Neurotrauma surgeon Geoffrey Manley is fighting a silent epidemic. Nearly 1.5 million cases of traumatic brain injury (TBI) occur annually in the United States, and it kills 50,000 people every year. Over five million Americans live with disabilities due to TBI.

At SFGH, Manley brings unique skills to the battle. Trained both as a doctor and as a medical researcher, he holds an M.D. degree and a Ph.D. in molecular neuroscience.

To help his patients, Manley uses the same kind of computer technology that helped map the human genome. This allows the intensive care unit (ICU) staff to precisely monitor their patients and to rapidly respond to the slightest changes in their condition. "We are creating new tools for clinical informatics," says Manley.

At first glance, a neurotrauma intensive care unit is an impressive high-tech operation, with as many as a dozen advanced instruments monitoring each patient. Yet when Manley walks into a typical ICU, he sees an electronic tower of Babel. "All the medical monitors have been designed to different standards and can't communicate with each other," say Manley. "It's left up to the doctors and nurses to integrate this information, often with very low-tech devices—pencil and paper."

Manley and his group at SFGH have helped create software and databases that combine data from these instruments along with patient records and medication orders. The goal is to standardize and improve care in the ICU for patients with head injuries. "The doctors and nurses in our ICU are stellar, " says Manley, "and the combination of their diligence and the latest computer techniques is already making a difference."

Manley's careful observations have shown that some standard emergency medical practices can be counter-productive for patients with TBI.

In an ambulance, unconscious trauma patients are often given high volumes of intravenous fluids while oxygen is pumped into their lungs. But Manley has shown that too much fluid can increase post-traumatic brain swelling, and excess oxygen can stimulate a cascade of chemical and biological changes that leads to less, not more, oxygen reaching the brain.

Even with the most consistent care, outcomes for patients with TBI often vary in a way that neurosurgeons cannot explain. "We may have three patients, each with similar head injuries resulting from an auto accident," says Manley. "One has died, one is in critical condition and is facing permanent disabilities, and the third is on the way to a full recovery. We want to know how to explain those differences."

The outcomes may be due in part to genetic differences in the way water is transported in and out of brain cells. Irregularities in water balance after a brain injury often create as much damage as the original injury itself. Cerebral edema—an abnormal increase in brain water content—causes an increase in intracranial pressure, leading to further damage and death.

"Despite its importance, the molecular mechanisms of brain water accumulation and clearance remain poorly understood," says Manley. "Current treatments aimed at reducing edema have not changed much since their introduction more than 80 years ago."

Manley is focusing his research on aquaporins, a family of small proteins that provide the major route for water movement across cell membranes. Discovered in the mid-1990s, aquaporins, and the genetic differences in how human tissue responds to them, may prove critical to understanding and controlling cerebral edema and help to develop new drugs to combat this problem.

By translating the latest research findings into improvements in patient care, Manley is saving lives that might have been lost a decade ago. "UCSF has created an environment that has allowed me to succeed both as a scientist and a clinician," says Manley. "At SFGH, I am able to affect people's lives and change the practice of medicine."

Source: Michael Barnes