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From the Division of Psychiatric Neuroimaging (Drs. Aylward, Li, Barta, and Pearlson), the Baltimore Huntington's Disease Center (Drs. Aylward, Li, Stine, Ranen, Bylsma, and Ross, and M. Sherr), and the Department of Neuroscience (Dr. Ross), Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD.
Supported by grants from the NINDS (16375), NIH Division of Research Resources/Johns Hopkins Outpatient Clinical Research Center (RR00722), and the Huntington's Disease Society of America.
Received May 7, 1996. Accepted in final form July 3, 1996.
Address correspondence and reprint requests to Elizabeth H. Aylward, PhD, Meyer 3-166, The Johns Hopkins University School of Medicine, 600 North Wolfe St., Baltimore, MD 21287-7362.
Article abstract-Cross-sectional MRI studies demonstrating an association between caudate atrophy and symptom severity and duration of symptoms in patients with Huntington's disease (HD) have been assumed to reflect longitudinal changes in basal ganglia, but such neuropathologic progression has never been directly demonstrated. Subjects in the current study were 23 HD patients at various stages of the disorder who had two MRI images at least 10 months apart (mean interimage interval = 20.8 months). We measured volumes of caudate, putamen, and globus pallidus blind to the order of the images. For each structure, we calculated a change score by subtracting the volume obtained on the follow-up imaging from that obtained on the initial imaging. Results indicated significant decreases over time in caudate, putamen, and total basal ganglia volume. Age at onset and length of trinucleotide repeat correlated significantly with amount of volume change in caudate and total basal ganglia, even after controlling for length of interimage interval, duration of disease, and measures of symptom severity. Amount of change in basal ganglia structures was not significantly correlated with neurologic symptom severity at the time of the initial imaging or duration of symptoms. This is the first longitudinal MRI study to document progressive basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with serial MRI may be useful in monitoring effectiveness of potential treatments. In addition, demonstration of greater rate of basal ganglia atrophy in patients with earlier symptom onset suggests that treatment effects may be more quickly observed in this subgroup of patients than in the general HD population.
NEUROLOGY 1997;48: 394-399
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