Background Information

My colleagues and I recently reported^1-3 that the endothelial nitric oxide synthase (eNOS) gene may be an important candidate enabling the distinction between rupture-prone versus rupture-resistant brain aneurysms. The transcription and translation of this gene ( take me to the Genomics Section now), leads to the production of the protein (enzyme) eNOS, which in turn synthesizes a very important molecule called nitric oxide (NO). NO is a critical mediator of blood vessel function throughout the body, including brain blood vessels.

The decision to select the eNOS gene over a large array of possible molecular candidates for our work was not coincidental. Rather, the decision to select eNOS was based on my work with this molecule since 1991,⁴ and the recognition of the importance of eNOS and nitric oxide to cerebral blood vessel biology and aneurysmal pathobiology.⁵

In our study,³ after receiving informed consent from all participants and the support of our Institution, we took a small sample of venous blood from 58 patients diagnosed with ruptured brain aneurysms and 49 patients diagnosed with unruptured brain aneurysms. We extracted genomic DNA from the white blood cells in these samples, and then developed a biochemical/genetic assay to screen each sample for the presence of subtle variations ("polymorphisms") in the eNOS gene. We found that there were striking genetic differences in the presence of such variations between patients with ruptured compared with unruptured brain aneurysms. The most novel finding of this study was that the presence of two-or-more eNOS gene polymorphisms in a person with a brain aneurysm was somewhere between 8-10 times more likely to be associated with brain aneurysm rupture. Our work also found and confirmed key anatomical differences in size and location between aneurysms that were ruptured versus unruptured. This work was published in the March 2005 issue of the Journal of Neurosurgery, along with an accompanying editorial, and was the recipient of the prestigious Galbraith Award of the Congress of Neurological Surgeons in 2003. It is now subject to a U.S. Patent (Patent pending).

What does all this mean for persons with brain aneurysms?

Well, our study will need to be confirmed by other investigators before this simple "aneurysm genescreen" test will become a standard of care as a screening tool for patients with brain aneurysms. Please note that for the moment, at least, this information is still "experimental" or "research", as opposed to clinically available. If indeed our findings are confirmed by others, especially in larger numbers of patients, this means that when persons are diagnosed with a brain aneurysm, a small sample of blood can be provided (just like we do for any other blood test) to an appropriate lab for eNOS gene screening. The turnaround for this test (i.e., time between providing a sample and obtaining the result) can be made to be within 24 hrs. If confirmed, the eNOS gene polymorphism profile of a patient may represent potentially important information that can be used by neurologists and neurosurgeons who may be counseling patients with brain aneurysms regarding observation (as we know that many brain aneurysms can be followed in time) versus earlier treatment.

Cited References: