Abstract: 134
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In multiple sclerosis (MS) cortical lesions contribute to disability, but are largely undetected at conventional MRI and their role in cortical atrophy development is uncertain.
Objective: To longitudinally study, using 7T and 3T MRI, the relative contribution of cortical and white matter lesion (CL, WML) and subcortical pathology accumulation to neurodegeneration in MS.
Methods: Eighteen MS patients (3 CIS, 9 RRMS, 6 SPMS; age 42±10 years; disease duration 13±8.0 years; median EDSS 2.5, range 1.0-6.5; follow-up 1.7±0.5 years) and 6 controls (age 39±9.4 years; follow-up 1.8±0.6 years) underwent longitudinal 7T T2*-weighted imaging (0.33x0.33x1.0 mm3) for manual segmentation of WML, intracortical and leukocortical lesions (ICL, LCL) and 3T scans (MEMPRAGE, 0.9 mm isotropic) for analysis in the longitudinal stream of FreeSurfer 5.3.0 (cortical thickness; corpus callosum volume) and VolBrain 1.0 (thalamic volume). Volumetric measurements were normalized to the intracranial volume. Annual percent changes were calculated by dividing the difference of the two time-points with their mean. A principal component cognitive index was calculated based on neuropsychological testing.
Results: At baseline ICL and LCL were found in 17 and 13 patients respectively. Mean global lesion volume at baseline was 2171 (range 93-10763) mm3 in the cortex (ICL 646, 0-2737; LCL 1525, 0-9052) and 5496 (range 120-22465) mm3 in WM. The annual lesion accumulation rate was higher in the cortex, 14±18% (ICL 17±22%, LCL 0.6±13%), than in WM (4.2±22%). Patients had thinner cortices than controls (2.42±0.09 vs. 2.50±0.08 mm). In patients, cortical lesion accumulation was associated with more pronounced cortical thinning (0.52, p=0.03). Higher CL volume correlated with higher EDSS (0.71, p=0.001) and lower cognitive index (-0.52, p=0.03). Similar findings were found for WML (0.72, p=0.001; -0.57, p=0.02). Lower normalized thalamic volume was associated with higher EDSS (-0.63, p=0.003) and lower cognitive index (0.64, p=0.006). Lower normalized corpus callosum volume and cortical thickness were correlated with higher EDSS (-0.64, p=0.004; -0.52, p=0.03).
Conclusions: Cortical lesions are found in all disease stages and are associated with cognitive and physical dysfunction. Lesion accumulation rate is higher cortically than in WM and coupled with cortical thinning. The findings highlight the clinical importance of cortical lesions and their association with neurodegeneration in MS.
Disclosure: This study was supported by the National MS Society (NMSS 4281 RG-A) and Karolinska Institutet (ALF grant). Dr. Mainero has received research support from EMD Merck Serono and speaker fees from Biogen.
Abstract: 134
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In multiple sclerosis (MS) cortical lesions contribute to disability, but are largely undetected at conventional MRI and their role in cortical atrophy development is uncertain.
Objective: To longitudinally study, using 7T and 3T MRI, the relative contribution of cortical and white matter lesion (CL, WML) and subcortical pathology accumulation to neurodegeneration in MS.
Methods: Eighteen MS patients (3 CIS, 9 RRMS, 6 SPMS; age 42±10 years; disease duration 13±8.0 years; median EDSS 2.5, range 1.0-6.5; follow-up 1.7±0.5 years) and 6 controls (age 39±9.4 years; follow-up 1.8±0.6 years) underwent longitudinal 7T T2*-weighted imaging (0.33x0.33x1.0 mm3) for manual segmentation of WML, intracortical and leukocortical lesions (ICL, LCL) and 3T scans (MEMPRAGE, 0.9 mm isotropic) for analysis in the longitudinal stream of FreeSurfer 5.3.0 (cortical thickness; corpus callosum volume) and VolBrain 1.0 (thalamic volume). Volumetric measurements were normalized to the intracranial volume. Annual percent changes were calculated by dividing the difference of the two time-points with their mean. A principal component cognitive index was calculated based on neuropsychological testing.
Results: At baseline ICL and LCL were found in 17 and 13 patients respectively. Mean global lesion volume at baseline was 2171 (range 93-10763) mm3 in the cortex (ICL 646, 0-2737; LCL 1525, 0-9052) and 5496 (range 120-22465) mm3 in WM. The annual lesion accumulation rate was higher in the cortex, 14±18% (ICL 17±22%, LCL 0.6±13%), than in WM (4.2±22%). Patients had thinner cortices than controls (2.42±0.09 vs. 2.50±0.08 mm). In patients, cortical lesion accumulation was associated with more pronounced cortical thinning (0.52, p=0.03). Higher CL volume correlated with higher EDSS (0.71, p=0.001) and lower cognitive index (-0.52, p=0.03). Similar findings were found for WML (0.72, p=0.001; -0.57, p=0.02). Lower normalized thalamic volume was associated with higher EDSS (-0.63, p=0.003) and lower cognitive index (0.64, p=0.006). Lower normalized corpus callosum volume and cortical thickness were correlated with higher EDSS (-0.64, p=0.004; -0.52, p=0.03).
Conclusions: Cortical lesions are found in all disease stages and are associated with cognitive and physical dysfunction. Lesion accumulation rate is higher cortically than in WM and coupled with cortical thinning. The findings highlight the clinical importance of cortical lesions and their association with neurodegeneration in MS.
Disclosure: This study was supported by the National MS Society (NMSS 4281 RG-A) and Karolinska Institutet (ALF grant). Dr. Mainero has received research support from EMD Merck Serono and speaker fees from Biogen.