Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis

Abstract

IMPORTANCE Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS.OBJECTIVE To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS. DESIGN, SETTING, AND PARTICIPANTSAn observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and wholebrain, 3-dimensional, 1.0-mm isotropic resolution magnetization-prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume. MAIN OUTCOMES AND MEASURESPhysical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery.RESULTS Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = −0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants with EDSS scores of 5.0 or more vs those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81 × 10 −4 [1.30 × 10 −4 to 7.90 × 10 −4 ] vs 1.50 × 10 −4 [0 to 1.01 × 10 −3 ]) and in cognitively impaired vs unimpaired individuals (count: 21 [0-99] vs 13 [1-54]; volume: 3.51 × 10 −4 [0 to 1.01 × 10 −4 ] vs 1.19 × 10 −4 [0 to 7.17 × 10 −4 ]). Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ = 0.59 vs 0.36). Increasing log[CL volume] conferred a 3-fold increase in the odds of cognitive impairment (odds ratio [OR], 3.36; 95% CI, 1.07-10.59; P = .04) after adjustment for age and sex and a 14-fold increase in odds after adjustment for WM lesion volume and atrophy (OR, 14.26; 95% CI,; P = .045). Leukocortical lesions had the greatest effect on cognition (OR for log [leukocortical lesion volume], 9.65; 95% CI, 1.70-54.59, P = .01). CONCLUSIONS AND RELEVANCEThis study provides in vivo evidence that CLs are associated with cognitive and ...

Pathology and MRI: exploring cognitive impairment in MS

“…In a similar study in 36 MS patients, 101 Harrison et al confirmed the strong impact of leukocortical lesions on cognition and reported higher cortical lesion counts and volumes in cognitively impaired vs unimpaired patients.…”

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T 2 * mapping at 7 T MRI

“…Cortical atrophy and cortical lesions are major predictors of cognitive dysfunction in multiple sclerosis (MS), a common clinical manifestation of this disease, affecting deleteriously social and vocational activities (Amato et al, 2004, Benedict et al, 2006, Calabrese et al, 2009, Calabrese et al, 2012, Harrison et al, 2015, Nielsen et al, 2013, Portaccio et al, 2006). Previous studies highlighted that atrophy in selective cortical areas, including frontal regions, precuneus and cingulate cortex is critical for cognition in MS (Louapre et al, 2014, Morgen et al, 2006, Nocentini et al, 2014, Riccitelli et al, 2011, Sbardella et al, 2013).…”

Improved Visualization of Cortical Lesions in Multiple Sclerosis Using 7T MP2RAGE

“…[1][2][3] In some individuals, cortical demyelination exceeds white matter demyelination, 2 and cortical lesions may be more strongly associated with disability and disability progression than white matter lesions. [4][5][6][7][8] Cortical and white matter lesions have potentially distinct origins and levels of inflammation, 3,[9][10][11][12][13] suggesting that they may have different clinical significance and response to treatment. Finally, the clinical course of MS is often not fully explained by volume and accumulation of white matter lesions, 14 making better understanding of other types of MS pathology, including cortical lesions, imperative.…”