Publications by authors named "Marignier R"

Objectives: To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability.

Methods: This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system.

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The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

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Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here we report the discovery of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens.

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Background: Currently, there are no available recommendations or guidelines on how to perform MRI monitoring in the management of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The issue is to determine a valuable MRI monitoring protocol to be applied in the management of NMOSD and MOGAD, as previously proposed for the monitoring of multiple sclerosis.

Objectives: The objectives of this work are to establish proposals for a standardized and feasible MRI acquisition protocol, and to propose control time points for systematic MRI monitoring in the management of NMOSD and MOGAD.

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Aim: To describe the impact of paediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) on academic and cognitive outcomes.

Method: This was an observational, retrospective, and descriptive single-centre study, carried out on a paediatric case series of children with MOGAD.

Results: A total of 51 patients were included (22 females); their median age was 8 years and the median follow-up duration was 31.

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What's new in NMOSD and MOGAD?

Rev Neurol (Paris)

November 2024

In this mini-review, we focus on novelties in the field of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). We first describe the proposed criteria for MOGAD and evaluate their impact and potential limitations, with a highlight on the subgroups of patients tested MOG-antibody positive only in the cerebrospinal fluid. We then propose a brief state of the art on the current knowledge on the so-call "double seronegative" NMOSD group, regarding nosology, clinical, biological and imaging features and the unmet need in this field.

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Article Synopsis
  • The study investigated immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) to better understand its characteristics, identify diagnostic biomarkers, and explore factors predicting patient outcomes.* -
  • It analyzed data from 67 patients (median age 69 years) diagnosed between 2015-2023, finding that 64% had focal syndromes (like limbic encephalitis) while 36% had meningoencephalitis, with the former showing worse treatment responses and higher mortality rates.* -
  • The presence of PNS-related antibodies and abnormal MRI findings were more common in focal encephalitis cases, highlighting important distinctions that could guide future diagnostics and therapeutic strategies.*
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Article Synopsis
  • MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease) is a new autoimmune disorder, and this study aims to examine the long-term outcomes and factors affecting relapse in adult patients.
  • The research included 128 patients from a French cohort with a follow-up period averaging over 6.5 years; results showed that a significant portion experienced relapses, with specific onset symptoms such as optic neuritis and myelitis.
  • Findings indicated that starting maintenance treatment after the first attack is linked to lower relapse risk, with notable impact on patients' disability scores over time.
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Background: A recent international consensus panel proposed diagnostic criteria for optic neuritis and a new classification. We aimed to investigate the clinical relevance of these diagnostic criteria and classification, in a cohort of patients hospitalized for a suspected diagnosis of optic neuritis.

Methods: We included all patients hospitalized between 2017 and 2022 in our tertiary center for (sub)acute loss of visual acuity suggestive of optic neuritis.

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Article Synopsis
  • The study aimed to describe the clinical features of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD), focusing on how these disorders affect the retina.
  • Researchers analyzed data from 25 individuals with DN-NMOSD and compared it to those with aquaporin-4 antibody positive neuromyelitis optica (AQP4-NMOSD) and healthy controls, using optical coherence tomography (OCT) to assess retinal damage.
  • The findings revealed significant thinning of the retinal nerve fiber layer and ganglion cell layers in DN-NMOSD patients, even after just one optic neuritis episode, indicating severe retinal damage and neurodegeneration regardless of an ON history.
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Objective: This retrospective study aimed to describe a cohort of 38 pediatric patients with MOGAD and to investigate the clinical differences between patients with CSF-negativity and CSF-positivity for MOG-abs.

Methods: The clinical and laboratory characteristics of pediatric patients with MOGAD were retrospectively studied. Demographics, clinical characteristics, CSF analysis, treatments and prognosis of patients were recorded.

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Objective: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease.

Methods: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy.

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Background: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported.

Methods: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries.

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Purpose Of Review: The clinical landscape associated to myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) has undergone a remarkable transformation over the past two decades, primarily driven by advancements in antibody detection techniques that have enhanced both the specificity and sensitivity of assays, enabling the identification of novel clinical phenotypes.

Recent Findings: Recent pivotal research publications, comprehensive reviews from established research groups, and most notably the first proposed international criteria for MOG-Ab associated disease (MOGAD) have substantially enriched our understanding of the clinical features associated with MOG-Ab. This review presents a comprehensive overview of the clinical characteristics of patients with MOG-Ab, systematically examining each core clinical syndrome defined by the proposed international MOGAD criteria.

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Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk.

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Objectives: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation.

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Background: Eculizumab, a humanized monoclonal antibody targeting the C5 complement protein, has been approved for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). The aim of this study is to evaluate the long-term effectiveness and safety of eculizumab in French adults with NMOSD and to describe patients' characteristics, disability, and quality of life using data collected in a real-world setting.

Methods: This is the protocol for ECUP4, an ongoing prospective, observational, non-comparative, multicenter study conducted in 32 reference centers in France.

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Background: Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients.

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Background: Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs.

Objectives: This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort.

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Background And Objectives: Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) serum levels are useful to define disease activity in different neurologic conditions. These biomarkers are increased in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) during clinical attacks suggesting a concomitant axonal and glial damage. However, there are contradictory results in double seronegative NMOSD (DS-NMOSD).

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Background: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein not previously described in the human central nervous system (CNS).

Objectives: We determined MFAP4 CNS expression and measured cerebrospinal fluid (CSF) and serum levels.

Methods: Tissue was sampled at autopsy from patients with acute multiple sclerosis (MS) ( = 3), progressive MS ( = 3), neuromyelitis optica spectrum disorder (NMOSD) ( = 2), and controls ( = 9), including 6 healthy controls (HC).

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