Introduction: Diagnosis of moyamoya requires imaging which include risks associated with anesthesia and angiography. We describe the novel application of non-invasive urinary biomarkers to assess preoperative ischemia, development of transdural collaterals and predict 1-year angiographic outcomes from preoperative samples.
Hypothesis: We tested the hypothesis that urinary levels of netrin-1 and vascular endothelial growth factor (VEGF) correlate with disease severity at diagnosis and prospectively identify patients better able to grow surgical collaterals, as quantified by Matsushima grade.
Methods: Preoperative urine samples were collected from patients (age<22 years). Radiographic data (Suzuki stage, presence/location of preoperative transdural collaterals and postoperative Matushima grade) were performed by neuroradiologists and obtained from clinical records. Quantitative analysis of protein levels was performed with ELISA, normalizing for protein and subjected to statistical comparison between groups.
Results: A total of 132 patients with moyamoya had samples and imaging for analysis. Urinary VEGF and netrin-1 levels were significantly elevated in moyamoya patients compared to matched controls (6.6 vs. 4.4pg/ug and 0.6 vs. 2.3pg/ug, p<0.05 respectively). In patients without transdural collaterals, VEGF and netrin-1 urinary levels were higher than in those with collaterals (n=68 without, 64 with, p= 0.03 netrin, NS VEGF) Higher preoperative urine levels of both VEGF and netrin-1 correlated with better postoperative Matsushima grade (n=38,29,16 for Matsushima A,B,C, p<0.01 for VEGF and p<0.05 for netrin-1).
Conclusions: Urinary levels of VEGF and netrin-1 are elevated in moyamoya patients and may correlate with an increased angiogenic drive that is higher in patients without spontaneous collaterals (who may be more ischemic than those who have already established collaterals) and whose presence may aid in development of surgical collaterals after indirect revascularization. These experiments provide proof-of-principle data that urinary biomarkers may have utility in augmenting clinical decision-making.