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

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 over two 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 six tracts and basal ganglia volumes best distinguished amongst 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. Lastly, 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 two years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington’s diagnosis.

Movement Disorder Society Task Force Viewpoint: Huntington's Disease Diagnostic Categories

“…Many years of study have consistently shown that progressive changes in structural magnetic resonance imaging (and likely functional magnetic resonance imaging and magnetic resonance spectroscopy) begin well before manifest HD, and perhaps even before the period of prodromal HD. Blood and cerebrospinal fluid biomarkers, especially mutant Huntingtin (Htt) and neurofilament light‐chain levels, are becoming increasingly relevant.…”

Regional subcortical shape analysis in premanifest Huntington's disease

“…Given that the PREDICT‐HD study was both multi‐centered and longitudinal in nature, implementation of the standardized image acquisition protocol was heterogeneous secondary to multiple vendors (GE, Phillips, and Siemens) and different field strengths (1.5 and 3 Tesla), and culminated in more than 20 variations in MR acquisition. Details of the acquisition information can be found in previous PREDICT‐HD studies (Harrington et al, ; Misiura et al, ). Our study data is comprised of MPRAGE data from 3 T scanners at 21 collection sites.…”

Longitudinal white matter microstructural change in Parkinson's disease

“…Both cross-sectional and longitudinal studies of neurodegenerative disorders have reported encouraging results regarding the use of DWI as a biomarker for disease progression (Bozzali et al, 2002; Canu et al, 2010; Goveas et al, 2015; Gregory et al, 2015; Harrington et al, 2016; Mayo et al, 2017; Phillips et al, 2014; Phillips et al, 2016; Poudel et al, 2015; Stricker et al, 2009; Weaver et al, 2009; Weiler et al, 2015; Yu et al, 2009). While studies in PD have reported cross-sectional differences in DWI measures between PD and control subjects (Agosta et al, 2014; Bertrand et al, 2012; Duncan et al, 2016; Goveas et al, 2015; Hattori et al, 2012; Melzer et al, 2013; Rae et al, 2012; Zhang et al, 2011), information regarding differential progression of WM change between PD patients and normal aging adults is relatively limited (Melzer et al, 2015; Rossi et al, 2014; Zhang et al, 2016).…”