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ON SUNDAY, AUG. 9, 2009, VALENTINE Filipov, a handsome and energetic manag- er at a refrigeration factory in Pazardzhik, Bulgaria, decided to change a burned-out lamp in his garden. His daughter Anna refers to what happened next as "my fa- ther's ridiculous accident," Filipov lost his balance on the 3-ft. (0.9 m) stepladder and fell, hitting his head on the pavement. The blow put him in a coma for five days. When he opened his eyes, doctors determined that the damage he sustained had left him in a vegetative state, a condition defined by unresponsive wakefulness, in which patients follow a normal sleep-wake cycle, breathe without assistance and make re- flexive movements such as swallowing, yawning, grunting and fidgeting but have

Photographs by Peter van Agtmael for TIME ness

Window into the soul Valentine Filipov's eyesfollow a mirror during a test doctors used to confirm he has retained some level of consciousness

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no awareness of their environment and leave remarkable room for recovery. Pa- can't respond to commands. tients labeled vegetative typically stay After FiliI>OVspent a month in the hos- that way-but sometimes they don't. So pital, the doctors discharged him. They where's the line between resignation and told his family there was nothing more hope? Various studies in the past decade, they could do, that he would be in a veg- including one by Belgian and U.S.experts etative state for the rest of his life. in 2009, have found that about 40% of pa- But Filipov, who was then 45, seemed tients diagnosed as vegetative are actually less lost to the world than the doctors as- conscious and fall into a category adopted sumed. He would sometimes laugh with in 2002called minimally conscious, a state family members. He would sometimes cry in which some awareness exists and im- with them-especially with Sofiya, his provement is possible. wife of 23 years. Vegetative patients have In the Nov. 10issue of the medical jour- been known to cry, but their outbursts are nal the Lancet, a research team that includ- typically spontaneous and not associated ed Laureys illustrated this point starkly. with external stimuli. Filipov's seemed They studied 16 patients diagnosed as triggered by things going on around him. vegetative, hooking them up to an electro- Desperate for a reappraisal, his family encephalogram (EEG)and asking them to took him to see Dr. Steven Laureys, head of imagine squeezing their right hand and the Coma Science Group at the University wiggling their toes on command. Three of of Liege in Belgium, one of the few centers the subjects apparently imagined it well, in the world that study vegetative patients. with the proper EEG tracings appearing Laureys asked the Filipovs if they could in the premotor cortex of their brain. Did make Valentine cry. They circled his bed, they hear? Were they conscious? and Sofiya approached him. She bent over Those are terrifying questions. Patients him, cradling his cheeks in her hands. wrongly diagnosed as vegetative are sen- "Will you cry with me, my love?"she whis- tenced to a life of being tended to by care- pered. "Will you weep with me, my dear?" givers (who may never take the trouble His face began to contort. His eyes fixed on to engage them because it seems point- his wife's face. He started crying, loudly. less) even as a partly functioning mind weeps or dreams or rages within. "The no- The Consciousness Conundrum tion of a conscious person treated as not THERE'SANODDCIRCULARITYTOSTUDIES conscious-to me that's the ultimate por- of consciousness-a curious exercise in trait ofisolation," says Dr.Joseph Fins, chief the brain investigating the brain. Nobel of medical ethics at Weill Cornell Medical laureate Francis Crick took a reductionist College in New York City. "It's solitary con- view of things in the 1970s, coining the finement of the most troubling kind." The may leave other patients deaf or blind or term "the astonishing hypothesis": the idea Lancet study and others suggest that with so severely spastic, epileptic or paralyzed that all feelings, thoughts and actions are the right technologies and therapies, at that they cannot control their movements. just the products of a mass of brain tissue least some of these confined minds may They may be severely amnesiac and un- and that we all exist only one well-placed conceivably be set free. able to remember what is asked of them. head trauma away from the irrevocable They may suffer from akinetic mutism, erasure of the self. Most people choose to A Look in the Mirror in which the part of the brain responsible see things more lyrically; consciousness is EACHYEARIN THE U.s. AT LEAST14,000 for decisionmaking and drive is damaged. the ineffable ghost in the machine that dis- victims of brain damage are diagnosed as What's more, minimally conscious tinguishes us from plants and bacteria and vegetative. If the 40% misdiagnosis figure patients almost always suffer from fluctu- perhaps even other animals-the quality is correct, that means 5,600 of them are in ating vigilance; for them, consciousness that makes us wondrously special. But sci- better shape-perhaps far better-than flickers on and off like faulty Christmas- entists aren't lyricists, and Crick's mecha- their records show. tree lights. "A doctor goes to the bedside, nistic view has prevailed, with scientists There are a lot of reasons the error rate gives five commands, gets no response and treating the brain as merely another organ, is so high, not least that truly reliable pronounces the patient vegetative. But a albeit a highly complex one. tests for consciousness have not been de- different doctor might see the patient at a Nowhere is that complexity more veloped. To date, the only accepted diag- different time and come away with a total- evident than in our understanding of nostic method remains a bedside exam. ly different impression," says Joe Giacino, how consciousness works-and fails to Clinicians ask patients to respond to director of rehabilitation neuropsychol- work. Minor accidents like Filipov's can commands like "Squeeze my hand" and ogy at Boston's Spaulding Rehabilitation lay waste to cognitive processes. Major "Look at the ball." But many postcoma Hospital, who led the effort to have the traumas like the shooting wounds of patients suffer from aphasia, the inabil- "minimally conscious" diagnosis accepted Congresswoman Gabrielle Giffords can ity to understand language. Brain damage by the medical community. 44 1

culated in front of him. While he failed to respond to nearly every other test in the CRS-R,he became transfixed by his reflec- tion and avidly followed it with his eyes. "If every doctor in every emergency room carried a mirror in their pocket, it would immediately and significantly reduce the misdiagnosis rate," Laureys says. Even the most rigorous neurological exam cannot circumvent another diag- nostic obstacle, though. Many vegetative patients do not emerge into minimal consciousness until several months after waking from a coma, by which time they have been discharged from the hospital. "Afamily might tell a nurse in a care home that something's changed, but the nurse sees the vegetative label and dismisses this as wishful thinking," Laureys says. The irony-a cruel one-is that often doctors give up on recovery at the worst stage possible. The first few months after an injury can be a quiescent time fora damaged brain, with all its energy going to recovering from the wound it suffered. It's only later that it has the luxury to begin recovering some of its lost faculties. "You want to change the world?" asks Nicholas Schiff, a neurologist at Weill Cornell Medical College who, along with Laureys and a Canadian research group, is in the middle of a three-year project to study 500 patients with consciousness disorders. "Get these patients a six-month follow-up by experts who can do a behav- ioral assessment. Give them a safety net." To improve diagnostic accuracy, Giacino designed a rigorous, standardized The Eye of the Scanner bedside assessment called the coma recov- 40% WHILE BEHAVIORAL EXAMS REMAIN THE ery scale-revised (CRS-R),which Laureys SHAREOFPATIENTS primary diagnostic tools for assessing and others promote as the gold-standard DIAGNOSEDAS consciousness, a handful of neurologists exam. Some elements of the old method VEGETATIVEWHO around the world are using brain scans have been retained in the CRS-R,includ- AREMINIMALLY to try to map what they call the neural ing object recognition, in which the exam- CONSCIOUS correlates of consciousness, the cerebral iner holds two objects and asks the patient mechanisms that make us aware. For to fixate on one. But the CRS-R requires years, doctors assumed that consciousness each test to be repeated multiple times to was a diffuse and global brain process. But allow for fluctuating vigilance. studies of sleeping, anesthetized and veg- The primary reason for the CRS-R's etative brains have shown that it is instead improved accuracy, however, is a simple localized in a network consisting of three but revolutionary innovation. The test discrete parts: a section of the prefrontal measures patients' eye-tracking ability cortex; a section of the parietal cortex; and by moving a mirror in front of their face the thalamus, a structure deep in the brain rather than a finger or pen-the method that acts as a sort of traffic cop, mediating most neurologists use. "Patients respond signals between the two other parts of the powerfully to their own image," Laureys The long wait consciousness triad. Should connections explains. "It's remarkable to witness." Anna Filipova struggles among the three sections be severed-or Indeed, Filipov's awareness became with herfather's uncertain should one be destroyed-consciousness indisputable as soon as a mirror was cir- prognosis ceases. "Youdon't need a lot of gray matter

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to be conscious. You only need the right parts of the brain to function together. That was a huge surprise," Laureys says. With this knowledge, neurologists are getting better at developing imaging tests that can conclusively capture con- sciousness onscreen. Last year in the jour- nal Neuroimaqe, Spanish neuroscientist Davinia Fernandez-Espejo published a study of 25 patients with disorders of con- sciousness in which she used magnetic resonance imaging (MRI) to differenti- ate patients identified with the CRS-Ras vegetative from the minimally conscious and achieved 95% accuracy. Similarly, Lau- reys' group has developed software that can interpret results of positron emission tomography (PET) scans, which measure metabolic activity in various regions of the brain. Last year the group published a study in Neuroimaqe in which the program was able to distinguish fully conscious pa- tients from vegetative patients with roo% accuracy. And while the just-published EEG findings were not as dramatic, they showed \ that promising diagnoses can be made with way as a healthy volunteer's. She also ac- were lobbying to be euthanized, a vast simple, inexpensive hardware'too. tivated spatial brain networks associated majority said they were "happy" despite with navigation when she was told to their condition. "That result showed that A Rich Inner Life imagine walking around her home. we should be very careful not to presume WHAT SUCH TESTS CAN'T A,NSWER IS THE Kate Bainbridge, a former school- that we know the subjective experience question that intrigues-and frightens- teacher who was similarly misdiagnosed of a noncommunicative patient," Laureys people most: What is life like for minimal- in the I990S in England, has since recov- says. "That has profound implications for ly conscious patients? Is it silent agony, or ered enough to communicate by using a families and doctors considering whether is there a primal serenity to their muted computer. "It really scares me to think to withdraw life-sustaining treatment." interior world? The answer may depend what might have happened to me had I But those implications can cut two on their quality of care. PET scans show not had the scans," she wrote in an e-mail ways. Truly vegetative patients who re- that when minimally conscious patients to a journalist in 2007."They show it was main awake but unresponsive for more are thought to be in pain, parts ofthe brain worth carrying on even though my body than I2 months following traumatic brain associated with emotion light up, just as was unresponsive." injury or three months after cardiac arrest in healthy volunteers, Vegetative patients This year, Laureys further challenged or stroke are classified as permanently show no such response. Yet,Laureys says, presumptions of the quality of life for vegetative. The U.S. Supreme Court ruled minimally conscious patients often don't postcoma patients with a survey in the in I990 that such patients may have their receive basic pain medication, which he British Medical Journal of locked-in pa- feeding tube withdrawn if they have a liv- calls "very disturbing" given these results. tients. Such people sustain a brain injury ing will, if their legal proxy so desires or if There are also tantalizing signs that that results in paralysis so severe they can there is strong evidence that the patient minimally conscious patients may some- control only their eye movement, even would want to die. times be capable of experiencing a rich as their consciousness network remains There is no known time limit, however, -- inner life. A recent study by Laureys of intact. The journalist [ean-Dominique for when a minimally conscious patient sleeping minimally conscious patients Bauby, perhaps the most famous such might suddenly return to full awareness. In showed brain waves associated with REM patient, earned fame through a memoir, 2003, 39-year-oldTerry Wallis of Arkansas sleep, which suggests they could have The Diving Bell and the Butterfly, which he emerged from minimal consciousness and dreams. In 2006, Laureys and Adrian dictated by blinking. regained fluent speech after lingering in a Owen at Cambridge University published In the immediate weeks after their in- nursing home for I9 years after a car crash. a study in Science in which they performed jury, locked-in patients show intense activ- Using diffusion tensor imaging, a novel a functional MRI (fMRI) scan on the brain ity in a region of the brain associated with brain-scanning technique that maps the of a 23-year-old woman diagnosed as veg- anxiety and emotion, but they eventually intact internal cables in the brain, Schiff etative. When she was asked to imagine adjust. Laureys' survey of I6810cked-in pa- found in 2006that Wallis' brain had under- playing tennis, her brain activated supple- tients found that while a minority-just gone axonal sprouting. New connections mentary motor areas in precisely the same 7%-reported life to be "miserable" and had been made among existing neurons. 46 was yes and to imagine navigating their home if the answer was no. One other- wise unresponsive minimally conscious patient was able to answer five of six ques- tions correctly. Many of the patients did not respond, and the paper is admittedly merely a proof of concept, since fMRIs are hardly affordable household appliances. But Laureys' Lancet study published this month shows that inexpensive EEGs could work too. Other far less expensive techniques may also help patients make the most of their residual communication powers. Zolpidem, a popular sleeping pill, seems to make a minority of minimally conscious patients immediately more alert. Prelimi- nary evidence suggests that amantadine, a Parkinson's drug, may be beneficial too. Many Parkinson's patients enjoy dramatic symptom reduction through deep brain stimulation (DBS),a surgical procedure in which a fine wire is threaded to the mis- firing region in the brain and regulated through a cardiac-pacemaker-like device. All families with a vegetative loved one This has also been shown to have poten- imagine that he or she will be tlie next tial benefits in some minimally conscious Wallis, though few are. So even with the 19 patients. Laureys recommended that Fili- dignity and perhaps comfort ofthe patient YEARS pov's family try to enroll him in a DBS on the line-not to mention the welfare TIME THATAMERICAN trial after trying amantadine as well. of the family's wallet-it can be agoniz- TERRYWALLISSPENTIN Before Laureys communicated this ingly difficult to pull the plug. "The right A MINIMALLYCONSCIOUS treatment plan to Filipov's family, he and to die is an important principle," Laureys STATEBEFOREREGAINING a team of doctors, neuropsychologists and says. "But doctors must also be clear that SPEECHAND FULL Ph.D.students crammed into a small meet- we can't always give a certain prognosis." AWARENESS ing room in Liege to review the results of Making things worse, even the best his tests. The group peered at a large screen scanners are still just inferential machines. at the front of the room. The areas of Fili- They reveal brain activity, and neurolo- pov's PET scan that showed functional gists must decide if that suggests thoughts. activity glowed with a purple aurora remi- In a healthy patient it typically does, and niscent of distant galaxies. The rest was it's easy enough to confirm the premise: as gray as wet concrete. Laureys discussed just ask the subject. There's no such proof what the scans suggested and then asked possible with the minimally conscious. a far deeper, more important question: "Opening up a communication channel "What is it like to be Mr. Filipov?" with these patients is the holy grail from No one in the room knew, of course. an ethics point of view," explains Weill Nor could they say if Filipov himself Cornell's Fins. "Right now the debate about knew. Eight months later, he has shown what these patients feel is missing the one no improvement. But Sofiya, his wife, voice it needs most-that of the patient." puts faith in the possibility that her hus- band's essence remains. And inside her The Stirring of the Silent head, in a way, it does. Each evening as THAT VOICE COULD SOON BE HEARD. LAST she prepares him for bed-as she checks year Laureys and the Cambridge team his tubes, cleans out his sores, pulls the reported using the methodology of the Vital signs covers over his shoulders-she says si- 2006 tennis study to show that some min- Dr. Steven Laureys.far lently to herself, "Good night, my dear, imally conscious patients can use mental left, searchesfor signs of my love, good night." She is working to visualization within an fMRI to commu- consciousness on brain scans keep two Valentines alive: the one lying nicate. Laureys asked patients to imagine like the one administered by before her; and the one working peace- playing tennis if the answer to a question Caroline Schnakers, center fully in the garden. _

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