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Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis

Soneson C, Fontes M, Zhou Y, Denisov V, Paulsen JS, Kirik D and Petersén A; The Huntington Study Group PREDICT-HD investigators.

Centre for Mathematical Sciences, Lund University, Sweden; Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, BMC D11, Lund University, Sweden; Lund University Bioimaging Center, Lund University, Sweden.

Neurobiology of Disease 40: 531-543 (2010)


Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regression analyses of cross-sectional MR images from 220 HD gene carriers and 75 controls in the Predict-HD study. We show that changes in the hypothalamic region are detectable before clinical diagnosis and that its grey matter contents alone is sufficient to distinguish HD gene carriers from control cases. In conclusion, our study shows, for the first time, that alterations in grey matter contents in the hypothalamic region occur at least a decade before clinical diagnosis in HD using MRI.