Charles Rg Guttmann1, Matthieu Rousset2, Jean A Roch3, Salem Hannoun4, Françoise Durand-Dubief5, Boubakeur Belaroussi6, Michele Cavallari1, Muriel Rabilloud7, Dominique Sappey-Marinier8, Sandra Vukusic9, François Cotton10. 1. Center for Neurological Imaging, Brigham and Women's Hospital, USA. 2. Service de Radiologie, Centre Hospitalier Lyon-Sud, France. 3. Service de Radiologie, Centre Hospitalier Lyon-Sud, France/CREATIS, Université de Lyon, France. 4. CREATIS, Université de Lyon, France. 5. CREATIS, Université de Lyon, France/Service de Neurologie, Hospices Civils de Lyon, France. 6. BioClinica SAS, France. 7. Service de Biostatistique, Hospices Civils de Lyon, France. 8. CREATIS, Université de Lyon, France/Département IRM, CERMEP-Imagerie du Vivant, France. 9. Service de Neurologie, Hospices Civils de Lyon, France. 10. Service de Radiologie, Centre Hospitalier Lyon-Sud, France/CREATIS, Université de Lyon, France francois.cotton@chu-lyon.fr.
Abstract
BACKGROUND: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. OBJECTIVE: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. METHODS: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing-remitting MS (RRMS). RESULTS: Active lesions (n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. CONCLUSION: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an 'inside-out' genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.
BACKGROUND: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. OBJECTIVE: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. METHODS: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing-remitting MS (RRMS). RESULTS: Active lesions (n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. CONCLUSION: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an 'inside-out' genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.
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