Kirsten Timmons was navigating a frozen overpass one night when a passing car skidded out of control and slammed into her vehicle. As her car came to a stop, Timmons’s head probably snapped around its own axis, decelerating sharply when it struck the seat-belt holder next to her.
The impact produced a severe traumatic brain injury (TBI), knocking Timmons out and setting the stage for lasting brain damage. Luckily for her, emergency services rushed her to the hospital within an hour of the crash, greatly boosting her chances of survival. Prompt medical attention can, for example, prevent dangerous pressure buildup in the brain, remove perilous blood clots and thwart other life-threatening consequences of severe TBI.
After eight days in a medically induced coma, Timmons woke up to a daughter she did not recognize. Today, three years after the accident, Timmons knows her child but struggles to concentrate, recall numbers and perform simple calculations—disabilities that ended her career as a nurse practitioner. Similar problems often plague victims of mild TBI [see “Impact on the Brain,” by Richard J. Roberts]. “We’re not bad at getting people to survive [severe TBI],” says neurologist David Brody, a member of Timmons’s medical team at Washington University in St. Louis, “but we’re worse at getting good cognitive recovery.”
The best hope for improved healing lies neither in new medications, which have been disappointing so far, nor in exotic fixes involving stem cells and neural regeneration, which are at least a decade away, researchers say. Rather the biggest gains will likely result from advances in emergency room and intensive care practices that curtail the secondary damage from TBI. The methods include slowing the brain’s metabolism with cooling techniques, removing part of the skull to relieve intracranial pressure and injecting an experimental polymer “glue” to repair damaged brain cells.
After a severe TBI, such as the one Timmons sustained, blood vessels broken in the initial injury can bleed into the brain, raising pressure inside the skull. These vessels also may dilate to feed oxygen-starved brain regions, increasing brain volume further. If the swelling goes unchecked, the brain pushes out in every direction. Not only does this expansion complicate oxygen delivery, but it may also push the brain through the only available hole, at the base of the skull, crushing the brain stem and killing the patient.
Initial treatment to prevent or relieve such swelling includes an agent such as a diuretic that extracts fluid from the blood and elevating the patient’s head so that blood flows away from the brain. In addition, however, doctors may employ any of various techniques to slow metabolism and thereby reduce the brain’s demand for oxygen-laden blood.
A standard way to reduce the metabolic activity of brain cells is to inject a patient with a sedative, but some doctors are also experimenting with quieting the brain by lowering a patient’s body temperature, called hypothermia therapy—say, by injecting chilled saline or covering a patient with a blanket that circulates cool water. Cooling acts as a brake on cellular metabolism. People who have fallen into icy lakes, for instance, often recover from long periods without breathing because the cold temperatures dramatically decrease the brain’s demand for oxygen.
A 2007 analysis by the Brain Trauma Foundation published in the Journal of Neurotrauma suggested that although hypothermia therapy had little or no effect on survival rates for TBI victims, it did improve mental capacity and responsiveness among survivors. In addition to slowing brain metabolism, hypothermia therapy also appears to suppress inflammation and other chemical reactions that can damage brain cells, according to intensive care specialist David Menon of the University of Cambridge.
When faced with a persistent pressure problem, physicians may resort to surgery. In one relatively simple technique, physicians drill a small hole in the base of the skull to drain excess cerebrospinal fluid. But in the most vexing cases, surgeons may remove a large flap of bone from the top of the skull so that the brain can expand into a larger space, effectively decompressing the brain and preventing it from crushing itself. An international team of doctors led by University of Cambridge neurosurgeon Peter Hutchinson is now comparing the efficacy of bone-flap surgery with that of last-resort nonsurgical remedies (such as drug-induced comas) in a 600-patient trial that the researchers aim to complete in 2012.
In the wake of a TBI, the release of biological poisons also threatens brain function: toxins ooze out of ruptured neurons and wreak havoc on neighboring cells. Some clinics monitor these minute chemical imbalances in the spaces between brain cells. In one such technique, intensive care specialists insert a millimeter-thick tube through the skull. The tube collects trace amounts of chemicals in the brain and delivers them to a nearby microdialysis machine for analysis.
Keeping a close eye on brain chemicals, such as the neurotransmitter glutamate, that exude from dying cells can help doctors fine-tune their treatments. Abnormally high levels of glutamate, for example, usually indicate a rapid rate of cellular damage. Such a sign might prompt physicians to try more aggressively to save cells by cooling the brain to decrease oxygen demand or boosting ventilation rates to improve oxygen delivery. Or if microdialysis indicated that cells near a blood clot were fading quickly, doctors might remove the clot to stem
Thus, many specialists believe that tracking a TBI patient’s brain chemistry can promote good cognitive recovery. At Addenbrooke’s Hospital in Cambridge, England, the introduction of a specialized brain injury intensive care unit in which doctors routinely perform microdialysis raised the fraction of TBI survivors who retained their independence from 40 to 60 percent. But no one really knows if microdialysis accounts for the difference. “There is not yet a consensus on whether [microdialysis] should be used for routine care and, if so, what value it adds,” Brody says. (The technique is more typically used in basic science experiments.)
In addition to responding to chemical warnings, ICU doctors ideally would like to prevent the release of toxic compounds from damaged cells in the first place. Biomedical engineer Richard Borgens of Purdue University and his colleagues are developing a technique that would repair cell membranes soon after injury using polymers such as polyethylene glycol. Just as bicycle tube sealant fills holes in bicycle tires, the polymer seals punctured membranes, restoring their ability to contain harmful chemicals.
In 2001 Borgens’s team confirmed in spinal cord tissue that polyethylene glycol mechanically mends burst cell membranes. More recently, in a study published in the June 2008 Journal of Biological Engineering, the researchers tested the technique on brain-injured rats. They injected the animals with polyethylene glycol at various time points after the injury. Rats given the injections within four hours navigated mazes, which test their spatial learning and memory, more proficiently than untreated rats did. No one knows whether polymer therapy would produce similar results in humans, but the scientists hope that ambulance workers might one day inject the polymer at the scene of an accident, jump-starting repair even before a patient reaches the hospital.
For now, improving a TBI victim’s quality of life often means extensive occupational, speech and physical therapy. These remedies can help form new neuronal links in the brain to circumvent the damaged pathways, rebuilding connections that underpin important skills and thought patterns. “We think there’s more than one way to get from A to B” in the brain, Brody says. “You’ve got [neuronal] wiring that goes from A to C and C to B, and you haven’t used it much—but with practice it gets stronger.”
For Timmons, such interventions have met with only partial success. The former nurse can now carry on a normal conversation and care for her daughter, but her injury has left her unable to manage the stressful multitasking necessary to return to work. She also continues to struggle to add or subtract numbers, a deficit she called “a major reality check” because she had been good at performing such calculations before the accident. Timmons describes her life as a frustrating blend of independence and disability.
Doctors hope that advances in intensive care for TBI victims will reduce the daily aggravations of patients like Timmons. Studies that point to the best low-tech TBI treatments and that evaluate new techniques to prevent secondary brain damage should help intensive care specialists create a standard of therapy that will improve the lives of thousands of brain injury victims every year.