The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

Acta Neuropathologica, Journal Year: 2020, Volume and Issue: 139(5), P. 875 - 892

Published: Feb. 11, 2020

Abstract We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay full length MOG its conformational form. MOGAD (ages 52 67) demonstrate spectrum histopathological observed within (median age, 10 years; range, 1–66; 56% female). Clinical, radiologic, laboratory characteristics course (78% relapsing) are consistent MOGAD. pathology is dominated coexistence both perivenous confluent white matter demyelination, over-representation intracortical demyelinated lesions compared typical MS. Radially expanding slowly smoldering as seen MS, not present. A CD4+ T-cell reaction granulocytic infiltration predominates. Complement deposition present all active lesions, but a preferential loss observed. AQP4 preserved, absence dystrophic astrocytes, variable axonal destruction. pathologically distinguished AQP4-IgG NMOSD, shares some overlapping MS ADEM, suggesting transitional pathology. selective protein suggest humoral mechanisms involved, however argue against endocytic internalization antigen. Parallels MOG-EAE may be amplification factor that augments possibly via complement mediated destruction or ADCC phagocytosis.

Language: Английский

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BCG-Induced Cross-Protection and Development of Trained Immunity: Implication for Vaccine Design

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Nov. 29, 2019

The Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens might be unrelated target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response microorganisms other than Mycobacterium tuberculosis, such as Candida albicans Staphylococcus aureus. Innate cells, including monocytes natural killer (NK) cells contribute this unspecific protection way independent of memory T or B cells. This phenomenon associated memory-like known "trained immunity". Epigenetic reprogramming through histone modification regulatory elements particular genes been reported one mechanisms induction trained immunity both, humans mice. Indeed, it shown vaccination changes methylation pattern histones specific circulating leading "trained" state. Importantly, these modifications can lead expression and/or repression are related increased secondary infections after vaccination, pathogen recognition faster inflammatory responses. In review, we will discuss BCG-induced acquisition potential heterologous effects recombinant vaccines.

Language: Английский

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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Language: Английский

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Multiple sclerosis

The Lancet, Journal Year: 2023, Volume and Issue: 403(10422), P. 183 - 202

Published: Nov. 7, 2023

Language: Английский

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Comorbidity in Multiple Sclerosis

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 21, 2020

Comorbidities in patients with multiple sclerosis (MS) has become an area of increasing interest the recent years. A comorbidity is defined as any additional disease that coexists individual a given index and not obvious complication disease. The aim this review to describe current evidence regarding range comorbidities population MS reported different countries knowledge about influence on clinical features therapeutic challenges MS. Certain are more prevalent people such depression, anxiety, cerebro- cardiovascular diseases certain autoimmune disorders diabetes, thyroid inflammatory bowel previous perception trend toward lower overall risk cancer appears be challenged, but there no higher occurrence malignancies may modify presentation MS, have implications for treatment choice, adherence outcome. Several comorbid conditions associated increased disability progression, including hypertension chronic obstructive pulmonary common from time diagnosis account some heterogeneity observed diagnostic delay, presentation, degree rate health care utilisation, working ability, employment status quality life. Coexisting polypharmacy increase complexity patient management poses major challenges, particularly number immunosuppressive disease-modifying therapies.

Language: Английский

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

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 14, 2022

Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) can be quantified by serum neurofilament light chain (sNfL) glial fibrillary acidic protein (sGFAP). We investigated sNfL sGFAP as tools for stratifying patients with MS based on progression disease activity status.We leveraged our Comprehensive Longitudinal Investigation at the Brigham Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data samples collected over more than 20 years. included a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds classifier high risk underlying pathology. analyzed within 6 months from EDSS corresponding baseline visit. Patients who further developed 6-month disability (6mCDP) were classified progressors. stratified into active/nonactive new brain/spinal cord lesions or relapses in 2 years before during follow-up. Statistical analysis log-transformed sGFAP/sNfL assessed association demographic, features associations future disability.We 257 had an average 4.0 median follow-up after 7.6 was higher (adjusted β = 1.21; 95% CI 1.04-1.42; p 0.016), first 1.17; 1.01-1.36; 0.042). not increased presence activity. Higher levels, but associated 6mCDP hazard ratio [HR] 1.71; 1.19-2.45; 0.004). The stronger low HR 2.44; 1.32-4.52; 0.005) nonactive prior sample.Higher levels correlated subsequent progression, particularly patients, whereas reflected acute Thus, may used to stratify clinical research studies trials inform care.

Language: Английский

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Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion

Journal of Neurology, Journal Year: 2022, Volume and Issue: 269(10), P. 5382 - 5394

Published: May 24, 2022

Abstract Multiple sclerosis (MS) is a chronic and progressive neurological disease that characterized by neuroinflammation, demyelination neurodegeneration occurring from the earliest phases of may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) represent best window opportunity to delay irreversible central nervous system damage MS-related hindering underlying heterogeneous pathophysiological processes contributing progression. In line this, growing evidence suggests early use HE-DMTs associated significant greater reduction not only inflammatory activity (clinical relapses new lesion formation at magnetic resonance imaging) but also progression, in terms accumulation clinical compared delayed HE-DMT escalation strategy. These beneficial effects seem acceptable long-term safety risks, thus configuring this treatment approach as most positive benefit/risk profile. Accordingly, it should mandatory treat people case prognostic factors suggestive aggressive disease, advisable offer an after diagnosis, taking into account drug profile, severity, and/or radiological activity, patient-related factors, including possible comorbidities, family planning, patients’ preference agreement EAN/ECTRIMS AAN guidelines. Barriers for include concerns safety, challenges management initiation monitoring, negative preferences, restricted access according guidelines regulatory rules, sustainability. However, these barriers do apply each none appear insuperable.

Language: Английский

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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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Clinical Features of Late-Onset Multiple Sclerosis: a Systematic Review and Meta-analysis

Multiple Sclerosis and Related Disorders, Journal Year: 2021, Volume and Issue: 50, P. 102816 - 102816

Published: Feb. 6, 2021

Language: Английский

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Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study

Multiple Sclerosis Journal, Journal Year: 2019, Volume and Issue: 26(13), P. 1670 - 1681

Published: Oct. 15, 2019

Background: A limited number of studies investigated associations between serum neurofilament light chain (sNfL) and cognition in persons with multiple sclerosis (PwMS). Objective: To assess cross-sectional longitudinal sNfL levels, clinical, cognitive performance PwMS age-matched healthy controls (HCs). Materials: One hundred twenty-seven (85 relapsing–remitting MS/42 progressive MS), 20 clinically isolated syndrome patients, 52 HCs were followed for 5 years. levels measured using the single-molecule array (Simoa) assay quantified picograms per milliliter. Expanded Disability Status Scale (EDSS), walking, manual dexterity tests obtained. At follow-up, Brief International Cognitive Assessment MS (BICAMS) was utilized. Cognitively impaired (CI) status derived HC-based z-scores. Age-, sex-, education-adjusted analysis covariance (ANCOVA) regression models used. Multiple comparison–adjusted values q < 0.05 considered significant. Results: In PwMS, cross-sectionally associated walking speed ( r = 0.235, 0.036), 0.337, 0.002), processing (CPS; =−0.265, 0.012). Baseline predicted 5-year EDSS scores 0.25, 0.012), 0.224, 0.033), CPS =−0.205, 0.049). CI patients had higher (27.2 vs. 20.6, p 0.016) greater absolute increase when compared non-CI (4.8 0.7, 0.04). Conclusion: Higher are poorer current future clinical performance.

Language: Английский

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