Decreased Diffusivity in the Caudate Nucleus of Presymptomatic Huntington Disease Gene Carriers: Which Explanation?

Multi-Modal Neuroimaging in Premanifest and Early Huntington’s Disease: 18 Month Longitudinal Data from the IMAGE-HD Study

“…There are a number of neuropathological and age-related processes that may possibly account for this pattern of longitudinal change. These include for example increased oligodendroglial numbers present in HD developmentally [30,52,54], homeostatic attempts to remyelinate [55], and iron accumulation. The latter occurs naturally with the aging process [56-58], but also increases with greater numbers of oligodendroglia and remyelination in HD [6,55,59].…”

“…Larger numbers of oligodendroglia, remyelination and iron accumulation may contribute to real and apparent decreases in diffusivity, the former two by increasing barriers to water diffusivity and the latter by introducing magnetic susceptibility effects. These processes may combine to produce a pattern of short-term striatal MD decreases against the backdrop of a long-term trend toward higher diffusivity (e.g., [30] reported reduced caudate MD in pre-HD far from diagnosis relative to controls). In the putamen, this pattern may be amplified due to the combination of two factors: the putamen has a higher iron concentration than the caudate [56,57]; and second, the rate of iron deposition keeps increasing throughout the lifespan in this structure whereas it plateaus in the caudate around the third decade of life [57,58].…”

“…We also subdivided pre-HD into farther from (pre-HD far ) and closer to (pre-HD close ) diagnosis at the group median years to diagnosis (median = 14.6 years). These two groups differed from each other in terms of age, UHDRS TMS, Disease Burden Score (DBS = age×[CAG repeats-35.5] [30]; and IQ (see Table 1). …”

Altered diffusion tensor imaging measurements in aged transgenic Huntington disease rats

“…Diffusion tensor imaging (DTI) has emerged as a sensitive tool for detection of altered tissue integrity at both preclinical and clinical stages of HD (Mascalchi et al 2004; Reading et al 2005; Rosas et al 2006; Seppi et al 2006; Bohanna et al 2008; Kloppel et al 2008; Douaud et al 2009; Mandelli et al 2010; Della Nave et al 2010; Rosas et al 2010; Sritharan et al 2010), and has been confirmed as a promising diagnostic tool for monitoring neuropathological changes in rat models of HD (Blockx et al 2011; Van Camp et al 2012). The in vivo imaging study of transgenic HD rats by Blockx et al (2011) was, however, limited by voxel resolutions insufficient to discriminate individual basal ganglia regions, and the apparent subtle neuropathology observed in 12 months old animals.…”

Magnetization Transfer MR Imaging Demonstrates Degeneration of the Subcortical and Cortical Gray Matter in Huntington Disease

“…1 Diffusion-weighted or diffusion tensor MR imaging studies have documented a distributed pattern of damage in the remaining WM in HD. [5][6][7][8] While increased diffusivity was reported in the striatal nuclei in symptomatic HD carriers, 5,9 recently Mandelli et al 10 reported a bimodal behavior of diffusion changes in the striatal nuclei of HD carriers with decreased diffusivity in the caudate but not in the putamen of presymptomatic subjects and increased diffusivity in the putamen and caudate in symptomatic subjects. However, no data, to our knowledge, about the capability of diffusion studies to detect cortical GM damage in HD are available.…”