Contributions
Abstract: P485
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Damage to select limbic and associative cerebral cortical areas and deep grey matter (DGM) structures have been associated with cognitive impairment in multiple sclerosis (MS). However, structural integrity of white matter (WM) tracts connecting these brain regions and their association with cognition have not been investigated at the earliest stage of the disease.
Objectives: (1) To investigate longitudinal diffusion changes in WM tracts connecting limbic and associative parts of the cerebral cortex with DGM over one year in patients with clinically isolated syndrome (CIS). (2) To investigate the association of microstructural changes to these tracts with cognition.
Methods: 41 patients recruited less than 6 months after a CIS and 55 matched healthy controls (HC) underwent neuropsychological assessments, including episodic memory (EMem) and information processing speed (IPS). All patients and a subgroup of 19 HC were scanned using 3T T1-weighted and diffusion tensor (DT) brain MRI. Freesurfer was used to segment the brain in cortical (associative, limbic and sensori-motor) and subcortical (thalamus, hippocampus and striatum) regions. Two-tensor unscented Kalman filter tractography was used to trace tracts connecting limbic/associative cortex with DGM and both fractional anisotropy and mean diffusivity (MD) were used to assess the microstructural integrity in CIS and HC at each time-point. Linear regression models were used to assess cognitive impairment by altered tracts.
Results: Baseline: IPS and visual EMem were worse in CIS vs. HC. MD was significantly higher in right hippocampal-associative and right striatal-associative tracts in CIS compared to HC. MD of the striatal-associative tract could explain 27% of the IPS impairment (beta=-0.39).
After one year of follow-up, cognitive impairment was no longer detected in CIS. However, the cortico-subcortical tracts showed more widespread damage (increased MD) in the bilateral hippocampal-associative, the right hippocampal-limbic, the bilateral thalamo-associative, the right thalamo-limbic and the right striatal-associative tracts.
Conclusion: Damage to the tracts connecting DGM and associative/limbic cortex appears early in the evolution of MS and is associated with early cognitive impairment. However, normal cognitive performances at follow-up in spite of widespread microstructural damage suggests that compensatory mechanisms are deployed at this early stage of the disease.
Disclosure: This study was supported by TEVA and Labex Translational Research and Advanced Imaging Laboratory (TRAIL).
Koubiyr I: Personal grant from TRAIL.
Palotai M: Nothing to disclose.
Deloire M: Nothing to disclose.
Charre-Morin J: Nothing to disclose.
Saubusse A: Nothing to disclose.
Tourdias T: Nothing to disclose.
Guttmann CRG: Dr. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.
Brochet B: Pr Brochet or its institution received honoraria for consulting, speaking at scientific symposia, serving in advisory board or research support from Actelion, Biogen Idec, Merck Serono, Sanofi-Genzyme, Bayer, Medday, Roche, Teva, Novartis (all with approval by general director CHU de Bordeaux).
Ruet A: Dr A Ruet or her institution received honoraria for consulting, speaking at scientific symposia, serving in advisory board or research support from Biogen Idec, Medday, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva (all with approval by general director of the Hospital of Bordeaux and the University of Bordeaux).
Abstract: P485
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Damage to select limbic and associative cerebral cortical areas and deep grey matter (DGM) structures have been associated with cognitive impairment in multiple sclerosis (MS). However, structural integrity of white matter (WM) tracts connecting these brain regions and their association with cognition have not been investigated at the earliest stage of the disease.
Objectives: (1) To investigate longitudinal diffusion changes in WM tracts connecting limbic and associative parts of the cerebral cortex with DGM over one year in patients with clinically isolated syndrome (CIS). (2) To investigate the association of microstructural changes to these tracts with cognition.
Methods: 41 patients recruited less than 6 months after a CIS and 55 matched healthy controls (HC) underwent neuropsychological assessments, including episodic memory (EMem) and information processing speed (IPS). All patients and a subgroup of 19 HC were scanned using 3T T1-weighted and diffusion tensor (DT) brain MRI. Freesurfer was used to segment the brain in cortical (associative, limbic and sensori-motor) and subcortical (thalamus, hippocampus and striatum) regions. Two-tensor unscented Kalman filter tractography was used to trace tracts connecting limbic/associative cortex with DGM and both fractional anisotropy and mean diffusivity (MD) were used to assess the microstructural integrity in CIS and HC at each time-point. Linear regression models were used to assess cognitive impairment by altered tracts.
Results: Baseline: IPS and visual EMem were worse in CIS vs. HC. MD was significantly higher in right hippocampal-associative and right striatal-associative tracts in CIS compared to HC. MD of the striatal-associative tract could explain 27% of the IPS impairment (beta=-0.39).
After one year of follow-up, cognitive impairment was no longer detected in CIS. However, the cortico-subcortical tracts showed more widespread damage (increased MD) in the bilateral hippocampal-associative, the right hippocampal-limbic, the bilateral thalamo-associative, the right thalamo-limbic and the right striatal-associative tracts.
Conclusion: Damage to the tracts connecting DGM and associative/limbic cortex appears early in the evolution of MS and is associated with early cognitive impairment. However, normal cognitive performances at follow-up in spite of widespread microstructural damage suggests that compensatory mechanisms are deployed at this early stage of the disease.
Disclosure: This study was supported by TEVA and Labex Translational Research and Advanced Imaging Laboratory (TRAIL).
Koubiyr I: Personal grant from TRAIL.
Palotai M: Nothing to disclose.
Deloire M: Nothing to disclose.
Charre-Morin J: Nothing to disclose.
Saubusse A: Nothing to disclose.
Tourdias T: Nothing to disclose.
Guttmann CRG: Dr. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.
Brochet B: Pr Brochet or its institution received honoraria for consulting, speaking at scientific symposia, serving in advisory board or research support from Actelion, Biogen Idec, Merck Serono, Sanofi-Genzyme, Bayer, Medday, Roche, Teva, Novartis (all with approval by general director CHU de Bordeaux).
Ruet A: Dr A Ruet or her institution received honoraria for consulting, speaking at scientific symposia, serving in advisory board or research support from Biogen Idec, Medday, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva (all with approval by general director of the Hospital of Bordeaux and the University of Bordeaux).