ARTICLE IN BRIEF
Experts identified what is known — and not known — about gender, racial, and other differences in traumatic brain injury.
BETHESDA—Just what is known about gender, race, and the demographics of traumatic brain injury (TBI)? That was the question here for panelists at a conference on trauma spectrum disorders, held in late September by the Department of Defense (DoD), Defense Centers of Excellence for Psychological Health & Traumatic Brain Injury (DCoE), and the Department of Veterans Affairs (VA). The NIH and Johns Hopkins University School of Medicine jointly sponsored the meeting.
“There's much more that isn't known on these disorders than is known,” said Karen Schwab, PhD, chief of the Statistics and Epidemiology Branch, Defense and Veterans Brain Injury Center (DVBIC) and chief of TBI Research for the DCoE.
Sixteen percent of veterans are women, and they tend to have a lower incidence of TBI than men, probably because they are not assigned to combat service, she said. But overall, gender differences in TBI incidence are narrower in the military than in civilian populations, possibly because active-duty men and women tend to be in good health, young, and at least high school-educated.
“Much of the difference by race remains unexplained,” said Dr. Schwab. Specifically, in the military, unlike the civilian population, whites tend to sustain more TBI than blacks, Dr. Schwab noted.
A particular issue now, said Dr. Schwab, is that troops are reporting multiple TBIs from multiple deployments, so in many cases they are facing recovery from more than one TBI.
BIOLOGICAL FACTORS: GENDER DIFFERENCES
Biological factors likely play a role in gender differences related to recovery after TBI, said Helen M. Bramlett, PhD, assistant professor in the Department of Neurological Surgery at the Miami Project to Cure Paralysis of the University of Miami Miller School of Medicine. “In our laboratory we have reported that intact female rats demonstrate a significantly smaller contusion volume compared to males and ovariectomized rats.”
Estrogen and progesterone may have neuroprotective properties because the hormones decrease excitatory pathways, Dr. Bramlett explained. Estrogen inhibits the NMDA (N-methyl D-aspartate) receptor and inhibit lipid peroxidation, she said.
Dr. Bramlett reported in the journal Pathophysiology in July 2005 that estrogen and progesterone tend to reduce brain edema in rodent models of TBI. She said that hypothermia does not confer significant neuroprotection after TBI in intact female rats, but it did so in male rats and ovariectomized female rats.
As for observed racial differences in TBI, Dr. Bramlett said there may be genetic variations within ethnic groups relating to factors such as brain edema — variations that need investigation.
RECOVERY FROM TBI
“Limited data are available for the experience of women and ethnic-racial minorities during recovery from traumatic brain injury,” emphasized Kathleen R. Bell, MD, professor and medical director of Rehabilitation Medicine, Ambulatory Care, and the Brain Injury Rehabilitation Program at the University of Washington Department of Rehabilitation Medicine.
Dr. Bell warned that, in women, TBI — depending on its severity — can lead to dysfunction of the frontal lobe that could impair memory and reason and lead to impulsivity. For example, she said, a woman with a TBI injury might neglect contraception and could be taken advantage of sexually.
“African-Americans and Hispanics have worse deficits and higher rates of disability than white Americans even after controlling for socioeconomic status and severity of injury,” Dr. Bell continued, perhaps because “there may be limitations to access for services for minorities,” she said. But she also noted that there are confounding variables relating to race and TBI, including the effect of the TBI person's neighborhood. Is it marked by continuous violence, danger, and unrest? Or is it tranquil and supportive?
David O. Okonkwo, MD, PhD, assistant professor, director of neurotrauma, and director of spinal deformity in the Department of Neurological Surgery at the University of Pittsburgh Medical Center, agreed that the impact of the surrounding neighborhood, as opposed to ethnicity, can affect recovery from TBI.
Race by itself, he said, is a tricky variable fraught with problems. “My mother's German, my father's Nigerian, and my wife is Dutch,” said Dr. Okonkwo. So, he asked, what race would his children claim?
“Genotype may be the most important factor when it comes to recovery from TBI,” he said. “You can't fake your genotype.”
TBI: ‘A LIFELONG SITUATION’
Regardless of a patient's gender, ethnicity, or socioeconomic status, “TBI is a lifelong situation, especially severe TBI,” said Henry Lew, MD, PhD, chief of physical medicine and rehabilitation in the Boston VA Healthcare System.
Dr. Lew cited these among other questions and challenges for investigators on TBI: What are the differences between concussive and blast-related TBI? What are the neurobehavioral factors which correlate with imaging markers? Given that there is overlap between TBI and post-traumatic stress disorder (PTSD), what imaging markers distinguish TBI from PTSD? What are the factors that predict readiness to return to active duty?
In addition, said Dr. Lew, there is a question about the best time to start treatment for a person who has had a TBI. “Sometimes if a patient has just come in [following the TBI] you don't want to overwhelm him,” noted Dr. Lew.
He said all these questions are ripe for clinical research studies, and strongly urged increased funding to conduct this research. He also recommended increased access to TBI databases for investigators conducting the TBI studies.
• Bramlett HM. Sex differences and the effect of hormonal therapy on ischemic brain injury. Pathophysiology
• Empey PE, McNamara PJ, Hatton J, et al. Cyclosporin A disposition following acute traumatic brain injury. J Neurotrauma
• Utagawa A, Truettner JS, Bramlett HM, et al. Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats. Exp Neurol 2008;211(1):283–291. E-pub 2008 Feb 20.