Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.

Neuroinflammation is often characterized by immune cell infiltrates in the cerebrospinal fluid (CSF). Here, we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious, and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression.

Vaccination as a risk factor for pediatric multiple sclerosis: Insights from a retrospective case-control study.

This study evaluated the association between pediatric multiple sclerosis and vaccinations within 5 years before diagnosis using German ambulatory claims data. Children with multiple sclerosis ( = 346) aged 9-17 were analyzed with logistic and Poisson regression. Control groups included children with Crohn's disease, psoriasis, and no autoimmune diseases.

Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated.

Unsupervised clustering analysis-based characterization of spatial profiles of inaccuracy in apparent diffusion coefficient values with varying acquisition plan orientation and diffusion weighting gradient direction - a large multicenter phantom study.

This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis. A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s mm) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function ().

Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.

Background: Inter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ.

Vaccination frequency in people newly diagnosed with multiple sclerosis.

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.

A Genetic Risk Variant for Multiple Sclerosis Severity is Associated with Brain Atrophy.

The minor allele of the genetic variant rs10191329 in the DYSF-ZNF638 locus is associated with unfavorable long-term clinical outcomes in multiple sclerosis patients. We investigated if rs10191329 is associated with brain atrophy measured by magnetic resonance imaging in a discovery cohort of 748 and a replication cohort of 360 people with relapsing multiple sclerosis. We observed an association with 28% more brain atrophy per rs10191329*A allele.

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis.

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.

A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases.

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers.

Lesion location across diagnostic regions in multiple sclerosis.

Background: 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.

Aim: First, to describe cross-sectionally the spatial lesion patterns in patients with MS.

Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis.

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.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

Purpose: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures.

Methods: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored.

Association of pregnancies with risk of multiple sclerosis.

Background: Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear.

Objective: To determine the relationships of pregnancies and gynecological diagnoses with MS risk.

Methods: In this retrospective case-control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS ( = 5720), Crohn's disease ( = 6280), or psoriasis ( = 40,555) and women without these autoimmune diseases ( = 26,729) in the 5 years before diagnosis.

Gray matter atrophy in relapsing-remitting multiple sclerosis is associated with white matter lesions in connecting fibers.

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.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

Purpose: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation.

Methods: Water phantom acquisitions were carried out on 39 scanners.

Shared associations identify causal relationships between gene expression and immune cell phenotypes.

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.

Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS.

Background: Upon treatment with biopharmaceuticals, the immune system may produce anti-drug antibodies (ADA) that inhibit the therapy. Up to 40% of multiple sclerosis patients treated with interferon β (IFNβ) develop ADA, for which a genetic predisposition exists. Here, we present a genome-wide association study on ADA and predict the occurrence of antibodies in multiple sclerosis patients treated with different interferon β preparations.

Genetic determinants of the humoral immune response in MS.

Objective: In this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS).

Methods: Using regression analyses, we tested genetic variants on chromosome 14 and imputed human leukocyte antigen (HLA) alleles for associations with intrathecal immunoglobulins in 1,279 patients with MS or clinically isolated syndrome and with blood and CSF B cells and plasmablasts in 301 and 348 patients, respectively.

Results: The minor alleles of variants on chromosome 14 were associated with higher intrathecal immunoglobulin G levels (β = 0.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy.

Background: We investigated whether the pattern of intensity-modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD).

Methods: A frequency-matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models.