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Massimiliano Calabrese, MD; Federica Agosta, MD; Francesca Rinaldi, MD; Irene Mattisi, MD; Paola Grossi, PhD; Alice Favaretto, MD; Matteo Atzori, MD; Valentina Bernardi, MD; Luigi Barachino, RT; Luciano Rinaldi, MD, PhD; Paola Perini, MD; Paolo Gallo, MD, PhD; Massimo Filippi, MD

Arch Neurol. 2009;66(9):1144-1150.

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.

Author Affiliations: Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Department of Neurosciences, University Hospital of Padua (Drs Calabrese, F. Rinaldi, Mattisi, Grossi, Favaretto, Atzori, Bernardi, L. Rinaldi, Perini, and Gallo) and Neuroradiology Unit, Euganea Medica, Albignasego (Mr Barachino), Padua, Italy; and Neuroimaging Research Unit, Institute of Experimental Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy (Drs Agosta and Filippi).

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