Prediction of Neuropsychological Impairment in Multiple Sclerosis

BACKGROUND: Cognition and magnetic resonance imaging correlations are well established in patients with multiple sclerosis (MS), but it is unclear whether lesion burden or atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies. No such study included measurement of the third ventricle, which was strongly predictive of neuropsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or depression. OBJECTIVE: To determine if conventional measures of lesion burden or atrophy predict cognitive dysfunction in MS while accounting for age, premorbid intelligence, and depression. METHODS: We studied 37 patients with MS and 27 controls matched according to demographic variables. Correlations between neuropsychological tests and the following magnetic resonance imaging indices were considered: T1 hypointense lesion volume, fluid-attenuated inversion recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and brain parenchymal fraction. Regression models predicting neuropsychological performance controlled for the effects of age, premorbid intelligence, and depression. We included only those tests discriminating patients with MS from controls. RESULTS: In each regression model, third ventricle width was the sole magnetic resonance imaging measure retained. When this variable was removed from consideration, brain parenchymal fraction was retained in all analyses. CONCLUSIONS: Brain atrophy accounts for more variance than lesion burden in predicting cognitive impairment in MS, and central atrophy in particular is strongly associated with neuropsychological morbidity. This finding may be explained in part by atrophy of the thalamus, a deep gray matter structure that mediates cognitive function via cortical and subcortical pathways. Enthusiasm for the clinical utility of third ventricle width is tempered by modest intraobserver and interobserver reliability.