GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci.

Tixagevimab/Cilgavimab does not prevent COVID-19 in patients with multiple sclerosis and related disorders on B-cell depleting therapies.

Background: Patients with MS and related disorders (pwMSARD) on B-cell depleting treatments have attenuated immune responses to vaccination and were eligible to receive tixagevimab/cilgavimab.

Objectives: Understand incidence and severity of COVID-19 in pwMSARD on B-cell depleting therapies who received tixagevimab/cilgavimab compared to an untreated group.

Methods: We conducted a retrospective medical records review of adult pwMSARD on B-cell depleting treatments who received tixagevimab/cilgavimab between 1/2022-1/2023.

A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis.

Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation.

Pregnancy and reproductive health in women with multiple sclerosis: an update.

Purpose Of Review: Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, neuro-degenerative disease of the central nervous system, prevalent in women of reproductive age. Today, many women want to start a family after MS diagnosis. There are over 20 treatments for MS, and safely navigating family planning is important.

A 28-Year-Old Woman With Left-Sided Weakness and Atypical MRI Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.

A 28-year-old woman presented with subacute relapsing left-sided weakness. MRI demonstrated both enhancing C3-C6 and nonenhancing T2-T4 lesions. Initial provisional diagnosis was inflammatory/autoimmune.

Multiple sclerosis lesions that impair memory map to a connected memory circuit.

Background: Nearly 1 million Americans are living with multiple sclerosis (MS) and 30-50% will experience memory dysfunction. It remains unclear whether this memory dysfunction is due to overall white matter lesion burden or damage to specific neuroanatomical structures. Here we test if MS memory dysfunction is associated with white matter lesions to a specific brain circuit.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine.

Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination.

Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab.

Sexual problems in MS: Sex differences and their impact on quality of life.

Background: Low sexual function and satisfaction are common problems among people with multiple sclerosis (PwMS), but the literature on which patient variables are associated with these issues is inconsistent.

Objective: To investigate the associations between sexual function and satisfaction in PwMS with clinical, demographic, and patient-reported quality of life (QOL) measures and determine if sex differences exist.

Methods: This analysis includes PwMS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB), who completed patient-reported outcome measures: Multiple Sclerosis Quality of Life-54 (MSQOL-54), Modified Fatigue Impact Scale (MFIS), and Center for Epidemiologic Studies Depression Scale (CES-D).

Assessment of Microglial Activation in Alzheimer Disease Using 18 F-PBR06 PET.

A 69-year-old woman with progressive short-term memory deficits was diagnosed with Alzheimer disease (MMSE 26/30, CDR 0.5) and underwent PET using 18 F-PBR06, a second-generation 18-kDa translocator protein ligand, targeting brain microglia and astrocytes. SUV and voxel-by-voxel binding potential maps (using simplified reference tissue method and a cerebellar pseudo-reference region) were generated.

Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients.

Background: Cognitive decline is inadequately captured by the standard neurological examination. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are biomarkers of neuronal damage and astrocytic reactivity that may offer an accessible measure of the multiple sclerosis (MS) pathology linked to cognitive decline.

Objective: To investigate the association of sNfL and sGFAP with cognitive decline in MS patients at high risk for progressive pathology.

Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis.

Background And Objectives: Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) and can be quantified by serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). We investigated sNfL and sGFAP as tools for stratifying patients with progressive MS based on progression and disease activity status.

Methods: We leveraged our Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data and serum samples collected over more than 20 years.

MeTooMS: Sexual, physical, and emotional abuse experience among women with multiple sclerosis.

Background: Sexual and physical violence against disabled individuals is widespread and linked to negative public health and social outcomes. The real-world prevalence of abuse in women with multiple sclerosis (MS) has not been well studied.

Objectives: To explore abuse prevalence in a real-world cohort of females with MS attending an academic MS Center.

Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors.

Background: There is concern that immune checkpoint inhibitors (ICPIs) can provoke relapses in people with multiple sclerosis (pwMS).

Objective: Analyze outcomes of pwMS who received ICPI treatment for malignancy.

Methods: We electronically identified pwMS who received ICPI treatment at Mass General Brigham hospital system.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

Background: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood.

Methods: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls.

Comparison of dimethyl fumarate and interferon outcomes in an MS cohort.

Background: To compare the effectiveness of dimethyl fumarate (DMF) with subcutaneous interferon beta-1a (IFNβ-1a) in controlling disease activity in patients with relapsing-remitting Multiple Sclerosis (MS).

Methods: Clinical and imaging data from patients treated with either IFNβ-1a or DMF for at least one year were reviewed. The proportion of patients with at least one clinical relapse within 3-15 months after treatment onset, the proportion of patients with new T2 or gadolinium-enhancing lesions, and the proportion of subjects who achieved no evidence of disease activity (NEDA) status were assessed.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

Background: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19.

Methods: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center.

Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets.

Background: Multiple sclerosis (MS) is an autoimmune condition of the central nervous system with a well-characterized genetic background. Prior analyses of MS genetics have identified broad enrichments across peripheral immune cells, yet the driver immune subsets are unclear.

Results: We utilize chromatin accessibility data across hematopoietic cells to identify cell type-specific enrichments of MS genetic signals.