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From the Departments of Neurology (M.K.H., J.S., Z.J., C.R.G.G., R.B.) and Radiology (R.K., C.R.G.G., R.B.), Brigham and Women's Hospital, Harvard Medical School, Partners MS Center, Boston, MA; and Jacobs Neurological Institute (R.H.B.B., B.S., B.W.-G.), University at Buffalo, NY.
Address correspondence and reprint requests to Dr. Rohit Bakshi, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur–HIM 730, Boston, MA 02115 rbakshi{at}bwh.harvard.edu
Objectives: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function.
Methods: We studied 79 patients with MS and 16 normal subjects. A subgroup of 31 MS subjects underwent cognitive testing. The thalamus was segmented in whole from three-dimensional MRI scans. We also determined whole brain atrophy (brain parenchymal fraction), third ventricular width, and whole brain T2-weighted (fluid-attenuated inversion recovery) hyperintense, T1 hypointense, and gadolinium-enhanced lesion volumes.
Results: Normalized thalamic volume was 16.8% lower in the MS group (p < 0.0001) vs controls. Cognitive performance in all domains was moderately to strongly related to thalamic volume in the MS group (r = 0.506 to 0.724, p < 0.005), and thalamic volume entered and remained in all regression models predicting cognitive performance. Thalamic volume showed a weak relationship to physical disability score (r = –0.316, p = 0.005).
Conclusion: These findings suggest that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.
Abbreviations: BDI-FS = Beck Depression Inventory–Fast Screen for Medical Patients; BPF = brain parenchymal fraction; BVMT-R-D = Brief Visuospatial Memory Test (Delayed Recall); BVMT-R-TR = Brief Visuospatial Memory Test (Total Recall); COWAT = Controlled Oral Word Association Test; CVLT-II = California Verbal Learning Test, second edition; CVLT-II-D = California Verbal Learning Test (Delayed Recall); CVLT-II-TR = California Verbal Learning Test (Total Recall); EDSS = Expanded Disability Status Scale; FLAIR = fluid-attenuated inversion recovery; FOV = field-of-view; JLO = Judgment of Line Orientation Test; MS = multiple sclerosis; NC = normal controls; NSA = number of signal averages; COWAT = Controlled Oral Word Association Test; PASAT = Paced Auditory Serial Addition Test; SPGR = spoiled gradient recall; SDMT = Symbol Digit Modalities Test; TE = echo time; TR = repetition time.
Supported in part by research grants from the NIH (NS42379-01—Dr. Bakshi) and National Multiple Sclerosis Society (RG 3574A1 and RG 3705A1—Drs. Bakshi and Guttmann) and a Clinical Investigator Training Program from Harvard/Massachusetts Institutes of Technology Health Sciences and Technology, Beth Israel Deaconess Medical Center, Pfizer, and Merck & Co. (Dr. Houtchens).
Disclosure: The authors report no conflicts of interest.
Received December 27, 2006. Accepted in final form April 16, 2007.
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