Multiple sclerosis: emerging epidemiological trends and redefining the clinical course

The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 44, P. 100977 - 100977

Published: Aug. 23, 2024

SummaryMultiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system major cause neurological disability in young adults. Its prevalence incidence are increasing, it has been estimated at over 2.8 million cases worldwide, addition to recent trends towards shift MS older ages, with peak estimates sixth decade life. Although historically relapsing progressive phases have considered separate clinical entities, evidence progression independent relapse activity (PIRA) led reconsideration multiple as continuum, which features variably coexist from earliest stages disease, challenging traditional view course. In this Series article, we provide an overview how description course epidemiological Europe evolved. For purpose, focus on concept PIRA, discussing its potential main mechanism by patients acquire disability, definition varies between studies, ongoing research field. We emphasise importance incorporating assessment hidden manifestations into patient management help uncover quantify PIRA phenomenon possible implications for future changes classification disease. At same time, insights overcoming challenges identifying defining adopting new understanding MS.

Language: Английский

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Using the Progression Independent of Relapse Activity Framework to Unveil the Pathobiological Foundations of Multiple Sclerosis

Neurology, Journal Year: 2024, Volume and Issue: 103(1)

Published: June 18, 2024

Progression independent of relapse activity (PIRA), a recent concept to formalize disability accrual in multiple sclerosis (MS) relapses, has gained popularity as potential clinical trial outcome. We discuss its shortcomings and appraise the challenges implementing it settings, experimental trials, research. The current definition PIRA assumes that acute inflammation, which can manifest relapse, neurodegeneration, manifesting progressive accrual, be disentangled by introducing specific time windows between onset relapses observed increase disability. term PIRMA (progression MRI activity) was recently introduced indicate absence both new brain spinal cord lesions. Assessing practice is highly challenging because necessitates frequent assessments scans. commonly assessed using Expanded Disability Status Scale, scale heavily weighted toward motor disability, whereas more granular assessment deterioration, including cognitive decline, composite measures or other tools, such digital would possess greater utility. Similarly, an outcome measure randomized trials also requires methodological considerations. underpinning pathobiology accumulation, not associated with may encompass chronic active lesions (slowly expanding paramagnetic rim lesions), cortical lesions, atrophy, particularly gray matter, diffuse focal microglial activation, persistent leptomeningeal enhancement, white matter tract damage. propose use understand main determinant observational, cohort studies, where regular scans are included, introduce "advanced-PIRMA" investigate contributions abovementioned processes, conventional advanced imaging. This supported knowledge reflects MS pathogenic mechanisms better than purely descriptors. Any residual remains unexplained after considering all these imaging, will highlight future research priorities help complete our understanding pathogenesis.

Language: Английский

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Smouldering‐Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(5), P. 826 - 845

Published: July 25, 2024

Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition "progression independent relapsing activity." We propose concept smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, remain unmet targets. provide a consensus-based framework possible substrates manifestations MS, we discuss clinical, radiological, serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, share considerations optimizing disease surveillance implications clinical trials to promote integration MS into routine practice future research efforts. ANN NEUROL 2024;96:826-845.

Language: Английский

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Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(11), P. 1119 - 1132

Published: Sept. 20, 2024

Language: Английский

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Personalized Use of Disease-Modifying Therapies in Multiple Sclerosis

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(1), P. 120 - 120

Published: Jan. 17, 2024

Multiple sclerosis is an important neurological disease affecting millions of young patients globally. It encouraging that more than ten disease-modifying drugs became available for use in the past two decades. These therapies (DMTs) have different levels efficacy, routes administration, adverse effect profiles and concerns pregnancy. Much knowledge caution are needed their appropriate MS who heterogeneous clinical features severity, lesion load on magnetic resonance imaging response to DMT. We aim updated review concept personalization DMT relapsing patients. Shared decision making with consideration preference expectation understand potential efficacy/benefits risks advocated.

Language: Английский

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Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2024, Volume and Issue: 11(4)

Published: May 24, 2024

The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or combination, central vein sign (CVS), paramagnetic rim lesion (PRL), cortical (CL), as well their association with outcomes.

Language: Английский

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Serum biomarkers at disease onset for personalized therapy in multiple sclerosis

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Abstract The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed investigate whether sNfL sGFAP values identify distinct subgroups of patients according the risk their response disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 18 August 2022, with follow-up until 26 September 2023. enrolled who had samples collected within 12 months disease onset before initiating DMTs. Multivariable regression models were used estimate relapse-associated (RAW), progression independent relapse activity (PIRA) Expanded Disability Status Scale (EDSS) score 3. Of 725 included, median age was 34.2 (interquartile range, 27.6–42.4) years, 509 (70.2%) female. duration 6.43 4.65–9.81) years. Higher associated an elevated RAW [hazard ratio (HR) 1.45; 95% confidence interval (CI) 1.19–1.76; P < 0.001], PIRA (HR 1.43; CI 1.13–1.81; = 0.003) reaching EDSS 3 1.55; 1.29–1.85; 0.001). Moreover, higher linked a achieving 1.36; 1.06–1.74; 0.02) and, low values, 1.86; 1.01–3.45; 0.04). also examined combined effect levels. Patients exhibited all outcomes served as reference. Untreated high showed RAW, Injectable or oral DMTs reduced these but failed mitigate Conversely, high-efficacy counteracted heightened outcomes, except increased 3, which remained unchanged either other In conclusion, evaluating at might phenotypes diverse immunological pathways acquisition therapeutic response.

Language: Английский

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B cell depletion with anti-CD20 promotes neuroprotection in a BAFF-dependent manner in mice and humans

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(737)

Published: March 6, 2024

Anti-CD20 therapy to deplete B cells is highly efficacious in preventing new white matter lesions patients with relapsing-remitting multiple sclerosis (RRMS), but its protective capacity against gray injury and axonal damage unclear. In a passive experimental autoimmune encephalomyelitis (EAE) model whereby T H 17 promote brain leptomeningeal immune cell aggregates, we found that anti-CD20 treatment effectively spared myelin content prevented myeloid activation, oxidative damage, mitochondrial stress the subpial matter. increased survival factor (BAFF) serum, cerebrospinal fluid, leptomeninges of mice EAE. Although demyelination, loss, neuronal atrophy, co-treatment anti-BAFF abrogated these benefits. Consistent murine studies, observed elevated BAFF concentrations after RRMS were associated better clinical outcomes. Moreover, promoted human neurons vitro. Together, our data demonstrate exerts beneficial functions MS EAE context treatment.

Language: Английский

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A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 21, 2024

Introduction Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers disability progression that insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing metformin for PMS. The objective this clinical trial is evaluate whether metformin, as add-on treatment, superior placebo delaying disease Methods analysis MACSiMiSE-BRAIN multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled trial, conducted at five sites Belgium. Enrollment 120 PMS planned. Each participant will undergo screening visit assessment baseline magnetic resonance imaging (MRI), tests, questionnaires, safety laboratory assessment. Following randomization, participants be assigned either the (metformin) or group. Subsequently, they 96-week follow-up period. primary outcome change walking speed, measured Timed 25-Foot Walk Test, from 96 weeks. Secondary measures include neurological (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) hand function (9-Hole Peg test). Annual brain MRI performed assess evolution volumetry diffusion metrics. As may not progress all domains, composite outcome, Overall Response Score additionally evaluated an exploratory outcome. Other outcomes consist paramagnetic rim lesions, 2-minute test health economic analyses well both patient- caregiver-reported like EQ-5D-5L, Multiple Sclerosis Impact Scale Caregiver Strain Index. Ethics dissemination Clinical authorization regulatory agencies [Ethical Committee Federal Agency Medicines Health Products (FAMHP)] was obtained after submission centralized European Trial Information System. results disseminated scientific conferences, peer-reviewed publications, patient associations general public. registration ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.

Language: Английский

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Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Recent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate immune response and effectively manage MS. However, relationship between anti-CD20 treatments immunoglobulin G (IgG) levels, particularly development hypogammaglobulinemia subsequent infection risks, remains a subject scientific interest variability. We aimed investigate intricate connection MS treatments, changes IgG associated risk infections.

Language: Английский

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