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Mov Disord Clin Pract. 2019 Nov 28;7(1):52-60. doi: 10.1002/mdc3.12866. eCollection 2020 Jan.

Characterizing White Matter in Huntington's Disease.

Author information

1
University College London Huntington's Disease Centre, Department of Neurodegenerative Disease University College London Queen Square Institute of Neurology, University College London London United Kingdom.
2
Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology University College London United Kingdom.
3
Leonard Wolfson Experimental Neurology Centre, University College London Queen Square Institute of Neurology University College London United Kingdom.
4
Department of Computer Science and Centre for Medical Image Computing University College London London United Kingdom.
5
Lysholm Department of Neuroradiology National Hospital for Neurology and Neurosurgery London United Kingdom.
6
Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences King's College London London United Kingdom.
7
Wellcome Trust Centre for Neuroimaging, Institute of Neurology University College London London United Kingdom.

Abstract

Background:

Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way in which disease spreads from the striatum.

Objectives:

We provide a detailed characterization of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging and then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light, a biofluid marker of axonal degeneration-in parallel with the mutant huntingtin protein.

Methods:

We examined WM change in HD gene carriers from the HD-CSFcohort, baseline visit. We used standard-diffusion magnetic resonance imaging to measure metrics including fractional anisotropy, a marker of WM integrity, and diffusivity; a novel diffusion model (neurite orientation dispersion and density imaging) to measure axonal density and organization; T1-weighted and T2-weighted structural magnetic resonance imaging images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of neurofilament light (in cerebrospinal fluid (CSF) and plasma) and mutant huntingtin protein (in CSF).

Results:

HD gene carriers displayed reduced fractional anisotropy and increased diffusivity when compared with controls, both of which were also associated with disease progression, CSF, and mutant huntingtin protein levels. HD gene carriers also displayed proxy measures of reduced myelin contrast and iron in the striatum.

Conclusion:

Collectively, these findings present a more complete characterization of HD-related microstructural brain changes. The correlation between reduced fractional anisotropy, increased axonal orientation, and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, whereas higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum.

KEYWORDS:

Huntington's disease; MRI; neurofilament light (NfL); white matter

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