Study Shows Urinary Biomarkers May Help Detect Pediatric Intracranial AVMs

May 1, 2013—The American Association of Neurological Surgeons (AANS) announced results from a recent study conducted by investigators from Boston Children's Hospital that showed that the urinary levels of hepatocyte growth factor (HGF) could serve as a biomarker capable of detecting the presence of arteriovenous malformations (AVMs). Edward Robert Smith, MD, presented data from the study at the AANS annual scientific meeting, which was held April 27 to May 1 in New Orleans, Louisiana. The presentation was titled Noninvasive Urinary Biomarkers Can Detect the Presence of Intracranial Arteriovenous Malformations.

According to the AANS announcement, the investigators have been using urinary biomarkers in their laboratory as a noninvasive method of diagnosing diseases of the central nervous system, including tumors, stroke, and moyamoya.

For this study, urine was collected from pediatric patients between the ages of zero and 18 with cerebral AVMs (as confirmed by both imaging and subsequent surgical pathology) and compared to age- and sex-matched controls, following a protocol approved by an institutional review board. A radiologist evaluated nidus size, location, and flow characteristics using both magnetic resonance imaging (MRI) and catheter-based angiography. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of urinary HGF, and data was normalized to protein concentration using Bradford assays. Results were subjected to univariate and multivariate statistical analyses.

As summarized in the AANS press release, the investigators found that HGF as a urinary biomarker by ELISA showed statistically significant, clinically relevant elevations in samples from patients with brain AVMs as compared to controls. In addition, HGF levels were predictive of nidus size and distinct from other central nervous system pathologies.

The investigators concluded that HGF demonstrates the potential of urinary biomarkers in diagnosing pediatric brain AVMs. This biomarker correlates not only with presence of disease but also with nidus size. These data support the hypothesis that the use of urinary HGF levels may have utility as a novel, noninvasive method to detect cerebral AVMs in children, according to the AANS announcement.

In the society's press release, Dr. Smith commented, “The initial goal for this type of biomarker work is not as a tool to screen for AVMs in the general population—it is very unlikely (at least yet) that this type of test will be sensitive and specific enough to be used in this manner. Rather, we hope that some initial translational work might be directed at kids who have been treated for known AVMs—using something like this test to ensure that the cure is permanent and long lasting.”

Dr. Smith continued, “For now, we have to rely on periodic MRIs and angiograms—invasive and expensive tests that can only be done infrequently. We know that children have a real risk of AVM recurrence in some cases. Also, other treatment tools, like radiation, may take years to work and the effectiveness of the treatment needs to be assessed during this time. We now have an ongoing national multicenter trial for a urine biomarker test for brain tumors in children and we would hope that a similar type of study might be the next step in this work. Knowing the size of the AVM—or other types of physiologic measures (size, flow, rate of producing chemicals that may relate to AVM growth)—may all be useful to measure the effectiveness of treatment, reassuring parents when things are well and helping to predict those cases that might need further treatment before problems occur when the first therapy might not have fully worked. In addition, it may be possible to use some of this information to discover new treatments for AVMs, based on which proteins we detect in the urine.”