Between our catastrophic injury and birth injury practices, we spend a lot of time at the firm immersed in the science and medicine of brain damage. Just as consciousness and dualism have vexed philosophers for ages (* see my comment), the real causes and treatment of brain injury have remained elusive for generations. There’s a reason for the phrase ‘not exactly brain surgery‘ — brain surgery is notoriously unpredictable.
After reading Jane Rosett’s compelling article in The New York Times about ‘starting again’ after injuring her right temporal lobe in a car accident (sample: “traumatic brain injuries destroy connections between and within people — so how are we to build a self-empowering community?”), and Diane Wyzga’s post about the Going the Distance documentary, I thought I’d write about some of the latest developments in the field. Rosett’s article (and David L. Brown’s documentary) seems to be part of a larger trend in the diagnosing, treatment, and public perception of brain injuries.
Traumatic brain injuries (TBI) are particularly difficult to treat in a meaningful way. Even treatments that seem obvious, like reducing intracranial pressure, don’t work the way we think they should. In April this year, the New England Journal of Medicine published a study that randomly assigned 155 diffuse traumatic brain injury patients to either undergo decompressive craniectomy or standard treatment. The results were surprising: the patients’ intracranial pressure went down and they left the intensive care unit faster, but six months later they scored lower on the Extended Glasgow Outcomes Scale. Sometimes it seems we haven’t progressed much since ancient trepanation: cut a hole in the patient’s head and hope that makes them feel better.
Three months after that study, the Harvard Gazette reported on two studies which may have identified some of the reasons why TBI doesn’t respond to the sorts of mechanical treatments (like surgery to reduce pressure, placing a shunt, etc.) we assume would fix the problem. In short, TBI doesn’t just damage the structures of the brain, it damages the cells on a cellular level:
Bioengineers at Harvard have, for the first time, explained how the blast of an exploding bomb can translate into subtly disastrous injuries in the nerve cells and blood vessels of the brain. …
Papers published in the journals Proceedings of the National Academy of Sciences (PNAS) and the Public Library of Science’s PLoS One provide the most comprehensive explanation to date of how abrupt mechanical forces cause catastrophic physiological changes within the brain’s neurons and vasculature. …
When the brain encounters a jarring force, such as an exploding roadside bomb, its delicate tissue slams against the skull. The result, if the patient survives, can be a temporary concussion, a more dangerous hemorrhage, or long-term TBI, which can lead to the early onset of Parkinson’s or Alzheimer’s diseases. …
Parker’s research has demonstrated that the forces unleashed by an explosion physically disrupt the structure of the focal adhesion complex, setting off a chain reaction of destructive molecular signals within the nerve cells of the brain.
The papers themselves are available online: A Possible Role for Integrin Signaling in Diffuse Axonal Injury and Blast-induced phenotypic switching in cerebral vasospasm.
It’s more than a little surprising to see that an explosion could, in some instances, not injure the structures of the brain, and not even break up the cell, but nonetheless cause changes in the way the cell operates, but that seems to be the case:
The blast from an explosion creates a surge in blood pressure, which stretches the walls of the blood vessels in the brain. To study this, Parker’s team of bioengineers built artificial arteries, made of living vascular cells, and used a specialized machine to rapidly stretch them, simulating an explosion. While this stretching did not overtly damage the cellular structure, it did cause an immediate hypersensitivity to the protein endothelin-1.
That might also explain why war veterans have a higher rate of dementia: not only have they suffered TBI, but they’ve suffered blast-induced TBI, which causes a cerebral vasospasm that induces the protein hypersensitivity. Even better, the researchers identified potential treatments, at least for the integrin disruption, in the form of an enzyme inhibitor administered soon after the blast.
As the researchers noted, these results have been expected for some time, they’ve just been difficult to prove. As we know from our birth injury work, one of the ironies of hypoxia is that the worst damage often isn’t caused by the deprivation of oxygen but by the reperfusion of oxygen once the asphyxia ends. The latest treatment for hypoxic ischaemic encephalopathy thus relies upon cooling the head or the body to slow down the metabolic processes that happen when the oxygen returns to the brain. The lower temperature minimizes the production of free radicals and gives the brain time to adjust, preventing apoptosis.
It’s all part of what appears to be a new era of TBI treatment. Last month two interesting studies discussed changing attitudes on the opposite ends of the spectrum of brain injury. A study in the Canadian Medical Association Journal found widespread variation in the circumstances under which life-sustaining therapy was withdrawn and urged more restrain in the practice. Around the same time, the Centers for Disease Control reported a 60% increase in the past ten years in “emergency department visits for sports– and recreation–related traumatic brain injuries, including concussions, among children and adolescents.” Ironically, that increase emergency room admissions might be a good thing: the CDC believes the increase is due primarily to parents and coaches of football — which is notoriously dangerous, consider the NFL players — and soccer (also worrisome) reporting injuries that were previously believed to be “minor” and appropriately taking their children in for evaluation.
Of course, TBI treatment can only go so far — the only reliable way to reduce the consequences of TBI is to reduce the incidence of TBI. But it does appear that, over the next decade or so, we will see a sea change in the treatments available and the patient outcomes, like we saw over the past decade with head cooling programs and birth injury.