Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome

Nicolás Fissolo; Sabine Schaedelin; Luisa M Villar; Jan D Lünemann; Jorge Correale; Konrad Rejdak; Nicholas Schwab; Andreu Vilaseca; Friederike Held; Antonio García-Merino; Stefan Bittner; María Trojano; Roberto Furlan; Hayrettin Tumani; Francisco Pérez-Miralles; Igal Rosenstein; Daniela Galimberti; Gary Álvarez-Bravo; Eric Thouvenot; Sara Llufriu; Samia J Khoury; Robert Hoepner; Sergio Martínez-Yélamos; Harald Hegen; Jelena Drulovic; Neus Téllez-Lara; Michael Khalil; Johanna Oechtering; Ángel Pérez-Sempere; Alfredo Rodríguez-Antigüedad; José Enrique-Martínez; Eva Strijbis; Joep Killestein; Sara Eichau; Elena Colombo; Jonas Schaller-Nagengast; Luciana Midaglia; Antonio J Sánchez-López; Enric Monreal; Andrew Chan; Friedemann Paul; Àlex Rovira; Mar Tintoré; Jan Lycke; Frauke Zipp; Bernhard Hemmer; Jens Kuhle; Xavier Montalban; Manuel Comabella; RIS Study Group

doi:10.1001/jamaneurol.2025.1481

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Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome

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Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome

Nicolás Fissolo, Sabine Schaedelin, Luisa M Villar, Jan D Lünemann, Jorge Correale, Konrad Rejdak, Nicholas Schwab, Andreu Vilaseca, Friederike Held, Antonio García-Merino, …

JAMA neurology, Vol.82(7), pp.722-733

01/07/2025

DOI: https://doi.org/10.1001/jamaneurol.2025.1481

PMID: 40455494

Résumé

Adult

Biomarkers - blood

Biomarkers - cerebrospinal fluid

Cohort Studies

Demyelinating Diseases - cerebrospinal fluid

Demyelinating Diseases - diagnostic imaging

Female

Humans

Magnetic Resonance Imaging

Male

Middle Aged

Multiple Sclerosis - cerebrospinal fluid

Multiple Sclerosis - diagnosis

Multiple Sclerosis - diagnostic imaging

Oligoclonal Bands

Prognosis

Risk Factors

Understanding the risk factors for symptom development will allow clinicians to stratify people with radiologically isolated syndrome (pwRIS) more effectively and tailor their management strategies accordingly. To identify prognostic factors at radiologically isolated syndrome (RIS) diagnosis associated with the development of multiple sclerosis (MS) symptoms. This cohort study was performed in samples collected between July 2004 and September 2022 and included 33 MS centers. All pwRIS who meet the 2017 McDonald criteria for dissemination in space with a sample collected near the diagnostic magnetic resonance imaging were included. No patients who met eligibility criteria were excluded. The data were analyzed from July 2024 to November 2024. Body fluid biomarkers and environmental factors in pwRIS. The main outcome was the development of MS symptoms. Analyses involved univariable and multivariable Cox proportional hazards models, including age, sex, and treatment following RIS diagnosis, as additional independent variables. The study included 273 pwRIS (mean age, 38.6 [SD 11.6] years; 207 women [75.8%] and 66 men [24.2%]) with a median follow-up of 5.0 [IQR, 2.5-7.7] years. A total of 101 pwRIS developed MS symptoms (37.0%). The presence of immunoglobulin G oligoclonal bands (OBs) (hazard ratio [HR], 5.09; 95% CI, 2.36-10.97; P < .001), immunoglobulin M OBs (HR, 2.58; 95% CI, 1.61-4.14; P < .001), and a κ free light chain index of 6.1 or more (HR, 2.79; 95% CI, 1.37-5.67; P = .005) were associated with MS symptoms. High cerebrospinal fluid neurofilament light chain (NfL) levels (HR, 1.31; 95% CI, 1.18-1.45; P < .001) and high serum NfL z scores (HR, 1.42; 95% CI, 1.16-1.72; P = .005) were also associated with an increased risk of MS symptoms. In contrast, high anti-cytomegalovirus titers (HR, 0.59; 95% CI, 0.38-0.93; P = .02) and high ultraviolet radiation exposure in the year before (HR, 0.52; 95% CI, 0.37-0.74; P < .001) and the year after (HR, 0.54, 95% CI, 0.38-0.75; P < .001) diagnosis reduced the risk of MS symptoms. For all these prognostic factors, the multivariable analysis yielded similar results. The combination of high serum NfL z scores and positive immunoglobulin G OBs conferred a 5-year risk of clinical symptoms of 58.3% (95% CI, 45.9-67.9). This risk increased to 81.6% (95% CI, 60.9-91.4) in pwRIS who were younger and positive for immunoglobulin M OBs. The study elucidates the prognostic factors that significantly impact the risk of developing MS symptoms in pwRIS at diagnosis, thereby, enhancing the potential for tailored clinical interventions.

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Titre: Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome
Créateurs - sans rôle: Nicolás Fissolo - Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII, Madrid, Spain
Sabine Schaedelin - Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Luisa M Villar - Departments of Neurology and Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria
Jan D Lünemann - Department of Neurology and Institute of Translational Neurology, University Hospital Münster, Münster, Germany
Jorge Correale
Konrad Rejdak - Medical University of Lublin
Nicholas Schwab - Department of Neurology and Institute of Translational Neurology, University Hospital Münster, Münster, Germany
Andreu Vilaseca - Servei de Neurologia and Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona, Barcelona, Spain
Friederike Held - Department of Neurology, School of Medicine and Health, Technical University of Munich, Klinikum rechts der Isar, München, Germany
Antonio García-Merino - Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain
Stefan Bittner - University Medical Center of the Johannes Gutenberg University Mainz
María Trojano - University of Bari Aldo Moro
Roberto Furlan - Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Hayrettin Tumani - University Hospital Ulm
Francisco Pérez-Miralles - Neuroinmunology Unit, University and Polytechnic La Fe Hospital, Valencia, Spain
Igal Rosenstein - Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Daniela Galimberti - University of Milan
Gary Álvarez-Bravo - Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), Girona, Spain
Eric Thouvenot - Institut de Génomique Fonctionnelle
Sara Llufriu - Service of Neurology, Laboratory of Advanced Imaging in Neuroimmunological Diseases, Center of Neuroimmunology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques, Barcelona, Spain
Samia J Khoury - Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
Robert Hoepner - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland
Sergio Martínez-Yélamos - Multiple Sclerosis Unit, Department of Neurology, Hospital Universitari de Bellvitge. Neurology and Neurogenetics Group, Neuroscience Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Department of Clinical Sciences, School of Medicine, Universitat de Barcelona (UB), L'Hospitalet de Llobregat, Spain
Harald Hegen - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Jelena Drulovic - Clinic of Neurology, University Clinical Center of Serbia, Belgrade, Serbia
Neus Téllez-Lara - Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Michael Khalil - Medical University of Graz
Johanna Oechtering - Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland
Ángel Pérez-Sempere - Hospital General Universitario de Alicante, Alicante, Spain
Alfredo Rodríguez-Antigüedad - Neurology Department, Cruces-BioCruces Bizkaia University Hospital, Barakaldo-Bizkaia, Spain
José Enrique-Martínez - Neurology Department, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Eva Strijbis - MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VU Medical Centre, Amsterdam, the Netherlands
Joep Killestein - MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Location VU Medical Centre, Amsterdam, the Netherlands
Sara Eichau - Neurology Department, Virgen Macarena University Hospital, Sevilla, Spain
Elena Colombo - Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy
Jonas Schaller-Nagengast - Department of Neurology, University Hospital Ulm, Ulm, Germany
Luciana Midaglia - Servei de Neurologia and Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron. Universitat Autònoma de Barcelona, Barcelona, Spain
Antonio J Sánchez-López - Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain
Enric Monreal - Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá, Madrid, Spain
Andrew Chan - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland
Friedemann Paul - Charité - Universitätsmedizin Berlin
Àlex Rovira - Universitat Autònoma de Barcelona
Mar Tintoré - Universitat de Vic - Universitat Central de Catalunya
Jan Lycke - University of Gothenburg
Frauke Zipp - Department of Neurology, Research Center for Immunotherapy (FZI) and Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Bernhard Hemmer - Munich Cluster for Systems Neurology
Jens Kuhle - University Hospital of Basel
Xavier Montalban - Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany
Manuel Comabella - Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII, Madrid, Spain
RIS Study Group
Détails de publication: JAMA neurology, Vol.82(7), pp.722-733
Identifiants: 99139528809311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English
Type de ressource: Journal article