Last year, six years after suffering brain damage in an assault, the man began showing dramatic improvement during deep-brain stimulation, a breakthrough therapy that involves sending electrical pulses to a specific brain region. The new treatment was first administered in 2005, researchers report this week's issue of Nature.
"[I thought], 'What could we lose?'" the man's mother said during a telephone press conference this morning, explaining why she accepted doctors' offer to try out the new therapy on her son. She also detailed the trials of caring for someone in a near-vegetative state, which included signing a "do not resuscitate" form soon after his 30th birthday and the inability to take her son out of his managed care facility even on a nice day (for fear he would aspirate, drawing liquid into his lungs).
But life improved dramatically after physicians used the new treatment. "My son can now speak, eat and watch a movie without falling asleep," she said. "The most important thing is he can say 'mommy' and 'pop'. I still cry when I see my son, but they are tears of joy."
Deep-brain stimulation, essentially a pacemaker for the brain, has previously been used to treat Parkinson's disease and to monitor neural activity in epileptics; it is now being tested in clinical trials for use in patients who suffer from obsessive-compulsive disorder and clinical depression.
According to the study's lead author Nicholas Schiff, a neurologist and neuroscientist at the Weill Cornell Medical College in New York City, the man was the perfect candidate for a deep-brain stimulation trial, because he was at the higher end of the spectrum of minimally conscious states, exhibiting minor language capability. "[These patients] show that the intrinsic brain systems may be there," he said at the press briefing, "and that they may be potentially restored."
Joseph Giacino, study co-author and a neuropsychologist at the New Jersey Neuroscience Institute in Edison, said that prior to the trial, the patient "tended to keep his eyes closed almost all the time." He could perform simple movements, "[but] at no point along the way was he able to communicate in a reliable manner"—rarely speaking.
In this case, the doctors targeted neurons in the thalamus for treatment. This midbrain structure has come to be known over the past 10 to 20 years to exert some control over global sensory function, communicating with the cerebral cortex, which Schiff called "the principle computing area of the brain," and the basal ganglia, another midbrain structure that is key to controlling movement.
During a 10-hour operation (performed by study co-author Ali Rezai, a neurosurgeon at Cleveland Clinic), electrodes were placed with millimeter precision on the central lateral nucleus of the man's thalamus to target the nerve cells there. "Immediately [after the surgery], the patient's level of arousal and alertness improved," Rezai says. Giacino adds that the man's eyes were open and he could turn his head to look at whomever was speaking to him.
The physicians turned off the deep-brain stimulation over the next 50 days to isolate its effects—making sure the sudden improvement was not from the surgery alone. The team then began an 18-week period of tuning the electric pulses to get the best therapeutic effects, followed by alternating phases during which the deep-brain stimulation was turned on and off to allow doctors to measure its efficacy.
Giacino said there were other gradual improvements beginning around postsurgery day 145. (The advances were most pronounced when he was receiving the pulses, but also persisted when the therapy was not being administered.) The patient began to talk, first mouthing single words and then progressing to speaking short phrases audibly. He still has significant memory lapses where he cannot remember the activities of the previous day, but is very good at off-the-cuff reasoning.
"The most compelling change I've seen," Giacino noted, detailing an event that took place within the past six weeks, is that "he was able to say the first 16 words of The Pledge of Allegiance.
In addition, the man, who now receives 12 hours of therapy daily (to mimic his sleep–wake cycle), can now feed himself as well as brush his teeth and hair and drink from a glass, rather than being nourished through a feeding tube. Due to extreme atrophy (from lack of use) of his limbs, however, his motor skills are very belabored. The doctors are prepping him for so-called release of tendons surgery that should enable him to increase his upper-body strength. (It is uncertain whether he will be able to walk again.)
In an editorial accompanying the article in Nature, Michael Shadlen and Roozbeh Kiani, neurologists at the University of Washington School of Medicine in Seattle, cautioned that while this offers new hope for patients with traumatic brain injury, it will not necessarily work for everyone. They noted that this is one patient in a single trial and that not all sufferers of disruptions to consciousness will respond to thalamic stimulation. "This patient had shown clear signs of interactive behavior and preservation of many of the important cortical structures before the surgery," they wrote. "Thalamic stimulation presumably increased both the level and consistency of activity in the preserved cortical structures, leading to arousal and behavioral improvements. Such stimulation would not benefit patients who have already lost the critical cortical structures."
The team behind the new study and the heartening recovery has received Food and Drug Administration approval to perform deep-brain stimulation on 11 other minimally conscious patients, and are actively trying to locate new subjects for the treatment.