Urinary Biomarkers May Help Detect Intracranial Arteriovenous Malformations

Newswise — NEW ORLEANS (May 1, 2013) — Today during the 81st American Association of Neurological Surgeons (AANS) Annual Scientific Meeting, researchers from Boston Children’s Hospital shared results from a recent study that showed the urinary levels of hepatocyte growth factor (HGF) could serve as a biomarker capable of detecting the presence of arteriovenous malformations (AVMs). The researchers have been using urinary biomarkers in their laboratory as a non-invasive method of diagnosing diseases of the central nervous system, including tumors, stroke and moyamoya.

For the 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 an IRB-approved protocol. Nidus size, location and flow characteristics were evaluated by a radiologist using both 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. The results of this study, Non-Invasive Urinary Biomarkers Can Detect the Presence of Intracranial Arteriovenous Malformations, will be presented by Edward Robert Smith, MD, FAANS, from 11:50 a.m.-12:01 p.m. on Wednesday, May 1. Co-authors are Brendan McNeish, BA; Michael Raber, MD; Xuezhe Han, MD, PhD; and Darren Orbach, MD, PhD.

Researchers found in their evaluation of 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 CNS pathologies. The researchers concluded that HGF demonstrates the potential of urinary biomarkers in diagnosing pediatric brain AVM. This biomarker correlates not only with presence of disease but also correlated with nidus size. These data support the hypothesis that the use of urinary HGF levels may have utility as a novel, noninvasive method to cerebral AVMs in children.

“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,” said Edward Robert Smith, MD, FAANS. “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 multi-center 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.”

Disclosure: The author reported no conflicts of interest.

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About the 2013 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals, the AANS Annual Scientific Meeting is the largest gathering of neurosurgeons in the nation, with an emphasis on the field’s latest research and technological advances. A record-breaking 1,003 scientific abstracts were presented for review at the 2013 AANS Annual Scientific Meeting, and the scientific presentations given at this year’s event represent cutting-edge examples of the incredible developments taking place within the field of neurosurgery. Additional information about the AANS Annual Scientific Meeting and the Meeting Program can be found at http://www.aans.org/Annual Meeting/2013/Main/Home.aspx.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with nearly 8,300 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the spinal column, spinal cord, brain and peripheral nerves. For more information, visit www.AANS.org.