Association of dilated perivascular spaces and disease severity in patients with Huntington's disease.

OBJECTIVE To quantify the percent volume of dilated perivascular spaces (PVS) in the subcortical forebrain in patients with early Huntington's disease (HD) and to explore the relationship between PVS and disease severity. METHODS MRI scans were performed on 25 HD patients and 23 healthy age-matched controls at Massachusetts General Hospital. The imaging data were analyzed using a novel algorithm to determine regional PVS volume. A fractional logistic regression analysis was used to quantify the association between regional percent PVS volume and (1) disease designation (HD or Control) and (2) disease severity as assessed by normalized caudate volume. RESULTS HD patients had the greatest percent volume of dilated PVS in the putamen (left putamen: odds ratio 2.06 [95% CI: 1.62-2.62], HD 3.27% [95% CI: 2.83-3.78] vs Controls 1.62% [1.32-1.97], pfdr < 0.001; right putamen odds ratio 1.66 [95% CI: 1.33-2.08], HD 3.43% [95% CI: 2.94-4.01] vs Controls 2.09% [95% CI: 1.79-2.45] pfdr < 0.001) and several subcortical white matter regions, as compared to controls. Dilated PVS increased with disease severity. CONCLUSIONS The objective quantification of dilated PVS suggests that PVS burden is high, associated with disease severity and may impact the distribution and success of treatments administered either intrathecally, such as antisense oligonucleotides (ASOs) or by intraparenchymal administration, such as cell and gene therapies. Classification of Evidence Review: This study provides Class II evidence that increased dilated PVS is associated with worse Huntington's disease severity. The study is rated Class II because of the cross-sectional design.