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Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis

From the National Institute of Neurological Disorders and Stroke (NINDS) (N.D.R., T.H., R.S., J. Ostuni, J. Ohayon, H.F.M.), Experimental Neuroimaging Section (J.A.F., C.B.), Laboratory of Diagnostic Radiology Research, NIH; and Radiology Department (C.B.), Uniformed Services University of the Health Sciences, Bethesda, MD.

Address correspondence and reprint requests to Dr. Nancy D. Richert, Neuroimmunology Branch, NINDS, NIH, Building 10, Room 5B16, 10 Center Drive, Bethesda, MD 20892-1400; e-mail: richertn{at}helix.nih.gov

Objective: To investigate the temporal relationship between inflammation and cerebral atrophy in a longitudinal study of 19 patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly contrast enhanced MRI examinations and monthly measurements of brain fractional volume (BFV) for an average of 4 (range 2.4 to 10) years.

Methods: In this retrospective study, all patients had an active MRI scan at entry with a minimum of two new contrast enhancing lesions (CEL) on baseline MRI examinations. Patients were followed for a minimum of 3 months during a baseline (pretreatment) phase and subsequently followed during treatment with recombinant interferon ß (IFN) and various other immunomodulatory agents. Pre- and post contrast axial images were obtained using 3-mm slice thickness and a gadolinium contrast dose of 0.1 mmol/kg. Monthly CEL were sequentially numbered on hardcopy films and monthly BFV was determined on precontrast T1W images using a semiautomated program. For BFV measurements, all T1W scans were registered to the entry examination, which served as a mask image. Cerebral atrophy was measured as percent brain fractional volume change (PBVC) compared to the entry baseline scan.

Results: The results demonstrate that cerebral atrophy paralleled that of contrast enhancing lesion accumulation. The correlation between cumulative CEL and PBVC ranged from R² = 0.47 to 0.81. Immunomodulatory agents that effectively reduced CEL accumulation also slowed the rate of atrophy.

Conclusions: The correlation between contrast enhancing lesions (CEL) and atrophy suggests that patients who are not responding to therapy with a decrease in CEL may also be at risk for developing increased atrophy.

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 February 28 issue to find the title link for this article.

Supported by the Intramural Research Program of The Neuroimmunology Branch, National Institute of Neurologic Disorders and Stroke, NIH.

Disclosure: The authors report no conflicts of interest.

Received April 27, 2005. Accepted in final form October 24, 2005.

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