Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis

Abstract

Background: Neuropsychological deficits in patients with multiple sclerosis (MS) have been shown to be associated with the major pathological substrates of the disease, ie, inflammatory demyelination and neurodegeneration. Double inversion recovery sequences allow cortical lesions (CLs) to be detected in the brain of patients with MS. Modern postprocessing techniques allow cortical atrophy to be assessed reliably. Objective: To investigate the contribution of cortical gray matter lesions and tissue loss to cognitive impairment in patients with relapsing-remitting MS. Design: Cross-sectional survey. Setting: Referral, hospital-based MS clinic. Patients: Seventy patients with relapsing-remitting MS. Main Outcome Measures: Neuropsychological performance was tested using the Rao Brief Repeatable Battery of Neuropsychological Tests, version A. Patients who scored 2 SDs below the mean normative values on at least 1 test of the Rao Brief Repeatable Battery of Neuropsychological Tests, version A, were considered to be cognitively impaired. A composite cognitive score (the cognitive impairment index) was computed. T2 hyperintense white matter lesion volume, contrast-enhancing lesion number, CL number and volume, normalized brain volume, and normalized neocortical gray matter volume were also assessed. Results: Twenty-four patients with relapsing-remitting MS (34.3%) were classified as cognitively impaired. T2 hyperintense white matter lesion volume and contrast-enhancing lesion number were not different between cognitively impaired and cognitively unimpaired patients. Cognitively impaired patients had a higher CL number (P = .01) and volume (P < .001) and decreased normalized brain volume (P = .02) and normalized neocortical gray matter volume (P = .002) when compared with cognitively unimpaired patients. Multivariate analysis revealed that age (β = 0.228; P = .02), CL volume (β = 0.452; P < .001), and normalized neocortical gray matter volume (β = 0.349; P < .001) were independent predictors of the cognitive impairment index (r2 = 0.55; F = 23.903; P < .001). Conclusion: The burden of CLs and tissue loss are among the major structural changes associated with cognitive impairment in relapsing-remitting MS. ©2009 American Medical Association. All rights reserved.