To characterize white matter (WM) alterations in Huntington Disease (HD) patients using diffusion tensor imaging (DTI) analysis.

Although HD symptoms have been mostly explained by degeneration in caudate, putamen, and amygdala, there is considerable variability in age of onset, symptom severity, and rate of neurodegeneration among patients. Therefore, there has been an additional effort to characterize better structural MRI alterations in HD. Imaging studies in HD patients may help to determine the differential vulnerability of CNS structures to neurodegenerative process as well as to more precisely identify when neurodegeneration starts, how it progresses and possible associated triggers.  

We obtained DTI from 37 controls and 36 patients, age-sex balanced. Patients underwent neurological evaluations: Unified HD rating scale – UHDRS, and MOCA. DTI was processed with ExploreDTI/MATLAB-2014. Ten tracts [3 parts of corpus callosum (CC), Corticospinal tract (CST), Infero-frontooccipital (IFO), Infero-longitudinal Fasciculus (ILF), dorsal and parahippocampal cingulum (PH-CINGULUM), uncinate and fornix body (FORNIX)] were delineated by tractography to yield fractional anisotropy (FA) (Figure). SPSS22 was used for correlations, univariate, multivariate analyses and Chi-square test. 

ANOVA analyses for bilateral tracts revealed significant dorsal and PH-cingulum FA reduction (p<0.004) in HD patients. MANOVA of CC segments and FORNIX showed reduced FA (p<0.0125). While there was no significant correlation between FA and CAG expansion, we identified significant correlation between UHDRS and CST (p<0.005), IFO (p<0.002) and left PH-CINGULUM (p=0.003). There was a positive correlation between MOCA and PH-CINGULUM  FA (p<0.002).

WM alterations were widespread, affecting midline and bilateral structures. Possible mechanisms underlying these findings: 1)Preferential connections loss along radial direction (striatopallidal connections); 2)Pathological processes combination (neuronal loss, astrocytosis, cell permeability); 3)Increased metalloprotein-bound-iron deposit.

The abnormal tracts are responsible for sensorimotor integration, motor control and planning, visuospatial function and emotional processing. Prospective studies are underway to characterize how the pattern of WM alterations progresses in HD.