Author Of 3 Presentations
P0565 - Different Temporal Evolution of Diffusely Abnormal White Matter Volumes in Relapsing Remitting and Secondary Progressive MS (ID 1712)
Abstract
Background
Background: Diffusely abnormal white matter (DAWM) regions have been found to transform over time into focal white matter lesions (FWML) and to associate with progression in secondary progressive MS (SPMS). However, few studies have assessed changes of DAWM and FWML over time in relapsing-remitting MS (RRMS). Hence, we compared volumetric changes of DAWM and FWML over time as well as the transformation of DAWM into FWML (DAWM-to-FWML) in RRMS and SPMS.
Objectives
Objectives: 1) To automatically segment FWML and DAWM and characterize the longitudinal evolution of FWML, DAWM and FWML/DAWM Ratio in RRMS vs. SPMS. 2) To compare the volume of DAWM (at each visit) that transforms into FWML in the last MRI scan.
Methods
Methods: The data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks, scanned at screening, weeks 24, 48, 72, 96, 108, and 156; and 2677 scans of 686 RRMS participants, followed for 96 weeks, scanned at screening, weeks 24, 48 and 96. FWML and DAWM were automatically segmented using a previously-validated, automated, 2-weighted-intensity thresholding technique. DAWM voxels at screening, weeks 24, 48, 72, 96, and 108 that transformed into FWML at the last MRI scan (w96 for RRMS, and w156 for SPMS) were identified.
Results
Results: Over time, SPMS participants showed volumes of FWML that significantly increased (t=2.5; p=0.01) along with a significant decrease of DAWM (t=-4.1; p<0.0001), and a significant Ratio increase (t=10.5; p<0.00001). RRMS participants only showed a significant increase in the Ratio (t=6.9; p<0.00001). Interestingly, the voxels of DAWM that transformed into FWML at the last visit significantly changed as disease duration progressed in both RRMS and SPMS, but in different directions, increasing in RRMS (t=3.8; p<0.001) and decreasing in SPMS (t=-12.2; p<0.00001).
Conclusions
Conclusions: A significant volume of DAWM transformed into FWML over time in both RR and SPMS. However, the volume of DAWM that experienced this transformation increased over time in RRMS, explaining why we do not see significant changes of the overall DAWM volumes at each visit. Conversely, the volume of DAWM-to-FWML transformation decreases progressively at each visit in SPMS, reflecting a decrease in the remaining portion of DAWM still available to transform into FWML. The finding that the transformation of DAWM-to-FWML accelerates with time in RRMS, but decelerates in SPMS, could suggest differences in the mechanisms underlying this transformation in RR and SPMS.
P0573 - Evolution of Diffusely Abnormal White Matter and its relationship to Progression in Primary Progressive MS (ID 1817)
Abstract
Background
Background: Diffusely abnormal white matter (DAWM) is associated with decreased axonal and myelin density, fibrillary gliosis, and inflammatory cell activation on histopathology, and has been linked to progression in secondary progressive MS (SPMS). However, few studies have focused on assessing DAWM in primary progressive MS exclusively. Hence, we aimed to characterize the longitudinal evolution of DAWM and its relationship with focal white matter lesions (FWML) and confirmed disability progression (CDP) in a PPMS population.
Objectives
Objectives: 1) To automatically segment and characterize the longitudinal evolution of FWML and DAWM in PPMS. 2) To assess associations of voxels of DAWM that transform into FWML at last visit with CDP (CDP=sustained increase in EDSS that persisted for 24 weeks).
Methods
Methods: The data included 1753 MRI scans of 376 PPMS participants, followed for 122 weeks, scanned at screening, weeks 06, 48, 96, and 122. FWML and DAWM were automatically segmented using a previously validated automated 2-weighted-intensity thresholding technique. All gadolinium enhancing and new white matter lesion voxels were excluded from the FWML mask, to capture the chronic component of FWML. DAWM voxels at screening, weeks 06, 48 and 96 that transformed into FWML at the last MRI scan (w122) were segmented.
Results
Results: As disease duration increased, PPMS participants showed volumes of chronic FWML that significantly increased (t=7.3; p<0.0001) but no significant changes in DAWM volumes. The voxels of DAWM in subsequent scans that transformed to FWML at the last visit significantly decreased as disease duration progressed (t=-8.8; p<0.0001) and were not significantly associated with CDP.
Conclusions
Conclusions: DAWM voxels show a dynamic transformation into FWML over time, with volumes of DAWM-to-FWML transformation in PPMS decreasing progressively as disease duration increases. These dynamic changes are similar to those observed in SPMS. However, unlike SPMS, where previous studies have shown an association between DAWM-to-FWML transformation and CDP, this group of PPMS participants did not show such an association. This finding would suggest that other factors, other than DAWM evolution, might have a stronger weight in disease progression in PPMS, compared to SPMS.
P0612 - New cortical lesions are rare in an MS cohort with stable white matter lesions: a 7T multicontrast longitudinal study (ID 1866)
Abstract
Background
Cortical lesions are common and often extensive in MS, and have been associated with worse disability and progressive disease. There is limited evidence that cortical lesions continue to form in progressive phases of the disease, when new white matter lesion formation is minimal, perhaps offering an explanation for worsening disability in progressive MS.
Objectives
We longitudinally characterized cortical lesions in an MS cohort with stable white matter lesion burden in the year prior to enrollment to determine whether new cortical lesions are more frequent in people with worsening disability.
Methods
45 adults with MS (30 relapsing remitting (RR), 13 secondary progressive (SP), and 2 primary progressive (PP)), underwent 7T brain MRI (T2*w and MP2RAGE, each with 0.5mm isometric resolution), 3T brain and spine MRI, and clinical evaluation annually for 1 year. Cortical lesions were segmented manually on 7T images and categorized as leukocortical, intracortical, or subpial. White matter and spinal cord lesion burden were also determined.
Results
At baseline, 93% of individuals (42/45) had at least 1 cortical lesion. Median cortical lesion number was higher in progressive MS (median 55, interquartile range (IQR) 96, range 2–177) than RRMS (median 15, IQR 21, range 0–108; p<0.01). Cortical lesion volume correlated with physical and cognitive measures of disability. There was only a weak correlation between subpial and white matter lesion volume (r=0.35, p<0.05). During 1 year of follow-up, 6 people (4 RR, 2 SP) developed 1 new cortical lesion each. 4 of the 6 new cortical lesions were leukocortical, 1 was intracortical, and 1 was subpial. 5 people developed new white matter lesions, none of whom developed a new cortical lesion. In 2 people, we observed white matter lesions expand into the cortex. 3/6 people with new cortical lesions were on highly effective disease-modifying therapy during the follow up period. There was no difference in new cortical lesion or new white matter lesion number in people with stable vs worsening disability.
Conclusions
Using sensitive 7T MRI techniques, cortical lesions are detected in almost all MS cases. Cortical lesions are associated with worse and progressive disability and may form independently from white matter lesions. New cortical lesions appear to form infrequently in people with stable white matter lesions, however current disease-modifying therapies may not be completely effective at stopping cortical lesion formation.
Presenter Of 2 Presentations
P0565 - Different Temporal Evolution of Diffusely Abnormal White Matter Volumes in Relapsing Remitting and Secondary Progressive MS (ID 1712)
Abstract
Background
Background: Diffusely abnormal white matter (DAWM) regions have been found to transform over time into focal white matter lesions (FWML) and to associate with progression in secondary progressive MS (SPMS). However, few studies have assessed changes of DAWM and FWML over time in relapsing-remitting MS (RRMS). Hence, we compared volumetric changes of DAWM and FWML over time as well as the transformation of DAWM into FWML (DAWM-to-FWML) in RRMS and SPMS.
Objectives
Objectives: 1) To automatically segment FWML and DAWM and characterize the longitudinal evolution of FWML, DAWM and FWML/DAWM Ratio in RRMS vs. SPMS. 2) To compare the volume of DAWM (at each visit) that transforms into FWML in the last MRI scan.
Methods
Methods: The data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks, scanned at screening, weeks 24, 48, 72, 96, 108, and 156; and 2677 scans of 686 RRMS participants, followed for 96 weeks, scanned at screening, weeks 24, 48 and 96. FWML and DAWM were automatically segmented using a previously-validated, automated, 2-weighted-intensity thresholding technique. DAWM voxels at screening, weeks 24, 48, 72, 96, and 108 that transformed into FWML at the last MRI scan (w96 for RRMS, and w156 for SPMS) were identified.
Results
Results: Over time, SPMS participants showed volumes of FWML that significantly increased (t=2.5; p=0.01) along with a significant decrease of DAWM (t=-4.1; p<0.0001), and a significant Ratio increase (t=10.5; p<0.00001). RRMS participants only showed a significant increase in the Ratio (t=6.9; p<0.00001). Interestingly, the voxels of DAWM that transformed into FWML at the last visit significantly changed as disease duration progressed in both RRMS and SPMS, but in different directions, increasing in RRMS (t=3.8; p<0.001) and decreasing in SPMS (t=-12.2; p<0.00001).
Conclusions
Conclusions: A significant volume of DAWM transformed into FWML over time in both RR and SPMS. However, the volume of DAWM that experienced this transformation increased over time in RRMS, explaining why we do not see significant changes of the overall DAWM volumes at each visit. Conversely, the volume of DAWM-to-FWML transformation decreases progressively at each visit in SPMS, reflecting a decrease in the remaining portion of DAWM still available to transform into FWML. The finding that the transformation of DAWM-to-FWML accelerates with time in RRMS, but decelerates in SPMS, could suggest differences in the mechanisms underlying this transformation in RR and SPMS.
P0573 - Evolution of Diffusely Abnormal White Matter and its relationship to Progression in Primary Progressive MS (ID 1817)
Abstract
Background
Background: Diffusely abnormal white matter (DAWM) is associated with decreased axonal and myelin density, fibrillary gliosis, and inflammatory cell activation on histopathology, and has been linked to progression in secondary progressive MS (SPMS). However, few studies have focused on assessing DAWM in primary progressive MS exclusively. Hence, we aimed to characterize the longitudinal evolution of DAWM and its relationship with focal white matter lesions (FWML) and confirmed disability progression (CDP) in a PPMS population.
Objectives
Objectives: 1) To automatically segment and characterize the longitudinal evolution of FWML and DAWM in PPMS. 2) To assess associations of voxels of DAWM that transform into FWML at last visit with CDP (CDP=sustained increase in EDSS that persisted for 24 weeks).
Methods
Methods: The data included 1753 MRI scans of 376 PPMS participants, followed for 122 weeks, scanned at screening, weeks 06, 48, 96, and 122. FWML and DAWM were automatically segmented using a previously validated automated 2-weighted-intensity thresholding technique. All gadolinium enhancing and new white matter lesion voxels were excluded from the FWML mask, to capture the chronic component of FWML. DAWM voxels at screening, weeks 06, 48 and 96 that transformed into FWML at the last MRI scan (w122) were segmented.
Results
Results: As disease duration increased, PPMS participants showed volumes of chronic FWML that significantly increased (t=7.3; p<0.0001) but no significant changes in DAWM volumes. The voxels of DAWM in subsequent scans that transformed to FWML at the last visit significantly decreased as disease duration progressed (t=-8.8; p<0.0001) and were not significantly associated with CDP.
Conclusions
Conclusions: DAWM voxels show a dynamic transformation into FWML over time, with volumes of DAWM-to-FWML transformation in PPMS decreasing progressively as disease duration increases. These dynamic changes are similar to those observed in SPMS. However, unlike SPMS, where previous studies have shown an association between DAWM-to-FWML transformation and CDP, this group of PPMS participants did not show such an association. This finding would suggest that other factors, other than DAWM evolution, might have a stronger weight in disease progression in PPMS, compared to SPMS.