The Injured Brain

WE WALK AROUND EACH DAY WITH OUR BRAIN, a three-pound organ with the consistency of custard, sloshing about inside a sealed chamber of cerebrospinal fluid. It’s protected, though only just, by a tough outer membrane, the dura mater, and by the skull, a layer of bone a quarter-inch thick. With every movement we make—sitting, rising, running, stumbling—the brain moves within the fluid, accelerating, shifting and twisting in response to external forces. But the brain is unlike other organs. It controls thought as well as physical function—it’s the seat of personality and identity. So when its integrity is violated, we may emerge, in almost every sense, as someone else.

Trauma sometimes comes as a penetrating injury—as it did in the form of the nine-millimeter bullet that last winter tore through the brain of U.S. Representative Gabrielle Giffords, entering the front of her head and exiting the rear. Other times, there may be a closed head injury—for example, from striking a car dashboard during an accident, as happened to Todd Lamkin of Holliston, Mass., who was driving home from a holiday party in 2003 when his car slammed into a tree. Brain tissue will bruise when it smashes against the skull, and blood vessels may hemorrhage. In the days, weeks and months that follow, there can be a cascade of secondary damage, with brain swelling (edema), increased intracranial pressure (which can cause high blood pressure), infection, epilepsy, low blood pressure (which can starve the brain of oxygen) and hematoma (a swelling of clotted blood), as well as cardiac and lung changes.

Public awareness of brain injuries was surging even before Giffords was shot. Concussions in sports have become a hot topic because of the growing realization that such head injuries, once considered relatively minor, can have lifelong implications for any athlete, whether playing in a youth soccer league or on a professional baseball team. And, in fact, some kind of traumatic brain injury, or TBI, happens to an estimated 1.7 million people in the United States each year, according to the Centers for Disease Control and Prevention. The top two causes for civilians are falls and motor vehicle accidents. During the military conflicts in Iraq and Afghanistan, blast-related injuries—from artillery, improvised explosive devices, rocket-propelled grenades and mines—have become common, affecting as many as one in five of those serving in war zones. That has led the Department of Defense to ramp up spending on TBI research, while Congress has increased funding at the National Institutes of Health and for TBI rehabilitation programs.

Though scientists have been studying traumatic brain injury for decades, there is still not a single therapeutic approach that has been proven to speed recovery or change TBI outcomes, says Joseph Giacino, director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital in Boston. That’s not to say people don’t get better—many do. Rather, in most cases, the reason for improvement remains a mystery.

Still, there’s progress across many fronts. Physicians and researchers are studying exactly what happens in the brain when it is injured, both in the immediate minutes, hours and days after the traumatic event and in the months and years following injury. They now recognize that TBI is not just an event, it’s a disease—and its symptoms continue for much longer than previously believed. Diagnosis presents its own unique challenges, so scientists are working toward identifying specific markers in the blood associated with brain injury. Clinical studies are gauging the effectiveness of several drug regimens that, anecdotally at least, have seemed to speed recovery for some patients. Meanwhile, cognitive rehabilitation is evolving, utilizing new insights into how the brain recovers to design individualized treatment programs that focus on the whole person and address both emotional difficulties and physical symptoms.

PHYSICIANS CLASSIFY TRAUMATIC BRAIN INJURIES AS mild, moderate or severe. Three out of four injuries, including concussions, are considered mild according to diagnostic guidelines, though physicians are beginning to recognize that even mild TBIs may trigger emotional difficulties, personality changes and dementia. Patients with mild trauma may or may not briefly lose consciousness, and even if they aren’t knocked out, they’re likely to feel dazed, with their thinking slowed and disorganized. They can suffer memory loss that lasts as long as a day.

Those meeting the definition of moderate traumatic brain injury lose consciousness for between 30 minutes and 24 hours, and their memory loss may persist for a week. Some 15% of all TBIs fall into this category, while a final 10% of brain injury patients have injuries classified as severe.

Victims of severe TBI will pass out at some point while the trauma is occurring and will remain in a coma, defined by a lack of functioning of the patient’s reticular activating system, the arousal part of the brain responsible for sleep-wake cycles. These patients’ eyes don’t open, and they require life support, because vital functions, including breathing, body-temperature regulation and heartbeat, don’t work properly. “In coma there are no treatments,” says Giacino, while in the case of less grievous injuries, physicians may be able to begin assessing damage and aiding recovery with drug treatments once a patient is medically stable. “You simply wait for the system to bring the brain back online,” he says.

For Giffords, that happened remarkably quickly. Within days of the shooting, her physicians reported that she was moving her arms and legs, sitting up and responding to friends and family members. Shortly afterward, her breathing tube was removed. In more typical cases, though, it may take two to four weeks for severely injured patients to open their eyes, indicating that the reticular activating system is working again, and to breathe on their own. But if there’s no purposeful behavior or language to indicate that cognitive faculties are functioning, patients are diagnosed as being in a vegetative state, sustained by a bare minimum of body functions (sleep-wake cycles, breathing, temperature regulation). If they show some evidence of conscious awareness, even if it’s inconsistent or subtle—being able to follow an object around the room with their eyes, for example, or responding to commands about half the time—patients will be considered minimally conscious.

Often, because they’re located near the surface, at the front and sides of the head, the frontal and temporal lobes are particularly vulnerable and may be most affected by a traumatic injury. The frontal lobe is responsible for executive functioning (planning, organizing and executing tasks, pulling together thoughts, prioritizing actions), motor functions, language and memory, and is considered the seat of personality. The temporal lobes contain the hippocampus, crucial to memory, and the amygdala, which helps regulate emotion.

When those parts of the brain are penetrated or shaken, symptoms very often include difficulties with problem solving, information processing and thinking; short-term memory and attention may also be compromised. There may be issues with speech, walking, coordination and strength. Giffords is currently relearning how to put complex thoughts into words, and she uses gestures to supplement her sentences. Lamkin couldn’t raise his right arm above his head for months, and he still walks with a limp.

If the frontal lobe is affected, a person may feel “like someone else” after an injury. Likes and dislikes, passions and desires may have changed significantly—alterations that can be as disturbing to family and friends as to victims themselves. Patients often have trouble processing sensory input; seizures, chronic pain and sleep disorders are common, as are emotional problems. Patients may be impulsive, irritable or aggressive. Lamkin says regulating his emotions and controlling impulses were major challenges of his recovery. “I only had two speeds,” he says. “I was either doing nothing or I was very agitated and excited about what was going on. And I would think of things and then immediately do them. I would say things I shouldn’t say, do things I shouldn’t do.”

TREATMENT FOR TBI OFTEN INVOLVES DRUGS USED TO TREAT OTHER neurological disorders, despite a lack of strong evidence that they actually help recovery. That’s the case with amantadine, an antiviral drug in use since the 1960s to treat influenza that more recently became a therapy for Parkinson’s disease. Clinicians prescribe it for patients with mild, moderate and severe TBI, although it’s unclear how and why it works for brain injuries or Parkinson’s. Researchers believe the drug may help because it increases the release of dopamine and stimulates dopamine receptors, which can affect attention, alertness and motivation. A randomized, double-blind, placebo-controlled study to determine whether amantadine positively affects irritability, aggression and other behavioral problems in patients with TBI is under way. Another double-blind study, conducted on 184 patients with severe TBI to determine whether amantadine improves recovery, was directed by Spaulding’s Giacino. The results, presented at the American Academy of Neurology annual meeting last April, suggested that amantadine resulted in faster recoveries, with patients in both vegetative and minimally conscious states showing more behaviors associated with full consciousness, such as following commands, recognizing objects and producing intelligible speech. Though the study lasted just six weeks, the benefits of amantadine continued even after the drug was discontinued, although the rate of improvement slowed.

Another drug showing promise is methylphenidate, usually used to treat attention deficit disorder. In a study completed in 2004, John Whyte, director of the Moss Rehabilitation Research Institute in Philadelphia, considered the effects of methylphenidate on patients with moderate to severe TBI. Not only did the patients’ ability to pay attention improve, but the drug also increased the speed of processing—the time required for the brain to take in information and act on it. Another study, at Monash University in Australia, showed similar effects for methylphenidate, and according to Mel Glenn, director of outpatient and community brain injury rehabilitation at Spaulding, the drug’s apparent ability to improve processing speed makes it particularly intriguing.

A third potential treatment was discovered serendipitously. When zolpidem, used to combat insomnia, was prescribed for patients with severe TBI to help them sleep, some showed a very different effect: Zolpidem actually restored their consciousness, and for as long as they continued to take the drug they remained awake and aware. “In some cases, patients went from rarely following commands, having no speech and little movement, to being at a near-conversational level, being able to perform self-care and following instructions consistently,” Giacino says.

SPURRED BY INCREASES IN FUNDING FOR TBI RESEARCH, trials of these and other medications could lead to a better understanding of which injuries may benefit from which treatments. Yet even as studies continue, there have been significant advances in treating brain injuries through new approaches to cognitive rehabilitation, a process by which physicians and therapists help patients learn to live with and compensate for their injuries.

Standard rehabilitation programs aim to accomplish two things. The first is to restore damaged areas of the brain through direct attention training, usually provided by a computer program that drills patients in specific skills to help restore their abilities to focus, process information and pay attention. At the same time, therapists teach compensatory strategies—“work-arounds”—that acknowledge limitations but seek alternative ways to function in the everyday world. Most programs focus on improving cognitive functioning and such practical life skills as dressing, balancing a checkbook and driving a car.

Newer holistic rehabilitation programs add an extra element, helping patients devise individualized strategies to deal with their difficulties. The goal is not only to overcome cognitive impairments but also to create a meaningful, satisfying life even when issues related to brain injury persist. Such programs typically involve interdisciplinary teams that may include speech-language pathologists, occupational therapists, physical therapists, psychologists, psychiatrists, social workers, case managers and even music therapists, therapeutic recreation specialists and low-vision specialists. “There is an emphasis on integrating many kinds of therapy, and all the therapists take the same approach and stick to the same message,” says Keith Cicerone, director of neuropsychology at the JFK Johnson Rehabilitation Institute and New Jersey Neuroscience Institute at JFK Medical Center in Edison, N.J.

An interdisciplinary approach makes sense, says Cicerone, because it enables clinicians to integrate interventions that until recently had been handled separately. “We now recognize you can’t treat one deficit by itself,” he says. A patient who has trouble remembering will likely also have problems with attention, and together those issues compromise the ability to make decisions and plans, organize thoughts and prioritize tasks. “These are not secondary phenomena,” Cicerone says. “They are direct effects of the brain injury, and the distinctions we’ve tended to make between cognitive functions, psychological functioning and emotional reactions are somewhat arbitrary.”

There also is a new understanding among clinicians that people’s attitudes about their ability to recover influence their progress. Patients who have confidence that they can improve in rehabilitation tend to be the ones who show the most progress, so clinicians now may begin trying to foster such feelings early in therapy. They’ll emphasize that recovery from a brain injury is a lifelong process that takes strength, perseverance, courage and motivation. And when it’s not possible for patients to change their abilities, they may need to adjust expectations. “We make it clear to patients that we are going to teach them how to live their lives despite the challenges,” Cicerone says.

In a randomized controlled trial that compared standard programs with the holistic approach, Cicerone’s team showed that a holistic program enabled patients to function better in their communities and to feel more satisfied with their lives. Similarly, a new approach involving metacognition—thinking about thinking—encourages patients to learn a different way to work with their own minds. So, for example, rather than trying to increase the speed at which patients can process information (which may be impossible to do directly), therapists teach them to manage delays. By paying attention to each task separately, for example, Lamkin can cope. “I’ll talk myself through something so I don’t forget what I’m doing,” he says.

When a patient’s job requires communicating complex ideas, multitasking or quick thinking, recovery can be especially difficult. “If you’re a physician or a pilot,” says Ross Zafonte, chief of physical medicine and rehabilitation at Massachusetts General Hospital and Spaulding, “you’re flipping four or five different thoughts in the air at one time, and you have to continuously bounce among them. That’s a very different level of functioning than just having a nice conversation with someone, and it’s awfully hard.”

Recently, working with a physician who had suffered a traumatic brain injury, Cicerone helped set up a structured interview for taking patient histories—instead of letting the patient take the lead, the doctor now works through a detailed list of specific questions that helps him make sure not to miss relevant pieces of information. “We emphasized that there is a benefit to taking a more deliberate approach,” Cicerone says.

These new methods of cognitive rehabilitation, often combined with drug therapies, are contributing to what most scientists consider slow but steady progress in treating traumatic brain injuries. While Giffords’s family has not revealed many details of her treatment, by all reports she has come a long way back from a devastating injury. And after several years of struggle, Lamkin, too, has made considerable progress. He now takes pleasure in things he enjoyed before he was hurt, especially landscaping and stonework, and says he has learned to focus on one thing at a time, giving all his attention to each task. “I feel very whole these days,” Lamkin says. “I think I’m as recovered as I’ll ever be. I’m not the same Todd I was precrash, but I feel competent and satisfied with my life overall.”