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Returning vets offer a window on neuroscience: military centers are leading the way on cerebral vasospasm, ALS, and rhabdomyolysis research.

The Comprehensive Neuroscience Program stands on the verge of discoveries in amyotrophic lateral sclerosis, peripheral nerve injury, and traumatic cerebral vasospasm, thanks to its unique research population: healthy young adults who habitually engage in high-risk behaviors--otherwise known as U.S. soldiers.

"Our patients are people who do extreme things in extreme environments--in the desert, under the ocean, in fighter planes, in the Hindu Kush," said neurologist Col. William Campbell, MC, USA, who designed the research program at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Md. "We're working to keep these people healthy and able to do their job of guarding and protecting the people of the United States."

The unavoidable consequences of war--injury and illness--provide valuable opportunities to research this understudied population in a controlled environment, said Patricia Tackitt, R.N., the program's executive director. But it's not only soldiers who will benefit from the research her colleagues perform. "Other people develop these problems, too--police officers, athletes, and those with traumatic injury. What we learn here will be applied to these other populations, and that transfer of knowledge is quite rapid: As soon as we publish, it's out there, and people are using it."

The Comprehensive Neuroscience Program (CNP) conducts its research at two primary sites--the National Naval Medical Center in Bethesda and the scheduled-for-closure Walter Reed Army Medical Center in Washington. It also shares resources and funding with the Conemaugh Memorial Medical Center in Johnstown, Pa. That association reflects the commitment of one of CNP's most dedicated supporters, Rep. John Murtha (D-Pa.), ranking member and former chairman of the House Appropriations Committee. Known on Capitol Hill for his passionate commitment to veterans' health issues, Rep. Murtha, himself a decorated U.S. Marine Corps veteran of combat in both Korea and Vietnam, pushed for CNP's creation and initial appropriation, a comparatively modest sum of $3 million.

What CNP has been able to accomplish with that amount is nothing short of remarkable, Ms. Tackitt said. "Because of our relationship with the military, we can make the money go quite far," she said. "We spent our first years identifying areas that have significant impact on soldiers, and now we're ready to go forward with some really exciting research programs that we think could have a huge impact on the civilian world."

Among those studies are a randomized treatment trial for posttraumatic cerebral vasospasm and preclinical testing of two potentially neuroprotective agents for amyotrophic lateral sclerosis (ALS).

Closed and penetrating head injuries are some of the most devastating consequences of battle, said Alexander Vo, Ph.D., of the Naval Medical Center. Cerebral vasospasm occurs in about 30% of victims, usually in the hemisphere contralateral to the injury. Dr. Vo is working with neurosurgeon Col. Rocco Armonda, MC, USA, also at the Naval Medical Center, to study both the incidence of this problem among battlefield soldiers and a new method of treating it.

Soldiers evacuated from Iraq or Afghanistan to the Naval Medical Center or Walter Reed typically arrive 24-72 hours after their injury. By then, vasospasm has usually already developed, often persisting for 2-4 weeks and resulting in cerebral ischemia, longer hospital stays, more ICU time, poorer transcranial Doppler blood flow values, and poorer neurologic outcomes. There is no consensus on treatment. The usual method is medical management with hypertensive, hypervolemic hemodilution (triple-H therapy).

"Here, we have begun using angioplasty to dilate the area of the spasm, followed by triple-H therapy," Dr. Vo said. "The first patients we treated this way did have better outcomes with regard to ICW length of stay and transcranial Doppler values."

Encouraged by that success, Dr. Armonda launched a randomized trial, comparing angioplasty with triple H to triple H alone. To date the trial has enrolled 30 patients, who are being followed through recovery. Based on early evidence, the method looks promising, Dr. Vo said.

Dr. Olavo M. Vasconcelos, a neurologist at USUHS, is about to embark on a series of animal studies that could offer hope to millions of ALS patients. Using a mouse model of the devastating disease, he will test the neuroprotective effects of high-dose riboflavin--a potent antioxidant-and a human growth hormone. "These trials will help us target pathways that we know have neuroprotective potential," Dr. Vasconcelos said. "A year from now, we hope to show that we've postponed death in these animals."

The ALS study has importance for the civilian population, he said, but could have a special impact on the military. Beginning with observations made with Gulf War veterans, "it's become evident that for unknown reasons, there's an increase in the incidence of ALS in veterans across all branches of the military. It's an alarming association that raises questions about the disease's etiology."

For his part, Dr. Campbell is most involved with a study of risk factors for rhabdomyolysis--a breakdown of muscle that releases nephrotoxic myoglobin into the bloodstream. The disorder can be caused by any condition that damages skeletal muscle, including excessive physical activity in a hot environment, just the kind of thing that happens in basic training at Fort Benning, Ga. "Most recruits experience only a mild soreness, but a small population does spill myoglobin into the blood, leading to the possibility of kidney damage and even life-threatening metabolic derangement," he said. "If they develop this, that's it; they're discharged."

The rhabdomyolysis study will examine not only the disorder's incidence, which is thought to be increased in military populations, but also genetic factors that impact both susceptibility and resistance.

There are other projects as well, involving the increased incidence of migraine among active duty personnel, posttraumatic epilepsy, and even stroke among veterans. But some projects may be endangered if proposed federal budget cuts are approved.

The annual appropriation is part of a larger grant that CNP shares with the Pennsylvania hospital. The portion allotted to CNP has remained fairly constant over the years, but fiscal year 2006-2007 may present a radically different prospect. Significant budget cuts loom over the program; if they come to pass, the research agenda will have to change, Ms. Tackitt said. "There are some tough decisions ahead."
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Title Annotation:Clinical Rounds; Comprehensive Neuroscience Program
Comment:Returning vets offer a window on neuroscience: military centers are leading the way on cerebral vasospasm, ALS, and rhabdomyolysis research.(Clinical Rounds)(Comprehensive Neuroscience Program)
Author:Sullivan, Michele G.
Publication:Family Practice News
Geographic Code:1USA
Date:Apr 1, 2006
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