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.

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This report demonstrates the presence of defensin in the human cornea and the capacity of corneal keratocytes to produce defensin mRNA in response to IL-1alpha and TNFalpha. Release of defensins by keratocytes in response to cytokines elaborated in corneal inflammation may contribute to the host defense response in microbial keratitis.