Structural and Clinical Correlates of a Periventricular Gradient of Neuroinflammation in Multiple Sclerosis

Autor: Charline Benoit, Vito A. G. Ricigliano, François-Xavier Lejeune, Bruno Stankoff, Bertrand Kuhnast, Matteo Tonietto, Emilie Poirion, G. Bera, Benedetta Bodini, Marine Boudot de la Motte, Michel Bottlaender
Přispěvatelé: Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université Paris-Saclay, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire
Rok vydání: 2021
Předmět:
Zdroj: Neurology
Neurology, American Academy of Neurology, 2021, pp.10.1212/WNL.0000000000011700. ⟨10.1212/wnl.0000000000011700⟩
Neurology, 2021, pp.10.1212/WNL.0000000000011700. ⟨10.1212/wnl.0000000000011700⟩
ISSN: 1526-632X
0028-3878
DOI: 10.1212/wnl.0000000000011700
Popis: ObjectivesTo explore in vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with multiple sclerosis (MS) using [18F]-DPA714 PET and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening.MethodsThirty-seven patients with MS and 19 healthy controls underwent MRI and [18F]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3-mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring. Two-year trajectories of disability worsening were collected to identify patients with and without recent disability worsening.ResultsThe percentage of DPA+ voxels was higher in patients compared to controls in the periventricular WM (p = 6.10e-6) and declined with increasing distance from ventricular surface, with a steeper gradient in patients compared to controls (p = 0.001). This gradient was found in both periventricular lesions and normal-appearing WM. In the total WM, it correlated with a gradient of microstructural tissue damage measured by MTR (rs = −0.65, p = 1.0e-3). Compared to clinically stable patients, patients with disability worsening were characterized by a higher percentage of DPA+ voxels in the periventricular normal-appearing WM (p = 0.025).ConclusionsOur results demonstrate that in MS the innate immune cell activation predominates in periventricular regions and is associated with microstructural damage and disability worsening. This could result from the diffusion of proinflammatory CSF-derived factors into surrounding tissues.
Databáze: OpenAIRE
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