Publications by authors named "Xavier Montalban"

Background And Objectives: Invasive procedures may delay the diagnostic process in multiple sclerosis (MS). We investigated the added value of serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), chitinase-3-like 1 (sCHI3L1), and the immune responses to the Epstein-Barr virus-encoded nuclear antigen 1 to current MS diagnostic criteria.

Methods: In this multicentric study, we selected patients from 2 prospective cohorts presenting a clinically isolated syndrome (CIS).

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Background And Objectives: Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation.

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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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Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

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Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

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Background And Objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

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Background And Objectives: The role of the complement system in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is not completely understood, and studies exploring its potential utility for diagnosis and prognosis are lacking. We aimed to investigate the value of complement factors (CFs) as diagnostic and prognostic biomarkers in patients with MOGAD.

Methods: Multicentric retrospective cohort study including patients with MOGAD, multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD) with available paired serum and CSF samples.

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Objective: The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.

Methods: We retrospectively identified patients evaluated for suspected PPMS at 5 European centers.

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Article Synopsis
  • - Organizing pneumonia (OP) has been identified in patients with inflammatory demyelinating diseases (IDDs) after COVID-19, particularly those treated with anti-CD20 therapies, but comprehensive data is scarce.
  • - This study analyzed 19 patients with conditions like multiple sclerosis and neuromyelitis optica who developed COVID-19-associated OP; symptoms included intermittent fever, and most required hospitalization, but none died.
  • - After about 1.5 years of follow-up, most lung issues resolved, although many patients experienced long-COVID symptoms; the study suggests that OP should be considered in anti-CD20-treated patients exhibiting specific CT findings and fever.
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Background: Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.

Objectives: We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).

Design: SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.

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Multiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system and a major cause of neurological disability in young adults. Its prevalence and incidence are increasing, and it has been estimated at over 2.8 million cases worldwide, in addition to recent trends towards a shift in MS prevalence to older ages, with peak prevalence estimates in the sixth decade of life.

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Article Synopsis
  • Evobrutinib, a BTK inhibitor, was evaluated for safety and efficacy against teriflunomide in treating relapsing multiple sclerosis in two phase 3 trials involving nearly 2,300 participants across 52 countries.
  • Participants aged 18-55 with specific disability scores were randomly assigned to receive either evobrutinib or teriflunomide, with both studies designed as double-blind to avoid bias among participants and researchers.
  • The primary endpoint was the annualized relapse rate over 156 weeks, with data collected from June 2020 to October 2023, showing that 66-67% of the participants were female across the trials.
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This review will briefly introduce microRNAs (miRNAs) and dissect their contribution to multiple sclerosis (MS) and its clinical outcomes. For this purpose, we provide a concise overview of the present knowledge of MS pathophysiology, biomarkers and treatment options, delving into the role of selectively expressed miRNAs in clinical forms of this disease, as measured in several biofluids such as serum, plasma or cerebrospinal fluid (CSF). Additionally, up-to-date information on current strategies applied to miRNA-based therapeutics will be provided, including miRNA restoration therapy (lentivirus expressing a specific type of miRNA and miRNA mimic) and miRNA inhibition therapy such as antisense oligonucleotides, small molecules inhibitors, locked nucleic acids (LNAs), anti-miRNAs, and antagomirs.

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Background: Infection by cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) play a prognostic role in multiple sclerosis (MS).

Objectives: To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers.

Methods: Ninety-eight MS patients with a median follow-up of 20 years were included in the study.

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Article Synopsis
  • - The study explored how serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels could predict worsening disability in multiple sclerosis (MS), enrolling 725 patients across 13 European hospitals from 1994 to 2023.
  • - Higher levels of sNfL were significantly associated with increased risks of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and reaching an Expanded Disability Status Scale (EDSS) score of 3, while elevated sGFAP levels were linked to a higher risk of reaching the EDSS score.
  • - Combining both sNfL and sGFAP levels indicated that low values represented low risk for worsening
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The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS.

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Article Synopsis
  • * The initiative has formed four working groups aimed at enhancing research, clinical management, eHealth, and healthcare system reforms, ensuring a collaborative effort among patients, caregivers, and other stakeholders.
  • * As it progresses, the initiative plans to boost the use of eHealth tools and passive PROs in research and clinical settings, while also refining statistical methods in clinical trials and fostering alignment among industry, regulatory bodies, and health policymakers regarding PROs in MS healthcare.
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Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which there are currently no effective disease-modifying treatments. Immunosenescence is associated with the production of the senescence-associated secretory phenotype (SASP), with IL-6 being one of the most prominent cytokines. IL-6 is a determinant for the development of autoimmunity and neuroinflammation and is involved in the pathogenesis of MS.

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Background And Objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).

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Artificial intelligence (AI) is the branch of science aiming at creating algorithms able to carry out tasks that typically require human intelligence. In medicine, there has been a tremendous increase in AI applications thanks to increasingly powerful computers and the emergence of big data repositories. Multiple sclerosis (MS) is a chronic autoimmune condition affecting the central nervous system with a complex pathogenesis, a challenging diagnostic process strongly relying on magnetic resonance imaging (MRI) and a high and largely unexplained variability across patients.

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Article Synopsis
  • Early treatment with immunomodulating therapy improves short-term clinical outcomes in multiple sclerosis (MS) patients, reducing the risk of conversion to clinically definite MS (CDMS) by 30.5%.
  • In a study of patients with clinically isolated syndrome (CIS), those who received early treatment demonstrated fewer relapses and maintained stable disability over 15 years compared to a delayed treatment group.
  • By the 15-year mark, 66.3% of patients treated early remained employed, further indicating the benefits of starting treatment early in the disease course.
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