Tweet
A Cure for Persistent Vegetative State?
Part the First:
Reborn
We have always been told there is no recovery from persistent vegetative state - doctors can only make a sufferer's last days as painless as possible. But is that really the truth? Across three continents, severely brain-damaged patients are awake and talking after taking ... a sleeping pill. And no one is more baffled than the GP who made the breakthrough. Steve Boggan witnesses these 'strange and wonderful' rebirths
Tuesday September 12, 2006
The Guardian
For three years, Riaan Bolton has lain motionless, his eyes open but unseeing. After a devastating car crash doctors said he would never again see or speak or hear. Now his mother, Johanna, dissolves a pill in a little water on a teaspoon and forces it gently into his mouth. Within half an hour, as if a switch has been flicked in his brain, Riaan looks around his home in the South African town of Kimberley and says, "Hello." Shortly after his accident, Johanna had turned down the option of letting him die.
Three hundred miles away, Louis Viljoen, a young man who had once been cruelly described by a doctor as "a cabbage", greets me with a mischievous smile and a streetwise four-move handshake. Until he took the pill, he too was supposed to be in what doctors call a persistent vegetative state.
Across the Atlantic in the United States, George Melendez, who is also brain-damaged, has lain twitching and moaning as if in agony for years, causing his parents unbearable grief. He, too, is given this little tablet and again, it's as if a light comes on. His father asks him if he is, indeed, in pain. "No," George smiles, and his family burst into tears.
It all sounds miraculous, you might think. And in a way, it is. But this is not a miracle medication, the result of groundbreaking neurological research. Instead, these awakenings have come as the result of an accidental discovery by a dedicated - and bewildered - GP. They have all woken up, paradoxically, after being given a commonly used sleeping pill.
Across three continents, brain-damaged patients are reporting remarkable improvements after taking a pill that should make them fall asleep but that, instead, appears to be waking up cells in their brains that were thought to have been dead. In the next two months, trials on patients are expected to begin in South Africa aimed at finding out exactly what is going on inside their heads. Because, at the moment, the results are baffling doctors.
The remarkable story of this pill and its active ingredient, zolpidem, begins in 1994 when Louis Viljoen, a sporty 24-year-old switchboard operator, was hit by a truck while riding his bike in Springs, a small town 30 minutes' drive east of Johannesburg. He suffered severe brain injuries that left him in a deep coma. He was treated in various hospitals before being settled in the Ikaya Tinivorster rehabilitation centre nearby. Doctors expected him to die and told his mother, Sienie Engelbrecht, that he would never regain consciousness. "His eyes were open but there was nothing there," says Sienie, a sales rep. "I visited him every day for five years and we would speak to him but there was no recognition, no communication, nothing."
The hospital ward sister, Lucy Hughes, was periodically concerned that involuntary spasms in Louis's left arm, that resulted in him tearing at his mattress, might be a sign that deep inside he might be uncomfortable. In 1999, five years after Louis's accident, she suggested to Sienie that the family's GP, Dr Wally Nel, be asked to prescribe a sedative. Nel prescribed Stilnox, the brand name in South Africa for zolpidem. "I crushed it up and gave it to him in a bottle with a soft drink," Sienie recalls. "He couldn't swallow properly then, but I helped him and sat at his bedside. After about 25 minutes, I heard him making a sound like 'mmm'. He hadn't made a sound for five years.
"Then he turned his head in my direction. I said, 'Louis, can you hear me?' And he said, 'Yes.' I said, 'Say hello, Louis', and he said, 'Hello, mummy.' I couldn't believe it. I just cried and cried."
Hughes was called over and other staff members gathered in disbelief. "Sienie told me he was talking and I said he couldn't be - it wasn't possible," she recalls. "Then I heard him. His mother was speechless and so were we. It was a very emotional moment."
Louis has now been given Stilnox every day for seven years. Although the effects of the drug are supposed to wear off after about two and a quarter hours, and zolpidem's power as a sedative means it cannot simply be taken every time a patient slips out of consciousness, his improvement continues as if long-dormant pathways in his brain are coming back to life.
I see Louis before his daily medication, yet he is conscious where once he would have been comatose. Almost blind because of a separate and deteriorating condition, there is a droop to one side of his mouth and brow because of brain damage. His right arm is twisted awkwardly into his side.
Louis is given a pill, and I watch. It is 8.30am. After nine minutes the grey pallor disappears and his face flushes. He starts smiling and laughing. After 10 minutes he begins asking questions. His speech is impaired because of the brain damage and the need, several years ago, to remove all his teeth, but I can understand him. A couple of minutes later, his right arm becomes less contorted and the facial drooping lessens. After 15 minutes he reaches out to hug Sienie. He pulls off her wedding ring and asks what it is. "It's a suffer-ring," she jokes. And he says, "Well, if you're suffering, you should make a plan!" The banter continues and he remembers conversations from the previous day and adds to them.
"Louis," I ask, "do you feel any change in awareness before and after the pill?" "No," he says. "None whatsoever." Whatever is happening, he feels the same. "How do you know this is your mother?" I ask, referring to Sienie. Remember, Louis cannot see. He says: "Because I recognise her voice and I know she loves me."
Nel was as amazed at Louis' awakening as everyone else. A GP in Springs for 40 years, when he isn't seeing up to 100 patients a day, he spends his time restoring vintage cars. Married with three grown-up children, he has lived in the same house all his life.
"Something strange and wonderful is happening here, and we have to get to the bottom of it," he says. "Since Louis, I have treated more than 150 brain-damaged patients with zolpidem and have seen improvements in about 60% of them. It's remarkable."
After Louis' awakening was publicised in the South African media, Dr Ralf Clauss, a physician of nuclear medicine - the use of radioactive isotopes in diagnostic scans - at the Medical University of Southern Africa, contacted Nel to suggest carrying out a scan on Louis. "The results were so unbelievable that I got other colleagues to check my findings," says Clauss, who now works at the Royal Surrey County Hospital in Guildford. "We did scans before and after we gave Louis zolpidem. Areas that appeared black and dead beforehand began to light up with activity afterwards. I was dumbfounded - and I still am."
Clauss says immediate improvements in the left parietal lobe and the left lentiform nucleus were visible. In lay terms, these are important for motor function, sight, speech and hearing.
"I remember saying to Dr Nel that we were witnessing medical history," says Clauss.
No one yet knows exactly how a sleeping pill could wake up the seemingly dead brain cells, but Nel and Clauss have a hypothesis. After the brain has suffered severe trauma, a chemical known as Gaba (gamma amino butyric acid) closes down brain functions in order to conserve energy and help cells survive. However, in such a long-term dormant state, the receptors in the brain cells that respond to Gaba become hypersensitive, and as Gaba is a depressant, it causes a persistent vegetative state.
It is thought that during this process the receptors are in some way changed or deformed so that they respond to zolpidem differently from normal receptors, thus breaking the hold of Gaba. This could mean that instead of sending patients to sleep as usual, it makes dormant areas of the brain function again and some comatose patients wake up.
In Kimberley, the once booming home of the De Beers diamond empire, Riaan Bolton's family heard of Nel's work after he and Clauss had papers published in the medical journal NeuroRehabilitation and the New England Journal of Medicine several months ago. Riaan suffered severe brain trauma when he was thrown from a car in a traffic accident in July 2003. A keen cricketer and rugby player, the 23-year-old was studying to become an industrial engineer but still found time to play guitar in a band.
"One specialist said he had a 5% chance of recovering, another said he had no chance whatsoever of regaining consciousness," says his mother, Johanna. She and her husband, Tinus, spend about £1,000 a month on round-the-clock care for their son in a converted garage at their home, but until June they had seen no sign of awareness in him. Then they asked their doctor, Clive Holroyd, to contact Nel for advice.
"There was no movement, no recognition, just nothing," says Tinus. "Then we gave him the pill and we noticed him moving the fingers in his left hand and touching them against each other. His eyes went big and he began looking from left to right.
"The doctor started asking Riaan questions. He said, 'Look at me, Riaan' and Riaan looked straight at him and focused on his face. Then the doctor asked him to move his hand and he moved it. And then he lifted his head from the pillow and began looking around. I couldn't believe it."
I watch as Riaan is given his medication. As with Louis, his face flushes and his eyes begin to sparkle and focus within minutes. Gone is the 1,000-yard stare. He hugs his mother and looks at her face, but even though I am amazed, the family reckon this isn't his best day so far. They show me a number of DVDs they shot in July. In them, Riaan responds to questioning, nods and shakes his head, drinks through a straw, often laughs and says, 'Hello.' He remains severely brain damaged, but there is clear evidence of understanding and communication.
"It has given us hope," says Johanna. "To have communication with him again, to know he becomes aware of us and to tell him we love him - knowing he can hear us - is simply beyond belief. It has been a very moving experience."
Holroyd remains perplexed. "There is a measurement of the depths of coma called the Glasgow scale, with three being the worst and 15 being normal," he says. "Riaan was six, but within 10 minutes of taking the pill he is up to nine. It's simply unbelievable. And the mind-boggling thing about this is that it's done with a sleeping pill.
"Some time ago, Riaan had a cardiac arrest and it was a difficult call as to whether or not to resuscitate him. His mother insisted he should be, and look at him now. From now on, this will cause serious ethical issues over whether to let such coma victims die." Those issues became even more complicated last week, when a British woman believed to be in a persistent vegetative state astonished doctors by responding to their voices.
We have always been told there is no recovery from persistent vegetative state - doctors can only make a sufferer's last days as painless as possible. But is that really the truth? Across three continents, severely brain-damaged patients are awake and talking after taking ... a sleeping pill. And no one is more baffled than the GP who made the breakthrough. Steve Boggan witnesses these 'strange and wonderful' rebirths
Tuesday September 12, 2006
The Guardian
For three years, Riaan Bolton has lain motionless, his eyes open but unseeing. After a devastating car crash doctors said he would never again see or speak or hear. Now his mother, Johanna, dissolves a pill in a little water on a teaspoon and forces it gently into his mouth. Within half an hour, as if a switch has been flicked in his brain, Riaan looks around his home in the South African town of Kimberley and says, "Hello." Shortly after his accident, Johanna had turned down the option of letting him die.
Three hundred miles away, Louis Viljoen, a young man who had once been cruelly described by a doctor as "a cabbage", greets me with a mischievous smile and a streetwise four-move handshake. Until he took the pill, he too was supposed to be in what doctors call a persistent vegetative state.
Across the Atlantic in the United States, George Melendez, who is also brain-damaged, has lain twitching and moaning as if in agony for years, causing his parents unbearable grief. He, too, is given this little tablet and again, it's as if a light comes on. His father asks him if he is, indeed, in pain. "No," George smiles, and his family burst into tears.
It all sounds miraculous, you might think. And in a way, it is. But this is not a miracle medication, the result of groundbreaking neurological research. Instead, these awakenings have come as the result of an accidental discovery by a dedicated - and bewildered - GP. They have all woken up, paradoxically, after being given a commonly used sleeping pill.
Across three continents, brain-damaged patients are reporting remarkable improvements after taking a pill that should make them fall asleep but that, instead, appears to be waking up cells in their brains that were thought to have been dead. In the next two months, trials on patients are expected to begin in South Africa aimed at finding out exactly what is going on inside their heads. Because, at the moment, the results are baffling doctors.
The remarkable story of this pill and its active ingredient, zolpidem, begins in 1994 when Louis Viljoen, a sporty 24-year-old switchboard operator, was hit by a truck while riding his bike in Springs, a small town 30 minutes' drive east of Johannesburg. He suffered severe brain injuries that left him in a deep coma. He was treated in various hospitals before being settled in the Ikaya Tinivorster rehabilitation centre nearby. Doctors expected him to die and told his mother, Sienie Engelbrecht, that he would never regain consciousness. "His eyes were open but there was nothing there," says Sienie, a sales rep. "I visited him every day for five years and we would speak to him but there was no recognition, no communication, nothing."
The hospital ward sister, Lucy Hughes, was periodically concerned that involuntary spasms in Louis's left arm, that resulted in him tearing at his mattress, might be a sign that deep inside he might be uncomfortable. In 1999, five years after Louis's accident, she suggested to Sienie that the family's GP, Dr Wally Nel, be asked to prescribe a sedative. Nel prescribed Stilnox, the brand name in South Africa for zolpidem. "I crushed it up and gave it to him in a bottle with a soft drink," Sienie recalls. "He couldn't swallow properly then, but I helped him and sat at his bedside. After about 25 minutes, I heard him making a sound like 'mmm'. He hadn't made a sound for five years.
"Then he turned his head in my direction. I said, 'Louis, can you hear me?' And he said, 'Yes.' I said, 'Say hello, Louis', and he said, 'Hello, mummy.' I couldn't believe it. I just cried and cried."
Hughes was called over and other staff members gathered in disbelief. "Sienie told me he was talking and I said he couldn't be - it wasn't possible," she recalls. "Then I heard him. His mother was speechless and so were we. It was a very emotional moment."
Louis has now been given Stilnox every day for seven years. Although the effects of the drug are supposed to wear off after about two and a quarter hours, and zolpidem's power as a sedative means it cannot simply be taken every time a patient slips out of consciousness, his improvement continues as if long-dormant pathways in his brain are coming back to life.
I see Louis before his daily medication, yet he is conscious where once he would have been comatose. Almost blind because of a separate and deteriorating condition, there is a droop to one side of his mouth and brow because of brain damage. His right arm is twisted awkwardly into his side.
Louis is given a pill, and I watch. It is 8.30am. After nine minutes the grey pallor disappears and his face flushes. He starts smiling and laughing. After 10 minutes he begins asking questions. His speech is impaired because of the brain damage and the need, several years ago, to remove all his teeth, but I can understand him. A couple of minutes later, his right arm becomes less contorted and the facial drooping lessens. After 15 minutes he reaches out to hug Sienie. He pulls off her wedding ring and asks what it is. "It's a suffer-ring," she jokes. And he says, "Well, if you're suffering, you should make a plan!" The banter continues and he remembers conversations from the previous day and adds to them.
"Louis," I ask, "do you feel any change in awareness before and after the pill?" "No," he says. "None whatsoever." Whatever is happening, he feels the same. "How do you know this is your mother?" I ask, referring to Sienie. Remember, Louis cannot see. He says: "Because I recognise her voice and I know she loves me."
Nel was as amazed at Louis' awakening as everyone else. A GP in Springs for 40 years, when he isn't seeing up to 100 patients a day, he spends his time restoring vintage cars. Married with three grown-up children, he has lived in the same house all his life.
"Something strange and wonderful is happening here, and we have to get to the bottom of it," he says. "Since Louis, I have treated more than 150 brain-damaged patients with zolpidem and have seen improvements in about 60% of them. It's remarkable."
After Louis' awakening was publicised in the South African media, Dr Ralf Clauss, a physician of nuclear medicine - the use of radioactive isotopes in diagnostic scans - at the Medical University of Southern Africa, contacted Nel to suggest carrying out a scan on Louis. "The results were so unbelievable that I got other colleagues to check my findings," says Clauss, who now works at the Royal Surrey County Hospital in Guildford. "We did scans before and after we gave Louis zolpidem. Areas that appeared black and dead beforehand began to light up with activity afterwards. I was dumbfounded - and I still am."
Clauss says immediate improvements in the left parietal lobe and the left lentiform nucleus were visible. In lay terms, these are important for motor function, sight, speech and hearing.
"I remember saying to Dr Nel that we were witnessing medical history," says Clauss.
No one yet knows exactly how a sleeping pill could wake up the seemingly dead brain cells, but Nel and Clauss have a hypothesis. After the brain has suffered severe trauma, a chemical known as Gaba (gamma amino butyric acid) closes down brain functions in order to conserve energy and help cells survive. However, in such a long-term dormant state, the receptors in the brain cells that respond to Gaba become hypersensitive, and as Gaba is a depressant, it causes a persistent vegetative state.
It is thought that during this process the receptors are in some way changed or deformed so that they respond to zolpidem differently from normal receptors, thus breaking the hold of Gaba. This could mean that instead of sending patients to sleep as usual, it makes dormant areas of the brain function again and some comatose patients wake up.
In Kimberley, the once booming home of the De Beers diamond empire, Riaan Bolton's family heard of Nel's work after he and Clauss had papers published in the medical journal NeuroRehabilitation and the New England Journal of Medicine several months ago. Riaan suffered severe brain trauma when he was thrown from a car in a traffic accident in July 2003. A keen cricketer and rugby player, the 23-year-old was studying to become an industrial engineer but still found time to play guitar in a band.
"One specialist said he had a 5% chance of recovering, another said he had no chance whatsoever of regaining consciousness," says his mother, Johanna. She and her husband, Tinus, spend about £1,000 a month on round-the-clock care for their son in a converted garage at their home, but until June they had seen no sign of awareness in him. Then they asked their doctor, Clive Holroyd, to contact Nel for advice.
"There was no movement, no recognition, just nothing," says Tinus. "Then we gave him the pill and we noticed him moving the fingers in his left hand and touching them against each other. His eyes went big and he began looking from left to right.
"The doctor started asking Riaan questions. He said, 'Look at me, Riaan' and Riaan looked straight at him and focused on his face. Then the doctor asked him to move his hand and he moved it. And then he lifted his head from the pillow and began looking around. I couldn't believe it."
I watch as Riaan is given his medication. As with Louis, his face flushes and his eyes begin to sparkle and focus within minutes. Gone is the 1,000-yard stare. He hugs his mother and looks at her face, but even though I am amazed, the family reckon this isn't his best day so far. They show me a number of DVDs they shot in July. In them, Riaan responds to questioning, nods and shakes his head, drinks through a straw, often laughs and says, 'Hello.' He remains severely brain damaged, but there is clear evidence of understanding and communication.
"It has given us hope," says Johanna. "To have communication with him again, to know he becomes aware of us and to tell him we love him - knowing he can hear us - is simply beyond belief. It has been a very moving experience."
Holroyd remains perplexed. "There is a measurement of the depths of coma called the Glasgow scale, with three being the worst and 15 being normal," he says. "Riaan was six, but within 10 minutes of taking the pill he is up to nine. It's simply unbelievable. And the mind-boggling thing about this is that it's done with a sleeping pill.
"Some time ago, Riaan had a cardiac arrest and it was a difficult call as to whether or not to resuscitate him. His mother insisted he should be, and look at him now. From now on, this will cause serious ethical issues over whether to let such coma victims die." Those issues became even more complicated last week, when a British woman believed to be in a persistent vegetative state astonished doctors by responding to their voices.
Comment