학술논문
Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.
Document Type
Academic Journal
Author
Cagol A; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Schaedelin S; Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Barakovic M; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Benkert P; Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Todea RA; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Rahmanzadeh R; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Galbusera R; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Lu PJ; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Weigel M; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland.; Melie-Garcia L; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Ruberte E; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.; Siebenborn N; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Battaglini M; Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.; Radue EW; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Yaldizli Ö; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Oechtering J; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Sinnecker T; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.; Lorscheider J; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Fischer-Barnicol B; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Müller S; Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; Achtnichts L; Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.; Vehoff J; Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; Disanto G; Neurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.; Findling O; Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.; Chan A; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Salmen A; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Pot C; Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.; Bridel C; Division of Neurology, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.; Zecca C; Neurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.; Derfuss T; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Lieb JM; Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Remonda L; Department of Radiology, Cantonal Hospital Aarau, Aarau, Switzerland.; Wagner F; Department of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Vargas MI; Department of Radiology, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland.; Du Pasquier R; Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.; Division of Radiology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.; Lalive PH; Division of Neurology, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.; Pravatà E; Neurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.; Department of Neuroradiology, Neurocenter of Southern Switzerland, Lugano, Switzerland.; Weber J; Department of Radiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; Cattin PC; Center for Medical Image, Analysis, and Navigation, Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland.; Gobbi C; Neurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.; Leppert D; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Kappos L; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Kuhle J; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.; Granziera C; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Source
Publisher: American Medical Association Country of Publication: United States NLM ID: 101589536 Publication Model: Print Cited Medium: Internet ISSN: 2168-6157 (Electronic) Linking ISSN: 21686149 NLM ISO Abbreviation: JAMA Neurol Subsets: MEDLINE
Subject
Language
English
Abstract
Importance: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood.
Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.
Design, Setting, and Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021.
Exposures: According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability.
Main Outcomes and Measures: Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models.
Results: Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity.
Conclusions and Relevance: Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.
Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.
Design, Setting, and Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021.
Exposures: According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability.
Main Outcomes and Measures: Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models.
Results: Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity.
Conclusions and Relevance: Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.