Contributions
Abstract: P786
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Patients with secondary progressive multiple sclerosis (SPMS), experience a faster clinical decline and more rapid neurodegeneration than patients still in the relapsing remitting (RR) phase of the disease. The underlying mechanisms that drive the conversion to SPMS are, however, still poorly understood and the specific point of conversion remains difficult to predict. The objective of this longitudinal study was therefore to identify structural and functional MRI measures that could predict conversion from RRMS to SPMS.
Methods: In the Amsterdam MS cohort, all RRMS patients who converted to SPMS (cRRMS; N=23) between baseline and follow-up measurements (median 4.5 years(4.3-5.3)) to SPMS were individually matched, based on age, sex and education, to RRMS patients who did not convert (ncRRMS; N=23) and to healthy controls (HC; N=23). Cognitive and MRI measures at baseline (i.e. before conversion) were compared between groups (p< 0.05; FDR-corrected). Structural measures included lesion load, global and regional brain volumes and the severity and extent of microstructural white matter (WM) damage based on fractional anisotropy. Functional connectivity was calculated between eleven well-known resting-state networks, after artefact removal with FMRIB's ICA-based X-noisefier (FIX). The correspondence between individual functional connectivity matrices and the average connectivity matrix (based on all HC of the cohort; N=96) was quantified.
Results: At baseline, cRRMS patients had higher EDSS scores than ncRRMS patients (p< 0.001), while no differences were observed in symptom duration. Verbal and visuospatial memory were only impaired in cRRMS patients relative to HC (p< 0.05). In addition, cRRMS patients showed a lower thalamus volume, a higher number of WM lesions and more extensive WM damage than ncRRMS and HC (p< 0.05). The functional network was different between cRRMS and HC (p< 0.01), while the functional network of ncRRMS patients was similar to that of the HC. A backward logistic regression model showed that a lower thalamus volume was the strongest MRI predictor for conversion within five years.
Conclusions: RRMS patients, who converted to SPMS within five years, already demonstrated more severe structural changes and a more abnormal functional network compared compared to matched RRMS patients who did not convert. Atrophy of the thalamus, one of the most important hubs in the brain network, was the primary predictor of conversion to SPMS.
Disclosure: Kim A Meijer receives funding from a research grant of Biogen. Anand JC Eijlers receives funding from the Dutch MS Research Foundation. Martijn D Steenwijk has nothing to disclose. Iris Dekker received speaking honoraria from Roche and receives funding from the Dutch MS Research Foundation, grant number 14-358e. Bernard MJ 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. Menno M 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 JG 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. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals
Abstract: P786
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Patients with secondary progressive multiple sclerosis (SPMS), experience a faster clinical decline and more rapid neurodegeneration than patients still in the relapsing remitting (RR) phase of the disease. The underlying mechanisms that drive the conversion to SPMS are, however, still poorly understood and the specific point of conversion remains difficult to predict. The objective of this longitudinal study was therefore to identify structural and functional MRI measures that could predict conversion from RRMS to SPMS.
Methods: In the Amsterdam MS cohort, all RRMS patients who converted to SPMS (cRRMS; N=23) between baseline and follow-up measurements (median 4.5 years(4.3-5.3)) to SPMS were individually matched, based on age, sex and education, to RRMS patients who did not convert (ncRRMS; N=23) and to healthy controls (HC; N=23). Cognitive and MRI measures at baseline (i.e. before conversion) were compared between groups (p< 0.05; FDR-corrected). Structural measures included lesion load, global and regional brain volumes and the severity and extent of microstructural white matter (WM) damage based on fractional anisotropy. Functional connectivity was calculated between eleven well-known resting-state networks, after artefact removal with FMRIB's ICA-based X-noisefier (FIX). The correspondence between individual functional connectivity matrices and the average connectivity matrix (based on all HC of the cohort; N=96) was quantified.
Results: At baseline, cRRMS patients had higher EDSS scores than ncRRMS patients (p< 0.001), while no differences were observed in symptom duration. Verbal and visuospatial memory were only impaired in cRRMS patients relative to HC (p< 0.05). In addition, cRRMS patients showed a lower thalamus volume, a higher number of WM lesions and more extensive WM damage than ncRRMS and HC (p< 0.05). The functional network was different between cRRMS and HC (p< 0.01), while the functional network of ncRRMS patients was similar to that of the HC. A backward logistic regression model showed that a lower thalamus volume was the strongest MRI predictor for conversion within five years.
Conclusions: RRMS patients, who converted to SPMS within five years, already demonstrated more severe structural changes and a more abnormal functional network compared compared to matched RRMS patients who did not convert. Atrophy of the thalamus, one of the most important hubs in the brain network, was the primary predictor of conversion to SPMS.
Disclosure: Kim A Meijer receives funding from a research grant of Biogen. Anand JC Eijlers receives funding from the Dutch MS Research Foundation. Martijn D Steenwijk has nothing to disclose. Iris Dekker received speaking honoraria from Roche and receives funding from the Dutch MS Research Foundation, grant number 14-358e. Bernard MJ 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. Menno M 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 JG 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. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals