Objective: Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS.
Methods: We conducted a retrospective observational study comparing BA and WA MS patients.
Importance: Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible fluid that most closely reflects central nervous system biology.
Objective: To identify CSF biological measures associated with progressive MS pathobiology.
The emergence of high-efficacy therapies for multiple sclerosis (MS), which target inflammation more effectively than traditional disease-modifying therapies, has led to a shift in MS management towards achieving the outcome assessment known as no evidence of disease activity (NEDA). The most common NEDA definition, termed NEDA-3, is a composite of three related measures of disease activity: no clinical relapses, no disability progression, and no radiological activity. NEDA has been frequently used as a composite endpoint in clinical trials, but there is growing interest in its use as an assessment tool to help patients and healthcare professionals navigate treatment decisions in the clinic.
View Article and Find Full Text PDFA small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology.
View Article and Find Full Text PDFQuantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to detect paramagnetic rims of iron-laden active microglia and macrophages in a subset of multiple sclerosis (MS) lesions, known as rim+ lesions, that are consistent with chronic active lesions. Because of the potential impact of rim+ lesions on disease progression and tissue damage, investigating their influence on disability and neurodegeneration is critical to establish the impact of these lesions on the disease course. This study aimed to explore the relationship between chronic active rim+ lesions, identified as having a hyperintense rim on QSM, and both clinical disability and imaging measures of neurodegeneration in patients with MS.
View Article and Find Full Text PDFBackground And Purpose: To compare quantitative susceptibility mapping (QSM) and high-pass-filtered (HPF) phase imaging for (1) identifying chronic active rim lesions with more myelin damage and (2) distinguishing patients with increased clinical disability in multiple sclerosis.
Methods: Eighty patients were scanned with QSM for paramagnetic rim detection and Fast Acquisition with Spiral Trajectory and T2prep for myelin water fraction (MWF). Chronic lesions were classified based on the presence/absence of rim on HPF and QSM images.
Background: Magnetic resonance imaging (MRI) provides insight into various pathological processes in multiple sclerosis (MS) and may provide insight into patterns of damage among patients.
Objective: We sought to determine if MRI features have clinical discriminative power among a cohort of MS patients.
Methods: Ninety-six relapsing remitting and seven progressive MS patients underwent myelin water fraction (MWF) imaging and conventional MRI for cortical thickness and thalamic volume.
COVID-19 affects a wide spectrum of organ systems. We report a 52-year-old man with hypertension and newly diagnosed diabetes mellitus who presented with hypoxic respiratory failure due to COVID-19 and developed severe brachial plexopathy. He was not treated with prone positioning respiratory therapy.
View Article and Find Full Text PDFBackground: Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron.
Objective: To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions.
Background And Purpose: To examine the impact of lesion location on longitudinal myelin water fraction (MWF) changes in chronic multiple sclerosis (MS) lesions. Relative hypoxia, due to vascular watershed regions of the cerebrum, has been implicated in lesion development but impact on ongoing demyelination is unknown.
Methods: Forty-eight patients with relapsing-remitting and secondary progressive MS had two MWF scans with fast acquisition, spiral trajectory, and T2prep (FAST-T2) sequence, at an interval of 2.
Purpose: The γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter and essential for normal brain function. The GABAergic system has been shown to have immunomodulatory effects and respond adaptively to excitatory toxicity. The association of the GABAergic system and inflammation in patients with multiple sclerosis (MS) remains unknown.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
January 2020
Objective: To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS.
Methods: In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions.
Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation.
View Article and Find Full Text PDFChronic active multiple sclerosis (MS) lesions have a rim of activated microglia/macrophages (m/M) leading to ongoing tissue damage, and thus represent a potential treatment target. Activation of this innate immune response in MS has been visualized and quantified using PET imaging with [11C]-(R)-PK11195 (PK). Accurate identification of m/M activation in chronic MS lesions requires the sensitivity to detect lower levels of activity within a small tissue volume.
View Article and Find Full Text PDFObjective: To investigate a single-course treatment with alemtuzumab in patients with relapsing-remitting multiple sclerosis.
Methods: We performed a retrospective chart review of all patients diagnosed with RRMS who were treated with alemtuzumab at our MS center and who had at least 12 month follow-up since the first dose. Data on radiological and clinical relapse were collected for the 2 years prior to patients' first dose of alemtuzumab and were tracked until the time of analysis.
Objective: The objective of this study is to longitudinally analyze the uptake of [C]PK11195-PET in multiple sclerosis patients after 3 and 6 months of natalizumab treatment.
Methods: Eighteen MS patients, starting treatment with monocloncal anti-VLA-4, were enrolled in a longitudinal PK-PET study. PK uptake was quantified by volume of distribution (VT) calculation using image-derived input function at baseline, 3 and 6 months.
Ther Adv Neurol Disord
June 2017
Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression.
View Article and Find Full Text PDFDisease activity in multiple sclerosis (MS) has classically been defined by the occurrence of new neurological symptoms and the rate of relapses. Definition of disease activity has become more refined with the use of clinical markers, evaluating ambulation, dexterity, and cognition. Magnetic resonance imaging (MRI) has become an important tool in the investigation of disease activity.
View Article and Find Full Text PDFIntroduction: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system (CNS) that classically occurs in children and adolescents. It characteristically presents with acute inflammation, resulting in demyelination, often following an infectious disease. ADEM has been described in adult patients, but the incidence in the adult and especially elderly population is low.
View Article and Find Full Text PDFNeuropsychiatr Dis Treat
August 2016
Objective: Identify aggressive onset multiple sclerosis (AOMS) and describe its clinical course.
Methods: AOMS patients were identified from a multiple sclerosis (MS) database based on a set of criteria. The subsequent clinical course of AOMS patients was then reviewed with the goal of potentially identifying the best approaches to manage these patients.
This study reveals the presence of dendritic cells (DCs) in the pituitary gland, which play a role in communicating immune activation to the hypothalamic pituitary adrenal (HPA) axis. Using enhanced yellow fluorescent protein (eyfp) expression as a reporter for CD11c, a marker of DCs, we demonstrate anatomically the presence of CD11c/eyfp+ cells throughout the pituitary. Flow cytometric analysis shows that the predominant cellular phenotype of pituitary CD11c/eyfp+ cells resembles that of non-lymphoid DCs.
View Article and Find Full Text PDFDendritic cells (DC) are specialized antigen-presenting cells, responsible for peripheral immune responses. Recently, resident brain dendritic cells (bDC) were identified and functionally characterized in the young adult Itgax (CD11c) EYFP+ transgenic mouse brain. In the present study, we describe changes in number, phenotype, and source of bDC in the aging mouse brain.
View Article and Find Full Text PDFThe immune response to stroke is comprised of inflammatory and regulatory processes. One cell type involved in both innate and adaptive immunity is the dendritic cell (DC). A DC population residing in the healthy brain (bDC) was identified using a transgenic mouse expressing enhanced yellow fluorescent protein (EYFP) under the promoter for the DC marker, CD11c (CD11c/EYFP Tg).
View Article and Find Full Text PDFDendritic cells (DC) are the professional antigen presenting cells (APC) that bridge the innate and adaptive immune system. Previously, in a CD11c/EYFP transgenic mouse developed to study DC functions, we anatomically mapped and phenotypically characterized a discrete population of EYFP(+) cells within the microglia that we termed brain dendritic cells (bDC). In this study, we advanced our knowledge of the function of these cells in the CD11c/EYFP transgenic mouse and its chimeras, using acute stimuli of stereotaxically inoculated IFNgamma or IL-4 into the CNS.
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