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Objectives: To analyse grey matter changes in early stages of Huntington’s disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM). Methods: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington’s disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington’s Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99). Results: In Huntington’s disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)—that is, atrophy—were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients. Conclusions: The topography of cerebral volume changes associated with Huntington’s disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length.

Topography of cerebral atrophy in early Huntington s disease: a voxel based morphometric MRI study