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From the Departments of Neurology (M.P.S., R.H.B.B., B.W.-G.) and Psychiatry (R.H.B.B.), SUNY-University at Buffalo School of Medicine and Biomedical Sciences; Buffalo Neuroimaging Analysis Center (M.P.S., R.H.B.B.); The Jacobs Neurological Institute (B.W.-G., R.H.B.B.), Buffalo, NY; and Center for Neurological Imaging (R.B.), Partners MS Center, Departments of Neurology and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Dr. Rohit Bakshi, Brigham & Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur–HIM 730, Boston, MA 02115; e-mail: rbakshi{at}bwh.harvard.edu
Background: The relationship of gray and white matter atrophy in multiple sclerosis (MS) to neuropsychological and neuropsychiatric impairment has not been examined.
Methods: In 40 patients with MS and 15 age-/sex-matched normal controls, the authors used SPM99 to obtain whole brain normalized volumes of gray and white matter, as well as measured conventional lesion burden (total T1 hypointense and FLAIR hyperintense lesion volume). The whole brain segmentation was corrected for misclassification related to MS brain lesions. To compare the effects of gray matter, white matter, and lesion volumes with respect to brain-behavior relationships, the MS group (disease duration = 11.2 ± 8.8 years; EDSS score = 3.3 ± 1.9) underwent neuropsychological assessment, and was compared to a separate, larger group of age-/sex-matched normal controls (n = 83).
Results: The MS group had smaller gray (p = 0.009) and white matter volume (p = 0.018), impaired cognitive performance (verbal memory, visual memory, processing speed, and working memory) (all p < 0.0001), and greater neuropsychiatric symptoms (depression, p < 0.0001; dysphoria, p < 0.0001; irritability, p < 0.0001; anxiety, p < 0.0001; euphoria, p = 0.006; agitation, p = 0.02; apathy, p = 0.02; and disinhibition, p = 0.11) vs controls. Hierarchical stepwise regression analysis revealed that whole gray and white matter volumes accounted for greater variance than lesion burden in explaining cognitive performance and neuropsychiatric symptoms. White matter volume was the best predictor of mental processing speed and working memory, whereas gray matter volume predicted verbal memory, euphoria, and disinhibition.
Conclusion: Both gray and white brain matter atrophy contribute to neuropsychological deficits in multiple sclerosis.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 14 issue to find the title link for this article.
Supported in part by an Alpha Omega Alpha Student Research Fellowship (M. Sanfilipo), a University at Buffalo School of Medicine and Biologic Sciences Summer Research Fellowship (M. Sanfilipo), and by research grants from the NIH (NIH-National Institute of Neurologic Disorders and Stroke 1 K23 NS42379-01, R. Bakshi), National Multiple Sclerosis Society (RG 3258A2/1, BWG, R. Bakshi; RG 3574A1, R. Bakshi), and National Science Foundation (DBI-0234895, BWG, R. Bakshi).
Disclosure: The authors report no conflicts of interest.
Received May 3, 2005. Accepted in final form November 10, 2005.
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