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



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.



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.



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.
Department of Radiology, University of California, San Diego, La Jolla, California, USA.|Research Service, Veteran's Affairs San Diego Healthcare System, San Diego, California, USA.
Deborah L
DL
Harrington
Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Jeffrey D
JD
Long
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Sally
S
Durgerian
Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Lyla
L
Mourany
Imaging Sciences, Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Katherine
K
Koenig
Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Ohio, USA.
Aaron
A
Bonner-Jackson
Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Jane S
JS
Paulsen
Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Stephen M
SM
Rao
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging*; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D062706:Prodromal Symptoms; D066127:White Matter / Q000000981:diagnostic imaging*
Huntington's disease; brain volume; cognition; diffusion tensor imaging; motor symptoms