New research may help unlock vegetative and minimally conscious patients.

New research may help unlock vegetative and minimally conscious patients.

New research may help unlock vegetative and minimally conscious patients.

Health and medicine explained.
April 23 2009 7:10 AM

State of Mind

New research may help unlock vegetative and minimally conscious patients.

Coma. Click image to expand.
Coma patient

Seventeen months ago, Joshua Hummel, now 24, was sleeping in his Seattle home when someone attacked him with an ax. He survived, but the penetrating blows to his skull left him in a minimally conscious state. Today he lives with his parents and two siblings in a St. Louis suburb. As I talk with his family in the kitchen, Joshua sits next to us in a wheelchair that he can't move himself. After a $17,000 remodel, his wheelchair can fit into the accessible bathroom, but he can't use the handrails on the walls. In the den there's a standing frame—when his mom uses a Hoyer lift to transfer him into it, the frame can support his body in a standing position, which is important for his circulation.

As a resident in physical medicine and rehabilitation, I handle the medical rehabilitation of people after disabling injuries. Severe traumatic brain injuries constitute one of my most challenging ICU consultations. After neurosurgery has saved lives (in Joshua's case, by cutting out portions of skull so that the swelling brain can expand), we're called in to answer the family's burning question: What's the potential for meaningful recovery? Unlike in brain death, where we can look for flat-lined brain waves or the cessation of intracranial blood flow, doctors don't have confirmatory tests for consciousness and its shades of gray. That's one reason studies uncover alarming rates of misdiagnosis of the vegetative state. About one-third of the time, "vegetative" patients are minimally conscious or even better.


Examining these patients can make me feel as if I'm apishly tapping on a black box flight recorder trying to get it to make sounds, cough, sputter, or blink when one day I'll simply plug it into the right data retrieval port, but I believe future clinicians won't view us as barbarians. We know that the location of the brain damage matters, and a surprising amount of brain tissue can be lost before there is no potential for recovery. The mechanism of injury also weighs strongly—losing blood flow to the brain during a heart attack (like Terri Schiavo) can result in a predictably permanent vegetative state.

After a severe brain injury, most patients progress through a familiar series of stages, at times reliving the worst parts of childhood emotional development. But that's if the brain comes back online at all. Directly after the injury, a coma lasting up to two or three weeks ensues, which is somewhat like a deep sleep. Unlike in sleep, however, the brain stem shuts down as well, necessitating life support. Within two to three weeks, patients come off ventilators and begin recovery, or they may enter a vegetative state of unknown duration. Vegetative patients do not react meaningfully to environmental stimuli. If you pinch them, you'll get reflex posturing. They may yawn or grunt; they may briefly stare but cannot sustain the gaze or track movements. Vegetative patients sleep, awaken, and breathe on their own, but they require feeding tubes.

Rather than spontaneously resuming normal consciousness, many vegetative patients enter into another state of mind, the minimally conscious state. MCS patients often fluctuate in and out of the vegetative state, and the only feature that defines their periods of consciousness is some evidence of purposeful behavior, however slight. They might twitch a thumb on command, or their eyes might track someone's movements around the room. Clinicians who oversee patient care in nursing homes can be forgiven for missing subtle signs of emergence from the vegetative state to the MCS. Fleeting behaviors may even have to be tabulated over time and calculated in a miniature experiment, a method developed by John Whyte at Moss Rehabilitation Research Institute.

Seven years after doctors first defined the minimally conscious state, which is 10 times as prevalent as the more recognized vegetative state, it still lacks an international classification of diseases code from the World Health Organization, making it essentially invisible in modern health care. In 2007, an Institute of Medicine panel identified the need for a study to gather basic data like how many MCS patients there are and where they live, but the institute couldn't raise the funding. These patients are not terminal, but doctors are ill-equipped to decide not only who will recover but to advise families on what the mental life of a person in MCS is like. Reports of dramatic "awakenings" led to the discovery that neuroplasticity—structural growth in brain networks—can continue even 19 years after severe traumatic brain injury. Few living wills contain the possibility of a prolonged period in and out of awareness, and many families are tormented by how long they should wait before withdrawing care, typically done by stopping tube feeds.


Whyte is trying to make sense of the paradoxical vegetative patients who perk up with Ambien—in some cases, dosing the sleeping drug bumps vegetative patients into MCS or higher states. Nicholas Schiff, a neurologist at Weill Cornell, has theorized that Ambien may shut down a deep brain structure called the globus pallidus that normally depresses the central thalamus, a blimp-shaped structure sitting atop the brain stem that acts as a relay station for diverse inputs from neurons across the brain as well as sensory information streaming in through the brain stem. Bilateral damage to the thalamus notoriously results in a permanent vegetative state. Schiff is testing his hypothesis by scanning the brains of Whyte's Ambien responders.

Schiff's theories have shown promise in the past. He's one of the players behind a dramatic trial of deep brain stimulation in 2007, which applied pacemaker stimulation, already used for Parkinson's and essential tremor, to an MCS patient's central thalamus. During rehabilitation, our therapists gave Joshua median nerve stimulation, a poor-man's alternative to DBS; he withdrew and grimaced. His apparent discomfort was a good sign, but he was well short of regaining speech, which occurred in the DBS trial.

Now, Schiff and his international team, supported by a landmark $3.9 million grant from the James S. McDonnell Foundation, are in a quest to accurately diagnose patients like Joshua. The grant recognizes that it's at least as important to find out if people are conscious as whether they're dead. And Schiff has assembled a consciousness dream team, including Steven Laureys at the University of Liege in Belgium and Adrian Owen of Cambridge, to make it happen.

In a 2006 Science report, Owen analyzed the real-time brain activity of a woman in a vegetative state five months after a vehicle accident. The 25-year-old, whose only response to the external world consisted of occasionally fixating on an object, was able to follow complex commands to imagine doing things like playing tennis or walking through the rooms of her home. Eleven months after her scan, the virtual tennis star began a visible recovery, and Owen has gone on to find similarly remarkable results in at least three more of the 40 patients he has studied to date.


Yet the collaborators' most revolutionary work may be in a cheaper, more portable technology than fMRI and other enormous, multimillion-dollar scanners that can't attach to an electric wheelchair. Andrea Kübler first described the concept of using brain-computer interfacing, driven by the brain's EEG waves, to diagnose patients with disorders of consciousness.

They're great for detecting seizures and sleep, but what can an EEG tell us about the brain's most significant function—consciousness? Until recently, the brain's analog wave seemed to pale in comparison with the diagnostic and prognostic powerhouse that is the heart's EKG. But digitally processing the EEG makes it possible to capture unique, reproducible signals—that's all you need to control a computer. Rudimentary commercial versions are entering the market—like one that will let you levitate a ball. We'll find therapeutic uses for these brainy toys almost as fast as the Wii.

In November, Laureys' group demonstrated that, as Kübler predicted, some low-level MCS patients who could seemingly only visually fixate or track for brief periods were able to follow basic instructions. In this case, they counted familiar and unfamiliar names played randomly into headphones—enough to prove low-level awareness but not enough to communicate. But Laureys is about to open a new frontier for BCI as a diagnostic tool. Using the BCI protocol, Laureys says he has found that some clinically vegetative patients are conscious.

So far, every case of digitally uncloaked consciousness has occurred within six months from injury. Still, I can make out Joshua's thalami, such as they are, on his MRI. Do they need a jump-start? Could BCI help us guide cognitive therapy or tell us more about how he's responding to stimulants? Many doctors harbor a therapeutic nihilism about these patients, but this research should give us good reason to keep our minds open. Even as we talk, Joshua's mother administers a range of motion therapy to her son's outstretched arm. She wants his body to be ready if his mind comes back.