Contributions
Abstract: 235
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: In recent multiple sclerosis (MS) studies with repeated magnetic resonance imaging (MRI) measures, calculation of linear regression slopes for estimation of individual rates of brain volume loss (BVL) was used. Although, linear course of BVL was assumed, a potential occurrence of non-linear BVL trajectories has not been investigated yet.
Aims: To investigate frequency of non-linear course of BVL in MS.
Methods: We included 1546 MS patients from the QMRI programme with ≥5 MRI scans (mean=9.3, median 7.0 scans) and ≥4 years (mean=7.0; median 6.3 years) follow-up. Majority of patients was treated with disease-modifying treatments. BVL was measured using ScanView software. We calculated coefficients of determination of individual linear (lin-R2) and quadratic (quad-R2) regression models. Non-linear trajectory was defined, if quadratic model was better fitting the trajectory of BVL compared with linear model (quad-R2 >5% or >10% compared with lin-R2; p< 0.01). Characteristics of patients with linear and non-linear BVL were compared using Mann-Whitney test and adjusted logistic regression.
Results: A total of 98 (6.3%) of patients had non-linear BVL (quad-R2 >5% higher than lin-R2). Prevalence of non-linear BVL decreased to 63 (4.0%) patients, if applied more strict definition (cut-off>10%). Non-linear BVL showed deceleration in 44 (2.8%) and acceleration in 19 (1.2%) of patients. Occurrence of non-linear BVL was 27.3% (cut-off>5%) or 11.3% (cut-off>10%) in patients with ≥10 years follow-up. Occurrence of non-linear BVL was 29.3% (cut-off>5%) or 12.6% (cut-off>10%) in patients with ≥15 MRI scans. Patients with non-linear BVL deceleration (cut-off>5%) had higher brain parenchymal fraction at baseline (p=0.003), higher rate of BVL (p< 0.0001), greater T2 lesion volume increase (p< 0.001), greater disability progression (p=0.001), younger age (p=0.002) and shorter disease duration (p=0.017) compared to patients with linear BVL. Patients with non-linear BVL acceleration were similar to those with linear BVL.
Conclusions: The vast majority of MS patients had a linear trajectory of BVL over short-term follow-up. However, considerable proportion of non-linear (i.e. quadratic) BVL trajectories was found in patients over longer follow-up and with higher number of MRI scans. Hence, the assumption of linearity of BVL should be verified, especially in long-term MRI studies. Factors associated with occurrence of non-linear BVL need to be investigated.
Disclosure: T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme and Merck Serono, as well as support for research activities from Biogen Idec.
L. Sobisek received financial support from Novartis, as well as support from long-term institutional support of research activities by Faculty of Informatics and Statistics, University of Economics, Prague.
Z. Seidl and J. Krasensky received financial support for research activities from Biogen Idec.
E. Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, Teva, Actelion and Receptos, as well as support for research activities from Biogen Idec and Merck Serono.
D. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
M. Vaneckova received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck L. Serono, and Teva, as well as support for research activities from Biogen Idec.
The project was supported by the Charles University Grant Agency (GAUK) 230217, Czech Ministry of Education project PRVOUK-P26/LF1/4, Czech Ministry of Health project RVO-VFN64165 and grant NV18-04-00168.
Abstract: 235
Type: Free Communications
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: In recent multiple sclerosis (MS) studies with repeated magnetic resonance imaging (MRI) measures, calculation of linear regression slopes for estimation of individual rates of brain volume loss (BVL) was used. Although, linear course of BVL was assumed, a potential occurrence of non-linear BVL trajectories has not been investigated yet.
Aims: To investigate frequency of non-linear course of BVL in MS.
Methods: We included 1546 MS patients from the QMRI programme with ≥5 MRI scans (mean=9.3, median 7.0 scans) and ≥4 years (mean=7.0; median 6.3 years) follow-up. Majority of patients was treated with disease-modifying treatments. BVL was measured using ScanView software. We calculated coefficients of determination of individual linear (lin-R2) and quadratic (quad-R2) regression models. Non-linear trajectory was defined, if quadratic model was better fitting the trajectory of BVL compared with linear model (quad-R2 >5% or >10% compared with lin-R2; p< 0.01). Characteristics of patients with linear and non-linear BVL were compared using Mann-Whitney test and adjusted logistic regression.
Results: A total of 98 (6.3%) of patients had non-linear BVL (quad-R2 >5% higher than lin-R2). Prevalence of non-linear BVL decreased to 63 (4.0%) patients, if applied more strict definition (cut-off>10%). Non-linear BVL showed deceleration in 44 (2.8%) and acceleration in 19 (1.2%) of patients. Occurrence of non-linear BVL was 27.3% (cut-off>5%) or 11.3% (cut-off>10%) in patients with ≥10 years follow-up. Occurrence of non-linear BVL was 29.3% (cut-off>5%) or 12.6% (cut-off>10%) in patients with ≥15 MRI scans. Patients with non-linear BVL deceleration (cut-off>5%) had higher brain parenchymal fraction at baseline (p=0.003), higher rate of BVL (p< 0.0001), greater T2 lesion volume increase (p< 0.001), greater disability progression (p=0.001), younger age (p=0.002) and shorter disease duration (p=0.017) compared to patients with linear BVL. Patients with non-linear BVL acceleration were similar to those with linear BVL.
Conclusions: The vast majority of MS patients had a linear trajectory of BVL over short-term follow-up. However, considerable proportion of non-linear (i.e. quadratic) BVL trajectories was found in patients over longer follow-up and with higher number of MRI scans. Hence, the assumption of linearity of BVL should be verified, especially in long-term MRI studies. Factors associated with occurrence of non-linear BVL need to be investigated.
Disclosure: T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme and Merck Serono, as well as support for research activities from Biogen Idec.
L. Sobisek received financial support from Novartis, as well as support from long-term institutional support of research activities by Faculty of Informatics and Statistics, University of Economics, Prague.
Z. Seidl and J. Krasensky received financial support for research activities from Biogen Idec.
E. Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, Teva, Actelion and Receptos, as well as support for research activities from Biogen Idec and Merck Serono.
D. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
M. Vaneckova received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck L. Serono, and Teva, as well as support for research activities from Biogen Idec.
The project was supported by the Charles University Grant Agency (GAUK) 230217, Czech Ministry of Education project PRVOUK-P26/LF1/4, Czech Ministry of Health project RVO-VFN64165 and grant NV18-04-00168.