Laird Harrison

April 11, 2014

SAN FRANCISCO — A gene may strongly affect the amount of perihematomal edema caused by intracerebral hemorrhage, a new study shows.

Patients with a mutation of the gene had 3.39 times greater edema than patients without the mutation.

"Even when you control for the major predictors of outcome in these patients, the gene's apparent effect on hematoma and edema volume is so large as to establish an independent association," Geoffrey Appelboom, MD, PhD, a research fellow at Columbia University in New York, New York, told Medscape Medical News.

Dr. Appelboom presented the finding here at the American Association of Neurological Surgeons (AANS) 82nd Annual Meeting.

Intracerebral hemorrhage strikes about 2 million people worldwide each year, killing about half of them within 12 months. These hemorrhages are becoming more common, and new treatments have so far failed to make a dent in these numbers.

Intracerebral hemorrhage can cause edema, which leads to increased intracranial pressure, causing a snowball effect that ends in severe brain damage.

Recent research has showed that a protein, aquaporin-4, plays an important role in edema by controlling cell water content. The protein forms channels that regulate water flow in and out of cells.

In effort to understand this mechanism and identify the patients most at risk for hemorrhage, Dr. Appelboom and his colleagues studied variants in the gene that codes for aquaporin-4.

The researchers tested the genes of 128 patients between February 2009 and March 2011.

They compared mutations of the gene with edema in these patients and found that a single nucleotide polymorphism, rs1058427, was associated with greater edema volume.

Nine patients had this polymorphism.

After adjustment for admission variables, including urea nitrogen, hypertension, systolic blood pressure, alkaline phosphatase, and score on the Glasgow coma scale, the edema volume was 339% greater in patients with this polymorphism. The association was statistically significant (P = .01).

The researchers hypothesized that the polymorphism may result in a slower upregulation of aquaporin-4, interfering with drainage during edema.

In future studies, the researchers hope to measure levels of aquaporin-4 to see how they correlate to the presence of this polymorphism. "Now the next step for us is to look at modulators of aquaporin-4 in the brain and see if we can improve the prognosis of these patients using these drugs," said Dr. Appelboom.

Asked to comment, session moderator Peter Nakaji, MD, a Phoenix, Arizona, neurosurgeon, told Medscape Medical News that the finding advances the understanding of intracerebral hemorrhage.

"Just knowing there is a group of people who are more at risk could lead to a change in their management," he said. "In the future we may be able to give them a therapy that restores their ability to manage edema in the brain."

Dr. Appelboom has disclosed no relevant financial relationships. Dr. Nakaji reported that he has been a consultant to Aesculap, has received research support from Carl Zeiss, and has received other financial or material support from AlloSource.

American Association of Neurological Surgeons (AANS) 82nd Annual Meeting. Abstract 722. Presented April 8, 2014.

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