Contributions
Abstract: 270
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Spontaneous myelin repair in white matter (WM) lesions fails in most of the patients with MS, but the mechanisms underlying the failure of this process remain unclear. Previous pathological studies suggested that myelin repair was less efficient in the periventricular WM, but no in-vivo data have supported this evidence. We have used 11C-PIB positron emission tomography (PET) to generate patient-specific maps of remyelination in WM lesions of patients with MS. The aim of this study is to explore in-vivo the relationship between the extent of remyelination and the distance from ventricles in MS.
Methods: Longitudinal 11C-PIB PET data were acquired in 19 patients with MS to calculate individual indices of remyelination potential, which were used to classify patients in “good” or “bad” remyelinators. For each patient, we calculated the probability of each demyelinated lesional voxel at baseline to remyelinate over the follow-up relative to its distance from ventricles. At the whole group level, the relationship between the probability of voxels to remyelinate and the distance from ventricles was tested using a mixed-effect linear model, where each patient was included as random effect, and the index of remyelination potential as covariate. The probability of voxels to remyelinate relative to the distance from ventricles was compared between “good” and “bad” remyelinators with a multiple regression adjusted for age and gender.
Results: At the whole group level, the probability of each voxel to remyelinate significantly increased with greater distance from the ventricular CSF surface, independently of the individual remyelination potential (p=0.001).
While the probability of remyelination was greater in “good” than in “bad” remyelinators in the first cm close to ventricular cerebrospinal fluid (p=0.03), this group difference lost significance at a greater distance from ventricles.
Conclusions: We found that spontaneous remyelination was significantly reduced in periventricular WM in patients, and that the difference in the probability of remyelination between “good” and “bad” remyelinators was significant in periventricular areas only. Our data suggest the presence of inhibitory factors around the ventricles, such as CSF-derived soluble mediators, immunoreactive stem cells, or pathologically activated innate immune cells. “Good” remyelinators might be more effective in counteracting these inhibitory factors compared with “bad” remyelinators.
Disclosure: EP: nothing to disclose
MT: nothing to disclose
FXL: nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
The study was funded by specific grants from ELA (European Leukodystrophy Association; grant no.: 2007‐0481) and INSERM‐DHOS (grant no.: 2008‐recherche clinique et translationnelle). The study was sponsored by APHP (Assistance Publique des Hôpitaux de Paris). The research also received funding from the “Investissements d´avenir” ANR‐10‐IAIHU‐06 grant.
Abstract: 270
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Spontaneous myelin repair in white matter (WM) lesions fails in most of the patients with MS, but the mechanisms underlying the failure of this process remain unclear. Previous pathological studies suggested that myelin repair was less efficient in the periventricular WM, but no in-vivo data have supported this evidence. We have used 11C-PIB positron emission tomography (PET) to generate patient-specific maps of remyelination in WM lesions of patients with MS. The aim of this study is to explore in-vivo the relationship between the extent of remyelination and the distance from ventricles in MS.
Methods: Longitudinal 11C-PIB PET data were acquired in 19 patients with MS to calculate individual indices of remyelination potential, which were used to classify patients in “good” or “bad” remyelinators. For each patient, we calculated the probability of each demyelinated lesional voxel at baseline to remyelinate over the follow-up relative to its distance from ventricles. At the whole group level, the relationship between the probability of voxels to remyelinate and the distance from ventricles was tested using a mixed-effect linear model, where each patient was included as random effect, and the index of remyelination potential as covariate. The probability of voxels to remyelinate relative to the distance from ventricles was compared between “good” and “bad” remyelinators with a multiple regression adjusted for age and gender.
Results: At the whole group level, the probability of each voxel to remyelinate significantly increased with greater distance from the ventricular CSF surface, independently of the individual remyelination potential (p=0.001).
While the probability of remyelination was greater in “good” than in “bad” remyelinators in the first cm close to ventricular cerebrospinal fluid (p=0.03), this group difference lost significance at a greater distance from ventricles.
Conclusions: We found that spontaneous remyelination was significantly reduced in periventricular WM in patients, and that the difference in the probability of remyelination between “good” and “bad” remyelinators was significant in periventricular areas only. Our data suggest the presence of inhibitory factors around the ventricles, such as CSF-derived soluble mediators, immunoreactive stem cells, or pathologically activated innate immune cells. “Good” remyelinators might be more effective in counteracting these inhibitory factors compared with “bad” remyelinators.
Disclosure: EP: nothing to disclose
MT: nothing to disclose
FXL: nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
The study was funded by specific grants from ELA (European Leukodystrophy Association; grant no.: 2007‐0481) and INSERM‐DHOS (grant no.: 2008‐recherche clinique et translationnelle). The study was sponsored by APHP (Assistance Publique des Hôpitaux de Paris). The research also received funding from the “Investissements d´avenir” ANR‐10‐IAIHU‐06 grant.