 0.001) and pneumococci (1.41, p < 0.001). Differences were strong but less pronounced after than before diagnosis (p < 0.001). The likelihood of vaccination was also lower compared to patients with Crohn’s disease or psoriasis.
Conclusions:
Patients with MS were not adequately vaccinated despite guideline recommendations. Increasing awareness about the importance of vaccination is warranted to reduce the risk of infection, in particular, in patients with MS receiving immunotherapies.
Purpose:
The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification ...criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C).
Methods:
This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0–3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved.
Results:
Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33).
Conclusion:
GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.
Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an ...experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6
, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.
Background:
Lesions of brain white matter (WM) and atrophy of brain gray matter (GM) are well-established surrogate parameters in multiple sclerosis (MS), but it is unclear how closely these ...parameters relate to each other.
Objective:
To assess across the whole cerebrum whether GM atrophy can be explained by lesions in connecting WM tracts.
Methods:
GM images of 600 patients with relapsing-remitting MS (women = 68%; median age = 33.0 years, median expanded disability status scale score = 1.5) were converted to atrophy maps by data from a healthy control cohort. An atlas of WM tracts from the Human Connectome Project and individual lesion maps were merged to identify potentially disconnected GM regions, leading to individual disconnectome maps. Across the whole cerebrum, GM atrophy and potentially disconnected GM were tested for association both cross-sectionally and longitudinally.
Results:
We found highly significant correlations between disconnection and atrophy across most of the cerebrum. Longitudinal analysis demonstrated a close temporal relation of WM lesion formation and GM atrophy in connecting fibers.
Conclusion:
GM atrophy is associated with WM lesions in connecting fibers. Caution is warranted when interpreting group differences in GM atrophy exclusively as differences in early neurodegeneration independent of WM lesion formation.
Genetic mapping studies have identified thousands of associations between common variants and hundreds of human traits. Translating these associations into mechanisms is complicated by two factors: ...they fall into gene regulatory regions; and they are rarely mapped to one causal variant. One way around these limitations is to find groups of traits that share associations, using this genetic link to infer a biological connection. Here, we assess how many trait associations in the same locus are due to the same genetic variant, and thus shared; and if these shared associations are due to causal relationships between traits. We find that only a subset of traits share associations, with many due to causal relationships rather than pleiotropy. We therefore suggest that simply observing overlapping associations at a genetic locus is insufficient to infer causality; direct evidence of shared associations is required to support mechanistic hypotheses in genetic studies of complex traits.
Background:
Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple ...sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions.
Objectives:
The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS.
Design:
Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium.
Methods:
Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score Multiple Sclerosis Treatment Decision Score (MS-TDS) through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI.
Results:
Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used.
Conclusion:
Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established.
Background
Optical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), ...retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course.
Material and methods
This study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis.
Results
Rarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor α and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio HR 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening.
Discussion
Optic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability.
Multiple sclerosis (MS) is a chronic inflammatory neurological disease of the CNS that goes along with demyelination and neurodegeneration. It is probably caused by an autoimmune response against the ...CNS, which emerges from the interplay of genetic and environmental factors. Although major progress has been made in the treatment of MS, it is still the leading cause for acquired nontraumatic neurological disability in young adults. Several therapeutic agents have been approved for the treatment of relapsing-remitting MS (RRMS), aiming at the reduction of relapses and a delay in disability progression. Three therapeutic monoclonal antibodies targeting CD20-positive B cells (rituximab, ocrelizumab and ofatumumab) were investigated in MRI-based Phase II and Phase III trials in RRMS, providing consistent evidence for a disease-ameliorating effect of B cell depleting therapies in MS. Here, we discuss the role of B cells and review current and future therapeutic approaches to target B cells in MS.
We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major ...histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.
Lesions in the periventricular, (juxta)cortical, and infratentorial region, as visible on brain MRI, are part of the diagnostic criteria for Multiple sclerosis (MS) whereas lesions in the subcortical ...region are currently only a marker of disease activity. It is unknown whether MS lesions follow individual spatial patterns or whether they occur in a random manner across diagnostic regions.
First, to describe cross-sectionally the spatial lesion patterns in patients with MS. Second, to investigate the spatial association of new lesions and lesions at baseline across diagnostic regions.
Experienced neuroradiologists analyzed brain MRI (3D, 3T) in a cohort of 330 early MS patients. Lesions at baseline and new solitary lesions after two years were segmented (manually and by consensus) and classified as periventricular, (juxta)cortical, or infratentorial (diagnostic regions) or subcortical—with or without Gadolinium-enhancement. Gadolinium enhancement of lesions in the different regions was compared by Chi square test. New lesions in the four regions served as dependent variable in four zero-inflated Poisson models each with the six independent variables of lesions in the four regions at baseline, age and gender.
At baseline, lesions were most often observed in the subcortical region (mean 13.0 lesions/patient), while lesion volume was highest in the periventricular region (mean 2287 µl/patient). Subcortical lesions were less likely to show gadolinium enhancement (3.1 %) than juxtacortical (4.3 %), periventricular (5.3 %) or infratentorial lesions (7.2 %). Age was inversely correlated with new periventricular, juxtacortical and subcortical lesions. New lesions in the periventricular, juxtacortical and infratentorial region showed a significant autocorrelative behavior being positively related to the number of lesions in the respective regions at baseline. New lesions in the subcortical region showed a different behavior with a positive association with baseline periventricular lesions and a negative association with baseline infratentorial lesions.
Across regions, new lesions do not occur randomly; instead, new lesions in the periventricular, juxtacortical and infratentorial diagnostic region are associated with that at baseline. Lesions in the subcortical regions are more closely related to periventricular lesions. Moreover, subcortical lesions substantially contribute to lesion burden in MS but are less likely to show gadolinium enhancement (than lesions in the diagnostic regions).
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