Significant longitudinal change in neostriatal volume in premanifest and manifest huntington's disease: The IMAGE-HD study.

Abstract

Background: Huntington's disease (HD), is accompanied by marked neostriatal atrophy that occurs more than 10 years before clinical onset. Multiple imaging modalities have been used in the search for a biomarker in HD, including the use of MRI for volumetric analysis of the neostriatum, most recently with automated measures. The gold standard for volumetric analysis of the neostriatum however remains manual segmentation. Using this method and scans from the Australian-based IMAGE-HD study we sought to extend the current understanding of neostriatal atrophy as a potential biomarker in HD. We used manual segmentation to quantify longitudinal changes in neostriatal volume in people with premanifest and manifest HD, compared with controls. Method(s): T1-weighted MRI scans were taken of 36 individuals with premanifest HD (pre-HD), 37 with early symptomatic HD (symp-HD), and 36 healthy matched control subjects. Individuals were scanned at baseline, 18 and 30 months. Neostriatal (putaminal and caudate) volumes for each scan were determined by manual tracing according to a validated protocol (intra-rater intraclass correlation (0.88-0.98)). Volumetric differences between groups were tested with multivariate analysis of covariance (with age and intracranial volume as covariates), while longitudinal changes were tested with one-way repeated measures ANOVA. Result(s): Cross-sectional caudate and putaminal volumes were found to be significantly different across all groups, with control volumes larger than pre-HD, and pre-HD larger than symp-HD (p >= 0.001). Furthermore, there was a significant decrease in putaminal volume from the initial scan to 18 months follow-up in both pre-HD and symp-HD (p < 0.001), but not in control subjects. Over 30 months there was a significant decrease in bilateral putamen volumes in control subjects (6.1% reduction, p = 0.002), pre- HD (9.9% reduction, p < 0.001) and symp-HD groups (19.3%, p < 0.001). Despite the differences between groups, no significant changes in caudate volume were observed over time. Conclusion(s): A significant decrease in putaminal volume was evident in both pre-HD and symp-HD groups over as little as 18 months. Our results confirm the suggestion that putaminal as opposed to caudate volume may be a sensitive biomarker of disease progression in HD.