title: Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis.
abstract: OBJECTIVE
  We assessed whether the extent of macro- and microscopic disease in the cortical and subcortical brain tissue, as revealed by MR and magnetization transfer (MT) imaging, correlates with cognitive dysfunction in patients with multiple sclerosis (MS).
  
  
  METHODS
  Dual-echo rapid acquisition with relaxation enhancement (RARE), fast fluid-attenuated inversion recovery (fast-FLAIR), T1-weighted, and MT MR images of the brain were obtained from 16 MS patients with cognitive impairment and from six without. Impaired and unimpaired patients were similar across demographic and other disease-related variables. Total and cortical/subcortical lesion loads were assessed using RARE, fast-FLAIR, and T1-weighted sequences. In each patient, cortical/subcortical disease was also assessed by means of MT ratio (MTR) histographic analysis.
  
  
  RESULTS
  All the impaired patients had multiple hyperintense lesions in the cortical/subcortical regions on both RARE and fast-FLAIR images; two unimpaired patients had such lesions on the RARE images and four had them on the fast-FLAIR images. Total and cortical/subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower MTR histographic values for all the variables. A multivariate regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment.
  
  
  CONCLUSIONS
  The extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients. MTR histographic findings suggest that subtle changes undetectable by conventional imaging are also important in determining MS cognitive decline.
authors.affiliation: Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rovaris
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: L
authors.initials: L
authors.lastname: Minicucci
authors.forename: G
authors.initials: G
authors.lastname: Iannucci
authors.forename: G
authors.initials: G
authors.lastname: Santuccio
authors.forename: F
authors.initials: F
authors.lastname: Possa
authors.forename: G
authors.initials: G
authors.lastname: Comi
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis*; D009483:Neuropsychological Tests