Metabolomics of Multiple Sclerosis Lesions Demonstrates Lipid Changes Linked to Alterations in Transcriptomics-Based Cellular Profiles.

Background And Objectives: People with multiple sclerosis (MS) have a dysregulated circulating metabolome, but the metabolome of MS brain lesions has not been studied. The aims of this study were to identify differences in the brain tissue metabolome in MS compared with controls and to assess its association with the cellular profile of corresponding tissue.

Methods: MS tissues included samples from the edge and core of chronic active or inactive lesions and periplaque white matter (WM).

Expanding clinical profiles and prognostic markers in stiff person syndrome spectrum disorders.

Objective: To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability.

Background: There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD.

Design/methods: Observational study from 1997 to 2022 at Johns Hopkins.

Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis.

Background: Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS).

Objective: To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast.

The many faces of gastrointestinal dysfunction in stiff person syndrome spectrum disorders.

Introduction: The effect of stiff person syndrome spectrum disorders (SPSD) on the gastrointestinal tract (GIT) is unknown. This case series aims to characterize the prevalence and types of GI dysfunction in individuals with SPSD.

Methods: A retrospective chart review included individuals diagnosed with SPSD with descriptors of GI symptoms in their medical records.

Respiratory symptoms are common in stiff person syndrome spectrum disorders and are associated with number of body regions involved.

Background And Purpose: Stiff person syndrome (SPS) spectrum disorders (SPSSD) cause spasms and rigidity throughout different body regions and can be associated with apnea and acute respiratory failure. There are limited data on the prevalence and predictors of respiratory symptoms with spasms (RSwS) in SPSSD. We sought to characterize the spirometry patterns and the frequency and predictors of RSwS in a large SPSSD cohort.

Effects of Myopia on Rates of Change in Optical Coherence Tomography Measured Retinal Layer Thicknesses in People with Multiple Sclerosis and Healthy Controls.

Purpose: To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC).

Methods: A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up < 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality.

Associations of sNfL with clinico-radiological measures in a large MS population.

Objective: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

Methods: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

Gender disparities in multiple sclerosis research and leadership: A Colombian perspective.

Background: The neurological academic field is an illustrative example of persistent gender-related disparities reflected in compensation, funding, leadership, promotion, publishing, and recognition. Several studies indicate that neurology is one of the most underrepresented specialties with female physicians as first authors, but also has one of the highest gender payment gaps. Neglecting the role of women in academic leadership positions hinders the visibility and recognition of research and leadership in multiple sclerosis (MS).

High-dose rifampin improves bactericidal activity without increased intracerebral inflammation in animal models of tuberculous meningitis.

Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation.

Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy.

Background: Sphingosine-1-phosphate receptor (S1P) modulators and anti-CD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Relatively few studies have assessed the impact of an array of disease modifying therapies (DMTs) for multiple sclerosis (MS) on T cell immune responses to SARS-CoV-2 vaccination.

Methods: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum.

Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy.

Background: Sphingosine-1-phosphate receptor (S1P) modulators and antiCD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Whether disease modifying therapies (DMTs) for multiple sclerosis (MS) also impact T cell immune response to vaccination is unknown.

Methods: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum.

Vitamin D and other environmental risk factors in Colombian patients with multiple sclerosis.

Objective: The aim of this study was to explore the association between MS and vitamin D levels, as well as Epstein-Barr virus (EBV) seropositivity and smoking history in a Colombian population.

Methods: We conducted a cross-sectional study between 2017 and 2018. We measured vitamin D levels and EBV antibody titers and administered a questionnaire to assess dietary habits, smoking, second-hand smoking and duration of smoking, sunlight exposure, physical activity, and personal and family history in individuals with and without multiple sclerosis during adolescence.

Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis.

Objective: To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.

Methods: Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment.

Postmortem magnetic resonance imaging to guide the pathologic cut: individualized, 3-dimensionally printed cutting boxes for fixed brains.

Interfacing magnetic resonance imaging (MRI) with pathology is critically important for understanding the pathologic basis of MRI signal changes in vivo and for clinicopathologic correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathologic sections, which are relatively thick and often nonparallel, is both time-consuming and insufficiently accurate. The aim of this project was to develop technology to integrate postmortem, high-resolution, whole-brain MRI into the planning and execution of pathologic analysis through precise localization of the target and coordinates of cut.