Contributions
Abstract: P1002
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background and Objectives: In subjects with relapse-onset MS it has been recently shown that a more severe periventricular white matter lesion burden is associated with a more marked thinning of the cortical ribbon, possibly pointing to a common pathogenetic mechanism between these two facets of MS pathology. Starting from this observation, we decided to explore if in subjects with primary progressive multiple sclerosis (PPMS) cortical lesion load is associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging (DWI).
Methods: Twenty-three subjects with PPMS and nineteen healthy controls were included in the study. T1 volumetric, PD/T2, phase-sensitive inversion recovery (PSIR) and DWI images were acquired at 3T for all subjects. WM lesions were identified on PD/T2 sequences and were then co-registered to diffusion data. Mean diffusivity (MD) NAWM maps were created excluding WM lesions and a 2 mm-thick peri-lesional rim. Skeletonized NAWM MD maps were then computed using the TBSS pipeline. In each skeletonized NAWM MD map those supra-tentorial voxels with a distance from the lateral ventricles between 2 and 6 mm were included in the periventricular NAWM mask while those voxels of skeletonized WM with a distance from the lateral ventricles higher than 6 mm were included in the deep NAWM mask. Mean MD values were computed separately for these two masks for each subject. Lastly, cortical lesions volumes were assessed on PSIR images.
Results: As expected skeletonized NAWM was abnormal in PPMS compared to HC. In the PPMS group, a significant correlation (r=0.69 p=0.001) was observed between skeletonized periventricular NAWM MD values and cortical lesion load with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation (p=0.18) between cortical lesion load and deep NAWM MD values. The same pattern of correlations was observed if juxta-cortical lesions load was used instead of total cortical lesion load.
Discussion: Our data suggest that a common factor play a role in the development of both cortical lesion and periventricular NAWM damage in subjects with PPMS. The proximity of cerebrospinal fluid (CSF) to both the cerebral cortex and periventricular NAWM and the role played by CSF in cortical lesion formation seem to imply that CSF-mediated soluble are also involved in modulating NAWM damage in PPMS.
Disclosure: Matteo Pardini: received support from Novartis
Lazar Fleysher: report no disclosures
Colleen Farrell: report no disclosures
Michelle Fabian: report no disclosures
Aaron Miller: has served as a consultant and/or participant in advisory board meetings for Genzyme/sanofi-aventis, Biogen Idec, Glaxo Smith Kline, EMD Serono (Merck Serono), Novartis, ONO, Acorda, Nuron Biotech,Teva, Questcor and Accordant Health Services. He has received research support from Acorda, Novartis, Genentech, Genzyme/sanofi-aventis, Biogen Idec, Roche, and Questcor. He has served as Editor of Continuum, a continuing medical education publication of the AAN and currently serves as Editor of Continuum Audio. He is a member of the editorial board of Multiple Sclerosis and Related Disorders.
Declan Chard: has received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss MS Society, Excemed (previously Serono Symposia International Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for advisory board work; meeting expenses from Merck, Teva, Novartis, the MS Trust and National MS Society; and has previously held stock in GlaxoSmithKline.
Fred Lublin "s sources of funding for research include: Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS; Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi-Aventis; Acorda; Questcor; Roche, Genentech; Celgene; Johnson & Johnson; Revalesio; Coronado Bioscience, Genzyme, MedImmune; Bristol-Myers Squibb, Xenoport, Receptos; Forward Pharma; Co-Chief Editor: Multiple Sclerosis and Related Diseases; Stock Ownership: Cognition Pharmaceuticals, Inc
Matilde Inglese: has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., and she is a consultant for Vaccinex Inc.
Abstract: P1002
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background and Objectives: In subjects with relapse-onset MS it has been recently shown that a more severe periventricular white matter lesion burden is associated with a more marked thinning of the cortical ribbon, possibly pointing to a common pathogenetic mechanism between these two facets of MS pathology. Starting from this observation, we decided to explore if in subjects with primary progressive multiple sclerosis (PPMS) cortical lesion load is associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging (DWI).
Methods: Twenty-three subjects with PPMS and nineteen healthy controls were included in the study. T1 volumetric, PD/T2, phase-sensitive inversion recovery (PSIR) and DWI images were acquired at 3T for all subjects. WM lesions were identified on PD/T2 sequences and were then co-registered to diffusion data. Mean diffusivity (MD) NAWM maps were created excluding WM lesions and a 2 mm-thick peri-lesional rim. Skeletonized NAWM MD maps were then computed using the TBSS pipeline. In each skeletonized NAWM MD map those supra-tentorial voxels with a distance from the lateral ventricles between 2 and 6 mm were included in the periventricular NAWM mask while those voxels of skeletonized WM with a distance from the lateral ventricles higher than 6 mm were included in the deep NAWM mask. Mean MD values were computed separately for these two masks for each subject. Lastly, cortical lesions volumes were assessed on PSIR images.
Results: As expected skeletonized NAWM was abnormal in PPMS compared to HC. In the PPMS group, a significant correlation (r=0.69 p=0.001) was observed between skeletonized periventricular NAWM MD values and cortical lesion load with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation (p=0.18) between cortical lesion load and deep NAWM MD values. The same pattern of correlations was observed if juxta-cortical lesions load was used instead of total cortical lesion load.
Discussion: Our data suggest that a common factor play a role in the development of both cortical lesion and periventricular NAWM damage in subjects with PPMS. The proximity of cerebrospinal fluid (CSF) to both the cerebral cortex and periventricular NAWM and the role played by CSF in cortical lesion formation seem to imply that CSF-mediated soluble are also involved in modulating NAWM damage in PPMS.
Disclosure: Matteo Pardini: received support from Novartis
Lazar Fleysher: report no disclosures
Colleen Farrell: report no disclosures
Michelle Fabian: report no disclosures
Aaron Miller: has served as a consultant and/or participant in advisory board meetings for Genzyme/sanofi-aventis, Biogen Idec, Glaxo Smith Kline, EMD Serono (Merck Serono), Novartis, ONO, Acorda, Nuron Biotech,Teva, Questcor and Accordant Health Services. He has received research support from Acorda, Novartis, Genentech, Genzyme/sanofi-aventis, Biogen Idec, Roche, and Questcor. He has served as Editor of Continuum, a continuing medical education publication of the AAN and currently serves as Editor of Continuum Audio. He is a member of the editorial board of Multiple Sclerosis and Related Disorders.
Declan Chard: has received honoraria (paid to his employer) from Ismar Healthcare NV, Swiss MS Society, Excemed (previously Serono Symposia International Foundation), Merck, Bayer and Teva for faculty-led education work; Teva for advisory board work; meeting expenses from Merck, Teva, Novartis, the MS Trust and National MS Society; and has previously held stock in GlaxoSmithKline.
Fred Lublin "s sources of funding for research include: Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS; Consulting Agreements/Advisory Boards/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi-Aventis; Acorda; Questcor; Roche, Genentech; Celgene; Johnson & Johnson; Revalesio; Coronado Bioscience, Genzyme, MedImmune; Bristol-Myers Squibb, Xenoport, Receptos; Forward Pharma; Co-Chief Editor: Multiple Sclerosis and Related Diseases; Stock Ownership: Cognition Pharmaceuticals, Inc
Matilde Inglese: has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., and she is a consultant for Vaccinex Inc.