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Original Contribution
August 2007

Association of Neocortical Volume Changes With Cognitive Deterioration in Relapsing-Remitting Multiple Sclerosis

Author Affiliations

Author Affiliations: Department of Neurology, University of Florence, Florence (Drs Amato, Portaccio, Goretti, Zipoli, Siracusa, and Sorbi), Neurology Unit, Hospital of Empoli, Empoli (Drs Bartolozzi and Guidi), and Department of Neurological and Behavioral Sciences, University of Siena, Siena (Mr Battaglini and Drs Stromillo, Federico, and De Stefano), Italy.

Arch Neurol. 2007;64(8):1157-1161. doi:10.1001/archneur.64.8.1157

Background  We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.

Objective  To assess the relevance of gray matter changes over time to changes in cognition in RRMS.

Design  A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis.

Setting  Two university MS clinics.

Patients  Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean ± SD age, 37.1 ± 8.9 years; mean ± SD MS duration, 7.3 ± 2.9 years; mean ± SD Expanded Disability Status Scale score, 1.8 ± 1.5).

Main Outcome Measures  We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.

Results  We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean ± SD percentage of brain volume changes (−2.1% ± 1.2% vs −1.3% ± 1.3%; P = .11), normalized deep gray matter volume changes (−2.1 ± 2.8 mL vs −0.6 ± 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 ± 2.6 mL vs 1.6 ± 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (−43.0 ± 18.9 mL vs −17.8 ± 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9).

Conclusion  Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.