Contributions
Abstract: 23
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Subpial cortical pathology in MS has been suggested to be partly caused by factors in the CSF. Therefore, we investigated in previous work whether tissue-changes in intracerebral areas close to CSF could be related to cortical pathology. In a single center study, we found the percentage of periventricular lesion (PVL) occupancy to be correlated with cortical thinning in RRMS but not in CIS.
Objective: To extend and corroborate these findings in a multicenter study of the MAGNIMS study group, comprising all phenotypes of MS including primary-progressive (PPMS) and secondary-progressive (SPMS) patients.
Methods: We analyzed MRI scans of 564 patients from centers of the MAGNIMS network (www.magnims.eu) that provided 1mm isotropic T1-MPRAGE and T2-FLAIR sequences and manually segmented lesion masks. Cortical thickness assessment and brain segmentation were performed using FreeSurfer 6.0. To classify PVL we used a region growing algorithm starting from the ventricle mask, implemented in MATLAB, as described. The PVL load percentage (PVL%) reflects the proportion of periventricular to non-periventricular lesions (non-PVL).
Results: PVL% correlated with cortical thinning in the entire cohort (R=-0.23, p=9.8E-9, N=564), while non-PVL volume did not (p=0.11). The analysis of different disease phenotypes revealed significant correlations also in the CIS group (R=-0.24, p=0.024, N=81), as well as in the RRMS group (R=-0.24, p=4.4E-5, N=280) and also in the PPMS group, which showed the strongest correlation coefficient (R=-0.32, p=0.0049, N=73). However, no correlation was found in the SPMS group only (p=0.31, N=99).
Conclusions: These results corroborate the previously observed association of PVL and cortical thinning in RRMS and extend this observation for CIS and PPMS in a multicenter setting. Beyond supporting the role of CSF related factors for disease related damage a PVL MS phenotype (associated with reduced cortical thickness) might have the potential to be explored regarding response to different disease modifying treatments.
Disclosure: L. Pirpamer has nothing to disclose.
A. Eshaghi has nothing to disclose.
O. Ciccarelli receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR UCLH Biomedical Research Centre; she is a consultant for Teva, Roche, and Novartis. She is an Associate Editor for Neurology, for which she receives an honorarium.
F. Barkhof serves as editorial board member of Brain, European Radiology, Neurology, Multiple Sclerosis Journal and Radiology and has accepted consulting fees from Bayer-Schering Pharma, Biogen-IDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd, GeNeuro, Apitope Ltd and speaker fees from Biogen-IDEC and IXICO.
A. Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
D. Pareto has received speaking honoraria from Novartis.
Prof. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
C. Gasperini fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
S. Ruggeri has received fee as speaking honoraria from Teva,Merck Serono, Biogen; travel grant from Biogen, Merck Serono; fee as advisory board consultant from Merck Serono and Novartis.
B. Bodini receives research support from ARSEP foundation. She has received funding for traveling and/or speaker's honoraria from Novartis, Genzyme, Roche and Merck Serono.
B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
S. Ropele has nothing to disclose.
F. Fazekas serves on scientific advisory boards for Biogen-Idec, Genzyme-Sanofi, Merck, Novartis, Roche and Teva Ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva Ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva Ratiopharm.
C. Enzinger received funding for traveling and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Novartis, Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis, Shire; received research support from Merck Serono, Biogen Idec, and Teva Pharmaceutical Industries Ltd./sanofi-aventis; and serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Genzyme, Roche, and Teva Pharmaceutical Industries Ltd./sanofi- Aventis.
Abstract: 23
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Subpial cortical pathology in MS has been suggested to be partly caused by factors in the CSF. Therefore, we investigated in previous work whether tissue-changes in intracerebral areas close to CSF could be related to cortical pathology. In a single center study, we found the percentage of periventricular lesion (PVL) occupancy to be correlated with cortical thinning in RRMS but not in CIS.
Objective: To extend and corroborate these findings in a multicenter study of the MAGNIMS study group, comprising all phenotypes of MS including primary-progressive (PPMS) and secondary-progressive (SPMS) patients.
Methods: We analyzed MRI scans of 564 patients from centers of the MAGNIMS network (www.magnims.eu) that provided 1mm isotropic T1-MPRAGE and T2-FLAIR sequences and manually segmented lesion masks. Cortical thickness assessment and brain segmentation were performed using FreeSurfer 6.0. To classify PVL we used a region growing algorithm starting from the ventricle mask, implemented in MATLAB, as described. The PVL load percentage (PVL%) reflects the proportion of periventricular to non-periventricular lesions (non-PVL).
Results: PVL% correlated with cortical thinning in the entire cohort (R=-0.23, p=9.8E-9, N=564), while non-PVL volume did not (p=0.11). The analysis of different disease phenotypes revealed significant correlations also in the CIS group (R=-0.24, p=0.024, N=81), as well as in the RRMS group (R=-0.24, p=4.4E-5, N=280) and also in the PPMS group, which showed the strongest correlation coefficient (R=-0.32, p=0.0049, N=73). However, no correlation was found in the SPMS group only (p=0.31, N=99).
Conclusions: These results corroborate the previously observed association of PVL and cortical thinning in RRMS and extend this observation for CIS and PPMS in a multicenter setting. Beyond supporting the role of CSF related factors for disease related damage a PVL MS phenotype (associated with reduced cortical thickness) might have the potential to be explored regarding response to different disease modifying treatments.
Disclosure: L. Pirpamer has nothing to disclose.
A. Eshaghi has nothing to disclose.
O. Ciccarelli receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR UCLH Biomedical Research Centre; she is a consultant for Teva, Roche, and Novartis. She is an Associate Editor for Neurology, for which she receives an honorarium.
F. Barkhof serves as editorial board member of Brain, European Radiology, Neurology, Multiple Sclerosis Journal and Radiology and has accepted consulting fees from Bayer-Schering Pharma, Biogen-IDEC, TEVA, Merck-Serono, Novartis, Roche, Jansen Research, Genzyme-Sanofi, IXICO Ltd, GeNeuro, Apitope Ltd and speaker fees from Biogen-IDEC and IXICO.
A. Rovira serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen Idec.
D. Pareto has received speaking honoraria from Novartis.
Prof. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
C. Gasperini fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
S. Ruggeri has received fee as speaking honoraria from Teva,Merck Serono, Biogen; travel grant from Biogen, Merck Serono; fee as advisory board consultant from Merck Serono and Novartis.
B. Bodini receives research support from ARSEP foundation. She has received funding for traveling and/or speaker's honoraria from Novartis, Genzyme, Roche and Merck Serono.
B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
S. Ropele has nothing to disclose.
F. Fazekas serves on scientific advisory boards for Biogen-Idec, Genzyme-Sanofi, Merck, Novartis, Roche and Teva Ratiopharm; serves on the editorial boards of the European Stroke Journal, Multiple Sclerosis Journal, Neurology, the Polish Journal of Neurology and Neurosurgery, and the Swiss Archives of Neurology and Psychiatry; provides consulting services for Actelion, Medday, Parexel and Teva Ratiopharm and has received speaker honoraria from Merck, Genzyme-Sanofi and Teva Ratiopharm.
C. Enzinger received funding for traveling and speaker honoraria from Biogen Idec, Bayer Schering Pharma, Merck Serono, Novartis, Genzyme and Teva Pharmaceutical Industries Ltd./sanofi-aventis, Shire; received research support from Merck Serono, Biogen Idec, and Teva Pharmaceutical Industries Ltd./sanofi-aventis; and serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Genzyme, Roche, and Teva Pharmaceutical Industries Ltd./sanofi- Aventis.