Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Abstract

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = -0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Keywords: Cerebrovascular circulation; cerebrovascular disorders; leukoencephalopathies; magnetic resonance imaging; mutation.

Figure 1.

Cerebrovascular reactivity in relation to age in RVCL-S patients (n = 21), mutation-negative family members (n = 23), and healthy controls (n = 31). CBF: cerebral blood flow; PetCO₂: partial pressure of end tidal CO₂; CVR: cerebrovascular reactivity; BOLD: blood oxygenation level dependent; RVCL-S: Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations.

Figure 2.

Correlation of white matter lesion volume with cerebrovascular reactivity in RVCL-S patients (n = 21). WML: white matter lesion; CVR: cerebrovascular reactivity.

Figure 3.

Voxel-wise comparison of cerebrovascular reactivity for RVCL-S patients (n = 21), mutation-negative family members (n = 23), and healthy controls (n = 31). (a) Regions of decreased gray matter CVR_CBF in RVCL-S patients versus mutation-negative family members; (b) regions of decreased gray matter CVR_CBF in RVCL-S patients versus healthy controls; (c) regions of decreased CVR_BOLD in RVCL-S patients versus mutation-negative family members; and (d) regions of decreased CVR_BOLD in RVCL-S patients versus healthy controls. Note: There were no regions of increased CVR in RVCL-S patients compared to the other groups. There were no differences in CVR between mutation-negative family members and healthy controls.