Save
Inflammatory demyelination in the cortex contributes to individual trajectory of disability worsening in MS
Author(s): ,
M. Boudot De La Motte
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225
,
E. Poirion
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225
,
M. Tonietto
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225
,
C. Louapre
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225; Neurology Department, APHP, Pitie-Salpetriere Hospital, Paris
,
B. Kuhnast
Affiliations:
IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
,
B. Bodini
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225; Neurology Department, APHP, St Antoine Hospital, Paris, France
B. Stankoff
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225; Neurology Department, APHP, St Antoine Hospital, Paris, France
ECTRIMS Online Library. Boudot De La Motte M. Oct 12, 2018; 228966
Marine Boudot De La Motte
Marine Boudot De La Motte
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Discussion Forum (0)
Rate & Comment (0)

Abstract: P1126

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: Post-mortem studies showed that innate immune cell activation and cortical demyelination are key mechanisms involved in neurodegeneration in MS. These mechanisms can be quantified in-vivo using TSPO 18F-DPA-714 positron emission tomography (PET) and Magnetization Transfer Imaging (MTR), respectively. We have developed a new approach to generate patient-specific maps of microglial activation and cortical demyelination. We previously reported a strong relationship between white matter (WM) neuroinflammation and individual trajectories of disability worsening in MS patients.
The aim of this study is to further explore the relationship between demyelination and microglial activation in cortical regions and to assess their contribution to disability worsening.
Methods: Patients with MS (n=26), and healthy controls (HC, n=12) underwent a dynamic 18F-DPA714 PET, and MRI including MTR sequences. For each patient, the trajectory of disability worsening was defined as the EDSS step-change (EDSS-SC) calculated over the 2 years before study entry.
In each patient, we derived the percentage of voxels characterized by (i) microglial activation and (ii) cortical demyelination, in the whole cortex, and in the inner and outer cortical layers.
We calculated the DICE coefficient reflecting the co-localization of inflammation and demyelination as the percentage of demyelinated voxels simultaneously characterized by microglial activation in inner, outer, and whole cortex. Spearman's correlation was used to assess the association between cortical demyelination, microglial activation and EDSS-SC.
Results: Taken separately, neither the percentage of demyelinated voxels (mean±sd=22%±5%) nor the percentage of voxels with microglial activation (mean±sd=16%±8%) in the whole, inner and outer cortex significantly correlated with EDSS-SC. However, a trend was found for microglial activation in the inner cortical layer (p=0.067). In the inner cortical layer, the DICE ranged from 1% to 47% (mean±sd=19%±10%), and was significantly associated with EDSS-SC (rho=0.39, p=0.049). The EDSS-SC also correlated with the extent of microglial activation in the WM (rho=0.47, p=0.0156).
Conclusion: These results suggest that inflammatory demyelination in the inner cortex, possibly affecting axonal initial segments of long distance projecting fibers, may contribute to a faster clinical worsening.
Disclosure: MBDLM: nothing to disclose
EP: nothing to disclose
MT: nothing to disclose
CL: nothing to disclose
BK: nothing to disclose
B. Bodini receives research support from ARSEP. She has received funding for traveling and/or speaker's honoraria from Novartis, Genzyme, Roche and Merck Serono.
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
The study was supported by a ANR MNP-2008-007125 specific grant, the program “Investissements d´avenir” ANR-10-IAIHU-06, MS research foundation ARSEP, INSERM (Institut National de la Santé et de la recherche médicale), ECTRIMS, JNLF (Journées de Neurologie de Langue Française), FRM (Fondation pour la Recherche Médicale), and sponsored by APHP (Assistance Publique des Hôpitaux de Paris).

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings