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A Longitudinal Study

Reisa A. Sperling, MD; Charles R. G. Guttmann, MD; Marika J. Hohol, MD; Simon K. Warfield, PhD; Marianna Jakab, MS; Marco Parente; Eli L. Diamond; Kirk R. Daffner, MD; Michael J. Olek, DO; E. John Orav, PhD; Ron Kikinis, MD; Ferenc A. Jolesz, MD; Howard L. Weiner, MD

Arch Neurol. 2001;58:115-121.

Objective  To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period.

Design  Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses.

Results  At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level–matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001).

Conclusions  Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

From the Departments of Neurology (Drs Sperling, Daffner, Olek, and Weiner and Messrs Parente and Diamond), Medicine (Dr Orav), and Radiology (Drs Guttmann, Warfield, Kikinis, and Jolesz and Ms Jakab), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; and the Department of Neurology, St Michael's Hospital, Toronto, Ontario (Dr Hohol).

Corresponding author: Reisa A. Sperling, MD, Memory Disorders Unit, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115 (e-mail: reisa{at}rics.bwh.harvard.edu).

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