Abstract
Moyamoya is a non-atherosclerotic intracranial steno-occlusive condition that places patients at high risk for ischaemic stroke. Randomized trials of surgical revascularization demonstrating efficacy in ischaemic moyamoya have not been performed, and as such, biomarkers of parenchymal haemodynamic impairment are needed to assist with triage and evaluate post-surgical response. In this prospective study, we test the hypothesis that parenchymal cerebrovascular reactivity (CVR) metrics in response to a fixed-inspired 5% carbon dioxide challenge correlate with recent focal ischaemic symptoms. Hypercapnic reactivity blood oxygenation level-dependent MRI (echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in moyamoya disease and syndromic participants (n = 73) were performed in sequence. Cerebrovascular reactivity uncorrected for response time (CVR(RAW)) was quantified, and time regression analyses were applied to quantify maximum cerebrovascular reactivity (CVR(MAX)) and cerebrovascular reactivity response time (CVR(DELAY)). Symptomatology was categorized by a stroke neurologist by hemisphere: symptomatic (lateralizing ischaemic symptoms < 6 months) or asymptomatic (no ischaemic symptom history). Values are presented as median [interquartile range]; logistic regression assessed the association of cerebrovascular reactivity metrics with symptoms, controlling for age and sex. A total of 109 hemispheres, including 39 symptomatic and 70 asymptomatic hemispheres, met inclusion criteria. Symptomatic hemispheres displayed reduced CVR(RAW) (P < 0.01) (symptomatic = 0.45 [0.28-0.70] z-statistic/ΔEtCO(2) versus asymptomatic = 0.67 [0.44-0.98] z-statistic/ΔEtCO(2)), lengthened CVR(DELAY) (P < 0.001) (symptomatic = 47.6 [37.7-57.0] seconds versus asymptomatic = 37.7 [30.4-46.4] seconds), and reduced CVR(MAX) (P = 0.037) (symptomatic = 1.31 [0.99-1.94] z-statistic/ΔEtCO(2) versus asymptomatic = 1.64 [1.29-2.12] z-statistic/ΔEtCO(2)). CVR(DELAY) (P < 0.001) was found to be significantly related to age in asymptomatic hemispheres (0.33-unit increase/year). Of assessed measures, the receiver operating characteristic curves suggest that CVR(DELAY) is associated most closely with recent ischaemic symptoms (P < 0.001). Findings support that cerebrovascular reactivity metrics are uniquely altered in hemispheres with recent ischaemic symptoms, further motivating their utilization as biomarkers of ischaemic symptomatology and potential treatment efficacy in moyamoya disease and syndrome.