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nside an office building one morning, a broken elevator forces everyone to the stairs. Hustling up flight after flight, a middle-aged man is suddenly struck by a painful headache and passes out. After being rushed to a hospital, doctors determine he has a subarachnoid hemorrhage, a certain type of bleeding in the brain that is often fatal. When not deadly, thinking, speaking, and moving can be severely affected.

Subarachnoid hemorrhage, or bleeding between the first two layers of tissue that protect the brain, is the subject of two papers published in January by Columbia Health Sciences researchers. One study examined predictors of cognitive dysfunction after such a hemorrhage and the other looked at whether an inflammatory marker can predict quality of life after the initial injury. By understanding what leads to impairment, doctors hope to develop interventions to prevent damage.

The publications employ data from a study on subarachnoid hemorrhage patients that Dr. Stephan Mayer, associate professor of clinical neurology (in neurological surgery) at P&S, and Kurt Kreiter, a doctoral student in neurology at P&S, began approximately five years ago. Dr. E. Sander Connolly, associate professor of neurological surgery, and his group later joined the study, which has about 500 patients enrolled.

A subarachnoid hemorrhage usually is caused by a ruptured aneurysm. Aneurysmal subarachnoid hemorrhage affects nearly 30,000 people in North America each year. The mortality rate in the first 30 days after the hemorrhage is about 50 percent, which is the highest for any type of stroke. Approximately half the survivors end up permanently disabled because of cognitive problems. While aneurysms can happen in any place in the circulatory system, these blood vessel dilations or balloonings typically occur in brain and heart arteries. In a subarachnoid hemorrhage, the aneurysm bursts and blood spills into the subarachnoid space around the brain, where the blood mixes with cerebrospinal fluid.

Spasm of the blood vessels—where the muscles that line the blood vessel wall contract and clamp down on the artery—and more bleeding from the original aneurysm can lead to death and stroke for a cerebral hemorrhage patient. If the bleeding vessel is surgically accessible, a clip can be put around the aneurysm or coils can be placed inside the aneurysm to speed clotting and close off the cavity. New York-Presbyterian Hospital has a neuro-intensive care unit that treats hemorrhage patients with surgery and other methods. But not much can be done to treat vasospasm.

The cognitive dysfunction study, led by Dr. Mayer, evaluated 113 patients three months after their hemorrhage and quantified the problems associated with subarachnoid hemorrhage, including location of the blood, hydrocephalus, edema (swelling), strokes, and infarction, or neural tissue death due to lack of blood. The research team found swelling and small strokes were the most important factors related to how badly the brain is affected. These findings were surprising to Dr. Mayer and his team because other published research had not investigated the effect of swelling on cognitive outcomes.

“The take-home message is that out of all the complications that can occur after a hemorrhage, cerebral edema seems to be very important,” says Mr. Kreiter, the lead author of the cognitive dysfunction paper published in the January issue of Stroke. “The swelling seems to be driving a large proportion of the cognitive outcomes.”

While it may be too soon to employ specific treatments from the findings, reducing swelling and removing leaked blood could limit harm. Strategies to reduce infarction, particularly on the brain’s left side where much of our verbal abilities are housed, are also needed, Mr. Kreiter says.

Dr. Mayer’s laboratory is continuing to study subarachnoid hemorrhage and improving questionnaires, rating scales, and operational definitions in the neuropsychological tests patients take. The revised tests should more easily identify levels of impairment, enabling research and treatment to focus on the deficit areas.

The other study, led by Dr. Connolly, looked at levels of one inflammation marker, intercellular adhesion molecule-1, or ICAM-1, in serum after hemorrhage. Based on assessments of 101 patients, the researchers concluded that ICAM-1 was elevated in subarachnoid hemorrhage and that these higher levels of the marker in the bloodstream were associated with poor quality of life for patients. The investigators checked ICAM-1 levels every other day for 12 days after the initial hemorrhage. The study appeared in the January issue of the Journal of Neurosurgery.

One reason the researchers chose ICAM-1 is that animal models of subarachnoid hemorrhage have shown that blocking ICAM-1 improved outcome. However, blocking ICAM-1 in human trials has not worked. A study done elsewhere that used an ICAM-1 antibody to treat stroke patients had to be halted because treated patients had adverse reactions to the antibody.

Dr. Connolly’s group now is investigating the correlation between ICAM-1 and vasospasm to determine if the marker is related to spasm. “We would like to identify patients going into vasospasm, with the hope of eventually preventing new neurological deficits,” says Dr. J Mocco, postdoctoral research fellow, one of the lead authors of the Journal of Neurosurgery paper and a member of Dr. Connolly’s laboratory. “Knowing more about vasospasm might also help in understanding stroke, which might lead to better treatments for both.”



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