AUTHOR=Sesen Julie , Driscoll Jessica , Moses-Gardner Alexander , Orbach Darren B. , Zurakowski David , Smith Edward R. 

TITLE=Non-invasive Urinary Biomarkers in Moyamoya Disease

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.661952

DOI=10.3389/fneur.2021.661952

ISSN=1664-2295

ABSTRACT=Introduction	
	
A major difficulty in treating moyamoya is the lack of effective methods to detect novel or progressive disease prior to the onset of disabling stroke. More importantly, a tool to better stratify operative candidates and quantify response to therapy could substantively complement existing methods.  Here we present proof-of-principle data supporting the use of urinary biomarkers as diagnostic adjuncts in pediatric moyamoya patients.  

Methods

Urine and cerebrospinal fluid specimens were collected from pediatric patients with moyamoya and a cohort of age and sex-matched control patients.  Clinical and radiographic data were paired with measurements of a previously validated panel of angiogenic proteins quantified by ELISA.  Results were compared to age and sex-matched controls and subjected to statistical analyses.

Results

Evaluation of a specific panel of urinary and cerebrospinal fluid biomarkers by ELISA demonstrated significant elevations of angiogenic proteins in samples from moyamoya patients compared to matched controls.  ROC curves for individual urinary biomarkers, including MMP-2, MMP-9, MMP-9/NGAL and VEGF, showed excellent discrimination.  The optimal urinary biomarker was MMP-2, providing a sensitivity of 88%, specificity of 100% and overall accuracy of 91%. Biomarker levels changed in response to therapy and correlated with radiographic evidence of revascularization.

Conclusions
 
We report, for the first time, identification of a panel of urinary biomarkers that predicts the presence of moyamoya.  These biomarkers correlate with presence of disease and can be tracked from the central nervous system to urine.  These data support the hypothesis that urinary proteins are useful predictors of the presence of moyamoya and may provide a basis for a novel, non-invasive method to identify new disease and monitor known patients following treatment.