Contributions
Abstract: P1072
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Cortical pathology may be a substrate of worsening clinical symptoms in MS patients. However, the rate at which cortical pathology develops and the brain locations affected are not well known. The goal of this study was to evaluate longitudinal, age-related reductions in cortical surface magnetization transfer ratio (csMTR) of MS patients. Such reductions may be sensitive to sub-pial demyelination occurring over time.
Methods: 25 MS patients and 12 controls, recruited from the MS Clinic of the Montreal Neurological Institute, were imaged using anatomical and magnetization transfer imaging with 3 T MRI. To evaluate longitudinal changes in csMTR, 18 patients and 10 controls were imaged at baseline and at a two-year time point. Cortical surface meshes were generated on the inner, middle and outer cortex. csMTR values were smoothed onto these surfaces. ROIs defined by the Desikan-Killiany cortical atlas were projected onto the three cortical surfaces. Using these ROIs, longitudinal, mixed model analysis was conducted to examine: (i) group-level, age-related decline in csMTR of MS patients relative to controls (ii) age-adjusted group mean differences in csMTR between MS patients and controls.
Results: Reductions in csMTR in MS patients relative to controls were significantly related to age, and were more prevalent in ROIs confined to the outer and mid cortices. Specifically, in ROIs defining the rostral anterior cingulate, paracentral, posterior cingulate and supramarginal gyri and the precuneus, age-related csMTR decreases were found only along the outer/mid cortices. These regions are involved in executive function and processing speed through thalamo-cortical circuits. In affected outer cortical ROIs, there was an average 0.092% MTR units/yr decrease with age. By contrast, along the mid and inner cortices, the corresponding csMTR decreases were 0.039% MTR units/yr and 0.046% MTR units/yr respectively. In the outer caudal anterior cingulate, precentral and postcentral cortices, group mean csMTR differed between MS patients and controls.
Conclusion: Reductions of csMTR in MS patients increase with age, but appear to hit a plateau in regions such as the outer caudal anterior cingulate, precentral and postcentral cortex, known to have high myelin content. We hypothesize that, for these regions, initial demyelination may be more severe, or may have occurred earlier in the disease course, resulting in csMTR values reaching minimum values earlier.
Disclosure: Dr. Rudko has not conflicts of interest or sources of funding to disclose.
Dr. Maranzano has not conflicts of interest or sources of funding to disclose.
Dr. Narayanan has received personal compensation from NeuroRx Research for consulting activities, and a speaker´s honorarium from Novartis Canada.
Dr. Arnold reports personal fees for consulting from Acorda, Biogen, Hoffman LaRoche, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
Abstract: P1072
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Cortical pathology may be a substrate of worsening clinical symptoms in MS patients. However, the rate at which cortical pathology develops and the brain locations affected are not well known. The goal of this study was to evaluate longitudinal, age-related reductions in cortical surface magnetization transfer ratio (csMTR) of MS patients. Such reductions may be sensitive to sub-pial demyelination occurring over time.
Methods: 25 MS patients and 12 controls, recruited from the MS Clinic of the Montreal Neurological Institute, were imaged using anatomical and magnetization transfer imaging with 3 T MRI. To evaluate longitudinal changes in csMTR, 18 patients and 10 controls were imaged at baseline and at a two-year time point. Cortical surface meshes were generated on the inner, middle and outer cortex. csMTR values were smoothed onto these surfaces. ROIs defined by the Desikan-Killiany cortical atlas were projected onto the three cortical surfaces. Using these ROIs, longitudinal, mixed model analysis was conducted to examine: (i) group-level, age-related decline in csMTR of MS patients relative to controls (ii) age-adjusted group mean differences in csMTR between MS patients and controls.
Results: Reductions in csMTR in MS patients relative to controls were significantly related to age, and were more prevalent in ROIs confined to the outer and mid cortices. Specifically, in ROIs defining the rostral anterior cingulate, paracentral, posterior cingulate and supramarginal gyri and the precuneus, age-related csMTR decreases were found only along the outer/mid cortices. These regions are involved in executive function and processing speed through thalamo-cortical circuits. In affected outer cortical ROIs, there was an average 0.092% MTR units/yr decrease with age. By contrast, along the mid and inner cortices, the corresponding csMTR decreases were 0.039% MTR units/yr and 0.046% MTR units/yr respectively. In the outer caudal anterior cingulate, precentral and postcentral cortices, group mean csMTR differed between MS patients and controls.
Conclusion: Reductions of csMTR in MS patients increase with age, but appear to hit a plateau in regions such as the outer caudal anterior cingulate, precentral and postcentral cortex, known to have high myelin content. We hypothesize that, for these regions, initial demyelination may be more severe, or may have occurred earlier in the disease course, resulting in csMTR values reaching minimum values earlier.
Disclosure: Dr. Rudko has not conflicts of interest or sources of funding to disclose.
Dr. Maranzano has not conflicts of interest or sources of funding to disclose.
Dr. Narayanan has received personal compensation from NeuroRx Research for consulting activities, and a speaker´s honorarium from Novartis Canada.
Dr. Arnold reports personal fees for consulting from Acorda, Biogen, Hoffman LaRoche, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.