The Living Dead: Shocking misdiagnosis of PVS (Persistent Vegetative State)
Fascinating piece on people in a persistent vegetative state (or so we thought). A little long, but if you're interested, well worth it.
Quote of one of the funnier stories in the article:
“Young man with motorbike head injury in a coma. His mum, a keen evangelical, comes every day with friends to sing Onward, Christian Soldiers by his bedside. She’s hoping to stimulate his brain into action. It works: he comes round, but he can’t speak. So they fit him up with one of those Stephen Hawking-type laptops, and the first words he speaks are: “For God’s sake, Mum, shut it!” That’s about as funny as it gets on a brain-injury ward, but there’s a serious take-home message. Even minimally aware patients can retain emotions, personality, a capacity to suffer – and, as the young biker showed, attitude.
Trapped inside their bodies, apparently switched off to the world, but still alive: they are the undead. Or so we thought. Forty per cent of patients in a ‘vegetative state’ are misdiagnosed. Now British scientists are leading the field in trying to put that right
Kate Bainbridge is a lively 37-year-old former schoolteacher. We are communicating in the conservatory of her parents’ home in south Cambridge. She has expressive eyes and a broad and ready smile, but she can utter only occasional single words with difficulty. She sits in a wheelchair “speaking” with the aid of a letter-board, using her left forefinger to spell out words individually.
Ten years ago, Kate went into a deep coma and was on a ventilator for several weeks. She had suffered severe brain inflammation after contracting a viral infection. When she came out of the coma, she opened her eyes and could breathe naturally, but she was unresponsive to speech and visual stimuli, and appeared to lack all conscious awareness. She was still in this condition four months after falling ill, and was later diagnosed to be in a persistent vegetative state, or PVS: in other words, persistently unaware. But the diagnosis was wrong.
Although Kate could not speak, or hear properly, or make any kind of signal, or take in sustenance except through a tube into the stomach, she was sometimes aware of herself and her surroundings. She had a raging thirst that was not alleviated by the ward staff. She was racked with pain. Sometimes she’d cry out, but the ward staff thought it was just a reflex action. Kate suffered so much pain and despair that she tried to take her own life by holding her breath.
Then a Cambridge neuroscientist called Dr Adrian Owen put her in a special kind of scanner and performed an unprecedented experiment. It revealed evidence of fluctuating levels of brain activation when she was presented with pictures of her parents. From that point, she started her long journey back into the world. This is a story about brain-impaired patients who come gradually out of coma into “minimal awareness” after being misdiagnosed as being in PVS: breathing, appearing to be wakeful, yet deemed to be dead to themselves and the world. It is also about the disastrous consequences of such misdiagnoses, estimated in the UK and other countries to be running at two in five cases. And, crucially, it is about a neuroscientific research programme that is set to transform the prospects of diagnosis, treatment and rehabilitation of brain-injured people the world over.
Only an estimated 20% of patients return, like the Top Gear presenter Richard Hammond after his car crash in September, to fully functioning normality after serious brain injury. The range of disability following brain damage is hugely varied in type and severity. It is not known how many PVS and minimally conscious patients there are in this country, since no central registry exists. It is likely, according to a canvass of many neurology professionals, to be in the tens of thousands. More certain is the grim reality of hospital wards and long-term care homes where the persistently vegetative and the minimally conscious languish, sometimes for decades.
To write this article I have had the sobering experience of witnessing the plight of patients with severely impaired consciousness – the intubations, the double incontinence, the stricken semicircle of wheelchairs parked before the unwatched day-room TV. And I have met the anguished families of those who are denied final grieving and closure for a loved one condemned to what appears a living death. All too often I have spoken to a wife or husband, or mother or father, who will travel anything up to two hours each way by taxi, every day, to spend time with an unresponsive child or spouse.
But here’s at least one mordantly amusing and true story told to me by a psychologist at Putney’s Royal Hospital for Neuro-disability. “Young man with motorbike head injury in a coma. His mum, a keen evangelical, comes every day with friends to sing Onward, Christian Soldiers by his bedside. She’s hoping to stimulate his brain into action. It works: he comes round, but he can’t speak. So they fit him up with one of those Stephen Hawking-type laptops, and the first words he speaks are: “For God’s sake, Mum, shut it!” That’s about as funny as it gets on a brain-injury ward, but there’s a serious take-home message. Even minimally aware patients can retain emotions, personality, a capacity to suffer – and, as the young biker showed, attitude.
The biggest, most tragic clinical myth about brain injury today is that PVS can be reliably diagnosed by bedside observation alone. It has in fact been known for at least a decade, ever since a key survey of brain-injured patients, that misdiagnosis of the condition runs at more than 40%, a statistic originally calculated by Professor Keith Andrews, former head of the Putney hospital, and confirmed by recent surveys in Europe and North America. This means that valuable rehabilitation strategies are routinely neglected, and misdiagnosed patients end up on unsuitable wards or in care homes where their needs are neither understood nor met.
Up to 12,000 people under 40 in this country suffer traumatic brain injury every year, and there are serious deficiencies in their rehabilitation, according to Professor John Pickard, head of neurosurgery at Addenbrooke’s hospital, Cambridge: “The tendency for patients to be left to languish on general medical, surgical and orthopaedic wards continues to their detriment.” The shocking term being used by campaigning neurologists and neurosurgeons is that unknown numbers of patients are being just “warehoused”.
Christine Simpson, a mother of two in her mid-fifties, and her husband, Colin, encountered the PVS misdiagnosis phenomenon two years ago. After suffering a brainstem stroke, Christine was first admitted to the intensive-care unit at the Princess Alexandra hospital, Harlow, then transferred to a general respiratory ward, where she remained for about a month.
“I was told that she would probably get a chest infection and not survive more than a few weeks,” says Colin. “Even on the respiratory ward I was told she was still in coma, though she was communicating with me at times through her eye movements. Only because myself and our two grown-up sons were constantly at her bedside did she get proper attention.
“On one occasion I found her lying flat with a deflated tracheotomy cuff. She was blue in the face and having difficulty breathing.”
Other instances of poor care, Colin claims, involved a catheter bag infrequently changed, and a gastric tube not replaced routinely according to clinical guidelines. He also contends that Christine was prematurely discharged from intensive care as a result of the PVS misdiagnosis. His formal petition that the hospital has not done enough to resolve his complaints was upheld by the Healthcare Commission on November 9.
Christine, now in a private neurological rehabilitation centre, is locked in rather than “vegetative”: she is conscious but can only communicate by moving her eyes up and down – up for “no”, down for “yes”. The sections of her motor cortex responsible for action have been affected, but not her understanding, reasoning or consciousness. Colin says that in his view a proper diagnosis was not made, nor appropriate treatment devised, until after a visit from a member of a Cambridge brain-research team.
The Cambridge initiative, which began with the experiment performed by Owen on Kate Bainbridge at Addenbrooke’s in 1998, is a story of remarkable determination and painstaking science. Owen is a high-tech neuroscientist funded by the Medical Research Council. Stooped and mildly self-deprecating, he is a youthful-looking 40-year-old raised in Gravesend. His hipster scrubby beard and pleasant, laid-back estuarese confirm a passion for rock music (he leads a band called, improbably, You Jump First). Like a voyager in a parallel universe, he has been travelling along those strange cortical frontiers where consciousness, language and perception emerge from our hundred-billion brain cells and their trillions of connections. He and a group of colleagues – a professor of neurosurgery, a professor of anaesthesiology and an experimental psychologist – have been collaborating on innovative diagnostic techniques for brain-damaged patients. There’s the soberly suited “Prof” – John Pickard, a brain surgeon, who manages the delicate task of bringing the experimental science and suffering patients together in a single project. It was Pickard who sited a scanning machine immediately next to the neurological intensive-care unit in his hospital, making it available for both diagnosis and research. Then there’s David Menon, originally from Pondicherry, India – who designs tests for levels of human consciousness using anaesthetics. Menon carries out volunteer trials, using anaesthetic sedation to study mental tasks that can be located to specific brain centres that might, or might not, be affected by injury – accidents, stroke, cardiac arrest or drowning.
Then there’s Martin Coleman – the earnest youngster of the squad, with a monk-like aura and a compulsive capacity for detailed diagnosis combining observation and neuro-imaging. He is creating a standardised assessment strategy for the variety of states of awareness that follow brain injury. “I’ll sit for hours,” he says, “watching a patient to see how he or she responds, however slightly or momentarily, to different kinds
of noise and atmosphere: a footfall in the corridor, a shaft of light. But the scanning evidence is also crucial. The more I work on these patients, the more I realise each one is unique because their brain injuries are unique.” The team, which calls itself the Impaired Consciousness Study Group and works out of the Wolfson Brain Imaging Centre at Addenbrooke’s hospital, has been looking for, and finding, “islands of significant awareness” in people thought to be “vegetative”. “We can actually see on the scanner,” says Owen, “why certain patients aren’t responding to aural stimuli. We can see if the auditory pathways have been disrupted. We can see that they’re deaf, or it might be we can see they are blind, even though they can’t tell us.” Crucially, the team has done ground-breaking work, using scanners, on the presence of acute pain in minimally conscious patients. This should enable clinicians one day to administer appropriate analgesics after diagnosing pain in uncommunicative patients.
It all began for Owen in the mid-1990s, the so-called “decade of the brain”, after neuroscience had taken off with the aid of genetics, molecular and cell biology, huge new computer capacity, and – above all – non-invasive scanners. For the brain scientists, the advent in the 1980s of Pet-scan (positron emission tomography) technology (less rapid than MRI but nevertheless detailed in locating brain blood flow) was as historically dramatic as the invention of the telescope. The difference is that the gaze of discovery could now be turned inwards instead of outwards. Up to this point, the mind-brain link had been dominated by behavioural psychologists who assessed “input” of stimuli and “output” of behaviour, treating the interior of the brain as an unknowable dark continent. The first discovery of speech-centre activation in the brain, with the aid of a scanner, took place in 1988. With scanner technology it was now possible to penetrate the interior of the brain without “murdering”, as William Blake would say, “what we dissect”.
At Addenbrooke’s, Owen was granted permission in 1997 to scan the brain of Kate Bainbridge, an infant-school teacher with a first-class degree in history from Southampton University. Today, Kate is a happy and healthy woman with a lovely mop of wavy hair and highly intelligent eyes, who is full of life even if challenged physically. She has reshaped and reasserted her highly imaginative personality through, and despite, her brain injury. It is hard to imagine the devastation of her mind and body 10 years ago. Kate had contracted a condition known as ADEM (acute disseminated encephalomyelitis), an unusual form of inflammation of the brain. A viral infection had resulted in an abnormal immune response: her antibodies had attacked her brain cells, treating them as invaders. After descending into coma, she was placed in the Addenbrooke’s neurosurgical intensive-care unit, where she lay for four months, dead to the world. Eventually came periods when she seemed to be awake but unresponsive to stimulation. She was diagnosed as in a “persistent vegetative state”.
Vegetative state and minimal-conscious state are different from brain death, which involves the total destruction of all brain areas and the consequent collapse of heart-lung function. They are different, too, from classic “locked-in state”, such as Christine Simpson’s, where a precise area of the motor cortex is affected, leaving the rest of the brain unharmed. If a vegetative state lasts for more than three months (longer in certain forms of brain insult), there is thought to be progressively less chance that the patient will return to even minimal consciousness.
A PVS diagnosis invariably means transfer from intensive care to a hospital ward, where the patient’s basic physical needs are looked after by staff untrained in rehabilitation techniques. From there they will go on to a long-stay care home. It has been known for relatives of such patients to apply to a judge for withdrawal of feeding to induce death – as with Tony Bland, the 18-year-old victim of the 1989 Hillsborough football-stand collapse, who was left permanently unconscious yet breathing independently.
Nine judges ruled that it would be humane to withdraw Tony’s feeding tube so he be allowed to die. About 20 patients diagnosed as in a PVS have had their feeding withdrawn in Britain since 1992, when the Bland decision was taken. Such requests, often made by relatives whose lives are on hold, their grieving in suspension, are increasingly controversial. There have been tales of patients, not unlike Kate and Christine, returning from “the dead” after months and even years, as well as accounts of sudden recuperation following vigorous massage, deep brain stimulation, and even the administration of sedatives. Members of the Cambridge team, as well as specialists at the Putney hospital, point out that these “Snow White” examples have as yet no reliable supporting scientific evidence that would lead to a routine diagnostic or treatment strategy.
Adrian Owen’s first experiment on Kate involved presenting her with photographs of her mother and father, followed by fuzzy, meaningless pictures, while her brain was being scanned. “We found,” he says, “that areas of Kate’s brain burst into activity when pics of her family were shown that accorded perfectly with the brain locations of healthy volunteers doing the same task.”
This did not necessarily mean that she was fully conscious. It has been established by David Menon’s research that an anaesthetised patient’s brain can respond to certain stimuli without being actually aware. But Owen’s first experiment revealed that Kate’s brain was not entirely devastated: there were islands of activation. In fact, Kate has no memory now of seeing the pictures. And as she returned to consciousness, she remembers people speaking without understanding what they were saying. The first words she understood as meaningful words, and not just noise, were spoken by her mother. Kate remained in hospital for a further six months, returning gradually to responsiveness in fits and starts. The scan had given her parents and the medical staff confidence that her brain might begin to heal itself slowly with systematic stimuli. They were right.
Many rehabilitation psychologists, such as Lesley Murphy, formerly of the Putney hospital, maintain that awareness is not unlike muscular fitness: it requires exercise, and a stamina of “consciousness” can be developed, provided there is something to build on. Rehabilitation psychologists maintain, however, that periods of rest are as important as periods of structured activity, and that posture and bodily health are also crucial. Every patient is different.
Today, Kate looks back on Owen’s intervention with gratitude. On returning home, she had a period of one-on-one interactive therapy with a clinical psychologist. Kate can now send and read e-mails, watch television, and listen to CDs of music and talking books – her favourite author is Jane Austen. She occasionally goes to the cinema, and she paints. She has a new life, rather than her old life back. When she fell ill, she was engaged to be married, but he eventually called it off. “But that’s my old life now.”
Since his early research on Kate, Owen and his collaborators have been taking their experiments to ever more sophisticated levels. He started employing MRI scans in 2004, using sound stimuli through sets of headphones instead of photographs. MRI can reveal blood and metabolic flow in the brain, and it can do it virtually in real time for long periods. He was able to show the difference in located brain responses between noise and silence, and between speech and mere noise, in different degrees of supposed vegetative state and minimal consciousness.
He has also shown in a number of minimally conscious patients the ability to make sophisticated “semantic” speech distinctions.
“If I start a sentence with the words ‘The shell was? ’, the majority of people begin to think of a shell on the seashore. But if I add ‘fired from the gun’, it requires a shift in understanding.” Owen looks at me triumphantly: “Believe it or not, you can see that semantic shift taking place in the brain on the MRI scanner.”
Owen says that comprehension of such ambiguities obviously requires more than just recognising speech as opposed to meaningless noise: “You can see the activation taking place in parts of the brain known as the inferior temporal lobe and the posterior temporal lobe.” In order to back up his comprehension and brain-location theory, his anaesthetist colleague David Menon put healthy volunteers under different levels of anaesthetic. As the volunteers went deeper into unconsciousness, the “semantic” comprehension areas became less active.
Owen’s next experiment has made medical history. He and his group discovered complex mental activation in a 23-year-old woman patient diagnosed as in a vegetative state after a road accident. During an MRI study she was asked first to imagine that she was playing tennis, and secondly to imagine that she was walking about her house, starting from the front door and visiting all the rooms. When she was asked to imagine playing tennis, the scanner recorded significant activity in a part of the brain known as the premotor cortex – associated with upper- body movement. When she was asked to imagine walking through the house, activity was recorded in her hippocampal gyrus, a part of the brain associated with navigation memory (it becomes enlarged in taxi drivers who have done “the knowledge”). The activations were identical to those recorded in healthy volunteers imagining the same activities. To overcome criticism that this might not indicate conscious control of thoughts, Owen devised a test that asks the patient to think of “playing tennis, in your own time”, indicating with reasonable certainty that they have a degree of volition or control.
A current research programme of the Impaired Consciousness Study Group, unreported until now, involves asking patients with awareness, but incapable of response even using eye movement, to answer “yes” and “no” just by thinking specific tasks. “It works like this,” says Owen. “Say you have a patient who responds positively, with proven volition, to the command ‘Imagine you’re playing tennis.’ You can then progress to an easy yes-no response.” Owen gives a crooked smile: “To coin a phrase, it’s a no-brainer. If the answer to a question is yes, the patient thinks of playing tennis; if it’s no, the patient doesn’t think of playing tennis.”
To have found a way of speaking to patients who cannot respond physically is a gigantic step forward. If Lesley Murphy is right – that one must use brain connections or lose them – it offers a remarkable new basis for rehabilitation techniques. The team is now experimenting with drawing parallels between scanners and EEG machines, which measure brainwaves. It is possible that EEG “markers” can be created that are identical to crucial brain locations found only by scanning techniques. The plan is to be able to make functional brain tests at the patient’s bedside that preclude the high cost and massive bulk involved in Pet and MRI scans. This should lead to “tailor-made” rehabilitation based on highly refined external observations in combination with precise interior knowledge of an impaired brain.
The Cambridge project is not, however, without potential ethical and social problems. Scanning for minimal consciousness in those who appear vegetative can in some cases yield ambiguous results. Evident brain reactions can sometimes be fickle: now here, now gone. Some experts worry the technology could have drastic consequences for relatives where there is scant prospect of a patient’s return to interaction. At the Putney hospital, which houses more than 220 brain-injured and neurological patients, I was told by a research psychologist about a patient in a PVS of about three years’ duration, known as Mrs K, whose family might well be devastated if a scan were to reveal indications of awareness.
“Imagine the case of this family who, after several years, want to finally grieve and get their lives back. Mr K has a new partner, their son plans to go to Australia, and their daughter has moved to Scotland. Their hospital visits have dwindled to once every three months. They’ve made their decision to apply for withdrawal of feeding and allow Mrs K to die. What if a scan now finds a trace of minimal awareness? The withdrawal will obviously be halted, there will be new feelings of guilt to be dealt with, and the family’s life is back on hold. The island of awareness might be temporary or insignificant, and Mrs K might still fail to interact.”
Such objections cannot override the palpable benefits of earlier, more reliable diagnosis.
And the neuro-imaging initiatives will have the scope, moreover, to settle lingering doubts about the difference between brain death and vegetative state.
According to Steven Laureys, professor of neurology at Liège University, there is constant pressure in many parts of the developed world to withdraw sustenance from vegetative patients in order to allow them to die so that their body parts can be harvested. In a recent study, Laureys reports, “slightly less than half of surveyed US neurologists and nursing-home directors believed that patients in a vegetative state could be declared dead”. His remarks should be set against the background of widespread shortages of organs and body parts for transplantation.
Apart from the ethical questions raised by wrongly equating vegetative state with brain death, the rate of misdiagnosis should challenge further moves to bring on the deaths of such patients.
Beyond medical science, moreover, fears have been voiced by sociologists. Could the advent of mechanical mind-readers herald an era of over-reliance on such procedures to profile criminals or deviant personalities, or to initiate widespread mental surveillance on the same scale as speed cameras? Professor Peter Lipton, head of the Cambridge University department of the history and philosophy of science, warned at a recent conference that advances in mind-reading technology could one day alter the entire premise of personal privacy in society, invading the dignity of the self and altering the human self-image. But if such mind-reading technology is possible, it is still in the remote future, says Adrian Owen, and he has his reasons.
Not so long ago, after a boozy evening, Owen visited his Cambridge lab in the dead of night to perform a weird procedure on himself with the aid of his department’s MRI scanner. Inserting his own head inside the roaring machine’s magnet tunnel, Owen set himself the task of concentrating on one specific private thought. The machine’s computer generated an image revealing marked activity in several brain locations, as if light had leached onto a dark x-ray film. In the early hours he e-mailed the result to 10 top brain radiographers around the world, inviting them to offer an interpretation. “They all got it way, way wrong,” Owen tells me with a mischievous smile. “One thought I was asleep. Another that I was playing sudoku. One even asked if I was listening to Bruce Springsteen!” So what had the MRI scan shown Owen doing? “In fact,” he says, “I was imagining I was telling a lie.”
Owen’s scanner, then, is a long way from being a lie-detector, let alone an all-purpose mind-reader with the capacity to spy on people’s innermost secret thoughts. But Owen and his team are well on their way to making a historic difference to the diagnosis and increased quality of life of minimally aware patients through long-term, multidisciplinary science.
“None of this would have been possible,” says Owen, “without the expanding reality of neuroscience in Cambridge today – an amazing collaboration between lots of specialists and departments, including neurology, engineering, anaesthesiology, pharmacology and even physics, as well as wide-ranging areas of psychology.”
The test of their efforts will be the eventual application to patients. It was, after all, the unusual partnership between Adrian Owen and Kate Bainbridge that gave the Cambridge project its special impetus. After my first meeting with Kate, she handed me a print-out from her laptop that declared: “Other scans show doctors what is wrong with your brain, but Dr Owen’s show what is working. It gave them a reason to carry on with my recovery. It really scares me to think where I would be if I hadn’t had it.”
Three cases that made legal history and one that is breaking new medical ground
Tony Bland Aged 18, Bland suffered severe brain damage in the 1989 Hillsborough disaster. After he had spent four years in a PVS, his parents and the hospital successfully applied to have his feeding tube removed. Tony’s case made legal history in the UK and he died on March 3, 1993.
Karen Ann Quinlan Her Catholic parents asked for Karen Ann to be taken off her ventilator after she failed to respond for several months. It was switched off in 1976 following a year of legal and religious disputes. But Karen Ann was able to breathe independently, surviving until 1985, when she was 31. Her case speeded up the introduction of “living wills”.
Terri Schiavo When her husband sought in 1998 to have feeding withdrawn from Terri, who had been in a PVS for eight years, seven years of legal wrangles ensued. Terri’s parents, the Florida legislature, Governor Jeb Bush and the Supreme Court all intervened before Terri was finally allowed to die in March 2005.
Louis Viljoen After being hit by a lorry in the mid-1990s, Louis went into a PVS. Several years later, he was being given the sedative zolpidem for muscle spasms when, incredibly, he stirred and began to respond to simple questions. Thanks to regular doses of the drug, now undergoing trials in South Africa, Louis, now 37, is conscious for several hours a day.
...sermons from this minbar come with tongue planted quite firmly in cheek.
"Let your boat of life be light, packed with only what you need -
a homely home and simple pleasures, one or two friends,
worth the name, someone to love and someone to love you,
a cat, a dog, and a pipe or two, enough to eat and enough to wear,
and a little more than enough to drink; for thirst is a dangerous thing."