'miracle drug' can wake brain-damaged patients

[Evo]

It doesn't sound like it does much, wakes the person up for a couple of hours a day, but they are still brain damaged. Does anyone know if the people that are being awakened can talk or have any normal function during the time that they are "awake"?

Perhaps this 'miracle drug' can wake brain-damaged patients. But what kind of life awaits them?

Marcel Berlins
Wednesday November 22, 2006
The Guardian


It is usually the other way around. Doctors want to put an end to a severely damaged life that, in their medical opinion, has no chance of revival; the family want their loved one kept alive; it is up to judges to make the final decision, which usually, though not always, goes in favour of the medical argument for death. The case of the 53-year-old woman in a persistent vegetative state (PVS), reported in the Guardian on Monday, has introduced a new dimension. Her family wanted her to die with dignity, but a judge ruled that, before any steps were taken that would result in her death, the doctors should treat her with a so-called "miracle drug", Zolpidem, which - and here the medical evidence is by no means clear or unanimous - has caused some patients in PVS to "wake up". (She may already have been given it, but, if so, we do not know the outcome.)

Article continues

http://www.guardian.co.uk/Columnists/Column/0,,1953915,00.html

 

[Astronuc]

It doesn't sound like it does much, wakes the person up for a couple of hours a day, but they are still brain damaged. Does anyone know if the people that are being awakened can talk or have any normal function during the time that they are "awake"?

Maybe for some it is possible, that is if the speech center and cognitive parts are still functioning. I think there have been a few cases of people just coming out of comma or PVS, and recovering although not fully, they were more or less functional. I think that is very rare though.

 

[Moonbear]

One suggestion in the article is that the people who respond to it are misdiagnosed and not truly in a PVS (I'm sure it's possible for there to be ambiguous cases). If that turns out to be the case, then this may be useful as a diagnostic tool. It seems to have a very odd effect that it works for about 2 hours, but then there's a long refractory period that stops it from working again. I'd have to read up on the drug and see what it's target is to see if this makes any sort of sense (though, I'm sure if it was that easy to make sense of, someone would have thought of it already, but you never know).

I'd like to know how awake these patients are when they take the drug. Are they just sitting there with their eyes open but still unable to communicate, or do they become aware enough to communicate their thoughts? If the former, I have to agree with the opinion presented in the article that it may be worse than doing nothing...what if it only wakes them up enough to feel pain, but not enough to communicate that to others? On the other hand, if they can communicate during that brief time, even if it's only simple phrases or yes/no answers, this could help in at least some cases to find out the patient's wishes regarding the decision to keep fighting or be allowed to die.

The part the author of the article clearly didn't ask enough questions about was the one on trying this out on other PVS patients. The nature of their condition is that they can't give consent for anything, and while it's one thing for next of kin to give consent for medical treatment, it's quite another sticky ethical gray area whether it's appropriate for the next of kin to enroll them as test subjects in a clinical trial of a drug unapproved for treating them, especially when we don't know the risks.

One risk that comes to mind that hasn't been addressed is what if the people who respond to the drug are those who would have woken from the injury on their own (i.e., not truly in PVS, but perhaps a "locked-in" state from which some patients do recover) and rather than these episodes of wakefulness actually helping as they are perceived, they are instead hindering the body from repairing itself in its own time frame and taking longer to fully wake? We know very little about how the repair takes place and why some people awaken and some don't, and I don't think we can be certain that the unconsciousness state isn't beneficial in the repair process by conserving energy from body functions to divert it toward brain remodeling, or to leave parts of the brain functioning differently so they can grow rather than perform their usual functions.

 

[Crosson]

The article doesn't mention that this drug is already sold under the brand name 'Ambien', as a sleeping pill.

Personally I am against elective treatment using chemicals that act in the brain. I think, while these results are encouraging, they should encourage us to produce bio-organic brain restorative mediations so that these people can truly heal. Should we keep them alive until then?

I think removing someolnes feeding tube amounts to letting them die, not to killing them. There is a big difference between Dr Kevorkian lethal style injections and removing a feeding tube.

Here is well written essay taking a 'Life' position in the right-to-die debate:

http://www.uhh.hawaii.edu/~ronald/OpEd-suicide2.htm

It changed my opinion.

 

[Evo]

Here is well written essay taking a 'Life' position in the right-to-die debate:

http://www.uhh.hawaii.edu/~ronald/OpEd-suicide2.htm

It changed my opinion.

From the article "it's not just a paranoid fantasy", uhm yeah, that's exactly what it is. Claiming that legalizing assisted suicide for terminally ill patients means that people are going to force people with disabilities to kill themselves is paranoid, to say the least. If a person wants to die instead of suffering horribly from a terminal illness, how dare someone tell them they can't do so?

 

[Evo]

Moonbear, you raise some excellent points, but I'm getting reeady for bed, so hopefuly tomorrow I can respond.

 

[raolduke]

its apparent ability to awaken PVS patients was discovered by pure accident in South Africa. But no one knows why it works in that way, and it is almost impossible to predict what effect - if any - it would have on any particular recipient.

Pure accident?

 

[Huckleberry]

I've seen a movie that is similar to this. The title is 'Awakenings' taken from the book written by neurologist Oliver Sacks. The movie stars Robert De Niro and Robin Williams and is about a personal experience of Dr. Sacks with several patients suffering from encephalitis lethargica in a clinic in the 1920's. He prescribed levodopa to them and they experienced periods of awakening. The effectiveness of the drug diminished after repeated use on a patient. I don't know how accurate the movie is to reality, but I rather enjoyed it.

http://en.wikipedia.org/wiki/Encephalitis_lethargica"
http://en.wikipedia.org/wiki/L-DOPA"

It seems levodopa targets the central nervous system by penetrating the blood-brain barrier. How does the modern miracle drug function?

Levodopa is used as a prodrug to increase dopamine levels for the treatment of Parkinson's disease, since it is able to cross the blood-brain barrier whereas dopamine itself cannot. Once levodopa has entered the central nervous system (CNS), it is metabolized to dopamine by aromatic L-amino acid decarboxylase. However, conversion to dopamine also occurs in the peripheral tissues, causing adverse effects and decreasing the available dopamine to the CNS, so it is standard practice to co-administer a peripheral DOPA decarboxylase inhibitor – carbidopa or benserazide – and often a catechol-O-methyl transferase (COMT) inhibitor.

 

[OSalcido]

Very strange, Zolpidem is marketed as Ambien. Nurses give Ambien to put them to sleep.

 

[raolduke]

What does waking them up for a few hours accomplish? Can they respond or converse in anyway?

 

[Evo]

That's what we need to figure out.

 

[Q_Goest]

Here's the article you want to read:
http://www.guardian.co.uk/medicine/story/0,,1870279,00.html

The article opens with a story about Louis, but this is only a short exerpt:

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."

 

[raolduke]

What are we hoping to accomplish? - By making them conscious for a couple hours are we going to ask if they are suffering when they are not conscious? It seemed as if that guy was getting better though.. We need more statistics.