Gray Area

As research begins to unlock the secrets of traumatic brain injury, many puzzles remain.

Dr. Jonathan Fellus, director of brain-injury services at Kessler Institute of Rehabilitation in West Orange, examines a brain scan.
Photo by John Emerson.

As candidates for science’s final frontier, the bottom of the ocean and intergalactic space have a lot going for them. But neither packs as much extraordinary complexity and mystery into as small a space as the gelatinous, three-pound mass we call the human brain.

Containing billions of nerve cells transmitting electrical and chemical signals at up to 200 miles per hour, the brain also accommodates about a trillion supporting (or glial) cells, as well as glands essential to the regulation of hunger, thirst, growth, memory, sexual response, waking, sleeping, and sensory experience.

Enclosed in the impossible-to-misplace breadbox known as the skull, the brain is well armored against minor assaults. But strong as it is, the skull is no match for the impact of auto crashes, full-speed helmet-to-helmet collisions on a football field, or the blast wave of a roadside bomb.

We know much more about traumatic brain injury (TBI)—and the brain itself—than we did a century ago. But our ability to undo brain trauma caused by external forces,  internal bleeding, or oxygen deprivation is still limited.

“Twenty years ago, for the most part, patients with severe TBI didn’t survive, and even if they did, there wasn’t much you could do for them,” says Dr. Caroline McCagg, medical director at the Center for Head Injuries at JFK Medical Center in Edison. In the 1980s, most victims of TBI were treated with the same protocol used for stroke patients. “It took a while for us to recognize that these patients are just much more complicated,” McCagg notes.

“Brain injury is a crapshoot,” admits Dr. Jonathan Fellus, director of brain injury services at Kessler Institute of Rehabilitation in West Orange. “A spinal-cord injury is a spinal-cord injury,” he explains, “and 99 percent of the time you know what you’re going to end up with from the get-go.”

TBI, on the other hand, might result in coma, minimal consciousness, a vegetative state, or a spontaneous recovery. At present, treatment of brain injuries is neither systematized nor standardized. But researchers, neuroscientists, and doctors—many of them, as it happens, working in the Garden State—are beginning to improve the odds for even the most severely injured. 

The revolution in TBI treatment began in the 1990s, which Congress officially dubbed the Decade of the Brain. “When I was a neuropsychology intern in 1980, neurosurgery had very high mortality and morbidity rates,” says Dr. Philip De Fina, founder of the International Brain Research Foundation (IBRF), a think tank with headquarters in Edison. Government initiatives and funding helped spur advances in neurosurgery, including laser-guided microsurgical techniques. “More people are now surviving brain injuries, which means we’re starting to make breakthroughs in treating them, and diagnosing them prior to treatment,” De Fina says.

One difficulty of diagnosing the extent of a brain injury—or even whether the brain has been traumatized—is that symptoms may manifest themselves over time and are not always present in the immediate aftermath of an accident or battlefield incident. Even the determination of a patient’s degree of consciousness—once considered fairly straightforward—is being recognized as a gray-matter gray area.

At the bedside of brain-injured patients, doctors used to ask rudimentary questions (“What’s your name?”) or issue basic commands: Close your eyes, open your mouth, raise your hand. If the patient didn’t respond verbally or move in response to a command, he was considered unconscious, and sometimes very little could be done except hope for a spontaneous recovery. The Coma Recovery Scale, developed at JFK sixteen years ago by a team including Dr. Joseph T. Giacino, now associate director of neuropsychology at JFK and of the New Jersey Neuroscience Institute, changed diagnosis by recognizing subtler signs of consciousness.

Now doctors note a patient’s ability to track an object visually or to manipulate objects with fingers even when they can’t raise their arm. That’s important, explains Giacino, “because TBI patients who do show even subtle and inconsistent signs of consciousness early in their recovery tend to have considerably better outcomes after a year than those who don’t.” It also has an impact on treatment: Doctors are more likely to try to develop systems of communication for patients who display signs of consciousness, however minimal. And being able to communicate with a patient, in turn, is essential to effective treatment.

Giacino and his colleagues are working on a more complex diagnostic tool, which has already yielded the kinds of results that produce headlines. He and his collaborators, including Nicholas Schiff of Cornell and Joy Hirsch of Columbia, are using functional MRIs to search for signs of consciousness in patients who don’t display any of the bedside criteria. The group has already witnessed several patients who appeared to be in a vegetative state by traditional diagnostic tools, but when listening to a family member speak or being asked to visualize a specific activity (like playing tennis or walking through the rooms of their house), displayed the same brain activity a normal, conscious individual would in response to the same stimuli.

The war in Iraq also has led to progress in the diagnosis and treatment of TBI. Improved armor and field expertise, as well as advances in rehabilitation, have allowed more soldiers to survive head injuries that would have killed them in previous conflicts. (In fact, doctors are calling TBI the war’s signature injury.)
Staff Sergeant Juan Roldan is a case in point. Assigned to a security detail in Sadr City, he saw a spike in sectarian violence in the days leading up to Saddam Hussein’s scheduled execution on December 30, 2006. On the night of December 29, he was in command of a Humvee.

“We rolled out, and I was in the last vehicle,” he remembers. “We got into some serious stuff, and out of nowhere the explosion came.” The source of the blast was a powerful improvised explosive device, which blew him 270 yards from the passenger seat of the truck. When a fellow sergeant found him, one of his legs was gone and the other, Roldan says, was “hanging by two threads.”  His rescuer applied tourniquets to each leg, threw Roldan into another Humvee, and raced to the casualty collection point.

“I died in Iraq,” Roldan says, and he’s not speaking metaphorically. He lost more than 60 percent of his blood, and by the time he arrived at the collection point, his heart had stopped beating. He had also suffered spinal cord damage, pelvic trauma, and severe traumatic brain injury.

After being stabilized in Iraq, Roldan was transferred to Germany and then to Walter Reed Army Medical Center in Washington, D.C. Roldan began to improve after he was weaned from an excess of pain medications. But his doctors suspected that, given the right environment, he could make a fuller recovery.

They contacted Jonathan Fellus, who is unlikely to forget the phone conversation: “Walter Reed called and said, ‘We want to send you this young man who was exposed to an IED, had a bilateral trifemoral amputation, severe traumatic brain injury, complete spinal cord injury [meaning no motion or sensation below the point of injury], an open wound in his back, and a colostomy bag. And he’s 22.’”

There was a time when a doctor might see a case as severe as Roldan’s once in a career. Today, cases like his have become almost commonplace. Often the most challenging ones find their way to doctors and therapists in the Garden State.

“The worst things that can happen to the brain will ultimately end up here,” says Fellus of the Kessler Institute. Nattily dressed in pink shirt and floral bowtie, he doesn’t look like anybody’s idea of a mad scientist, though that’s exactly how he describes himself. He works hands-on with patients to restore brain function using an individualized approach he describes as “creative, aggressive, no holds barred—a kaleidoscope of interventions to assault the injury from all sides.”

The treatment protocol he employs was developed in partnership with the International Brain Research Foundation under De Fina’s leadership. “The brain is essentially electrochemical, so we use both electrical and chemical interventions,” De Fina explains. “We take medications from many different neurological disorders, including psychiatric disorders like depression and anxiety, conditions like Parkinson’s, and so on, and we use electrical stimulation techniques that are applied externally, so that they’re noninvasive.”
In 2005, De Fina and his colleagues applied the protocol to a deeply comatose patient and succeeded in reviving him. This was, of course, the result they’d been hoping for, but they were still somewhat astonished about actually pulling it off. “It was an amazing feat,” he says.

It also represented an epiphany for De Fina, who realized that there was no organization devoted specifically to working with victims of severe brain injury or to developing advanced techniques to help them recover. That same year, he founded the IBRF to marshall the world’s top neuroscientists and research facilities to advance cutting-edge brain research.

In the past four years, the IBRF, working with the Kessler Institute, has awakened 27 of 33 comatose patients. (Its most famous patient may be Steven Domalewski, the Wayne Little League pitcher who was hit in the chest by a line drive in 2006, suffered cardiac arrest, fell into a coma, and was revived three months later.) What is striking about the IBRF protocol is that it draws from other medical specialties as well as from approaches that seem decidedly New Age.

Many of the medications traditionally given to TBI patients, including drugs to control seizures, have sedative side effects; some of those medications are still being prescribed today. The first thing Fellus, De Fina, and their colleagues do is remove those meds from the regimen, prescribing instead what Fellus calls “aggressive stimulants”—drugs like rasagiline and amphetamine—to boost natural neurotransmitters such as dopamine and adrenaline. By so doing, they hope to “ram maximum energy through whatever connections are left.” They’ll often put patients on as many as ten different meds at once in the hope of finding one or two that actually get the synapses firing. 

To stimulate the language area of the brain and, in turn, draw more oxygen to the damaged area, doctors using the IBRF protocol might attach an electrical stimulator to the wrist to send pulses through the right median nerve directly to the zone of the brain controlling the metabolism of oxygen and glucose. De Fina and his colleagues around the world have found that brain-injured patients experience a 20 to 30 percent decrease in oxygen and glucose. “As a result,” he says, “brain cells die off at a great rate.” He suspects that the death of brain cells from oxygen and glucose depletion sets off a downward spiral from which many patients never recover.

De Fina also uses “neutraceuticals”—herbs and other nutritional supplements that have a pharmaceutical effect. These include megadoses of fish oil to counteract brain inflammation and the Chinese herb huperzine to increase brain arousal. De Fina says the substances he uses have been approved by the FDA for the treatment of brain injury. Fellus, however, says, “95 percent of what I do every day is off-label as far as the FDA is concerned.”

One of the most valuable weapons in the new treatment arsenal involves a complex mix of brain-imaging techniques that give doctors a unique way to chart progress. “The process of therapy in this field is so slow,” says De Fina, “that it could be discouraging if we couldn’t see [progress] occur almost immediately through the use of brain maps.”

By using functional MRIs of the brain [which show real-time activity] to measure blood flow and PET scans to detect metabolic activity, doctors can literally see therapy starting to work long before a patient first opens his eyes or is able to tap his finger on command.

At JFK, Joseph Giacino and his team are working on another promising intervention—deep brain stimulation, or DBS. Traditionally used to tame the tremors of Parkinson’s disease, DBS involves implanting an electric stimulation device on the thalamus, a part of the brain that drives higher cognitive functions. In one highly publicized case, described last year in the journal Nature, Giacino used DBS on a patient who was in what neurologists term a minimally conscious state—a condition characterized by only intermittent evidence of awareness.

After a year of the therapy, the patient was beginning to speak and feed himself and was consistently communicating with staff and family. Giacino’s theory is that DBS works either by increasing function in damaged areas of the brain or by reaching healthy areas that have been left isolated by damage to surrounding tissues.

However promising these new treatments are, progress for many patients remains elusive. Christopher Hammett survived a fourteen-month tour of duty in Iraq without injury, but the West Point cadet barely survived his encounter with an SUV on a Maryland highway. In July 2007, he and two friends in a Honda Accord were slowing down for an exit when they were rear-ended by a Chevy Suburban going 60 miles an hour.

The Suburban pushed the Accord 110 feet across the highway; its impact caused Hammett’s head to accelerate and decelerate violently, resulting in what’s known as a diffused head injury. In a few seconds, millions of nerve endings in his brain were torn and his brain was twisted on an axis. He went into a deep coma. Doctors informed his mother, Diane Davidson, that the 26-year-old wasn’t likely to make it past surgery. But Hammett’s body rallied. Last March, just before Easter, he was transferred to JFK Johnson Rehab in Edison, his mother having convinced the military that he would fare better there than in the nursing home they had assigned him to.

A year later, his prognosis is cloudy. “Chris is borderline,” says Dr. Caroline McCagg, who handles his case. “I hate the word vegetative. It could be said that he is minimally conscious.” Davidson is convinced she sees signs of progress. “I feel like he responds, like he knows I’m there,” she says. “Today, when the therapist got him out of bed, she told him to lift his fingers, and it went very slowly, but he did it.”
No one has given up on Hammett. Since August he has received hyperbaric oxygen therapy—oxygen delivered at greater than atmospheric pressure—which doctors hope will rouse dormant brain cells. “There’s so much more to be done,” his mother says, and she might well be describing the still-nascent fight to conquer brain injury.

There is a growing number of hard-won victories in that fight—including the likes of Juan Roldan. When he arrived at Kessler, doctors prescribed several medications designed to enhance memory and boost cognition, and helped wean him from pain meds, regain his powers of speech and hearing, and move toward his goal of living independently. Today, he’s working to get behind the wheel of a car. “I’ve proved to myself what I’m capable of,” he says.

Roldan’s recovery may well be attributable to the willingness of doctors like Fellus to treat brain injury with courage and creativity. While the basics of treatment are starting to become systematized, the nuances still demand the intestinal fortitude to act on hunch and instinct. “You can get a pretty picture anywhere,” Fellus says. “I’m coloring outside the lines every day.”

If you enjoyed this story, you also might like this article about a doctor who gave hope to a couple that feared they might lose their unborn daughter. Click here to read: Saving Olivia.

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