Drug Found to Aid Vegetative Patients

Oxygen99 writes "BBC News is reporting on some amazing effects of a drug called Zolpidem on patients suffering from persistent vegetative state. Apparently the drug, usually used to treat insomnia, activates dormant areas of the brain that can make patients aware of their surroundings and even hold conversations. This raises several interesting points including the diagnosis of PVS and the attendant ethics of the associated life support, as well as the way the brain responds to injury and damage."

Important distinction

[fsckr]

PVS is not brain death. The two are completely different and unlike the parent post implied, very few families would consider pulling the switch on a patient's with PVS. Patients with PVS react to pain and other extreme stimuli, so cutting off their nutrient supply is tantamount to starving them to death.

"PVS is also known as cortical death, although it is not the same as coma or brain death."

As opposed to brain death, PVS is not recognized as death in any known legal system.

- wikipedia article

Re:Gaba stuff

[dirtyhippie]

Neuropsychopharmacology [wikipedia.org] is what you speak of.

GABA is far from the "only thing in our brains". Other neurotransmitters include serotonin (important in depression and hallucinogens), acetylcholine (why people smoke), dopamine (why some drugs are addictive), (nor)?epinephrine, glutamate and aspertate, etc. etc. The descriptions of what these chemicals do, of course, is vastly oversimplified here.

As for what anti-anxiety meds do, they mimic the effect of the naturally occuring GABA neurotransmitter, and have an inhibitory affect on cells with GABA receptors.

You *could* induce a vegitative state in someone by stopping the action of GABA, but it wouldn't exactly be "persistent" - GABA helps control some rather important functions in the brain stem, like breathing and heartbeat - in short, they'd die ;)

Re:Oblig. Terri Schiavo comment.

[pedantic bore]

Pull the plug too early? Her husband would say "we" waited many years too long...

According to the autopsy [washingtonpost.com], this drug would have had to have done a lot more than described here. Maybe if they'd given it to her when she first fell into a coma (we'll never know) but by the time she died, her brain was irreperable.

Re:Oblig. Terri Schiavo comment.

[RsG]

I seem to recall that her autopsy found what was essentially mush where her neocortex would be. I would tend to guess that that kind of damage really is irreparable - but IANANeurologist, so I don't know for sure.

Assuming we could fully repair braindeath (ie, restore the brain when higher functions have been lost), what would remain of the original person? Would we have an adult with infantile brain capabilities, a blank slate? How much of a person's identity is hardcoded? And what are the ethics of the situation - do we revive someone knowing that we'd be making them start over from scratch (and maybe not even that - most of early learning is made possible by infantile brain "plasticity", which an adult brain lacks).

It's not an easy question...

Re:Gaba stuff

[Anonymous Coward]

I happen to be a med student but this isn't medical advice. I don't mean to come down on you but you have to be very careful when you analyze the neurological effects of drugs. Your post is mostly correct until the last sentence which is off.

Zolpidem is a potent agonist of GABA A receptors. This means that it causes them to "open" and allow cholride ions in to hyperpolarize the cell membrane. This inhibits the firing of the neuron. Stopping the action of GABA could disrupt the delicate membrane potential balance mediated by a whole host of neurotransmitters.

The intravenous general anesthetic etomidate acts by potentiating GABA(A) receptors although different subunit type than zolpidem. Stopping the action of GABA would not cause someone's brain to shut down in the way the OP is thinking.

Let us doctor types handle the heavy lifting while you guys do your geeky thing. Merely summarizing Wikipedia articles doesn't make you a doctor or pharmD.

Re:Oblig. Terri Schiavo comment.

[clickclickdrone]

For those that didn't bother to read the medical reports and instead relied on the newspapers/media, Terri's brain had totally atrophied away, it was gone. Her skull contained the brain stem, a bit of shrivelled brain and an awful lot of fluid. There really was no hope, she was long gone.

Re:Important distinction

[Loquax]

onevulcanme-- As a Catholic who agrees with your desire to see all life cherished and preserved, I agree with your sentiment, but as a person who values logic, reason and most importantly, the law, I have to point out a few things. First, Mr. Schivo was given guardianship of Terri by a court of law. You and I may disagree with the judges decision, but we have to respect the law. I prayed daily for that Michael would reverse his stance and hand guardianship over to her parents, but in the end, he exercised his rights under our legal system. If you don't approve of that, cool, but in the end, in this case, it was nobody's decision but his that mattered. Second, as a pro-life Christian who also believes that it is wrong to bear false witness against another, I am embarassed and hurt that people chose to villify Michael Schivo. I understand her parents were not happy with him, I understand that emotions (and not reason) guide any parent's wishes for a terminally ill child, but the rest of us should have taken a step back and realized that none of us had any business judging the man. Have whatever opinion you like, but don't judge a man evil or damned in the eyes of God. We as Christians are forbidden to "judge" (in the sted of God) another, nor are we to slander a man. Michael Schivo was accused way after the point by Christians of beating her to death (way beyond what the scientific proof held), of being a money grubber looking to get his hands on her cash, and of being evil. I saw several interviews with Michael Schivo, and I felt (and still feel) that he was a man plauged by a complicated situation who acted out of love for a woman he made a promise to long ago. God only knows what was truly in his heart, and I hope and pray that it was good intent. The more Christian way to have handled this would have been to leave the man alone with his charge, his wife, and pray for him, and later petition our legislatures to assume a pro-life stance of preserving life in questionable situations such as these. It should be assumed that in absense of a living will or final directive that the person wanted to be preserved. I'm sure it would have been a relief to Michael Schivo to know that the decision was out of his hands in the case of questionable desires from Terri. I personally have written out a living will that directs my wife and thoes I love to take specific actions and filed it with a lawyer. I encourage everyone who feels one way or the other about the sanctity of life and the meaning of death to do the same, but for God's sake (litterally) make up your mind about what life and living mean to you and take a stand.

Re:Terri Shivo

[jonnythan]

No, according to the autopsy [wikipedia.org].

The brain itself weighed 615 g, only half the weight expected for a female of her age, height, and weight. Microscopic examination revealed extensive damage to nearly all brain regions, including the cerebral cortex, the thalami, the basal ganglia, the hippocampus, the cerebellum, and the midbrain. The neuropathologic changes in her brain were precisely of the type seen in patients who enter a PVS following cardiac arrest. Throughout the cerebral cortex, the large pyramidal neurons that comprise some 70 percent of cortical cells--critical to the functioning of the cortex--were completely lost.

The damage was, in the words of Thogmartin, "irreversible, and no amount of therapy or treatment would have regenerated the massive loss of neurons."

Re:Oblig. Terri Schiavo comment.

[demonlapin]

Do we consider a person dead if the human aspect (the conscious mind) is gone?

A private service by me to all of Slashdot who doesn't understand:

Brain death is defined legally as cessation of all brain activity, with the caveat that it is not due to a reversible cause. Brain dead people are, simply, legally dead. While we generally leave someone on ventilators and the like for a short period of time after brain death, because families often feel like death is when the heart stops (and they want to be there), there is no legal requirement to do so. Once a diagnosis of brain death is made, I can fill out a death certificate and turn off all the machines.

PVS is not the same; PVS patients have some brainstem activity but no evident higher function.

So, to answer your question, no, we don't. But you probably wouldn't want to live like that.

Re:Important distinction

[localman]

Yeah, my family revealed themselves on that one, too. After years of being vehemently pro-life, someone in the family had an abortion (not medically necessary) and they all found ways to justify it so they wouldn't have to condemn the person. It's paper-thin morality. And they haven't learned a thing from either experience or fessed up. Don't know what to do with people like that except ignore them. Which is hard when it's your family :)

Cheers.

The medical study, and this isn't the only drug

[Frangible]

Effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans. [nih.gov]

The study investigates the effect of zolpidem (CAS 82626-48-0) on brain injuries and cerebellar diaschisis. Four patients with varied brain injuries, three of them with cerebellar diaschisis, were imaged by 99mTc HMPAO Brain SPECT before and after application of zolpidem. The baseline SPECT before zolpidem showed poor tracer uptake in brain injury areas and cerebellar diaschisis. After zolpidem, cerebral perfusion through brain injury areas improved substantially in three patients and the cerebellar diaschisis was reversed. Observations point to a GABA based phenomenon that occurs in brain injury and diaschisis that is reversible by zolpidem.

The problem with this study is a small sample group and no control. You can't make many broad conclusions from that data.

Indications, efficacy and tolerance of drug therapy in view of improving recovery of consciousness following a traumatic brain injury [nih.gov]

... RESULTS: The synthesis provides evidence about the theoretical actions and efficacy of the available pharmacological agents. The clinical studies are less convincing: indications and therapeutic choices are empirical. Studies report often single cases. Randomised studies are rare, often heterogeneous concerning the aetiology of the brain lesions. The evaluation scales are varied and too wide. In this context, amantadin, amphetamine, methylphenidate and bromocryptin showed some positive effects. ...

All of the drugs described in the above study have dopaminergic function; either indirectly increasing dopamine levels (amantadin, amphetamine, and methylphenidate) or directly agonizing the receptors (bromocriptine). It is interesting that GABA, an inhibitory rather than excitatory neurotransmitter in most cases, shows efficacy here as well.

Worst web site this month

[Beryllium Sphere(tm)]

To save you frustration: Volume 21 Number 1/2006, pp. 23-28
Try, with low expectations, http://tinyurl.com/e6wgz [tinyurl.com] or http://tinyurl.com/krr39 [tinyurl.com]
There's a "free sample issue" button. Unfortunately it goes to the January 2004 issue. The actual article is at http://tinyurl.com/h6f79 [tinyurl.com], USD20 for online pay-per-view.

Re:Important distinction

[Lord Ender]

You were on meds because you are crazy. Modern western medicine is tested scientifically. The fact that you had bad side effects from some drugs is NOT scientific at all. The fact that you think careful vitamin use cured all your ills is NOT scientific. If it did cure you, you were probably malnourished, and the only person you have to blame for that is yourself (not "society" or whatever). Our society requires nutrition info to be labeled on food. Nice, eh?

You are right that psychology is one of the most difficult parts of medicine. It is hardest to study scientifically, and hardest to diagnose.

Most "western" medicine is FAR more precise than psychology. I take some very expensive maintenance medicine, and if I took your advice, my life would be MUCH worse. Without western medicine, I would be crippled by allergies, I would be bald, and I would have life-changing digestive problems. No herbs would change that. You show your insanity for suggesting so. Taking pills every day is much better than the alternative.

Re:This might help my daughter - more info?

[johansalk]

TALK TO YOUR DOCTOR FIRST before you try anything. You don't know for sure what effect it may have on her breathing and such.

Some information on euthanasia here...

[kitkatsavvy]

Why can't this world realise that if you are unable to think for yourself, or walk or talk or even function properly - that you would rather be better off DEAD!

For anyone who is interested in ending, say, their lives due to a terminal illness or whatever the case may be, we already have a doctor in Australia (as you all know, he did the world's first legal euthanasia here).

The website is here >> http://www.exitinternational.net/ [exitinternational.net]

The contact page here >>> http://www.exitinternational.net/contact.htm [exitinternational.net]

All of these medicines (including antidepressants too let me add), DONT make things any better - they just make you into zombies who are forced to live through numerous side effects without allowing to speak out! I would start protesting at all the pharmaceutical drug companies first, and if anyone is interested in having a look at the DSM-IV-TR book I "burnt" using photoshop - here it is - http://en.wikipedia.org/wiki/Image:Dsmbook.gif [wikipedia.org]