Contributions
Abstract: P795
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Previous studies have suggested that the grey matter atrophy rate may accelerate with progression in MS. Whether such an accelerated atrophy rate is primarily a result of cortical or deep grey matter atrophy or how it relates to cognitive decline, is so far unknown. Therefore, in this study, we measured cortical and deep grey matter atrophy rates in patients with relapsing-remitting (RRMS) and progressive MS (PMS) and correlated these changes to cognitive decline over five years in a large, longitudinal cohort of patients with MS.
Methods: we prospectively included a total of 230 patients with MS and 59 healthy controls (HC), part of the Amsterdam MS cohort. Cognitive function was assessed by an extended version of the BRB-N at both time points and average cognitive decline was quantified using the reliable change index (RCI). MR images were acquired at both time-points on a 3T MRI system using identical pulse sequences. Volumes of cortical and deep grey matter were measured on 3D T1-weighted images using SIENAX and FIRST respectively and lesion volumes on fluid-attenuated inversion recovery images using kNN-TTP.
Results: At baseline, 179 patients had RRMS and 51 patients PMS (19 primary and 32 secondary progressive). During the follow-up period (mean = 4.9 years, SD = 0.94 years), cognitive decline was faster in PMS patients (RCI = -0.10/yr) than RRMS patients (RCI = -0.03/yr, p< 0.01) and HC (RCI = 0.00/yr, p< 0.01). Interestingly, the deep grey matter atrophy rate did not differ between MS phenotypes, but was 0.47%/yr faster in RRMS and 0.56%/yr faster in PMS compared to HC (p< 0.01 for both). The cortical atrophy rate was faster in PMS compared to both RRMS and HC (0.31%/yr faster vs RRMS and 0.39%/yr faster vs HC, both p< 0.01), with no differences between RRMS and HC. Within the RRMS group, cognitive decline was associated with an increase in lesion volumes (r = -0.20, p< 0.01) and deep grey matter atrophy (r = 0.15, p=0.04). In the PMS group, however, cognitive decline was associated with cortical atrophy only (r = 0.35, p=0.01).
Conclusions: These results show that cortical atrophy accelerates in the course of disease progression, notably it proceeds faster in PMS than in RRMS. Importantly, substrates of cognitive decline were different for the disease phases: in PMS cortical atrophy was the sole correlate of cognitive decline, while cognitive decline in RRMS was associated with deep grey matter atrophy and increased lesion volume.
Disclosure: Anand Eijlers receives funding from the Dutch MS Research Foundation, grant number 14-358e.
Iris Dekker received speaking honoraria from Roche and receives funding from the Dutch MS Research Foundation, grant number 14-358e
Martijn Steenwijk reports no disclosures.
Kim Meijer receives funding from a research grant of Biogen.
Hanneke Hulst receives research support from the Dutch MS Research Foundation, grant number 12-548, and has received compensation for consulting services or speaker honoraria from Sanofi Genzyme, Merck Serono and Biogen Idec.
Petra Pouwels receives research support from the Dutch MS Research Foundation, grant number 14-876
B.M.J. Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
Frederik Barkhof is supported by the NIHR UCLH biomedical research centre, 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.
Hugo Vrenken has received research grants from Novartis, Teva and MerckSerono, speaker honoraria from Novartis and consulting fees from MerckSerono; all funds were paid directly to his institution.
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.
Jeroen Geurts is an editor of MS Journal. He serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.
Abstract: P795
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Previous studies have suggested that the grey matter atrophy rate may accelerate with progression in MS. Whether such an accelerated atrophy rate is primarily a result of cortical or deep grey matter atrophy or how it relates to cognitive decline, is so far unknown. Therefore, in this study, we measured cortical and deep grey matter atrophy rates in patients with relapsing-remitting (RRMS) and progressive MS (PMS) and correlated these changes to cognitive decline over five years in a large, longitudinal cohort of patients with MS.
Methods: we prospectively included a total of 230 patients with MS and 59 healthy controls (HC), part of the Amsterdam MS cohort. Cognitive function was assessed by an extended version of the BRB-N at both time points and average cognitive decline was quantified using the reliable change index (RCI). MR images were acquired at both time-points on a 3T MRI system using identical pulse sequences. Volumes of cortical and deep grey matter were measured on 3D T1-weighted images using SIENAX and FIRST respectively and lesion volumes on fluid-attenuated inversion recovery images using kNN-TTP.
Results: At baseline, 179 patients had RRMS and 51 patients PMS (19 primary and 32 secondary progressive). During the follow-up period (mean = 4.9 years, SD = 0.94 years), cognitive decline was faster in PMS patients (RCI = -0.10/yr) than RRMS patients (RCI = -0.03/yr, p< 0.01) and HC (RCI = 0.00/yr, p< 0.01). Interestingly, the deep grey matter atrophy rate did not differ between MS phenotypes, but was 0.47%/yr faster in RRMS and 0.56%/yr faster in PMS compared to HC (p< 0.01 for both). The cortical atrophy rate was faster in PMS compared to both RRMS and HC (0.31%/yr faster vs RRMS and 0.39%/yr faster vs HC, both p< 0.01), with no differences between RRMS and HC. Within the RRMS group, cognitive decline was associated with an increase in lesion volumes (r = -0.20, p< 0.01) and deep grey matter atrophy (r = 0.15, p=0.04). In the PMS group, however, cognitive decline was associated with cortical atrophy only (r = 0.35, p=0.01).
Conclusions: These results show that cortical atrophy accelerates in the course of disease progression, notably it proceeds faster in PMS than in RRMS. Importantly, substrates of cognitive decline were different for the disease phases: in PMS cortical atrophy was the sole correlate of cognitive decline, while cognitive decline in RRMS was associated with deep grey matter atrophy and increased lesion volume.
Disclosure: Anand Eijlers receives funding from the Dutch MS Research Foundation, grant number 14-358e.
Iris Dekker received speaking honoraria from Roche and receives funding from the Dutch MS Research Foundation, grant number 14-358e
Martijn Steenwijk reports no disclosures.
Kim Meijer receives funding from a research grant of Biogen.
Hanneke Hulst receives research support from the Dutch MS Research Foundation, grant number 12-548, and has received compensation for consulting services or speaker honoraria from Sanofi Genzyme, Merck Serono and Biogen Idec.
Petra Pouwels receives research support from the Dutch MS Research Foundation, grant number 14-876
B.M.J. Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
Frederik Barkhof is supported by the NIHR UCLH biomedical research centre, 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.
Hugo Vrenken has received research grants from Novartis, Teva and MerckSerono, speaker honoraria from Novartis and consulting fees from MerckSerono; all funds were paid directly to his institution.
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.
Jeroen Geurts is an editor of MS Journal. He serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.