WASHINGTON – Researchers have discovered two areas of brain atrophy in Gulf War veterans who responded differently to a heart-rate test, leading scientists to believe that even those with the same Gulf War Illness symptoms may need different kinds of treatments.
"It was shocking to us," said Rakib Rayhan, lead author of the study and a researcher at Georgetown University Medical Center. "We were just floored."
Each subgroup had distinct areas of damage to different parts of the brain.
The study will be released today in PLOS ONE journal.
Gulf War Illness affects about 30% of the 700,000 people who served in the 1991 Persian Gulf War. Symptoms include fatigue, headaches, gastrointestinal problems, cognitive impairment and pain. After exercise, the ill veterans don't get the endorphin rush that appears in healthy people. Instead, they can be physically "knocked out for days," Rayhan said.
In a recent study, researchers at Georgetown University Medical Center took 28 sick veterans' and a control group's blood pressure while lying down. Then, they took their blood pressure after they stood up. Normally, the body senses how much blood needs to be pumped to force blood back up to the brain when a person stands.
But there was an immediate, unexpected difference: The control group's blood pressure levels went up within normal ranges. But within the group of 28 ill veterans who had essentially the same symptoms, 10 experienced an abnormal – 30 or more beats above what it had been while lying down -- jump in blood pressure, while the 18 other ill veterans remained within normal blood pressure range but had an increased perception of pain.
"I thought this would be a waste of the nursing staff's time," said James Baraniuk, explaining that the researchers did not expect the veterans to be different from the control group – or for there to be pronounced differences in the veterans. "It became a fundamental way of splitting the two veteran groups." Baraniuk is the school lab's senior investigator.
Next, the study volunteers underwent an fMRI scan while completing a simple exercise to test short-term memory. An fMRI, or "functional" MRI, is a scan that measures activity by detecting how blood flows through the brain.
Again, the findings were unexpected. The control group's brains lit up in the expected manner, showing activity along the normal cognitive path. But both ill veteran groups showed brain activity in a circuitous route, which usually signifies that the normal path is dysfunctional.
People with Alzheimer's Disease or Multiple Sclerosis compensate in a similar way, though the paths they take are different from what the doctors saw in the sick veterans. Baraniuk said there's no connection at all to those diseases. Rayhan said the veterans essentially used different parts of their brains as "crutches" to make up for the loss of function in the part of the brain that typically performs the work.
"I'd say it's unique to Gulf War veterans," Baraniuk said, adding that the damage may show degeneration of the nervous system. "The brain has to find other routes to get the job done."
"We wanted to know why does exercise make these people completely fall off a cliff," Rayhan said. "It was as if you took the crutches away – those areas of the brain don't light up after exercise."
When they analyzed the brain scans further, they found atrophy to the brain stem and cerebellum in the abnormal heart rate group. This is the area that controls blood pressure and heart rate. In the pain group, they found a decrease in gray matter volume in the right superior parietal lobe, which is the area that processes pain.
"We've identified two pathological pathways," Baraniuk said. "If we understand the mechanisms, we can come up with a more rational approach to developing new drugs."
The finding ran counter to what they expected to find: that the ill patients would exercise on a stationary bicycle, which would cause pain and fatigue, and then they would not perform as well when they rode the bicycle again.
"Those changes were not dramatic at all," Baraniuk said. "But Rakib combed back through the data and found the tachycardia—it's detective work."
The scientists then realized that the patients with the abnormal heart rate increase also had higher anxiety scores than those with the higher pain response.
The scientists hope for funding to allow them to repeat the study with a new group of veterans to verify their findings. This study was funded by the Defense Department through the Congressionally Directed Research Programs. In the meantime, Baraniuk recommends cognitive behavioral therapy to help the veterans come to terms with their illnesses, as well as triptan drugs to help with migraines. In the past, much research has been about psychological causes of Gulf War illness, which has led some doctors to assume the migraines are psychosomatic.
In previous research Baraniuk and Rayhan found differences in the white matter of the ill veterans by using an fMRI, which means there is an objective diagnosis for Gulf War Illness, they say.
"You can't fake it," Baraniuk said. "It's legitimate."