Affiliations: [a] Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK
| [b] Icahn School of Medicine at Mount Sinai, New York, NY, USA
| [c] Biomedical Engineering and Imaging Institute at Mount Sinai School of Medicine, New York, NY, USA
| [d] Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
Correspondence:
[*]
Correspondence to: Annabelle Coleman, Huntington’s Disease Centre, UCL Queen Square Institute of Neurology, 2nd Floor Russell Square House, 10-12 Russell Square, London, WC1B 5EH, UK. E-mail: [email protected].
Abstract: Background:
Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington’s disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies. Objective:
To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined. Methods:
White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured. Results:
PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found. Conclusions:
This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted.
Keywords: Huntington’s disease, magnetic resonance imaging, perivascular spaces, PVSSAS
