Associations of with clinico-radiological measures in a large population
Sotirchos, Elias S. (Johns Hopkins University School of Medicine)
Fitzgerald, Kathryn (Johns Hopkins University School of Medicine)
Singh, Carol (Biogen)
Smith, Matthew D. (Johns Hopkins University School of Medicine)
Reyes-Mantilla, Maria (Johns Hopkins University School of Medicine)
Hersh, Carrie (Cleveland Clinic)
Hyland, Megan H. (University of Rochester Medical Center)
Canissario, Ryan (University of Rochester Medical Center)
Simmons, Sarah B. (Mellen Center, Neurological Institute, Cleveland Clinic)
Arrambide, Georgina (Hospital Universitari Vall d'Hebron)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Comabella, Manuel (Hospital Universitari Vall d'Hebron)
Naismith, Robert (Washington University in St. Louis)
Qiao, Min (Washington University in St. Louis)
Krupp, Lauren B. (New York University)
Nicholas, Jacqueline A. (Riverside Methodist Hospital)
Akgün, Katja (University Clinic Carl-Gustav Carus)
Ziemssen, Tjalf (University Clinic Carl-Gustav Carus)
Rudick, Richard ((formerly) Biogen)
Fisher, Elizabeth (Biogen)
Bermel, Robert (Mellen Center, Neurological Institute, Cleveland Clinic)
Mowry, Ellen (Johns Hopkins University School of Medicine)
Calabresi, Peter A. (Johns Hopkins University School of Medicine)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17. 8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Annals of Clinical and Translational Neurology, Vol. 10 (november 2022) , p. 84-97, ISSN 2328-9503

DOI: 10.1002/acn3.51704
PMID: 36427295

14 p, 2.2 MB

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