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Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.
Cagol, Alessandro; Schaedelin, Sabine; Barakovic, Muhamed; Benkert, Pascal; Todea, Ramona-Alexandra; Rahmanzadeh, Reza; Galbusera, Riccardo; Lu, Po-Jui; Weigel, Matthias; Melie-Garcia, Lester; Ruberte, Esther; Siebenborn, Nina; Battaglini, Marco; Radue, Ernst-Wilhelm; Yaldizli, Özgür; Oechtering, Johanna; Sinnecker, Tim; Lorscheider, Johannes; Fischer-Barnicol, Bettina; Müller, Stefanie; Achtnichts, Lutz; Vehoff, Jochen; Disanto, Giulio; Findling, Oliver; Chan, Andrew; Salmen, Anke; Pot, Caroline; Bridel, Claire; Zecca, Chiara; Derfuss, Tobias; Lieb, Johanna M; Remonda, Luca; Wagner, Franca; Vargas, Maria I; Du Pasquier, Renaud; Lalive, Patrice H; Pravatà, Emanuele; Weber, Johannes; Cattin, Philippe C; Gobbi, Claudio; Leppert, David; Kappos, Ludwig; Kuhle, Jens; Granziera, Cristina.
Affiliation
  • Cagol A; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Schaedelin S; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Barakovic M; Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Benkert P; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Todea RA; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Rahmanzadeh R; Clinical Trial Unit, Department of Clinical Research, 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.
  • Lu PJ; 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; Division of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of 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.
  • Ruberte E; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, 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.
  • Battaglini M; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • 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; 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; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Sinnecker 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.
  • Lorscheider J; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland.
  • Fischer-Barnicol B; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Müller S; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Achtnichts L; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Vehoff 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.
  • Disanto G; Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
  • Findling O; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Chan A; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Salmen A; Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
  • Pot C; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Bridel C; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Zecca C; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, 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; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Remonda L; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Wagner F; Medical Image Analysis Center (MIAC) and Quantitative Biomedical Imaging Group, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
  • Vargas MI; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Du Pasquier R; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
  • Lalive PH; Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • Pravatà E; Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
  • Weber J; Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • Cattin PC; Neurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.
  • Gobbi C; Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
  • Leppert D; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Kappos L; Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Kuhle J; Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
  • Granziera C; Division of Neurology, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
JAMA Neurol ; 79(7): 682-692, 2022 07 01.
Article in En | MEDLINE | ID: mdl-35575778
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Central Nervous System Diseases / Neurodegenerative Diseases / Multiple Sclerosis, Relapsing-Remitting / Multiple Sclerosis / Nervous System Malformations Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: JAMA Neurol Year: 2022 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Central Nervous System Diseases / Neurodegenerative Diseases / Multiple Sclerosis, Relapsing-Remitting / Multiple Sclerosis / Nervous System Malformations Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: JAMA Neurol Year: 2022 Document type: Article Affiliation country: Country of publication: