Some important science on disorders of consciousness – part 1

Well Liège has made it into the news again!

The Coma Science Group here at our hospital, working with other centres,

has published another significant study of persistent disorders of consciousness. It’s worth having a look at this; in a subsequent post we’ll look at another very important paper by these researchers. I’ll also  place these reports into some kind of context in terms of Michael Schumacher’s situation (or more correctly, presumed situation).

First a link to an article about today’s study:

And a link to the article itself:

The background

Remember how we said that the vegetative state is defined as a state where the patient shows signs of wakefulness (notably open eyes) without behavioural responsiveness (as a marker of consciousness or awareness). Because of the emotionally laden and ambiguous nature of the word “vegetative”, some, including the Coma Science Group, prefer to use the term “unresponsive wakefulness syndrome” (henceforth UWS) for this state.

The key in differentiating a patient with unresponsive wakefulness syndrome from a minimally conscious state is the presence in the latter of fluctuating signs of awareness, with consistent but intermittent appropriate responses to stimuli.

Distinguishing these states can be difficult, but is absolutely crucial, medically, socially, ethically and therapeutically. A patient who is genuinely in a UWS, has, by definition, no self awareness. No voices are recognised, no sensation of hunger, none of pain, none of thirst. This is why clinicians caring for patients in a UWS are authorised almost everywhere to withdraw medical support, if and when appropriate, (including food and water – remember this is not cruel because there is no hunger or thirst perceived) from UWS patients. This is not the case once the patient has demonstrated any consciousness at all. Prognostically, as we’ve mentioned previously, persistence of a clinically correctly diagnosed (and that’s the point here) UWS for one year after the inciting trauma pretty much means any meaningful recovery is impossible. On the other hand, a minimally conscious state raises the possibility of continued progress.

Unfortunately, it can sometimes be remarkably difficult to show conclusively what state the patient is in. The problem is double.

First of all, there is the fluctuating nature of awareness. Episodes of interaction can appear randomly, or might be associated with a certain time of day, the presence of certain people, etc. The key is to do sufficient evaluations, sufficiently often, to reliably ascertain what the patient’s best level of awareness is.

Second, let’s remember that these patients have suffered devastating brain damage, whether caused by trauma (as is the case with Michael), infections, massive strokes, global anoxia, etc. This means that these patients will almost always have severe restrictions in their ability to show their responses to external (and internal) stimuli – spastic limbs which preclude reliable movements, visual or auditory deficits, etc.

Because of this, current guidelines for the management of patients with prolonged disorders of consciousness are becoming more and more insistent as to the FREQUENCY and QUALITY of the evaluations that are done. Standardised measurement scales are used, and the training necessary to administer them are well defined. Despite this, doubt remains at the edges between the diagnoses. Help is clearly needed to reliably diagnose the presence of these difficult-to-demonstrate degrees of awareness.

The study published today is an attempt to validate the use of imaging techniques, in addition to clinical evaluation, to help determine whether a patient is or is not AWARE.

The study

Steve’s study looked at the ability of two imaging techniques, FDG PET scanning and fMRI imaging, to help distinguish between UWS and minimally conscious states. FDG PET images show brain areas that are actively using glucose. This is known to correlate with activity in those same areas. FDG PET images show the pattern of brain activity at rest. On the other hand, fMRI images look for use of oxygen in the brain. It is particularly useful to do when asking the subject to do a mental task – whether visualising something, imagining something, or DOING something moving fingers, pressing buttons, etc).

It is also known with high confidence that certain brain areas show normal activity in normally conscious patients, essentially no activity in UWS patients, and intermediate (but significantly reduced) activity in patients who are minimally conscious.

This study looked at the reliability of using activity in these areas to help confirm the diagnosis made clinically, and to help determine the patient’s prognosis.

Briefly, the study showed that FDG PET imaging is highly correlated with a previously validated (and widely if not universally used) clinical scoring scale. Importantly, one third of patients (13 of 41) diagnosed clinically as being in a UWS were shown by FDG PET to have activity in centres associated with awareness. Over the next year, nine of these 13 patients (remember, they were classified clinically as UWS!) had moved “up” to a clinical diagnosis of minimal consciousness or better, while of those with an imaging “confirmation” of UWS had terribly dismal outcomes. Of these 26 patients, 35% were still unconscious after one year . . . and 56% were dead. This shows that these images may well sensitively show the possibility of awareness, and seem to contain the same prognostic information that a clinical diagnosis of minimally conscious state contains. Further the numbers track what I’ve said in previous posts in terms of prognosis.

It is absolutely vital that we understand what the study didn’t show. It did NOT show that these 32% of patients were aware, or conscious. It showed that these patients, who clinically were felt to be unconscious, “had cerebral activity compatible with consciousness” (the authors’ words). But importantly, these patients had significantly better CLINICAL courses subsequently than those in whom PET confirmed an absence of activity compatible with consciousness.

Conclusion: it’s looking like at some point in the not distant future FDG PET imaging may well be a standard test in addition to clinical scoring, to determine whether awareness is or is not present in patients with disorders of consciousness. Remember: 1) it’s not yet fully validated, meaning more research is necessary before making this a standard tool with fully accepted statistical notions of reliability and validity; 2) until it IS validated, it remains a research tool.

Implications for Michael Schumacher

Actually, to the extent that Michael has been reliably shown clinically to have signs of awareness/consciousness (this would appear to be the case based on direct quotes of Sabine Kehm), this type of imaging would have no real utility, as a diagnosis of minimally conscious state would then have been made clinically.  On the other hand, my next post will deal with another paper by our Coma Science Group, one with fascinating clinical and even philosophical implications.



49 thoughts on “Some important science on disorders of consciousness – part 1

  1. Bruce, both would be like being trapped in hell. If either would be true for MS it is a very, very sad situation for a man who so enjoyed life.

  2. KC and Mimi – thank you for your comments.
    I suppose the uncomfortable question is whether it is better for a patient to be unaware or to have limited awareness while being almost unable to interact.
    The first – at least to me – is indistinguishable from being dead and hard decisions can be made using clear criteria. The second sounds very like a patient is offered a lifetime in solitary confinement with a small chance of a reprieve. From the patient’s perspective, more awareness may actually be worse.
    Although, I expect the few who recover will have a totally different opinion.
    It is a sad business, which ever way you look at it.

  3. Doc, a fascinating insight.
    Without meaning to be callous, cruel or cynical, I got to wondering on the ethics. In particular, who is likely to experience the greatest benefit from this technology. I’m certain that knowledge of a patient’s true condition enables optimal care from the medical staff and guides the patient’s family… but does it really help the patient? Of course, we shudder to think of removing sustenance from a conscious person but is it plausible that we might be maintaining someone in a state where there is very little prospect of improvement and no ability to interact? When either choice is bad, how does one apply the dictum “Primum non nocere”?

    If it’s of interest, the BBC has uploaded a report on this important work

    • Hi Bruce in my favorite city, Toronto.
      I just finished reading the Mosaic article reprinted by the BBC. I recommend it to all who have a serious interest in what may be going on with Michael Schumacher, or their loved ones, albeit none of us know what state Michael is really in because we have not been given any real specific truth from his medical team. On the other hand, Gary Hartstein has been a gift who keeps on giving.
      I also found your comments compelling, sincere and very thought provoking.
      I also could not help but think, there but for the grace of God go we.

    • Bruce, I find that article frightening!!!!! I couldn’t even get through it. IMO, death would be better than any one of those conditions.

  4. I believe he was airlifted from the ski slope itself. I think there videos of the helicopter taking off from the scene of the accident.
    I’ve done some reading about why a person is ventilated and sedated when there is a severe head injury. It has to do somewhat with keeping them quiet so that more damage is not done to the brain with the patient flalling and their bp rising. It’s all so complicated. There is so much to read and to digest.

  5. “Schumacher’s medical team has told Germany’s Stern magazine that the Moûtiers stopover helped save the driver’s life. They told Stern that the decision to land at the smaller hospital, which is only five minutes by air from the accident site, was necessary to stabilise their patient.

    Stern said the medical team had told the magazine that Schumacher had become comatose shortly after the rescue helicopter took off from the accident site and that he needed to be stabilised at Moûtiers hospital before undertaking the longer flight to Grenoble.”

    I think this indicates that there was a medical emergency soon after Schumacher was air-lifted. I think this is what Gary has expressed concern over for a long time – the issue of stabilising a TBI person before being air-lifted.

    • Jason, how do you ventilate someone on a mountain side?
      I’m not sure I understand why he had to be placed on a ventilator. Was he unconscious or immediately in a coma?
      So many unanswered questions….answers we, the public, may never get.

      • Hi Mimi,
        Didn’t the Doc say once that you do ventilate, if there is a severe head injury? But of course you have to know how severe it is. I am not a doctor at all, just thinking.

      • Hi Mimi, as per Gina’s response. This is what I would like to know more about (not necessarily specifically to MS but in a general sense). As Gina said I think the Doc said that before taking someone into an air ambulance following a hefty head impact you have to “stabilise them” if they show signs of incoherency – remember if the reports are true, the helmet was broken into two or three parts. I imagine MS was taken back to the chalet where the helicopter had somewhere flat to land on rather than being winched up onto an airborne helicopter on the actual ski-slope itself. I don’t know the protocols but the doc seemed pretty certain of what was possible and what could (should) have been done in such circumstance.

  6. I find your Blogg very interesting and insightful; thank you. I follow with interest Michael’s progress, not because I am a motor racing fan but because he is an outstanding sportman. His accident is tragic and so very sad and I wish beyond hope that he regains consciousness and is able to use his, previously demonstrated, will, determination and strength to recover. My thoughts are with his family and friends. Keep up the good work.
    Susan, Sunshine Coast, Queensland, Australia

  7. Came across this old BBC report about communicating with a patient who had believed to be in a PVS:
    “Vegetative patient Scott Routley says ‘I’m not in pain’
    A Canadian man who was believed to have been in a vegetative state for more than a decade, has been able to tell scientists that he is not in any pain. It’s the first time an uncommunicative, severely brain injured patient has been able to give answers clinically relevant to their care. Scott Routley, 39, was asked questions while having his brain activity scanned in an fMRI machine. His doctor says the discovery means medical textbooks will need rewriting”

    This seems to be exactly the area of research Dr Hartstein is reporting upon – where the technique of fMRI is being used and where 13 of 41 patients were shown to exhibit awareness. The difference in the BBC report is that they appear to have actually effected a communication with the PVS (UWS) patient Scott Routley through apparently asking questions and then examining and interpreting which parts of his brain “lit up”.

  8. Doc, what do you think of the allegations made by Stern magazine that MS should have been ventilated immediately and was not because the rescue people first on the scene where unaware of the severity of his condition due to his physical conditioning. And that the stop over before heading to Grenoble was to ventilate him.
    The magazine is stating that had he been ventilated promptly the outcome would be significantly different in MS’ favor.
    Why put all of this out there now? This can only serve to make the family and fans angry. We can’t change the past but I guess experience can surely help in the future.

  9. Excellent post, Gary. I have been a regular, albeit silent follower of your posts since Michael’s unfortunate accident. I am not a doctor nor am I qualified to speak about neuroscience. However, I had a thought that the prognosis for TBI may keep improving through generations for human beings. In earlier times, an injury to the brain may have meant that it leaves the victim vulnerable to other hazards (a prey, etc…). With human beings not having to deal with those security issues and with better care keeping the person alive, I would hypothesise that there is a better chance for nerve cells to “learn” how to cope with TBI and repair themselves and be part of an evolutionary process which may improve our ability to deal with TBI (in a few hundred thousand years???).

    • Hi Rmexx – it has already happened: a skull to protect the brain, suspended in a protective fluid, a maintenance and repair systems and back up systems for component failure. Also add “intelligence” & an instinctual behaviour for self-preservation.

      However there are ultimate limits, such as the Laws of Physics, in the protection of soft tissue from hard objects.

    • If we are allowed to describe and comment on what has been written in that media article: there is a claim that the stopover at Moutiers was unplanned and was part of a medical emergency that occurred within the first few minutes of airlifting MS … an emergency that potentially could have been avoided if MS had have been prepared differently for airlift.

      Now the question is can this claim be discussed in public, in private or not at all.

      It seems from the latest comment of the MS family via Sabine Kehm via the “German talk show”: the MS family would prefer no discussion of any matter related to MS post accident anywhere … as, repeating what SK is purported to have said on the chat show – this may be taken up by the media to create lies.

      I would respond by suggesting that it is valid to discuss this as it has implications far beyond any individual such as MS – it is a discussion of the procedure of handling all potential head trauma injured persons – including those that don’t make the news … in order to assess whether procedures could be improved.

      • Jason
        My guess is that if this question/issue is going to be discussed, it may/will be through legal means, possibly at some point in the future when someone can make a reasonable and defendable prognosis. Just a guess.

      • Jason, the stop over at Moutiers was to ventilate him which should have been done before he was airlifted according to the article I read. And according to the article is was because MS was in such great physical shape he did not appear to be in trouble. That makes no sense to me. Either he was or he wasn’t. Supposedly, his condition deteriorated dramtically in the helicopter forcing the stop at Moutiers.

        This is not me talking….I repeating what I read in an article.

  10. I saw Sabine Kehm in germans Talkshow (Jauch, Subject Boulevard Journalismn) last Sunday. She has spoken 10 Minutes but she said ‘nothing’ – at least nothing we did not new two weeks before. So why she went in the show? It’s ridiculoous. In this show she criticised the ‘remote’ diagnose from Gary as very bad manner and inaceptable. In contrary the german ‘yellow press’ she said makes a great job! Sounds crazy. made also many (wrong) headlines in past.
    I ask myselves why she not give us clean details (Brain Scan, professional Medical Statements, etc). Yes he is a private person and cannot give feedbac ant moment – I know. MS is an idol for many people and he has ‘brought’ about 600 Mio. Euros to switzerland and has contracts for commercial, etc. for 5 Mio. in year. So I think he is a kind of ‘public’ person. Who has an disadvantage if Kehm would say the ‘truth’? At the end of day rest only speculations! In this show she said MS has ‘moments of consciousness’ but we should respect he cannot speak because he is still in coma. So he is in coma or not?
    However: this blog I read with great interest and learned a lot about mecial but also ‘human’ things – thanks Gary!! And maybe if we had not so much space for speculations (or assumptions) this blog had not so a active life.

  11. This blog is so exciting and good. I have a question, that is maybe childish or silly, It is about the machines that tell us about the different states an injured person is in, that for example a patient is brain dead. How can you be so sure that the machines show a picture of the true reality of the patient?

    • Thanks for your kind words.

      Remember, a diagnosis is made by a team of caregivers, who painstakingly examine the patient. They then go on and use all the tools available to help them make the most accurate diagnosis possible at a given time. These tools include imaging (CT scans, PET scans, MRI images), physiological studies (evoked potentials, EEG, etc), and so on. The Lancet study is part of the process that validates a test for use by all care teams as an accepted and reliable measure of that which it purports to measure.

      Hope this helps.

    • Hi Gina – an example is the PET scan. When you use the brain to think something (what to eat in the evening, imagining kicking a ball) or use the brain to do something (e.g. clench a fist, or wriggle your toes) or use the brain to sense something (listening to someone speaking, or seeing someone waving at you) – different parts of the brain “light up”. That is different parts of the brain are being used.

      Different parts of the brain “being used” means the brain cells in those parts of the brain are “active”, Active cells consume glucose: glucose is the “chemical fuel” used to energise and power up the brain cells when they are being used. The brain cells draw the glucose from the blood supply. With the PET scan the glucose molecules are “radio-labelled”, that means they are radio-active with a half life of about 2 hours. This “radio-labelled” glucose is injected into the blood supply just before you go for the PET scan.

      When you use the brain the glucose is sent to those parts of the brain via the blood supply to the brain cells that need it – the concentration levels of glucose in those brain cells INCREASE. This INCREASED level of glucose acts as a source of RADIOACTIVITY inside the brain. The scanner picks up the radioactive emission and is able to localise that emission to the particular area of the brain being used.

      This is then “graphed” onto an image of the brain in a computer and the doctor gets to see that image of the brain on a computer display with the part of the brain being used “lit up”. Parts of the brain that are “not being used” are dark. Parts of the brain that are being used are “lit up”. The stronger the “light” on the display the more active are the brain cells being used.

      When the brain is “brain dead” (as per KC’s comment) the whole brain is “black” – nothing “lights up”. When you a looking and seeing someone waving at you – the visual processing centre at the back of the brain “lights up”. When you hear someone speaking to you – the audio processing centre at the side of the brain “lights up” … and so forth.

      Now the “radio labelled” glucose is a “low level” source of radiation so it doesn’t “damage” the brain. It works by replacing one of the oxygen atoms in the glucose molecule with a radioactive fluorine atom. When that radioactive fluorine atom decays (into an oxygen atom) it releases a positron – hence the name Positron Emission Tomography (PET), where Tomigraphy is the name of the “graphing” process that creates the image of the brain with the “lights on”.

      If you need to know more – you can access Wikipedia 🙂

      • Jason – Thanks for the answer. I meant my question in a “practical human” or philosophical way. Our good doctor answered that way, I think.

        Your text about how the PET scan works was very interesting to read. It was appreciated.

  12. Hi KC, I am talking beyond my area of expertise but I guess that hasn’t stopped me in the past … there is something strange in what you have described. PVS is not brain dead so something must have happened to turn a PVS patient into a brain dead patient.

    e.g. read

    Having a quick look at the case (Wikipedia) there is no indication that she was brain dead – the 2001 image shows facial expression which you wouldn’t get if brain dead. Moving on to the autopsy report it is mentioned that the brain had half the mass and there was massive structural abnormality. Also shown is a 2002 CT scan carried out when she was still alive – this doesn’t show she was brain dead – just that there was significant loss of brain tissue and large vacuoles forming. From what was mentioned elsewhere and the images of her “interacting” with her mother it looks like she was somewhere between PVS and MCS but the CT scans indicated no chance of significant recovery.

    How she went from having a normal brain to a brain that had lost half its mass is a puzzle but I would have thought it must have happened quite early on after the initial oxygen deprivation event. Or maybe it was some secondary infection she developed later on but before 2002 when the CT was taken. The aging brain loses mass but from what I have read that is not necessarily due to loss of neurones – it could be neurones losing water. But the autopsy said she had lost 70 % of the neurones in the cerebral cortex.

    Hi Mimi: I don’t know exactly what is happening with the time stamps. I am in England which is currently British Summer Time – but the time stamp on my comments are currently showing GMT (1 hour behind BST). NY time is currently 4 hours behind GMT so I am not sure where your 3 hour difference is coming from. It may be something to do with your local PC setting or something else. Thanks for pointing that out.

    • Jason – I read, probably, some of the pieces that you have referred to as well as the Wikipedia piece. From what I have learned from Dr. Gary over the last several months has been amazing and so informative which has led me to looking into things I never knew about and often it seems that the more I am informed about, the less I know; that’s a good thing. What is exciting is that the brain, today, is being looked at, studied, considered in many more ways than before. The tragedy is that people suffer and often knowledge about the brain is a very expensive process physically, emotionally, spiritually as is affects those we deeply love or admire.

      I am however still curious as to if the injured brain’s ability to heal itself if given attention or if it decays without THAT attention. I’ll keep looking and stay in touch.

  13. Doctor Gary
    As you probably there was a highly publicized case in the U.S., Terri Schiavo, who suffered massive brain injury due to full cardiac arrest. Her life support was in place from 1990 to 2005 as she had been diagnosed to be in a PVS.

    Her family insisted that she was responsive and fought for her vigorously through the legal system. Her brain scan on Google images shows, clearly, a brain dead person. (I don’t know the date of the scan or even if it is hers albeit the doctors claimed that the scan proved that they were right all along – which now I question since, apparently, it represents the last brain scan only).

    My question is this: if she was actually in a MCS and was inaccurately diagnosed, without rehabilition could the brain atrophy into a ‘nothingness’ – as would an unused muscle due to a spinal cord injury that paralyzed the patient from the chest down – and then be seen as brain dead?

    BTW, again, thanks for all of you willingness to stay involved and I LOVE your new series!

    • Hi KC, a muscle would atrophy but the muscle tissue itself wouldn’t die (unless blood stopped reaching it). I would imagine the same with the brain – it would have been the initial lack of oxygen that would have killed the brain tissue. When the body was functioning “normally” afterwards there wouldn’t have been any death of remaining brain tissue unless the blood supply to it was restricted or being blocked in some way.

      Hi Mimi – yes (but check the timing of the comments and responses).

      • Hi there Jason
        You are absolutely right about “a muscle” and brain tissue being VERY different. DUH on my part. I absolutely chose a poor analogy. Terri was in a coma for two 1/2 months and some therapys were applied after that time which suggests that the early scans may have had shown some encouraging information. I do know that brain cells die very quickly w/o oxygen; I do not know how long her brain was w/o and if it was way beyond the Golden Hour (as I believe that it is referred to).
        To simplify my question would be, if possibility of a long term rehabilition therapy might/could/would have been helpful, and by not doing anything can a brain atrophy in the MCS and as a consequence over time die?
        Good to hear from you

      • Hi, Jasonv2.0. With most here being in Europe and me in the good ole USA the times posted for messages is very confusing. My last message was written at approx. 3:15 pm on Wed. 3/16/14. But the the time on the message was 6:15pm 3/16/14. Isn’t there a six hour difference with the exception of England….

  14. Points of clarifications as regards consciousness & wakefulness. (thank you).

    It seems to me that one can show wakefulness without being conscious. Is the reverse also true is it possible to show moments of consciousness in the absence of wakefulness?

    Is REM in sleep an example of moments of consciousness in the absence of wakefulness? Similarly sleep talking and sleep walking are these evidences of consciousness in the absence of wakefulness?

    Thank you.

    • It is perhaps less ambiguous to use the word “arousal” rather than wakefulness. It means the patient would appear to be able to pay attention to something. Consciousness however, requires wakefulness. REM sleep is not consciousness. Dreaming probably does REFLECT consciousness, in that it consists of representations of both self and the external world, but is not itself a conscious state.

      One can be awoken from sleep, but during sleep one is not conscious. Locked in patients are normally conscious, but they have almost no way to show it. They’re . . . locked in.

      Hope this helps.

  15. Two Questions on “unresponsive wakefulness syndrome”

    Do patients in the this state
    1) show reflexes? I would assume yes because this is a spinal cord relay effect and not a brain processing effect.
    2) feel pain? I would assume no because pain is a product of brain processing (as far as I know).

    Thank you once again Dr Hartstein.

    • Yes to reflexes. This is one of the hard things for evaluators to deal with – it is absolutely necessary that any reactions to external stimuli NOT be reflexes, spinal or otherwise.

      There is no pain, by definition. Pain is a conscious experience. No thirst or hunger, no wanting, dreaming, thinking. No hopes, wishes or sadness.

      • Thank you, doc for the response. I did read somewhere….probably here that when a feeding tube is removed a person is deprived of food but they are not starving to death because they don’t feel hunger. They don’t feel anything. It just shakes me to my core thinking of how these people are just “there”…existing, not living.
        This is not how I would want to live..

      • Hi Mimi, in your example they will “starve to death”, but they won’t be conscious of it.

        ps: This type of consideration puts a strain on the very meaning of “they” and “self”

  16. Locked-in syndrome is a relatively specific situation that results from brainstem damage which leaves most, if not all, of the higher centres intact. These patients therefore have normal consciousness and cognitive function, but they can only interact with their environment using an extremely sparse range of output. This is classically limited to eye movements (in the full-blown syndrome these are limited to up and downward gaze!), but these can obviously then be used to communicate. LIS usually results from strokes, but can also be due to infections, trauma, and degenerative diseases.

    While none of us is sure what form the “consciousness” that Sabine speaks about is actually taking, what is significant is not so much the subjective content, but the simple fact of consistent and unambiguous interaction with the environment. As for what exactly the brain is DOING with the information thus entering its conscious awareness, I can only hope that Michael will tell us what it was like in a book he writes in the future!

  17. I have to find a quiet space and reread the good doc’s lastest message to fully digest what he is telling us.
    But in the mean time….Can someone answer this for me please. If MS is awake and sees his wife….what does he think at this stage. Is it all a blank or is he thinking there is my wife. When he smiles does he think something is funny? Is he smiling at someone or something or just smiling.
    If he is aware and can’t respond is that the same as locked in syndrome. How is LIS determinded?
    I find this all so interesting and those who work in this field have to find it so rewarding when they uncover some secret of the brain.

  18. Thanks Gary. It sounds like Michael is lucky because he is already showing clinical signs on coma recovery scale and is recovering both consciousness and eye opening at the same rate. Do you think he may still be in Grenoble because bone flaps still need to be replaced following decompressive craniectomy?

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