The Corticospinal Tract in Huntington's Disease

Abstract

Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T 2 *-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the "dying back" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.

Mapping the order and pattern of brain structural MRI changes using change‐point analysis in premanifest Huntington's disease

“…Previous DTI studies have demonstrated white matter deficits in the corpus callosum [Crawford et al, 2013], internal capsule [Rosas et al, 2006], corticospinal tract [Phillips et al, 2015], cortico-striatal circuit [Novak et al, 2014], and across extensively distributed white matter fibers [Novak et al, 2014;Reading et al, 2005], years before symptoms occur. In addition to the existing findings, our data provide a more comprehensive spatial and temporal view of the changing pattern.…”

Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case–control study

“…For instance, diffuse increases in corticospinal FA are observed throughout childhood and adolescence as part of normal neural development [49; 60]. Reduced corticospinal FA, on the other hand, is common in diseases associated with loss of motor and executive function, including Huntington’s disease [47], multiple sclerosis [32], cerebral palsy in children [48], multiple system atrophy [33], and amyotrophic lateral sclerosis [9]. In contrast, increased corticospinal FA is observed with recovery of motor function following diffuse axonal injury [31], and more commonly with motor learning.…”

Deep White Matter in Huntington's Disease

“…T2* weighted volumes, which are sensitive to iron/ferritin [21] , [22] are useful to investigate the iron content that is associated with the remyelination process [2] . The few studies present in literature show a non-univocal picture of the regional white matter iron content changes in HD, with no iron level differences in the callosal splenium, but decreased iron levels in the frontal lobe white matter [2] , the callosal isthmus [14] and the cortical spinal white matter tract [15] . However, no studies to date in HD have combined the sensitivity of DTI tractography to identify the deep white matter in-vivo with T2* weighted volume images.…”

“…Changes in iron content (reduction) manifest in the early stages of HD, likely indicating a failure of the remyelination processes at that time. Then we focused on the cortical spinal tract, which is the brain's main motor fiber [15] . We found that a likely active repair mechanism (as indicated by increased iron) helps keep the cortical spinal tract at a normal functional level in the presymptomatic stage.…”