Diffusion Tensor Imaging in Huntington’s disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits

Abstract

White matter (WM) degeneration is an important feature of Huntington's disease (HD) neuropathology. To investigate WM degeneration we used Diffusion Tensor Imaging and Tract-Based Spatial Statistics to compare Fractional Anisotropy, Mean Diffusivity (MD), parallel diffusivity and perpendicular diffusivity (λ⊥) in WM throughout the whole brain in 17 clinically diagnosed HD patients and 16 matched controls. Significant WM diffusivity abnormalities were identified primarily in the corpus callosum (CC) and external/extreme capsules in HD patients compared to controls. Significant correlations were observed between motor symptoms and MD in the CC body, and between global cognitive impairment and λ⊥ in the CC genu. Probabilistic tractography from these regions revealed degeneration of functionally relevant interhemispheric WM tracts. Our findings suggest that WM degeneration within interhemispheric pathways plays an important role in the deterioration of cognitive and motor function in HD patients, and that improved understanding of WM pathology early in the disease is required.

The Corticospinal Tract in Huntington's Disease

“…In the present paper, independent of age, we found a weak connection between high CAG repeat length and brain abnormality: high CAG repeats correlated with high connectivity impairment. This genetic basis for WM alterations was not found in two previous diffusion CC studies (Rosas et al 2010;Bohanna, Georgiou-Karistianis, Sritharan et al 2011), where CAG repeat length did not correlate with diffusivity measures. This may have to do with the increased sensitivity of tractography to elucidate the microstructural changes in WM or variations in subjects' demographics.…”

“…Nevertheless, these previous macro-and microstructural studies focused on wholebrain WM or Region of Interest analyses. Only a few studies investigated a specific tract in its entirety, for example, the whole commissural fiber (Magnotta et al 2009;Muller et al 2011;Di Paola et al 2012;Dumas et al 2012), the motor corticostriatal circuit (Kloppel et al 2008;Bohanna, Georgiou-Karistianis, Sritharan et al 2011) or the WM pathway of the sensorimotor cortex (Dumas et al 2012).…”

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

“…In line with our finding, diffusion tensor imaging studies have shown structural disconnecitivty in symp-HD individuals in the motor-cortical projection region of putamen. 61 A PET study revealed a corticostriatal motor network that discriminated pre-HD individuals from controls. 15 A further PET study showed that altered excitation of the striatum can modulate widespread cortical networks.…”

Assessment of Whole-Brain White Matter by DTI in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

“…30,31 Herein, by using TBSS, we present another common feature of ARSACS with these diseases: extensive WM alterations in the brain. 32,33 Our current study was distinguished in several ways: First, to the best of our knowledge, our study was the first that investigated whole-brain WM in patients with ARSACS. Second, it quantified the abnormal pattern of diffusion indices, including RD and AD, indicating widespread WM disintegration.…”