Contributions
Abstract: P1107
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: In recent years, thalamic atrophy has been shown to play a crucial clinically relevant role in multiple sclerosis (MS). The mechanisms by which thalamic atrophy may induce clinical impairments, however, remain unclear. This study investigated how thalamic atrophy and thalamic resting-state functional connectivity (FC) changes relate to disability and cognitive impairment, as well as each other, in two large MS cohorts.
Methods: Structural and resting-state functional MR imaging at 3T was obtained in 673 subjects from Amsterdam (MS: N=332, healthy controls (HC): N=96) and Graz (MS: N=180, HC: N=65). All patients underwent EDSS testing, disability was defined as EDSS>4. Extensive cognitive assessments were only available in Amsterdam, cognitive impairment (CI) was defined as Z< -2 below HC in at least two domains. Thalamic FC with six well-known cortical resting-state networks was calculated using segmentations from FSL-FIRST and the cortical Brainnetome atlas. Connectivity variables that correlated with EDSS or cognition were fed into forward multivariate regression models to identify the most important patterns of change.
Results: Thalamic volumes and FC in HC were comparable between cohorts. EDSS and cognition were related to thalamic FC with the visual, motor, dorsal and ventral attention (VAN) networks. Regression showed that higher EDSS was most strongly related (adjusted R2=0.42) to higher age, thalamic atrophy, higher thalamus-motor FC and lower thalamus-VAN FC. Cognitive dysfunction was most strongly related (adjusted R2=0.43) to thalamic atrophy, lower level of education and higher thalamus-VAN FC. Thalamic atrophy and thalamus-motor FC remained significant predictors of EDSS in both centres when analysed separately. Patients with disability showed increased thalamus-motor FC compared to non-disabled patients (p=0.02), but no change in thalamus-VAN FC. Patients with CI showed increased thalamus-VAN FC compared to preserved patients (p=0.02), which correlated with verbal memory, information processing speed and attention. Thalamic atrophy was not related to thalamic FC.
Conclusions: Increased thalamic FC with the motor network was related to disability, while increased thalamic FC with the VAN was related to cognitive impairment. Thalamic atrophy was related to both clinical measures, but did not correlate with thalamic FC increases, which may therefore reflect a response to pathology in connected cortical or white matter regions instead.
Disclosure: Menno Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen.
Daniela Pinter receives funding from the Austrian Science fund (T 690- B23) and has received funding for travel from Merck and funding from Genzyme/Sanofi-Aventis.
Kim Meijer receives funding from a research grant of Biogen.
Anand Eijlers receives funding from the Dutch MS Research Foundation, grant number 14-358e.
Lukas Pirpamer reports no disclosures.
Michael Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.
Alexander Pichler reports no disclosures.
Siegrid Fuchs serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Merck, Novartis ; Roche, TEVA Pharmaceutical Industries and Sanofi-Aventis.
Franz Fazekas serves on scientific advisory boards for Biogen-Idec, Genzyme-Sanofi, Merck, Novartis, 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.
Bernard Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
Frederik 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.
Christian 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.
Jeroen Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation and has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.
Abstract: P1107
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: In recent years, thalamic atrophy has been shown to play a crucial clinically relevant role in multiple sclerosis (MS). The mechanisms by which thalamic atrophy may induce clinical impairments, however, remain unclear. This study investigated how thalamic atrophy and thalamic resting-state functional connectivity (FC) changes relate to disability and cognitive impairment, as well as each other, in two large MS cohorts.
Methods: Structural and resting-state functional MR imaging at 3T was obtained in 673 subjects from Amsterdam (MS: N=332, healthy controls (HC): N=96) and Graz (MS: N=180, HC: N=65). All patients underwent EDSS testing, disability was defined as EDSS>4. Extensive cognitive assessments were only available in Amsterdam, cognitive impairment (CI) was defined as Z< -2 below HC in at least two domains. Thalamic FC with six well-known cortical resting-state networks was calculated using segmentations from FSL-FIRST and the cortical Brainnetome atlas. Connectivity variables that correlated with EDSS or cognition were fed into forward multivariate regression models to identify the most important patterns of change.
Results: Thalamic volumes and FC in HC were comparable between cohorts. EDSS and cognition were related to thalamic FC with the visual, motor, dorsal and ventral attention (VAN) networks. Regression showed that higher EDSS was most strongly related (adjusted R2=0.42) to higher age, thalamic atrophy, higher thalamus-motor FC and lower thalamus-VAN FC. Cognitive dysfunction was most strongly related (adjusted R2=0.43) to thalamic atrophy, lower level of education and higher thalamus-VAN FC. Thalamic atrophy and thalamus-motor FC remained significant predictors of EDSS in both centres when analysed separately. Patients with disability showed increased thalamus-motor FC compared to non-disabled patients (p=0.02), but no change in thalamus-VAN FC. Patients with CI showed increased thalamus-VAN FC compared to preserved patients (p=0.02), which correlated with verbal memory, information processing speed and attention. Thalamic atrophy was not related to thalamic FC.
Conclusions: Increased thalamic FC with the motor network was related to disability, while increased thalamic FC with the VAN was related to cognitive impairment. Thalamic atrophy was related to both clinical measures, but did not correlate with thalamic FC increases, which may therefore reflect a response to pathology in connected cortical or white matter regions instead.
Disclosure: Menno Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen.
Daniela Pinter receives funding from the Austrian Science fund (T 690- B23) and has received funding for travel from Merck and funding from Genzyme/Sanofi-Aventis.
Kim Meijer receives funding from a research grant of Biogen.
Anand Eijlers receives funding from the Dutch MS Research Foundation, grant number 14-358e.
Lukas Pirpamer reports no disclosures.
Michael Khalil has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen, Roche and Teva ratiopharm; serves on scientific advisory boards for Biogen and Roche and received a research grant from Teva ratiopharm.
Alexander Pichler reports no disclosures.
Siegrid Fuchs serves on scientific advisory boards and / or has received speaker honoraria from Biogen Idec, Merck, Novartis ; Roche, TEVA Pharmaceutical Industries and Sanofi-Aventis.
Franz Fazekas serves on scientific advisory boards for Biogen-Idec, Genzyme-Sanofi, Merck, Novartis, 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.
Bernard Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
Frederik 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.
Christian 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.
Jeroen Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation and has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.