MRI-visible perivascular spaces as an imaging biomarker in Fabry disease.

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting in vascular glycosphingolipid accumulation and increased stroke risk. MRI findings associated with FD include white matter hyperintensities (WMH) and cerebral microbleeds (CMBs), suggesting the presence of cerebral small vessel disease. MRI-visible perivascular spaces (PVS) are another promising marker of small vessel disease associated with impaired interstitial fluid drainage. We investigated the association of PVS severity and anatomical distribution with FD.

Patients And Methods: We compared patients with genetically proven FD to healthy controls. PVS, WMH, lacunes and CMBs were rated on standardised sequences using validated criteria and scales, blinded to diagnosis. A trained observer (using a validated rating scale), quantified the total severity of PVS. We used logistic regression to investigate the association of severe PVS with FD.

Results: We included 33 FD patients (median age 44, 44.1% male) and 20 healthy controls (median age 33.5, 50% male). Adjusting for age and sex, FD was associated with more severe basal ganglia PVS (odds ratio (OR) 5.80, 95% CI 1.03-32.7) and higher total PVS score (OR 4.03, 95% CI 1.36-11.89). Compared with controls, participants with FD had: higher WMH volume (median 495.03 mm vs 0, p = 0.0008), more CMBs (21.21% vs none, p = 0.04), and a higher prevalence of lacunes (21.21% vs. 5%, p = 0.23).

Conclusions: PVS scores are more severe in FD than control subjects. Our findings have potential relevance for FD diagnosis and suggest that impaired interstitial fluid drainage might be a mechanism of white matter injury in FD.