Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease - PubMed (original) (raw)

. 2016 Nov;31(11):1664-1675.

doi: 10.1002/mds.26803. Epub 2016 Sep 13.

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Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease

Deborah L Harrington et al. Mov Disord. 2016 Nov.

Abstract

Objectives: Diffusivity in white-matter tracts is abnormal throughout the brain in cross-sectional studies of prodromal Huntington's disease. To date, longitudinal changes have not been observed. The present study investigated cross-sectional and longitudinal changes in white-matter diffusivity in relationship to the phase of prodromal Huntington's progression, and compared them with changes in brain volumes and clinical variables that track disease progression.

Methods: Diffusion MRI profiles were studied for 2 years in 37 gene-negative controls and 64 prodromal Huntington's disease participants in varied phases of disease progression. To estimate the relative importance of diffusivity metrics in the prodromal phase, group effects were rank ordered relative to those obtained from analyses of brain volumes, motor, cognitive, and sensory variables.

Results: First, at baseline diffusivity was abnormal throughout all tracts, especially as individuals approached a manifest Huntington's disease diagnosis. Baseline diffusivity metrics in 6 tracts and basal ganglia volumes best distinguished among the groups. Second, group differences in longitudinal change in diffusivity were localized to the superior fronto-occipital fasciculus, most prominently in individuals closer to a diagnosis. Group differences were also observed in longitudinal changes of most brain volumes, but not clinical variables. Last, increases in motor symptoms across time were associated with greater changes in the superior fronto-occipital fasciculus diffusivity and corpus callosum, cerebrospinal fluid, and lateral ventricle volumes.

Conclusions: These novel findings provide new insights into changes within 2 years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington's diagnosis. © 2016 International Parkinson and Movement Disorder Society.

Keywords: Huntington's disease; brain volume; cognition; diffusion tensor imaging; motor symptoms.

© 2016 International Parkinson and Movement Disorder Society.

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Figures

Figure 1

Figure 1

Longitudinal change in MRI variables in gene-negative and positive individuals. Graphs display individual trajectories of longitudinal change for each variable that showed a group by time interaction (Table 3). Variability of individual trajectories (gray) around the group mean trajectory (wide colored line) is shown for each group. The superior-fronto-occipital fasciculus tract is displayed (top right) in axial (z=18.5) and coronal (y=2.5) views.

Figure 2

Figure 2

Association between annualized linear change in MRI variables and linear change in the Unified Huntington’s Disease Rating Scale (UHDRS) in gene-positive individuals. Standardized residuals (adjusted for age, CAP, and the number of years between the baseline and final MRI visits) are plotted for the linear slopes of MRI variables that correlated with the slope for the UHDRS total motor score (partial correlations and q-values displayed). Solid lines show the best-fitting linear regression line and 95% confidence intervals. Colored dots designate participants in each prHD group.

References

    1. Harrington DL, Smith MM, Zhang Y, Carlozzi NE, Paulsen JS. Cognitive domains that predict time to diagnosis in prodromal Huntington disease. J Neurol Neurosurg Psychiatry. 2012;83(6):612–619. -PMC -PubMed
    1. Paulsen JS, Long JD, Ross CA, et al. Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study. Lancet Neurol. 2014;13(12):1193–1201. -PMC -PubMed
    1. Paulsen JS, Long JD, Johnson HJ, et al. Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study. Front Aging Neurosci. 2014;6:78. -PMC -PubMed
    1. Dominguez DJ, Egan GF, Gray MA, et al. Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study. PLoS ONE. 2013;8(9):e74131. -PMC -PubMed
    1. Dominguez DJ, Stout JC, Poudel G, et al. Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data. Br J Psychiatry. 2015 -PubMed

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