Medicine › Pathology and Forensic Medicine

Multiple Sclerosis Research Studies

Works Count: 77048

Wikipedia

Description

This cluster of papers focuses on the diagnosis, pathogenesis, and treatment of multiple sclerosis (MS) and related disorders such as neuromyelitis optica. It covers topics such as the diagnostic criteria for MS, genetic risk factors, immune mechanisms involved in MS, cognitive impairment, axonal injury, and the autoimmune pathology underlying the disease. The papers also discuss the use of various therapies and their effects on MS patients.

Keywords

Multiple Sclerosis; Diagnostic Criteria; Neuromyelitis Optica; Demyelination; Immune Mechanisms; Genetic Risk; B-Cell Depletion; Cognitive Impairment; Axonal Injury; Autoimmune Pathology

Immunopathology of multiple sclerosis

2015-08-07

Calliope A. Dendrou , Lars Fugger , Manuel A. Friese

Multiple Sclerosis — The Plaque and Its Pathogenesis

2006-03-01

Elliot M. Frohman , Michael K. Racke , Cedric S. Raine

Substantial advances have elucidated some of the central mechanisms underlying the inflammation, demyelination, and neurodegeneration that occur in multiple sclerosis. Correspondingly, the clinical strategies available for the management of the … Substantial advances have elucidated some of the central mechanisms underlying the inflammation, demyelination, and neurodegeneration that occur in multiple sclerosis. Correspondingly, the clinical strategies available for the management of the disease have widened. This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque.

Meta-analysis of prevalence

2013-08-20

Jan J. Barendregt , Suhail A.R. Doi , Yong Yi Lee +2 more

Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such … Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such as incidence and prevalence. In this article we present methods for the meta-analysis of prevalence. We discuss the logit and double arcsine transformations to stabilise the variance. We note the special situation of multiple category prevalence, and propose solutions to the problems that arise. We describe the implementation of these methods in the MetaXL software, and present a simulation study and the example of multiple sclerosis from the Global Burden of Disease 2010 project. We conclude that the double arcsine transformation is preferred over the logit, and that the MetaXL implementation of multiple category prevalence is an improvement in the methodology of the meta-analysis of prevalence.

Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis

1995-07-01

K. P. Johnson , Benjamin Brooks , J. A. Cohen +7 more

we studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n … we studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2-year relapse rate was 1.19 ± 0.13 for patients receiving copolymer 1 and 1.68 ± 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two-neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by ≥1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection-site reaction. Rarely, a transient self-limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo. This reaction was characterized by flushing or chest tightness with palpitations, anxiety, or dyspnea and commonly lasted for 30 seconds to 30 minutes. This rigorous study confirmed the findings of a previous pilot trial and demonstrated that copolymer 1 treatment can significantly and beneficially alter the course of relapsing-remitting MS in a well-tolerated fashion.

Interpreting scores on the Kessler Psychological Distress Scale (K10)

2001-12-01

Gavin Andrews , Tim Slade

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

2011-08-01

Stephen Sawcer , Garrett Hellenthal , Matti Pirinen +7 more

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Cortical demyelination and diffuse white matter injury in multiple sclerosis

2005-10-17

Alexandra Kutzelnigg , Claudia F. Lucchinetti , Christine Stadelmann +6 more

Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, … Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.

The clinical course of neuromyelitis optica (Devic’s syndrome)

1999-09-01

Dean M. Wingerchuk , William F. Hogancamp , Peter C. O’Brien +1 more

To evaluate the spectrum of neuromyelitis optica (NMO), including characteristics of the index events (optic neuritis [ON]) and myelitis), neuroimaging, CSF, and serologic studies, and to evaluate the long-term course.Review … To evaluate the spectrum of neuromyelitis optica (NMO), including characteristics of the index events (optic neuritis [ON]) and myelitis), neuroimaging, CSF, and serologic studies, and to evaluate the long-term course.Review of 71 patients with NMO evaluated at the Mayo Clinic between 1950 and 1997.NMO was either monophasic or relapsing. Patients with a monophasic course (n = 23) usually presented with rapidly sequential index events (median 5 days) with moderate recovery. Most with a relapsing course (n = 48) had an extended interval between index events (median 166 days) followed within 3 years by clusters of severe relapses isolated to the optic nerves and spinal cord. Most relapsing patients developed severe disability in a stepwise manner, and one-third died because of respiratory failure. Features of NMO distinct from "typical" MS included >50 cells/mm3 in CSF (often polymorphonuclear), normal initial brain MRI, and lesions extending over three or more vertebral segments on spinal cord MRI.Clinical, laboratory, and imaging features generally distinguish neuromyelitis optica from MS. Patients with relapsing optic neuritis and myelitis may have neuromyelitis optica rather than MS. Patients with a relapsing course of neuromyelitis optica have a poor prognosis and frequently develop respiratory failure during attacks of cervical myelitis.

Cognitive dysfunction in multiple sclerosis.: I. Frequency, patterns, and prediction

1991-05-01

Stephen M. Rao , Gary J. Leo , Linda Bernardin +1 more

Previous frequency estimates of cognitive dysfunction in multiple sclerosis have ranged from 54 to 65 percent. These studies may overestimate the frequency in the general MS population, since the … Previous frequency estimates of cognitive dysfunction in multiple sclerosis have ranged from 54 to 65 percent. These studies may overestimate the frequency in the general MS population, since the patients in these studies were recruited from clinic populations. In the present study, we administered a comprehensive neuropsychological test battery to 100 community‐based MS patients and 100 demographically matched healthy controls. Of 31 cognitive test indices examined, 48 MS patients and five controls were impaired on four or more test indices, yielding an overall frequency rate of 43% for the MS group. The pattern of cognitive decline was not uniform: MS patients were more frequently impaired on measures of recent memory, sustained attention, verbal fluency, conceptual reasoning, and visuospatial perception, and less frequently impaired on measures of language and immediate and remote memory. We developed a brief (20‐minute) screening battery empirically by selecting the four most sensitive test indices from the comprehensive battery. The brief battery yielded a sensitivity value of 71% and a specificity value of 94% in discriminating cognitively intact from impaired MS patients, as defined by the comprehensive battery. Cognitive impairment was not significantly associated with illness duration, depression, disease course, or medication usage, but was significantly (albeit weakly) correlated with physical disability. NEUROLOGY 1991;41:685‐691

Defining the clinical course of multiple sclerosis

1996-04-01

Fred Lublin , Stephen C. Reingold

Standardization of terminology used to describe the pattern and course of MS is essential for mutual understanding between clinicians and investigators. It is particularly important in design of, and recruitment … Standardization of terminology used to describe the pattern and course of MS is essential for mutual understanding between clinicians and investigators. It is particularly important in design of, and recruitment for, clinical trials statistically powered for expected outcomes for given patient populations with narrowly defined entry criteria. For agents that prove safe and effective for MS, knowledge of the patient populations in definitive clinical trials assists clinicians in determining who may ultimately benefit from use of the medication. An international survey of clinicians involved with MS revealed areas of consensus about some terms classically used to describe types of the disease and other areas for which there was lack of consensus. In this report, we provide a summary of the survey results and propose standardized definitions for the most common clinical courses of patients with MS.

Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis

2012-09-19

Ralf Gold , Ludwig Kappos , Douglas L. Arnold +7 more

BG-12 (dimethyl fumarate) was shown to have antiinflammatory and cytoprotective properties in preclinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging (MRI) in a … BG-12 (dimethyl fumarate) was shown to have antiinflammatory and cytoprotective properties in preclinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging (MRI) in a phase 2, placebo-controlled study involving patients with relapsing-remitting multiple sclerosis.We conducted a randomized, double-blind, placebo-controlled phase 3 study involving patients with relapsing-remitting multiple sclerosis. Patients were randomly assigned to receive oral BG-12 at a dose of 240 mg twice daily, BG-12 at a dose of 240 mg three times daily, or placebo. The primary end point was the proportion of patients who had a relapse by 2 years. Other end points included the annualized relapse rate, the time to confirmed progression of disability, and findings on MRI.The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons). The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group, as compared with 0.36 in the placebo group, representing relative reductions of 53% and 48% with the two BG-12 regimens, respectively (P<0.001 for the comparison of each BG-12 regimen with placebo). The estimated proportion of patients with confirmed progression of disability was 16% in the twice-daily BG-12 group, 18% in the thrice-daily BG-12 group, and 27% in the placebo group, with significant relative risk reductions of 38% with BG-12 twice daily (P=0.005) and 34% with BG-12 thrice daily (P=0.01). BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted hyperintense lesions (P<0.001 for the comparison of each BG-12 regimen with placebo). Adverse events associated with BG-12 included flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as well as decreased lymphocyte counts and elevated liver aminotransferase levels.In patients with relapsing-remitting multiple sclerosis, both BG-12 regimens, as compared with placebo, significantly reduced the proportion of patients who had a relapse, the annualized relapse rate, the rate of disability progression, and the number of lesions on MRI. (Funded by Biogen Idec; DEFINE ClinicalTrials.gov number, NCT00420212.).

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A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis

2006-03-01

Chris H. Polman , Paul O’Connor , Eva Havrdová +7 more

Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with … Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan-Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent).Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300.).

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A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis

2010-01-21

Ludwig Kappos , Ernst‐Wilhelm Radue , Paul O’Connor +7 more

Oral fingolimod, a sphingosine-1-phosphate–receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with … Oral fingolimod, a sphingosine-1-phosphate–receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with either placebo or intramuscular interferon beta-1a, in phase 2 and 3 studies of multiple sclerosis.

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Defining the clinical course of multiple sclerosis

2014-05-29

Fred Lublin , Stephen C. Reingold , Jeffrey A. Cohen +7 more

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on … Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

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Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis

2001-06-26

W. I. McDonald , Alistair Compston , Gilles Edan +7 more

Abstract The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and … Abstract The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with clinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as “clinically definite” and “probable MS” are no longer recommended. The outcome of a diagnostic evaluation is either MS, “possible MS” (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or “not MS.”

The spectrum of neuromyelitis optica

2007-08-14

Dean M. Wingerchuk , Vanda A. Lennon , Claudia F. Lucchinetti +2 more

Measuring the Functional Impact of Fatigue: Initial Validation of the Fatigue Impact Scale

1994-01-01

John D. Fisk , Paul G. Ritvo , Lynn Ross +3 more

Journal Article Measuring the Functional Impact of Fatigue: Initial Validation of the Fatigue Impact Scale Get access John D. Fisk, John D. Fisk From the Department of Psychology, Camp Hill … Journal Article Measuring the Functional Impact of Fatigue: Initial Validation of the Fatigue Impact Scale Get access John D. Fisk, John D. Fisk From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Reprints or correspondence: Dr. John D. Fisk, Department of Psychology, Camp Hill Medical Centre, 1763 Robie Street, Halifax, Nova Scotia, Canada B3H 3G2. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul G. Ritvo, Paul G. Ritvo From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn Ross, Lynn Ross From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar David A. Haase, David A. Haase From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Marrie, Thomas J. Marrie From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter F. Schlech Walter F. Schlech From the Department of Psychology, Camp Hill Medical Centre; the Departments of Psychiatry, Psychology, and Medicine, Dalhousie University; and the Departments of Medicine and Psychology, Victoria General Hospital, Halifax, Nova Scotia, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 18, Issue Supplement_1, January 1994, Pages S79–S83, https://doi.org/10.1093/clinids/18.Supplement_1.S79 Published: 01 January 1994

Rating neurologic impairment in multiple sclerosis

1983-11-01

John F. Kurtzke

One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional … One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 … 9) now divided into two (1.0, 1.5, 2.0 … 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.

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IMMUNOLOGY OF MULTIPLE SCLEROSIS

2005-01-19

Mireia Sospedra , Roland Martinꝉ

▪ Abstract Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the … ▪ Abstract Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4 + autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8 + T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4 + T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.

Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

2011-01-11

Chris H. Polman , Stephen C. Reingold , Brenda Banwell +7 more

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system … New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

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International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

2015-06-20

Dean M. Wingerchuk , Brenda Banwell , Jeffrey L. Bennett +7 more

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve … Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

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New diagnostic criteria for multiple sclerosis: Guidelines for research protocols

1983-03-01

Charles M. Poser , Donald W. Paty , Labe C. Scheinberg +7 more

Cognitive impairment in multiple sclerosis

2008-11-12

Nancy D. Chiaravalloti , John DeLuca

Revised diagnostic criteria for neuromyelitis optica

2006-05-01

Dean M. Wingerchuk , Vanda A. Lennon , Sean J. Pittock +2 more

Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS). However, some patients with otherwise typical NMO have additional symptoms … Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS). However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions. Furthermore, some patients are misclassified as NMO by the authors’ earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS. A serum autoantibody marker, NMO-IgG, is highly specific for NMO. The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status. Methods: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS. The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model. Results: Fourteen patients with NMO (14.6%) had extra-optic-spinal CNS symptoms. NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO. The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity. Conclusions: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. CNS involvement beyond the optic nerves and spinal cord is compatible with NMO.

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Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis

1996-03-01

Lawrence Jacobs , Diane L. Cookfair , Richard A. Rudick +7 more

Abstract The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression … Abstract The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta‐1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double‐blinded, placebo‐controlled, multicenter phase I11 trial of interferon beta‐la. Interferon beta‐la, 6.0 million units (30 μg), was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression ( p equals; 0.02). The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta‐la‐treated group. Patients treated with interferon beta‐la also had significantly fewer exacerbations ( p = 0.03) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images (pvalues ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients. There were no major adverse events related to treatment. Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images. This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis.

B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis

2008-02-13

Stephen L. Hauser , Emmanuelle Waubant , Douglas L. Arnold +7 more

There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes … There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes.In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing-remitting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15. The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12, 16, 20, and 24. Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse.As compared with patients who received placebo, patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P<0.001) and of total new gadolinium-enhancing lesions over the same period (P<0.001); these results were sustained for 48 weeks (P<0.001). As compared with patients in the placebo group, the proportion of patients in the rituximab group with relapses was significantly reduced at week 24 (14.5% vs. 34.3%, P=0.02) and week 48 (20.3% vs. 40.0%, P=0.04). More patients in the rituximab group than in the placebo group had adverse events within 24 hours after the first infusion, most of which were mild-to-moderate events; after the second infusion, the numbers of events were similar in the two groups.A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks. This trial was not designed to assess long-term safety or to detect uncommon adverse events. The data provide evidence of B-cell involvement in the pathophysiology of relapsing-remitting multiple sclerosis. (ClinicalTrials.gov number, NCT00097188 [ClinicalTrials.gov].).

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New Multiple Sclerosis Phenotypic Classification

2014-01-01

Fred Lublin

Background: In 1996, the clinical course of multiple sclerosis (MS) was characterized as relapsing-remitting, primary progressive, secondary progressive or progressive relapsing. Since then, an increased understanding of MS and its … Background: In 1996, the clinical course of multiple sclerosis (MS) was characterized as relapsing-remitting, primary progressive, secondary progressive or progressive relapsing. Since then, an increased understanding of MS and its pathology prompted a re-examination of these clinical phenotypes. Main recommendations of the 2013 revisions are provided herein. Summary: Clinically isolated syndrome has been added, and progressive relapsing MS has been eliminated, from the clinical course descriptions. All forms of MS should be further subcategorized as either active or non-active. Active MS is defined as the occurrence of clinical relapse or the presence of new T2 or gadolinium-enhancing lesions over a specified period of time, preferably at least one year. An additional subcategory for patients with progressive MS differentiates between those who have shown signs of disability progression over a given time period and those who have remained stable. The term ‘worsening' is recommended to describe patients whose disease is advancing for any reason, whereas ‘disease progression' should be reserved for those with progressive disease who are truly progressing (as opposed to worsening from a relapse). The term ‘benign' should be used with caution as the course of MS can worsen at any time, even after many years of apparent stability. Key Messages: Newer characterizations of MS phenotypes include a consideration of disease activity (based on the clinical relapse rate and imaging findings) and disease progression. Accurate clinical course descriptions are useful for communication, prognostication, clinical trial design and to guide everyday clinical decision-making. © 2014 S. Karger AG, Basel

IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

2005-08-08

Vanda A. Lennon , Thomas J. Kryzer , Sean J. Pittock +2 more

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed … Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

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Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination

2000-06-01

Claudia F. Lucchinetti , Wolfgang Br�ck , Joseph E. Parisi +3 more

Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course, neuroradiological appearance of the lesions, involvement of susceptibility gene loci, and response to therapy. These features are supported … Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course, neuroradiological appearance of the lesions, involvement of susceptibility gene loci, and response to therapy. These features are supported by experimental evidence, which demonstrates that fundamentally different processes, such as autoimmunity or virus infection, may induce MS-like inflammatory demyelinating plaques and suggest that MS may be a disease with heterogeneous pathogenetic mechanisms. From a large pathology sample of MS, collected in three international centers, we selected 51 biopsies and 32 autopsies that contained actively demyelinating lesions defined by stringent criteria. The pathology of the lesions was analyzed using a broad spectrum of immunological and neurobiological markers. Four fundamentally different patterns of demyelination were found, defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction, and the immunopathological evidence of complement activation. Two patterns (I and II) showed close similarities to T-cell–mediated or T-cell plus antibody–mediated autoimmune encephalomyelitis, respectively. The other patterns (III and IV) were highly suggestive of a primary oligodendrocyte dystrophy, reminiscent of virus- or toxin-induced demyelination rather than autoimmunity. At a given time point of the disease—as reflected in autopsy cases—the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient. This pathogenetic heterogeneity of plaques from different MS patients may have fundamental implications for the diagnosis and therapy of this disease. Ann Neurol 2000;47:707–717

Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis

2010-01-20

Jeffrey A. Cohen , Frederik Barkhof , Gıancarlo Comı +7 more

Fingolimod (FTY720), a sphingosine-1-phosphate–receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. Fingolimod (FTY720), a sphingosine-1-phosphate–receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis.

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Multiple Sclerosis: An Immune or Neurodegenerative Disorder?

2008-06-17

Bruce D. Trapp , Klaus‐Armin Nave

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the … Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the third or fourth decade of life, and transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. We review data that support neurodegeneration as the major cause of irreversible neurological disability in MS patients. We question whether inflammatory demyelination is primary or secondary in the disease process and discuss the challenges of elucidating the cause of MS and developing therapies that will delay or prevent the irreversible and progressive neurological decline that most MS patients endure.

Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study

2007-07-30

David A. Hafler , Alastair Compston , Stephen Sawcer +7 more

Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis.We used DNA microarray technology to identify … Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis.We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis.A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10(-4)); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional nonoverlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor alpha gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10(-8)), as were a nonsynonymous SNP in the interleukin-7 receptor alpha gene (IL7RA) (P=2.94x10(-7)) and multiple SNPs in the HLA-DRA locus (P=8.94x10(-81)).Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis.

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Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis

1993-04-01

D. W. Paty , D.K.B. Li

We performed yearly MRI analyses on 327 of the total 372 patients in a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB). Clinical results are presented in the preceding … We performed yearly MRI analyses on 327 of the total 372 patients in a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB). Clinical results are presented in the preceding companion paper. Baseline MRI characteristics were the same in all treatment groups. Fifty-two patients at one center formed a cohort for frequent MRIs (one every 6 weeks) for analysis of disease activity. The MRI results support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans (median 80% reduction, p = 0.0082) and appearance of new lesions. In addition, there was an equally significant reduction in MRI-detected burden of disease in the treatment as compared with placebo groups (mean group difference of 23%, p = 0.001). These results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients.

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Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis

1998-11-01

George C. Ebers

Intramuscular Interferon Beta-1A Therapy Initiated during a First Demyelinating Event in Multiple Sclerosis

2000-09-28

Lawrence Jacobs , Roy W. Beck , Jack H. Simon +6 more

Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating … Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.

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Rate of Pregnancy-Related Relapse in Multiple Sclerosis

1998-07-30

Christian Confavreux , Michael Hutchinson , Martine Hours +2 more

Multiple sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood. We studied 254 women with multiple sclerosis during 269 pregnancies in 12 … Multiple sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood. We studied 254 women with multiple sclerosis during 269 pregnancies in 12 European countries. The women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability). The relapse rate in each trimester was compared with the rate during the year before the pregnancy. The effects of epidural analgesia and breast-feeding on the frequency of relapse during the first three months post partum and the disability score at 12 months post partum were also determined.

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Axonal Transection in the Lesions of Multiple Sclerosis

1998-01-29

Bruce D. Trapp , John W. Peterson , Richard M. Ransohoff +3 more

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most … Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis.

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Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

2016-12-21

Stephen L. Hauser , Amit Bar‐Or , Gıancarlo Comı +7 more

B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.

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Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

2016-12-21

Xavier Montalbán , Stephen L. Hauser , Ludwig Kappos +7 more

An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing … An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease.In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis.The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570 .).

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Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

2017-12-21

Alan J. Thompson , Brenda Banwell , Frederik Barkhof +7 more

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Multiple sclerosis – a review

2018-10-10

Ruth Dobson , Gavin Giovannoni

Multiple sclerosis ( MS ) is the commonest non‐traumatic disabling disease to affect young adults. The incidence of MS is increasing worldwide, together with the socioeconomic impact of the disease. … Multiple sclerosis ( MS ) is the commonest non‐traumatic disabling disease to affect young adults. The incidence of MS is increasing worldwide, together with the socioeconomic impact of the disease. The underlying cause of MS and mechanisms behind this increase remain opaque, although complex gene–environment interactions almost certainly play a significant role. The epidemiology of MS indicates that low serum levels of vitamin D, smoking, childhood obesity and infection with the Epstein–Barr virus are likely to play a role in disease development. Changes in diagnostic methods and criteria mean that people with MS can be diagnosed increasingly early in their disease trajectory. Alongside this, treatments for MS have increased exponentially in number, efficacy and risk. There is now the possibility of a diagnosis of ‘pre‐symptomatic MS’ being made; as a result potentially preventive strategies could be studied. In this comprehensive review, MS epidemiology, potential aetiological factors and pathology are discussed, before moving on to clinical aspects of MS diagnosis and management.

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Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”

2005-11-10

Chris H. Polman , Stephen C. Reingold , Gilles Edan +7 more

Abstract New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The “McDonald Criteria” have been extensively assessed and … Abstract New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The “McDonald Criteria” have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity. Ann Neurol 2005

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Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition

2020-11-11

Clare Walton , Rachel King , Lindsay Rechtman +7 more

Background: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support … Background: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support advocacy efforts. Objectives: The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country, regional and global levels. Methods: Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis. Regional analyses and comparisons with 2013 data were conducted. Results: A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population). MS prevalence has increased in every world region since 2013 but gaps in prevalence estimates persist. The pooled incidence rate across 75 reporting countries is 2.1 per 100,000 persons/year, and the mean age of diagnosis is 32 years. Females are twice as likely to live with MS as males. Conclusions: The global prevalence of MS has risen since 2013, but good surveillance data is not universal. Action is needed by multiple stakeholders to close knowledge gaps.

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Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

2022-01-14

Kjetil Bjørnevik , Marianna Cortese , Brian C. Healy +7 more

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in … Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis

1993-04-01

We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-lb (IFNB) in 372 ambulatory patients with relapsing-remitting multiple sclerosis (MS). Entry criteria included an Expanded Disability Status Scale (EDSS) … We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-lb (IFNB) in 372 ambulatory patients with relapsing-remitting multiple sclerosis (MS). Entry criteria included an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and at least two exacerbations in the previous 2 years. One-third of the patients received placebo, one-third 1.6 million international units (MIU) of IFNB, and one-third 8 MIU of IFNB, self-administered by subcutaneous injections every other day. The primary end points were differences in exacerbation rates and proportion of patients remaining exacerbation-free. The annual exacerbation rate for patients receiving placebo was 1.27; for 1.6 MIU IFNB, 1.17; and for 8 MIU IFNB, 0.84 after 2 years. Exacerbation rates were significantly lower in both treatment groups compared with the placebo group (8 MIU versus placebo, p = 0.0001; 1.6 MIU versus placebo, p = 0.0101; and 8 MIU versus 1.6 MIU, p = 0.0086), suggesting a dosage effect. The reduction in exacerbation severity in the 8 MIU group was attributable to a twofold reduction in the frequency of moderate and severe attacks. More patients in the 8 MIU group (n = 36) were exacerbation-free at 2 years compared with the placebo group (n = 18; p = 0.007). EDSS scores changed little from baseline in both the placebo and treatment arms. Accordingly, a significant change in disability could not be discerned in this trial. Finally, in serial MRIs, MS activity was significantly less in the high-dose IFNB group. IFNB treatment was well tolerated: the significant reductions in exacerbation rates, severity of exacerbations, and accumulation of MRI abnormalities occurred in the absence of serious side effects. IFNB is the only treatment that has substantially altered the natural history of MS in a properly controlled clinical trial.

Multiple sclerosis

2018-03-23

Alan J. Thompson , Sergio E. Baranzini , Jeroen J.G. Geurts +2 more

Multiple sclerosis

2008-10-01

Alastair Compston , Alasdair Coles

Multiple sclerosis

2002-04-01

Alastair Compston , Alasdair Coles

Multiple Sclerosis

2000-09-28

John H. Noseworthy , Claudia F. Lucchinetti , Moses Rodriguez +1 more

More than 100 years has passed since Charcot, Carswell, Cruveilhier, and others described the clinical and pathological characteristics of multiple sclerosis.1 This enigmatic, relapsing, and often eventually progressive disorder of … More than 100 years has passed since Charcot, Carswell, Cruveilhier, and others described the clinical and pathological characteristics of multiple sclerosis.1 This enigmatic, relapsing, and often eventually progressive disorder of the white matter of the central nervous system continues to challenge investigators trying to understand the pathogenesis of the disease and prevent its progression.2 There are 250,000 to 350,000 patients with multiple sclerosis in the United States.3 Multiple sclerosis typically begins in early adulthood and has a variable prognosis. Fifty percent of patients will need help walking within 15 years after the onset of disease.4 Advanced magnetic resonance imaging (MRI) . . .

Multiple Sclerosis

2018-01-10

Daniel S. Reich , Claudia F. Lucchinetti , Peter A. Calabresi

Multiple sclerosis affects more than 2 million people worldwide and is currently incurable. A number of interventions to modify the course of multiple sclerosis have been developed that offer new … Multiple sclerosis affects more than 2 million people worldwide and is currently incurable. A number of interventions to modify the course of multiple sclerosis have been developed that offer new insight into disease mechanisms.

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Treatment Options for the Comorbidity of Multiple Sclerosis With Other Chronic Inflammatory Diseases.

2025-08-08

Stefan Bittner , Martin Kriegel , Britta Siegmund +2 more | PubMed

Approximately 280 000 people in Germany suffer from multiple sclerosis (MS), an autoimmune disease of the central nervous system. Of these, approximately 5% have a comorbid chronic inflammatory disease: the … Approximately 280 000 people in Germany suffer from multiple sclerosis (MS), an autoimmune disease of the central nervous system. Of these, approximately 5% have a comorbid chronic inflammatory disease: the more common ones are psoriasis, rheumatoid arthritis (RA), and chronic inflammatory bowel diseases (IBDs, of which the main types are ulcerative colitis and Crohn's disease). This narrative review is based on pertinent publications retrieved by a literature search in PubMed, as well as relevant guidelines. All statements in this article reflect a consensus among the authors, who represent different medical disciplines. As the data from clinical trials to date are limited, judgments about the proposed treatments are a matter of expert opinion. In general, TNFα blockers should not be used in patients with MS, as they can worsen the disease. In patients with MS and psoriasis, dimethyl fumarate is a useful option for mild disease activity. In MS with comorbid RA, azathioprine and leflunomide/teriflunomide are suitable for mild disease activity. For more severe disease activity, anti-CD20 antibodies have been approved for both diseases and should be used. In MS with comorbid IBD, azathioprine is suitable for mild disease activity. Ozanimod has been approved for patients who have MS and comorbid ulcerative colitis with more severe disease activity, especially those who are JC-negative; it shares its mechanism of action (VLA-4 blockade) with natalizumab. The treatment of patients who have both MS and another chronic inflammatory disease should be interdisciplinary and personalized, and treatments must be planned with due attention to potential adverse effects. Further studies of treatment for this group of patients are needed.

Oligoclonal banding analysis: assessing plasma use and time interval requirements for paired CSF and blood

2025-06-25

Lily Olayinka , Yu Chen , Karina Rodríguez-Capote +7 more | Clinical Chemistry and Laboratory Medicine (CCLM)

Multiple Sclerosis-related Fatigue: An Updated Review of Pathophysiology and Associated Variables Contributing Factors

2025-06-25

Kübra Yeni , Murat Terzi | Journal of Multiple Sclerosis Research

Temporal progression of axonal degeneration in the visual system in experimental autoimmune encephalomyelitis: Insights from high-resolution neuropathology

2025-06-25

Chang Liu , Athanasios S. Alexandris , Marjan Gharagozloo +3 more | Journal of Neuropathology & Experimental Neurology

Abstract Multiple sclerosis (MS) is characterized by inflammation, demyelination, and axonal degeneration in the CNS, leading to progressive neurological disability is generally regarded as an autoimmune disorder. Visual impairment, a … Abstract Multiple sclerosis (MS) is characterized by inflammation, demyelination, and axonal degeneration in the CNS, leading to progressive neurological disability is generally regarded as an autoimmune disorder. Visual impairment, a frequent symptom, results from damage to retinal ganglion cells (RGCs) and their axons in the anterior visual pathway. Using the experimental autoimmune encephalomyelitis (EAE) model in mice, we used several methods, including high-resolution neuropathology with a novel immunohistochemical technique on ultrathin sections, to characterize axonal pathology and demyelination, terminal disruption, perikaryal degeneration, and visual acuity. Electron microscopy demonstrated early axonopathy and myelin splitting, progressing to severe degradation of axons and myelin sheaths. Severe transport deficits in the optic nerve correlated with loss of labeling of retinocollicular terminals. Visual acuity, assessed by optomotor response (OMR), significantly declined at peak stage in the EAE group and remained impaired throughout the course of disease. These findings reveal the temporal progression of neurodegeneration with a dying-back pattern in EAE and emphasize the importance of early intervention to prevent permanent damage. They also point to the importance of novel methods in generating new insights in classical models of neurological disease.

High‐Dose Pulse Glucocorticoid Treatment Prevents White Matter Spinal Cord Pseudoatrophy in Newly Diagnosed Multiple Sclerosis

2025-06-24

Simone Sacco , Nico Papinutto , Vinícius Andreoli Schoeps +7 more | Annals of Neurology

Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation … Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation of disease-modifying therapy (DMT) may be followed by early pronounced central nervous system (CNS) volume loss due to resolution of inflammation (pseudoatrophy) and confounding the interpretation of atrophy. High-dose glucocorticoids (HDGs) reduce inflammation and might therefore modify pseudoatrophy. One hundred twenty-three newly diagnosed and DMT-naïve MS participants (relapsing-remitting, 70% female participants, median age = 36 years, Expanded Disability Status Scale [EDSS] 2.0) were followed for up to 3 years. Forty-two participants received HDG before baseline magnetic resonance imaging (MRI; DMT-HDG; median = 52 days, interquartile range [IQR] = 37-71), whereas 60 did not (DMT/no-HDG). Twenty-one participants remained untreated (no-DMT), and 102 started DMT after baseline MRI. SC total cervical cord cross-sectional area (TCA), gray matter area (GMA), and white matter area (WMA) and regional brain volumes were analyzed using mixed effects models. The DMT-HDG, DMT/no-HDG, and no-DMT groups had similar demographic, clinical, and radiological features. Pronounced SC pseudoatrophy was observed based on more year 1 versus year 2 volume loss for DMT/no-HDG (-2.06% vs. 0.83%; P = 0.02) but not DMT-HDG (-0.51% vs. 0.66%; P = 0.8) and more year 1 volume loss for DMT/no-HDG compared to DMT-HDG (-2.06% vs. 0.51%; P = 0.02). HDG preceding baseline MRI suppresses CNS white matter (WM) pseudoatrophy after DMT initiation, most conspicuously for the SC. Suppression of pseudoatrophy with HDG may improve the fidelity of clinical trials and enhance the feasibility for short-term trials with SC and brain MRI outcomes in active MS by pretreatment with HDG. ANN NEUROL 2025.

Understanding stigma in multiple sclerosis: workplace discrimination, social challenges and psychological impacts

2025-06-24

Nazlı Gamze Bülbül , Abdülkadir Tunç , Sena Destan Bünül +7 more | Acta Neurologica Belgica

Impact of physical therapy on multiple sclerosis patients

2025-06-24

Álvaro J. Montiel‐Jarquín , Anel Gómez‐García , Angélica Porras-Juárez +5 more | Anales Médicos de la Asociación Médica del Centro Médico ABC

Early treatment with ofatumumab increases the likelihood of stabilizing disease in patients with relapsing-remitting multiple sclerosis.

2025-06-24

Adam Stępień , Aleksandra Pogoda-Wesołowska , Jacek Staszewski +7 more | Archives of Medical Science

Introduction The methods of multiple sclerosis (MS) treatment are evolving rapidly with numerous classes of disease-modifying therapies (DMTs). A more aggressive approach to early and effective treatment of MS with … Introduction The methods of multiple sclerosis (MS) treatment are evolving rapidly with numerous classes of disease-modifying therapies (DMTs). A more aggressive approach to early and effective treatment of MS with defined treatment target increases the chance of achieving a state of no no evidence of disease activity (NEDA). Currently, B cell–depleting monoclonal antibodies have been proven as high effective strategy for the treatment of relapsing-remitting MS (RRMS). Ofatumumab (OFA), anti-CD-20 monoclonal antibody is effective in treatment of RRMS, as it positively affects relapse rates, magnetic resonance imaging (MRI) measures of disease activity and disability progression. Material and methods A retrospective observational study conducted in six MS clinical centers in Poland, including a cohort of patients with RRMS treated with OFA over a two-year period was presented. Results The results of this study showed a statistically significant decrease in the relapse activity of the disease in the course of a year of OFA therapy. The percentage of patients free of relapses increased from 45% before treatment to 88% after one year of follow-up. Moreover, the disability assessment index measured by the Expanded Disability Status Scale (EDSS) remained stable after a two years of follow-up. Conclusions In the presented study the high efficacy of OFA therapy in reducing recurrent disease activity as well as in inhibiting disability progression, with a favorable safety profile was confirmed. Moreover, it was emphasized that to achieve the best possible inhibition of disease activity and its progression, it is necessary to implement the treatment as soon as possible after the diagnosis.

Multiple sclerosis associated with adalimumab: a case report and systematic review

2025-06-24

A.A. Tappakhov , T. Ya. Nikolaeva , Natalia Gorokhova +3 more | Neurology neuropsychiatry Psychosomatics

Yakutsk 58, Belinskogo St., Yakutsk 677000, Russia; 4, Sergelyakhskoye Sh., Yakutsk 677010, Russia The role of medications as risk factors for the development of multiple sclerosis (MS) remains controversial, although … Yakutsk 58, Belinskogo St., Yakutsk 677000, Russia; 4, Sergelyakhskoye Sh., Yakutsk 677010, Russia The role of medications as risk factors for the development of multiple sclerosis (MS) remains controversial, although there is a limited number of studies addressing the influence of immunomodulatory drugs, contraceptives, and antibiotics on the onset of this disease. One group of medications associated with the development of demyelinating disorders (including MS) is tumor necrosis factor alpha (TNF-α) inhibitors. The limited number of reported cases of demyelination associated with this group of drugs (specifically, adalimumab), both in domestic and international medical practice, prompted the writing of this article. It presents a clinical case of a female patient who was prescribed adalimumab for the treatment of ankylosing spondylitis and developed MS in the fourth year of the disease (second year of therapy). In addition, a systematic review is presented including 13 patients described in the literature as well as our own case report.

A multi-domain lifestyle intervention in multiple sclerosis: a longitudinal observational study

2025-06-24

Ilse M. Nauta , Keeva N M Loughlin , Arianne S Gravesteijn +7 more | Journal of Neurology

Abstract Objective To examine the effects of a multi-domain lifestyle intervention that advocated a Mediterranean style diet, and concurrently targeted physical activity, stress and sleep, on multiple sclerosis. Methods A … Abstract Objective To examine the effects of a multi-domain lifestyle intervention that advocated a Mediterranean style diet, and concurrently targeted physical activity, stress and sleep, on multiple sclerosis. Methods A longitudinal observational study investigating the effect of a multi-domain lifestyle intervention (i.e., diet, exercise, stress, and sleep management) at four timepoints: start run-in, start and stop 3-month intensive interval, and 3-month follow-up. The primary outcome (i.e., impact of multiple sclerosis on daily functioning) and secondary outcomes (i.e., quality of life, general health, multiple sclerosis-specific symptoms, and lifestyle factors) were analyzed using mixed models. Analyses were repeated among subgroups based on program compliance, body mass index, education level, and multiple sclerosis-subtype. Results Out of 668 participants, 579 were included (age 46.2 ± 10.5 years, 84.5% women, and 71% relapsing–remitting multiple sclerosis). The impact of multiple sclerosis on physical functioning remained stable during the run-in period, but reduced significantly from baseline to both post-intervention ( β = −2.50 [−3.40, −1.60]) and to 3-month follow-up ( β = −2.00 [−2.93, −1.07]). The impact of multiple sclerosis on mental functioning decreased significantly across all time periods (run-in β = 1.86 [0.78, 2.94], post-intervention β = −3.48 [−4.58, −2.39], and 3-month follow-up β = −2.44 [−3.56, 1.31]). Effect size was greatest among participants with higher compliance, lower education, and obesity. Interpretation The lifestyle program was associated with reduced impact of multiple sclerosis on daily functioning, multiple sclerosis-related symptoms, mental quality of life, and general health determinants. Future randomized trials are needed to establish causal effects of lifestyle adjustments on multiple sclerosis.

The Future of PET Imaging in Multiple Sclerosis: Characterisation of Individual White Matter Lesions

2025-06-23

Chris W.J. van der Weijden , Jan F. Meilof , Anouk van der Hoorn +2 more | Journal of Clinical Medicine

Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) … Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) remodelling and glial cell activation, has a decisive effect on lesion development and disease progression. Understanding the biological and pathological features of lesions would aid in prognosis and personalised treatment decision making. Positron emission tomography (PET) is an imaging technique that uses radio-labelled tracers to detect specific biological phenomena. Recent PET hardware developments enable high-resolution, quantitative imaging, which may allow biological characterisation of relatively small MS lesions. PET may complement MRI by offering objective, quantitative insights into lesion characteristics, including myelin density, inflammation and axonal integrity. Moreover, PET may provide information on lesion traits supporting decision making on upcoming therapeutic strategies for progressive MS, such as the availability of oligodendrocyte progenitor cells and ECM composition that affect remyelination and/or axon regeneration. This review explores the cellular and molecular ECM signatures and neuropathological processes of white matter MS lesions, discusses current and potential novel PET targets that may help characterise MS lesions in vivo, and addresses the potential of PET as a decision tool for selection and evaluation of therapeutic strategies, with a focus on remyelination.

Myelin oligodendrocyte glycoprotein-antibody disease (MOGAD) with leukodystrophy-like presentation

2025-06-23

Viveka Biswas , Laura B. Martin , Emma Lim +7 more | Practical Neurology

Myelin oligodendrocyte glycoprotein-antibody disease (MOGAD) is an immune-mediated demyelinating disorder, distinct from MS, which typically affects the optic nerve, spinal cord, brain and/or brainstem. Diffuse white matter involvement that resembles … Myelin oligodendrocyte glycoprotein-antibody disease (MOGAD) is an immune-mediated demyelinating disorder, distinct from MS, which typically affects the optic nerve, spinal cord, brain and/or brainstem. Diffuse white matter involvement that resembles a leukodystrophy has been reported only in children. We present a woman aged 29 years with new right optic neuritis on a background of previously unexplained, longstanding, bilateral, reduced visual acuity. MR scan of the brain and orbits showed confluent, bilateral, posterior predominant white matter changes reminiscent of a leukodystrophy, along with bilateral optic atrophy. She was strongly MOG-seropositive. Positron-emission tomography scanning showed enlarged cervical lymph nodes, and biopsy found necrotising granulomata without tuberculosis. She showed a marked clinico-radiological response to corticosteroids, going from legally blind to functioning independently. Most strikingly, the chronically affected left eye improved significantly, 5 years after symptom onset. This expands the phenotypic spectrum of MOGAD as well as therapeutic expectations after a delayed presentation.

Optical coherence tomography angiography biomarkers in multiple sclerosis and neuromyelitis optica spectrum disorders: a systematic review

2025-06-23

Omid Mirmosayyeb , Mohammad Yazdan Panah , Reza Kord +4 more | International Journal of Retina and Vitreous

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune disorders of the central nervous system with overlapping clinical manifestations but distinct treatments and prognoses. Imaging markers are necessary … Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune disorders of the central nervous system with overlapping clinical manifestations but distinct treatments and prognoses. Imaging markers are necessary to differentiate between these disorders, especially when serologic testing is unavailable or unclear. Optical coherence tomography angiography (OCT-A) serves as a non-invasive imaging tool that assesses retinal microvascular alterations, potentially as a modality for differentiating MS and NMOSD. This review aimed to assess and consolidate evidence on retinal vascular alterations, measured by OCT-A, in people with MS (PwMS) and people with NMOSD (PwNMOSD) to help discriminate between these disorders. PubMed/MEDLINE, Web of Science, Scopus, and Embase were systematically searched up to August 27, 2024, to identify original English studies that compared OCT-A parameters between PwMS and PwNMOSD. The risk of bias across studies was evaluated utilizing the Newcastle-Ottawa Scale (NOS). Findings were consolidated using a narrative synthesis method. Nine studies involving 181 PwMS and 166 PwNMOSD were included. Compared to PwMS, PwNMOSD exhibited significantly lower vessel densities in the peripapillary and macular regions, reduced radial peripapillary capillary (RPC) density, and smaller foveal avascular zone (FAZ) areas, particularly in optic neuritis (ON)-affected eyes. Minimal differences were observed in eyes without ON, suggesting that ON may be crucial when utilizing OCT-A biomarkers for disease discrimination. OCT-A metrics demonstrate potential as biomarkers that may help distinguish MS and NMOSD, with PwNMOSD showing more severe retinal vascular alterations. These preliminary findings highlight that OCT-A may hold promise as a diagnostic tool for differentiating MS and NMOSD. Further studies are needed to validate these findings.

Sexual Dysfunction in Multiple Sclerosis: Prevalence, Risk Factors, and Impact on Quality of Life in a Large Cohort Study

2025-06-23

Özlem Totuk , Merve Türkkol , Feyzullah Yadi +6 more | Research Square (Research Square)

<title>Abstract</title> Background Sexual dysfunction (SD) is a prevalent but underreported symptom in people with multiple sclerosis (pwMS), significantly affecting quality of life (QoL). Despite its clinical relevance, SD is often … <title>Abstract</title> Background Sexual dysfunction (SD) is a prevalent but underreported symptom in people with multiple sclerosis (pwMS), significantly affecting quality of life (QoL). Despite its clinical relevance, SD is often overlooked during routine care. This study aimed to determine the prevalence of SD, identify associated risk factors, assess its impact on depression and QoL, and explore help-seeking behaviors among pwMS. Methods A cross-sectional study was conducted with 504 pwMS followed at a tertiary MS clinic between November 2023 and May 2024. Data on demographics, disease characteristics, and medications were collected. The Arizona Sexual Experiences Scale (ASEX) was used to assess SD, the Beck Depression Inventory (BDI) for depression, and the Short Form-12 (SF-12) for QoL. EDSS scores were used to evaluate disability. Statistical analyses included t-tests, ANOVA, chi-square, and correlation analyses, with significance set at p < 0.05. Results SD was identified in 69.0% of patients (73.9% of women, 57.6% of men). SD was significantly associated with female gender (p = 0.001), older age (p = 0.006), higher EDSS scores (p = 0.046), and increased depression levels (r = 0.38). SF-12 scores were significantly lower among those with SD (p < 0.001). No significant associations were found between SD and MS type, disease duration, or type of disease-modifying therapy. Only 16.9% of patients with SD reported seeking medical or psychological support. Conclusion SD is highly prevalent among pwMS and is closely linked to age, disability, depression, and reduced QoL. Despite this burden, most patients do not seek help. We recommend routine screening and multidisciplinary management approaches are essential for addressing SD in this population.

Beyond the Timed Up and Go: Dual-Task Gait Assessments Improve Fall Risk Detection and Reflect Real-World Mobility in Multiple Sclerosis

2025-06-22

Michael VanNostrand , Myeongjin Bae , Natalie Lloyd +2 more | Sclerosis

Background: Falls are common among individuals with multiple sclerosis (MS), yet standard clinical mobility assessments—such as the Timed Up and Go (TUG)—may not fully capture the complexities of real-world ambulation, … Background: Falls are common among individuals with multiple sclerosis (MS), yet standard clinical mobility assessments—such as the Timed Up and Go (TUG)—may not fully capture the complexities of real-world ambulation, leading to suboptimal fall identification. There is a critical need to evaluate the ecological validity of these assessments and identify alternative tests that better reflect real-world mobility and more accurately detect falls. This study examined the ecological validity of the TUG and novel dual-task clinical assessments by comparing laboratory-based gait metrics to community ambulation in individuals with MS and evaluated their ability to identify fallers. Methods: Twenty-seven individuals with MS (age 59.11 ± 10.57) completed the TUG test and three novel dual-task mobility assessments (TUG-extended, 25-foot walk and turn, and Figure 8 walk), each performed concurrently with a phonemic verbal fluency task. After lab assessments, the participants wore accelerometers for three consecutive days. Gait speed and stride regularity data was collected during both the in-lab clinical assessments and identified walking bouts in the community. The participants were stratified as fallers or non-fallers based on self-reported fall history over the previous six months. Findings: Significant differences were observed between the TUG and real-world ambulation for both gait speed (p < 0.01) and stride regularity (p = 0.04). No significant differences were found in gait metrics between real-world ambulation and both the 25-foot walk and turn and TUG-extended. Intraclass correlation coefficient analysis demonstrated good agreement between the 25-foot walk and turn and real-world ambulation for both gait speed (ICC = 0.75) and stride regularity (ICC = 0.81). When comparing the TUG to real-world ambulation, moderate agreement was observed for gait speed (ICC = 0.56) and poor agreement for stride regularity (ICC = 0.41). The 25-foot walk and turn exhibited superior predictive ability of fall status (AUC = 0.76) compared to the TUG (AUC = 0.67). Conclusions: The 25-foot walk and turn demonstrated strong ecological validity. It also exhibited superior predictive ability of fall status compared to the TUG. These findings support the 25-foot walk and turn as a promising tool for assessing mobility and fall risk in MS, warranting further study.

Advancing Treatment in Pediatric Multiple Sclerosis: The Promise of B-Cell-Targeting Therapies

2025-06-22

Charalampos Skarlis , Maria Kotsari , Maria Anagnostouli | International Journal of Molecular Sciences

Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared … Pediatric-onset multiple sclerosis (POMS) is a rare yet increasingly recognized demyelinating disease of the central nervous system, characterized by a highly inflammatory disease course and an elevated relapse rate compared to adult-onset MS (AOMS). Given the unique immunopathogenesis of POMS, recent therapeutic strategies have shifted toward early initiation of high-efficacy disease-modifying therapies (DMTs) to minimize irreversible neurological damage. Among these, B-cell-targeting therapies, particularly anti-CD20 monoclonal antibodies, have shown efficacy in adult MS and are emerging as promising candidates for POMS treatment. The present review summarizes the current knowledge of the role of B-cells in POMS pathophysiology and evaluates the therapeutic potential of anti-CD-20 agents. It also highlights ongoing clinical trials and future perspectives, including novel B-cell-directed approaches such as anti-CD19 therapies, Bruton’s tyrosine kinase (BTK) inhibitors, and BAFF-targeting agents.

What is the effect of education on fatigue in adults with neurological conditions? A systematic review and meta-analysis

2025-06-22

Alex Delbridge , Owen Howlett , Coralie English +1 more | Clinical Rehabilitation

Objective To determine the effect of education programs on fatigue outcomes in people with neurological conditions. Data sources MEDLINE, CINAHL, EMBASE, PEDRO until May 2025, according to PRISMA guidelines. Review … Objective To determine the effect of education programs on fatigue outcomes in people with neurological conditions. Data sources MEDLINE, CINAHL, EMBASE, PEDRO until May 2025, according to PRISMA guidelines. Review methods Systematic review with meta-analysis of randomised controlled trials comparing education versus no education/other intervention on the outcome of fatigue for people with neurological conditions. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias Tool. Pooled effects were calculated using standard mean difference (SMD). Results We included 19 clinical trials of education for fatigue ( n = 1970 participants) in five different neurological conditions. Education duration ranged from 4 to 12 weeks, 79% ( n = 15) of trials included people with multiple sclerosis and 18% ( n = 3) included people with stroke. Most education (11 trials, 58%) was delivered in a group setting. Education reduced fatigue compared with usual care by a SMD −0.28, 95% CI [−0.45 to −0.11]. Greater benefits for fatigue were observed when education was delivered one-to-one (SMD −0.44, 95% CI [−0.77 to −0.12]) than in group sessions (SMD −0.17, 95% CI [−0.36 to 0.01]). Mode of delivery (in-person versus telehealth) did not appear to influence the effect of education for fatigue. Conclusions Fatigue education programs may improve fatigue for people with neurological conditions. One-to-one delivered sessions may have greater benefits than group programs and remote delivery could improve accessibility for people living in regional and rural locations.

Quantitative susceptibility mapping of paramagnetic rim lesions in early multiple sclerosis: A cross-sectional study of brain age and disability

2025-06-21

Lars Skattebøl , Rigmor Lundby , Mathias H. Øverås +6 more | Neuroimage Reports

Prevalence of hypertension in pediatric-onset multiple sclerosis and associations with disease course: A case-control study

2025-06-21

Darina Dinov , Alexia Richie , Brian D. Kent +3 more | Multiple Sclerosis and Related Disorders

Reconsideration of conversion to multiple sclerosis: one-year cerebral lesion appearance rate of Japanese aquaporin-4 antibody-negative optic neuritis patients

2025-06-21

Satoshi Ueki , Yukari Hasegawa , Tetsuhisa Hatase +2 more | Japanese Journal of Ophthalmology

Correction: Rationale for a 4-month, parallel-group, randomized controlled trial to assess the Feasibility and Efficacy of a Remotely delivered exercise training intervention for Hispanics/Latinos with Multiple Sclerosis (FERLA MS)

2025-06-20

Victoria Flores , Stephanie L. Silveira , David X. Márquez +5 more | Pilot and Feasibility Studies

Does ChatGPT help patients access reliable and comprehensive information about psoriasis?

2025-06-20

Funda Tamer , Muhterem Polat | Baylor University Medical Center Proceedings

Acute Effects of Intermittent Walking on Gait Parameters and Fatigability in People with Mild Multiple Sclerosis

2025-06-20

Cintia Ramari , Ana R. Diniz , Felipe von Glehn +1 more | Sclerosis

Introduction: Walking is perceived as the most important bodily function for persons with multiple sclerosis (pwMS) and is impaired in more than 70% of pwMS. In addition, the effect of … Introduction: Walking is perceived as the most important bodily function for persons with multiple sclerosis (pwMS) and is impaired in more than 70% of pwMS. In addition, the effect of multiple sclerosis (MS) on gait pattern increases in fast walking and during fatiguing exercises, altering the spatiotemporal gait parameters and walking reserve. Objectives: The objective of this study is to investigate the impact of a 12 min intermittent-walking protocol on spatiotemporal gait parameters and on the fatigability of pwMS, as well as the association with perceived exertion and reported symptoms of fatigue. Methods: Twenty-six persons with relapse-remitting MS and twenty-eight healthy controls (HCs) were included in this cross-sectional study. The Modified Fatigue Impact Scale and the Symbol Digit Modality Test were used to evaluate fatigue symptoms and cognitive function, respectively. Participants walked six times during an uninterrupted 2-min period. Before, during the rest periods and after the last 2 min walk, the rate of perceived exertion (RPE) was measured using the Borg Scale, and the spatiotemporal gait parameters were assessed with GaitRite. The cut-off value of 10% deceleration of the distance walked index classified pwMS into two groups: MS Fatigable (MS-F) and MS Non-Fatigable (MS-NF). One-way and two-way Analyses of variance (ANOVAs) were used to verify the effect of time and groups, respectively. Results: PwMS walked slower, travelled shorter distances, and presented shorter step lengths compared to HCs. No effects of the intermittent-walking protocol were found for all pwMS, but the MS-F group had deteriorated walking speed, step length, and cadence. Walking dysfunction was associated with perceived fatigability, reported symptoms of fatigue, cognitive function, and disability. Reported symptoms of fatigue was associated with perceived exertion but not with performance fatigability. Conclusions: Changes in gait parameters were weak to moderately associated with performance fatigability and the perception of effort and disability but not with reported fatigue symptoms, highlighting distinct constructs. The walking speed reserve and step length reserve also emerged as potential early markers of performance decline.

Critical insights on changes in circulating pro-inflammatory lymphocytes and cortical excitability with extended-interval natalizumab dosing in multiple sclerosis

2025-06-20

Syed Ahmad Farooqi , Sadia Siddique , Umair Ali +3 more | Neurological Sciences

Improving Quality of Life in Polish patients with multiple sclerosis: a multicentre analysis

2025-06-20

Joanna Tarasiuk , Katarzyna Kapica-Topczewska , Agata Czarnowska +7 more | Neurologia i Neurochirurgia Polska

Neutropenia Associated With B Cell–Depleting Therapies in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

2025-06-19

Greer Waldrop , Nikki Sisodia , Shane Poole +6 more | Neurology Neuroimmunology & Neuroinflammation

Neutropenia is described as a rare adverse event associated with B cell-depleting therapy (BCDT) use in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, little is … Neutropenia is described as a rare adverse event associated with B cell-depleting therapy (BCDT) use in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, little is known about longitudinal clinical outcomes. We estimated the real-world incidence of neutropenia among patients with neuroinflammatory disease treated with BCDT and characterized the clinical course. We conducted a retrospective cohort study using electronic medical records to estimate the incidence rate of neutropenia in adults with MS/NMOSD from a neuroimmunology clinic in California between January 6, 2006, and November 2, 2015, treated with ocrelizumab, rituximab, ofatumumab, ublituximab, or inebilizumab. Each clinical course (recurrence, time to recovery of absolute neutrophil count [ANC], postneutropenia treatment) of neutropenia was then presented in a case series. In this cohort of 1,825 patients (6,009 person-years on BCDT), the largest cohort addressing this question to date, 37 developed neutropenia. The estimated incidence rate of neutropenia was 0.62 (95% CI 0.45-0.85) per 100 person-years. The median time from last infusion of current BCDT was 4 months (interquartile range [IQR] 1-6). The median nadir ANC was 390 (IQR 40-960); the nadir ANC was 0 for 6 patients (16%). All patients ultimately recovered to normal counts, except 2 patients developing fluctuating ANCs for months. Among the 32 patients not receiving filgrastim, the median time to ANC recovery was 11 days (95% CI 7-26). Course severity was asymptomatic/mild in 32% (n = 12) while 54% (n = 20) required hospitalization. A confirmed simultaneous infection or infectious prodrome occurred in 23 (62%). After recovery, 30 patients (81%) continued BCDT and 2 (7%) changed within BCDT class. Neutropenia recurred in 13 patients (35%), including 3 who discontinued BCDT after initial neutropenia. The estimated incidence rate of recurrent neutropenia was 0.22 (95% CI 0.13-0.39) per 100 person-years. The mean (SD) time to recurrence from initial neutropenia was 251 (SD: 355) days. This study is comprehensive and reflects a large cohort, examining incidence rates of neutropenia with BCDT in MS and NMOSD. Overall, neutropenia was still rare, occurring at a rate of 0.66 per 100 person-years, and infections were associated triggers in some patients. Yet, of relevance to clinicians, neutropenia was not benign: half required hospitalization and 35% experienced recurrence, which is higher than what was reported in clinical trials.

Role of CSF flow and meningeal barriers in the development of inflammatory lesions at the CNS–PNS transition zone of cranial nerves in autoimmune demyelinating diseases

2025-06-19

Xin Li , Hideaki Nishihara , Adrian Madarasz +7 more | Acta Neuropathologica

Abstract Patients with autoimmune inflammatory demyelinating diseases have been shown to present with trigeminal and cochlear nerve lesions restricted at the root transition zone, which contrasts with the relatively extensive … Abstract Patients with autoimmune inflammatory demyelinating diseases have been shown to present with trigeminal and cochlear nerve lesions restricted at the root transition zone, which contrasts with the relatively extensive distribution of lesions in optic neuritis. To better understand the mechanism underlying the different distribution pattern for cranial nerve lesions in these autoimmune neuroinflammatory diseases, we focused on the CNS–PNS transition zone (TZ) of the trigeminal and cochlear nerves in a MOG-driven active EAE model. These nerves were found to exhibit unique arrangements of anatomical barrier layers including the arachnoid and glia limitans, which affected cerebrospinal fluid (CSF) tracer distribution as well as CCR2 + immune cell infiltration. Our data demonstrated that CCR2 + immune cells accumulate at the TZ on both CNS side and PNS side of the trigeminal nerve and cochlear nerve, which mirror the locations of cranial nerve pathology observed clinically in patients with inflammatory demyelinating disease. On the other hand, the optic and olfactory nerves, which both lack a TZ, did not exhibit restrictions in immune cell localization. Overall, our results reconcile with the hypothesis that the segment of the cranial nerve that is exposed to CSF flow is more susceptible to CCR2 + immune cell infiltration.

Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis

2025-06-19

Radmila Kancheva , Eva Havrdová , Marta Velíková +7 more | International Journal of Molecular Sciences

Multiple sclerosis (MS) is a long-term disease that causes inflammation and damage to the nervous system. This study evaluated steroidomic alterations related to MS in 57 female MS patients during … Multiple sclerosis (MS) is a long-term disease that causes inflammation and damage to the nervous system. This study evaluated steroidomic alterations related to MS in 57 female MS patients during the follicular phase and 17 during the luteal phase, as well as in age- and phase-matched controls. The data showed that (1) unconjugated and conjugated steroids were strongly linked between the blood and CSF. (2) MS patients have lower levels of unconjugated steroids compared to controls. However, unchanged levels of conjugated steroids suggest a possible increase in steroid sulfotransferase functioning. (3) MS patients show altered levels of steroids linked to 11β-hydroxylase (CYP11B1) function. While direct enzyme activity was not measured, disrupted cortisol biosynthesis-potentially linked to reduced functioning of both CYP11B1 and 17α-hydroxylase/17,20-lyase-is associated with more severe cases of MS. (4) Reduced levels of 5α/β-steroids and protective GABAergic 3α-hydroxy-5α/β-steroids in MS patients might be linked to the pathophysiology of MS. (5) A potential increase in AKR1C3 function in MS could contribute to inflammation, as this enzyme catalyzes the synthesis of both steroids and prostaglandins. However, direct measurements of enzyme activity are needed to confirm this hypothesis. (6) Lower pregnenolone levels in MS patients might weaken neuroprotection, while higher pregnenolone sulfate levels could support cognitive function. (7) Lower levels of protective pregnenolone, DHEA, and androstenediol were associated with worse MS, suggesting these steroids may help shield against the disease.

The Cambridge Centre for Myelin Repair trial Two (CCMR Two): a trial protocol for a phase 2a, randomised, double-blind, placebo-controlled clinical trial of the ability of the combination of metformin and clemastine to promote remyelination in people with relapsing-remitting multiple sclerosis already on disease-modifying therapy

2025-06-19

Gioia Riboni-Verri , Christopher E McMurran , Trisha Mukherjee +7 more | Research Square (Research Square)

<title>Abstract</title> Background: In multiple sclerosis (MS) progressive disability occurs following degeneration of demyelinated axons. A tractable approach to delay, prevent, or reverse disability progression is through enhancement of endogenous remyelination. … <title>Abstract</title> Background: In multiple sclerosis (MS) progressive disability occurs following degeneration of demyelinated axons. A tractable approach to delay, prevent, or reverse disability progression is through enhancement of endogenous remyelination. Clinical trials have deployed drugs, such as clemastine, to target the rate limiting step in this process: differentiation of oligodendrocyte progenitor cells (OPCs). Preclinical research has shown that metformin can reverse an age-associated deficit in the responsiveness of OPCs to pro-differentiation factors. The purpose of the Cambridge Centre for Myelin Repair trial Two (CCMR Two) is to evaluate the efficacy of the combination of metformin and clemastine to promote remyelination in people with MS. Methods: Participants with relapsing remitting MS (RRMS) will be randomised 1:1 to the combination of metformin and clemastine or matched placebos and followed for 24 weeks of treatment. All participants must be stable on a disease modifying therapy and have evidence of chronic stable optic neuropathy in at least one eye (defined by P100 latency of the visual evoked potential (VEP) ≥118 ms, and the absence of a history of acute optic neuritis in the preceding two years). The primary outcome measure will be the change in the P100 latency of the full-field VEP between baseline and week 26. It is planned to recruit a total of 70 participants. This will have 80% power to detect a reduction of 3 ms in VEP P100 latency between the two treatment groups. Secondary outcome measures will examine the change in multifocal-VEP, and the change in lesional magnetisation transfer ratio (MTR) for lesions stratified by location and tissue-specific cohort baseline lesional MTR values. Discussion: We set out the trial design, the rationale for participant and outcome measure selection, and the pre-specified analyses. With this trial, we expect to be able to detect the structural and functional consequences of remyelination within a sample size feasible for our single-centre trial. Trial registration: The trial was registered with ClinicalTrials.gov, NCT05131828, prior to participant enrolment.

The potential of visual evoked potentials latency and amplitude to be a subclinical predictor of clinical prognosis in multiple sclerosis

2025-06-19

Elif Banu Söker , Miray Erdem , Derya Özdoğru +3 more | Irish Journal of Medical Science (1971 -)

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal demyelinating lesions, axonal dysfunction/degeneration, and gliosis, which can lead to various clinical … Abstract Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal demyelinating lesions, axonal dysfunction/degeneration, and gliosis, which can lead to various clinical disabilities. Visual evoked potentials (VEP) is sensitive and repeatable techniques capable of monitoring significant short-term changes in neuroaxonal integrity and alterations in nerve conduction triggered by acute optic neuritis. Aim This study aims to evaluate whether VEP latency and amplitude could serve as subclinical predictors of clinical outcomes in MS patients over short-term follow-ups. Methods This study was planned to include MS patients diagnosed according to the McDonald Criteria 18 who did not have any psychiatric, neurological, or ocular disorders that could interfere with the main purpose. The VEP test was performed for routine evaluation of demyelination or axonal damage. Results A total of 83 patients were included in the study, with a mean age of 33.6 ± 9.3 years. Of all the patients, 54 were female (65.1%) and 29 were male (34.9%). Right pattern reversal visual evoked potential (PVEP) P100 (OR for PVEP1: 0.802, p = 0.001; OR for PVEP2: 0.879, p = 0.002) was statistically significant in showing right VEP abnormality at both baseline and at 6 months. Left VEP abnormalities were associated with left PVEP P100 at PVEP1 (OR: 0.852, p = 0.003) and left PVEP N75 at PVEP2 (OR: 0.935, p = 0.029). Conclusion VEPs have the potential to predict short-term subclinical stability or progression, making them valuable candidates for early treatment adjustments and evaluating future pharmacotherapy-supported remyelination.

Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis

2025-06-19

Emilio Portaccio , M. Betti , Ermelinda De Meo +7 more | Multiple Sclerosis Journal

Objectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS). … Objectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS). Methods: A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date. The risk of first 24-week confirmed disability accumulation (CDA) on EDSS in HE versus platform DMTs after 2 years and the entire follow-up was assessed through Cox regression models. Results: After 1:1 propensity score matching, we evaluated 1698 pwMS initiating HE-DMTs and 1698 initiating platforms. After 2 years follow-up, the proportion of CDA events was lower in patients on HE-DMTs (12.2%) than those on platform DMTs (15%), as confirmed by Cox regression analysis (hazard ratio (HR) = 0.22, 95% confidence interval (CI) = 0.10–0.47; p < 0.001). HE-DMTs were more effective in patients under 45 years of age (HR = 0.49, 95% CI = 0.39–0.63; p < 0.001), but not in patients over 45 (HR = 0.77, 95% CI = 0.54–1.08, p = 0.125). Notably, prolonged exposure to any DMT during follow-up reduced disability accumulation even in patients over 45 (HR = 0.13, 95% CI = 0.02–0.99; p = 0.050). Conclusion: This real-world study of relapsing pwMS demonstrates that the benefit of initial HE treatment diminishes with age. However, even in older patients, DMT exposure, regardless of the efficacy level, appears to reduce disability accumulation, and so, on an individual level, initial HE treatment could still be more effective.

Eculizumab for the acute attack of neuromyelitis optica spectrum disorder

2025-06-18

Qingqing Zhuang , Wenjuan Huang , Jingzi ZhangBao +7 more | medRxiv (Cold Spring Harbor Laboratory)

Abstract Objective To assess clinical outcomes in patients treated with eculizumab for acute attacks of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Methods We retrospectively analyzed prospectively collected data from … Abstract Objective To assess clinical outcomes in patients treated with eculizumab for acute attacks of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Methods We retrospectively analyzed prospectively collected data from the Huashan NMOSD registry cohort, and included patients who received eculizumab within 30 days of attack onset. Eculizumab was administered at 900 mg weekly for four weeks, followed by an eight-week observation period. Primary outcomes included visual acuity and visual field for optic neuritis (ON) and muscle strength, assessed using the Medical Research Council (MRC) scale for longitudinally extensive transverse myelitis (LETM). Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels were also monitored. Results Nine patients (seven with ON, two with LETM) were included. All patients received high-dose intravenous methylprednisolone prior to eculizumab treatment. Following eculizumab, six of the seven ON patients showed significant improvements in visual acuity and visual fields, with five recovering to near-normal or pre-attack vision. Visual field mean deviation improved from −22.4 dB to −2.0 dB (p = 0.008). Among LETM patients, one regained substantial lower limb strength (MRC grade 0 to 3 proximally, 4 distally), while the other showed improvement in distal strength (MRC grade 0 to 3). Serum sGFAP decreased from 278.0 to 130 pg/mL (p = 0.027), while sNfL levels transiently increased before stabilizing. LETM patients developed urinary tract infections, and one had Klebsiella pneumoniae pneumonia; all infections were effectively treated. Conclusion Eculizumab may yield favorable outcomes in acute NMOSD attacks, with infection monitoring being particularly important in severe cases.

Serum levels of tumor necrosis factor and TNFRSF1A gene polymorphisms in Egyptian multiple sclerosis patients: the influence on susceptibility and severity

2025-06-18

Maged Abdel Naseer , Mohamed Tharwat Hegazy , Karim Elmehdawy +3 more | Journal of Neuroimmunology

AFRICTRIMS: a step towards broadening multiple sclerosis conversations

2025-06-18

Dilraj Sokhi , Deanna Saylor | The Lancet Neurology

Optic neuritis: a comprehensive review of current therapies and emerging treatment strategies

2025-06-18

Pareena Chaitanuwong , Heather E. Moss | Frontiers in Neurology

Background Optic neuritis (ON) is an inflammatory condition of the optic nerve that can lead to significant visual impairment. It is often associated with multiple sclerosis (MS) but can also … Background Optic neuritis (ON) is an inflammatory condition of the optic nerve that can lead to significant visual impairment. It is often associated with multiple sclerosis (MS) but can also occur in other demyelinating diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Understanding the current therapeutic approaches and emerging treatment strategies is critical for optimizing patient outcomes. Objective This review provides a focused overview of current therapies for demyelinating optic neuritis associated with MS, NMOSD, and MOGAD. Less common autoimmune optic neuropathies, non-autoimmune causes (e.g., infections) and pediatric optic neuritis are not covered. Methods A review of the literature was conducted, including clinical trials, observational studies, and expert recommendations on the treatment and management of demyelinating ON. The efficacy, safety, and limitations of various therapeutic modalities were assessed. Results High-dose intravenous corticosteroids remain the mainstay of acute demyelinating ON treatment, accelerating visual recovery but not altering long-term visual outcomes. Immunomodulatory therapies, such as disease-modifying treatments for MS, play a crucial role in preventing recurrent episodes in demyelinating diseases. Emerging therapies, including re-myelination agents, neuroprotective strategies, and novel immunotherapies, show promise in improving visual prognosis and reducing long-term disability. Conclusion While corticosteroids remain the primary treatment for acute demyelinating ON, ongoing research into neuroprotective and re-myelinating therapies offers hope for better visual recovery and long-term management. Future studies should focus on optimizing treatment strategies and exploring novel therapeutics to enhance patient outcomes.

Gynecological health: A missing link in comprehensive treatment monitoring for multiple sclerosis

2025-06-18

Melika Arab Bafrani , Viviana Ríos , Min Ji Kim +2 more | Multiple Sclerosis Journal

Safety monitoring of disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) has largely overlooked the domain of gynecological health. This topical review aims to provide MS clinicians with an … Safety monitoring of disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) has largely overlooked the domain of gynecological health. This topical review aims to provide MS clinicians with an overview of the three categories of complications described to date, as well as risk mitigation strategies. These are increased risk of human papilloma virus (HPV) positivity and related cervical dysplasia/cancers; inflammatory and infectious vaginitis and susceptibility to bacterial vaginosis (BV); and herpesvirus infections, including genital Herpes Simplex Virus (HSV). Current knowledge may be biased due to limited studies and lack of gynecological focus in neurological encounters. Risk mitigation strategies include promoting HPV vaccination, following guidance for immune compromised individuals relating to cervical cancer screening and antiviral suppression, and proactive communication with patients about gynecological health when starting DMTs. Together, these might improve gynecological health and thereby quality of life in females with neuroinflammatory diseases.

Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials

2025-06-18

Noemi Montobbio , Francesca Bovis , Alessio Signori +7 more | EBioMedicine

Exploring the Clinical Utility of Neurofilament Light Chain Assays in Multiple Sclerosis Management

2025-06-18

Amit Bar‐Or , Jacqueline Nicholas , Jenny Feng +2 more | Neurology Neuroimmunology & Neuroinflammation

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that affects nearly 1 million adults in the United States. Owing to its unpredictable disease course, diverse phenotypes, and an … Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that affects nearly 1 million adults in the United States. Owing to its unpredictable disease course, diverse phenotypes, and an array of currently available disease-modifying therapies, a personalized approach to MS management is required. There is an unmet need to identify, validate, and incorporate prognostic, monitoring, and predictive biomarkers into routine clinical practice for MS. A mounting body of evidence supports the use of blood biomarkers, such as neurofilament light chain (NfL), in predicting disease activity and monitoring treatment response. Previous hurdles for the widespread use of NfL in the clinical management of patients, such as invasive sampling methods and limited assay availability, are being overcome through the development and validation of new commercial serum NfL (sNfL) assays. With rising availability, there is now potential for incorporating sNfL testing to support traditional clinical assessments such as MRI, relapse rates, and disability progression measurements. However, clinical and technical limitations to the interpretation of NfL, such as comorbidities, and lack of measurement standardization and well-established reference ranges still pose challenges to its use. Based on the most recent evidence, this review aims to educate healthcare professionals on the potential utility of NfL in the clinical management of people living with MS and provide practical information on the development and availability of new assays.

Cladribine Effects on Emotional Awareness and Reasoning: The CLEAR Study

2025-06-18

Julie D. Henry , Sarah P. Coundouris , Lauren Gomes +3 more | Multiple Sclerosis and Related Disorders

Targeting smouldering neuroinflammation in multiple sclerosis: insights from tolebrutinib clinical trials

2025-06-18

María Trojano , Damiano Paolicelli | The Lancet Regional Health - Europe

Multiple sclerosis-like manifestations in systemic autoimmune and inflammatory disorders: Αn update

2025-06-17

Sylvia Raftopoulou , Ioanna Kapsali , Maria‐Eleftheria Evangelopoulos +1 more | Expert Review of Clinical Immunology

Multiple sclerosis (MS) is the most recognized CNS autoimmune demyelinating disease, characterized by neuroinflammation, myelin loss, and axonal damage. Due to clinical overlap with several disorders such as systemic autoimmune … Multiple sclerosis (MS) is the most recognized CNS autoimmune demyelinating disease, characterized by neuroinflammation, myelin loss, and axonal damage. Due to clinical overlap with several disorders such as systemic autoimmune diseases (SADs), which can closely resemble MS, the diagnostic process can be challenging. SADs with CNS involvement can present with neurological symptoms such as transverse myelitis, optic neuritis, and white matter lesions. This diagnostic uncertainty contributes to a significant rate of misdiagnosis which can lead to improper treatment, worsening symptoms and increasing disability. In this review we discuss the physiology of myelin in the CNS, the pathophysiology of MS and other immune-mediated demyelinating diseases that can mimic MS. We also discuss similar presentations between MS and MS-like clinical entities, and their appropriate treatment regimes. SADs and other clinical entities are key MS mimickers, significantly complicating diagnosis at a first neurological episode. Careful clinical evaluation, imaging, and exclusion of alternative diagnoses are crucial to avoid misdiagnosis. Understanding the subtle distinctions between MS and SADs and looking out for, and further investigating atypical presentations, is vital for ensuring accurate diagnosis and proper treatment, thereby improving patient outcomes and reducing unnecessary disability.

Factors associated with delay to diagnosis of multiple sclerosis in Zambia

2025-06-17

Malya Sahu , Mashina Chomba , Dominique Mortel +7 more | Multiple Sclerosis Journal

Background/Objectives: Delays to diagnosis of multiple sclerosis (MS) are largely unknown in sub-Saharan Africa. This study utilizes a quantitative approach to determine factors independently associated with delays to diagnosis among … Background/Objectives: Delays to diagnosis of multiple sclerosis (MS) are largely unknown in sub-Saharan Africa. This study utilizes a quantitative approach to determine factors independently associated with delays to diagnosis among a cohort of Zambian people with MS. Methods: This cross-sectional study enrolled people with a confirmed diagnosis of MS at a public outpatient neurology clinic in Lusaka, Zambia. Standardized surveys were administered. Diagnostic delay was categorized into patient delay, health-system delay, and all delay. A multivariable linear regression model was used to determine factors independently associated with time to diagnosis. Results: A total of 22 participants had a confirmed diagnosis of MS. Median all delay from symptom onset to MS diagnosis was 11.4 months (interquartile range (IQR) = 4–35.5), with health-system delay accounting for the majority. Asian race correlated with a decrease in all delay, while evaluation outside of Zambia was associated with a decrease in patient delay and birthplace outside of Zambia correlated with decreased health-system delay. Conclusion: Black African people born in Zambia and evaluated in Zambia experienced prolonged diagnostic delays when compared to non-black Zambians born and/or evaluated outside Zambia, likely due to a combination of health system and patient factors, which necessitate further study to shorten time to diagnosis.

Acute Myocardial Infarction and Diffuse Coronary Artery Disease in a Patient with Multiple Sclerosis: A Case Report and Literature Review

2025-06-17

Eugen Țieranu , Silvana Isabella Cureraru , Georgică Târtea +4 more | Journal of Clinical Medicine

Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease that leads to disabilities such as difficulty moving and slowed cognitive processing. It is the leading non-traumatic cause of disability worldwide. … Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease that leads to disabilities such as difficulty moving and slowed cognitive processing. It is the leading non-traumatic cause of disability worldwide. MS also has a high potential to become a model for neurodegenerative diseases with a progression like Alzheimer's or Parkinson's. Cardiovascular diseases (CVDs) remain the leading cause of global deaths and have a considerable economic impact. The higher incidence of cardiovascular comorbidities in patients with MS compared to healthy individuals of the same age worsens the prognosis of neurological pathology, leading to a higher level of disability, poorer physical outcomes, higher depression scores, cognitive aging, and diminished quality of life. Classical observational studies often have questionable elements that can represent a source of error, making it difficult to establish a causal relationship between MS and CVD. Genetic studies, including genome-wide evaluation, may resolve this issue and may represent a topic for future research. We report the case of a 31-year-old male patient with a history of multiple sclerosis (MS) diagnosed seven years prior, who presented with acute chest pain upon returning from vacation. Despite the previous recommendation for disease-modifying therapy, the patient had discontinued treatment by personal choice. Electrocardiography (ECG) revealed ST-segment elevation in inferior leads, and emergent coronary angiography identified severe multi-vessel coronary artery disease (CAD), requiring immediate revascularization. This case highlights the potential cardiovascular risks in young patients with MS and the importance of continuous medical supervision.

Effects of Intrinsic Foot Muscle Training in Improving Stability in Multiple Sclerosis Patients: A Single-Blind Randomized Clinical Trial

2025-06-17

Daniel García-García , Jorge Juan Alvarado‐Omenat , Rocío Llamas‐Ramos +2 more | Applied Sciences

Background: Stability deficit is one of the most common and disabling signs of multiple sclerosis; therefore, balance training is essential for most patients. Intrinsic foot muscles are a key element … Background: Stability deficit is one of the most common and disabling signs of multiple sclerosis; therefore, balance training is essential for most patients. Intrinsic foot muscles are a key element in stability, but their influence in multiple sclerosis patients has not been assessed. Objective: The aim of the study was to assess the efficacy of intrinsic foot muscle training on stability in patients with multiple sclerosis. Methodology: A randomized single-blind clinical trial was conducted using a sample of multiple sclerosis patients divided into a control group (CG) and an intervention group (IG). Subjects in the intervention group completed an eight-week intrinsic foot muscles training programme. Static and dynamic stability were measured using the Activities-specific Balance Confidence questionnaire (AsBC), the Four Square Step Test (FSST), the Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT), and the Six Spot Step Test (SSST). Pre- and post-intervention outcomes and differences between groups were calculated. Results: The amount of change comparing pre- and post-intervention results was −0.94 (CG) and 5.59 (IG) in the AsBC questionnaire (p 0.17); −1.0 (CG) and −1.5 (IG) in the FSST (p 0.72); 0.0 for both groups in FICSIT (p 0.629); and −1.5 (CG) and −2.0 (IG) in SSST (p 0.692). Conclusions: Intrinsic foot muscle training produces positive changes in dynamic stability and self-perceived confidence in multiple sclerosis patients.

Exploring factors driving the evolution of chronic lesions in multiple sclerosis using machine learning

2025-06-17

Hai Hu , Long Ye , Ping Wu +3 more | European Radiology

Fatigue in natalizumab-treated multiple Sclerosis patients: How much is wearing-off to blame?

2025-06-17

Giuseppe Magro , Stefania Barone , Angelo Pascarella +7 more | Brain Research

Brain-derived blood biomarkers in multiple sclerosis—current trends and beyond

2025-06-16

Shamundeeswari Anandan , Karina Maciak , Regina Breinbauer +4 more | Frontiers in Immunology

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the nervous system and a main cause of neurological disability in young adults. Most disease-modifying therapies are administrated as … Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the nervous system and a main cause of neurological disability in young adults. Most disease-modifying therapies are administrated as long-term maintenance therapies and may, thereby, increase the risk of infections and other immune-mediated side effects. In the last years, several cerebrospinal fluid and soluble blood biomarkers have been suggested as potential key tools for diagnosis, prognosis, and treatment monitoring of MS. Recently, the specific ability of brain-derived blood extracellular vesicles (EVs) that cross the blood-brain barrier into the bloodstream, reflecting the current immune status of the central nervous system, has kindled interest as potential biomarkers. In this review, we discuss the current trends of clinical brain-derived blood biomarkers, with a special focus on the emerging role of brain-derived blood EVs in MS.

Real-World Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates in the USA

2025-06-16

Sophia Woodson , Edward Gettings , Chu‐Yueh Guo +7 more | Neurology and Therapy

Multiple sclerosis (MS) is a heterogeneous disease affecting a diverse population. Compared with white people with MS (PwMS), Black PwMS have more severe disease and higher incidence of MS, whereas … Multiple sclerosis (MS) is a heterogeneous disease affecting a diverse population. Compared with white people with MS (PwMS), Black PwMS have more severe disease and higher incidence of MS, whereas Hispanic PwMS experience earlier onset disease; however, MS is not adequately studied in these groups. We compared the effectiveness of fumarates across Black, Hispanic, Asian, and white PwMS. This retrospective analysis using the Komodo Health database included PwMS. Patients with a claim for diroximel fumarate or dimethyl fumarate were followed from disease-modifying therapy (DMT) initiation to loss of follow-up or discontinuation. Outcomes included annualized relapse rate (ARR), time to post-index first relapse, healthcare resource use (HRU), healthcare costs (HCCs), and change in absolute lymphocyte counts (ALCs). Race/ethnicity was self-reported. This study included 6800 PwMS (Black, n = 1241; Hispanic, n = 777; Asian, n = 132; white, n = 4650). The average exposure duration of fumarates was 449-559 days. Black PwMS had higher baseline disease burden versus white PwMS, were less likely to have commercial insurance plans, and were more likely to reside in a state with a higher poverty rate. ARRs (12-month pre-index to post-index) were significantly reduced across groups. The Kaplan-Meier estimated proportion of relapse-free patients at 2 years was similar across groups (Black, 77.0%; Hispanic, 75.4%; Asian, 81.7%; white, 80.5%). There was a smaller decline in ALC from month 0 to month 12 in Black PwMS versus other racial/ethnic groups. Consistent with prior studies, these results demonstrate the effectiveness of fumarates across racial and ethnic MS subgroups. This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Infographic available for this article.

Kappa free light chain index predicts long-term disease activity and disability accrual in multiple sclerosis

2025-06-16

Klaus Berek , Martin Schmidauer , Gabriel Bsteh +7 more | Multiple Sclerosis Journal

Background: The prognostic value of κ-free light chain (κ-FLC) index over the long term is unknown. Objectives: The objective of the study was to determine whether κ-FLC index determined at … Background: The prognostic value of κ-free light chain (κ-FLC) index over the long term is unknown. Objectives: The objective of the study was to determine whether κ-FLC index determined at disease onset predicts relapse activity and disability accrual during long-term follow-up. Methods: Patients with a first demyelinating event of the central nervous system who had cerebrospinal fluid and serum sampling were eligible for inclusion. At baseline, demographics, clinical data, number of T2 hyperintense (T2L) and contrast-enhancing lesions (CEL) on MRI were assessed. During follow-up occurrence of relapses, Expanded Disability Status Scale (EDSS) scores and disease-modifying treatments (DMT) were registered. κ-FLC was measured by nephelometry and κ-FLC index calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. Results: Sixty-four patients with a median age at onset of 32 years (25th−75th percentile: 27−39) and a female predominance of 75% were followed over a median of 113 (90−129) months. Forty-six (72%) patients experienced relapse, 30 (47%) showed disability accrual. Multivariable Cox regression analysis adjusted for age, sex, disease duration, T2L, CEL and DMT revealed that κ-FLC index independently predicts time to relapse (per increase of 10: hazard ratio (HR) = 1.04, lower limit (LL)-confidence interval (CI) = 1.001, p = 0.044) and disability accrual (per increase of 10: HR = 1.05, LL-CI = 1.009, p = 0.022). Conclusions: κ-FLC index predicts long-term disease activity independently of other risk factors.

Impact of visual discomfort symptoms on SDMT performance among persons with MS

2025-06-16

Michelle H. Chen , Timothy J. Rich , Nancy D. Chiaravalloti +2 more | Frontiers in Neurology

Background Visual problems are common among persons with multiple sclerosis (MS) and may interfere with the assessment of cognitive functioning using visually mediated neuropsychological tests. The current study explored visual … Background Visual problems are common among persons with multiple sclerosis (MS) and may interfere with the assessment of cognitive functioning using visually mediated neuropsychological tests. The current study explored visual discomfort symptoms among persons with MS compared to healthy controls (HCs), using the Visual Discomfort Scale (VDS), which measures somatic and perceptual visual discomfort symptoms that interfere with reading. Methods Eighty-nine persons with MS and 30 HCs completed the VDS and the Symbol Digit Modalities Test (SDMT), a visually mediated test of information processing speed and gold standard for screening for MS-related cognitive dysfunction. Results Persons with MS endorsed higher frequencies of visual discomfort symptoms, including seeing the text or background moving or fading, headache/eye soreness, blurriness/diplopia, having to re-read, and slow reading, compared to HCs. More frequent visual discomfort symptoms were associated with worse performance on the SDMT. For participants with MS reporting moderate/high levels of visual discomfort symptoms, having a longer disease duration or progressive disease courses were correlated with worse performance on the SDMT. Conclusion It is important for clinicians to ask about specific visual discomfort problems that the patient experiences when interpreting a visually-mediated neuropsychological test such as the SDMT, especially for MS patients with longer disease duration or a progressive disease course.