Tag Archives: fMRI

The Undiscovered Brain (revisited)

Human BrainIt has been a while since I reported and commented on progress in understanding the minimally conscious state. Over recent months some exciting news reports have appeared which I feel it is appropriate to refer to here.

Firstly this article appeared in The Guardian last November about Rom Houben, a man who laid for 23 years, assumed to be in a Persistent Vegetative State (PVS), the state of being unaware of everything around you, oblivious to the world, when in fact he was hearing everything. A neurologist at the University of Liège (Dr Steven Laureys) examined him with new scanning technology and found that his brain seemed to be working quite normally. Most of the article continues to talk about an ability to communicate that was also thought to have been found, which it is now thought was a mistake, but a notable point comes toward the end of the write-up. The Guardian article quotes Dr Laureys, who is very experienced in these cases, as saying that of 44 patients he examined who were diagnosed as being in a vegetative state, 18 of them responded to communication. Furthermore, while it is not uncommon for patients with reduced levels of consciousness to have as little as one assessment by a professional which will determine their diagnosis, Steven Laureys said that such patients should be tested ten times, and that such states were like sleep, having varying stages which need to be monitored. This is an observation that I fully support from my experience with Ladan, there are times when Ladan is clearly out of it, there are times where there seems to be some very basic responsiveness to what is happening around her, often including to actual words being said, and then there are much less frequent occasions where for about 30 seconds or so she can interact with her eyes.  There is a clear difference even in Ladan’s appearance when she is in the most responsive state but it would be impossible to make a plan that would ensure  an expert examined her or scanned her during such an infrequent opportunity, even if she was tested ten times that moment would probably not be caught, but such a policy would probably suffice to catch Ladan at a time that she wasn’t at her least responsive. Luckily for Ladan she was found to have a degree of awareness on her second clinical neurological examination, but it could have taken more.   The more accredited professionals do generally maintain that there is no sure test that can prove an individual is not aware of what is happening around them, all the tools that science has can only help to make an educated guess and, more importantly, attempt to discover if somebody is suitable for a programme of rehabilitation. Unfortunately finding  some degree of awareness is not in itself sufficient for finding a rehabilitation method.

In this blog post a few years ago I referred to a study in Cambridge that, in the long term, may offer hope of rehabilitation techniques to the least able of minimally conscious patients, as well as uncover signs of consciousness in patients otherwise held to be in the persistent vegetative state.  I also looked at some of the potential dangers of misdiagnosis of PVS. That posting referred to a study by a team in Cambridge, including Dr Adrian Owen, in which a woman who was thought to be in a persistent vegetative state was asked to imagine playing tennis while she was scanned using a relatively new technique (fMRI) with an MRI scanner. The resulting changes in the  images on the scan were much the same as the changes witnessed in a fully conscious individual carrying out the same request.

At the beginning of February Channel 4 News ran a story about further research into this technique by teams led by both Dr Adrian Owen from Cambridge and Dr Steven Laureys from Liège.  Again taking a patient formerly thought to be in PVS, the same request of  imagining playing tennis was made to the patient but this time it was to be used  by the patient as a tool to indicate yes or no responses to questions.

“It works like this,” Dr Owen said, explaining the idea in this  Sunday Times article back in 2007, “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.” […] “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.”

Below is a news clip from Channel 4 News adding a little more detail about the successful experiment:

Where this technique is currently going to be most important is where it will make a difference to the long term plans for the patient. Here in North-East England the policy of medical and care staff is – as I understand it – to act on the assumption that even somebody thought to be in PVS may actually be aware and understanding everything around them, obviously there is no extra harm that will come from talking to somebody who can’t hear you, but it is not kind to completely ignore somebody who is fully aware of everything you are saying. Ladan is known to have some awareness and the nursing home she is in would, as a rule, treat her on that assumption even if she had been diagnosed as being completely unaware, but still I get disheartened when occasionally a carer will come into her room and assist with her needs without saying so much as a “hello” to her. I cannot imagine how much the frustration of being unable to communicate would be made worse for an individual diagnosed as being in a persistent vegetative state if it was acceptable to ignore them as a matter of policy because of their misdiagnosis. But beyond the doctors and carers there are – of course – the families, and a black and white misdiagnosis of PVS may make them even more likely to just stand and stare at a relative who would actually love to hear them talk to them. Dealing with trauma in a family is difficult enough as it is, if a family are informed through a misdiagnosis that their presence cannot possibly be known to their loved one, then the chances of the patient losing the support of their family must be greatly increased. It is important that families are not given assumptions of probability as fact, they have tough decisions to make ad should know the full picture, even if that picture is full of  “probably not“s and “we don’t know“s, rather than definitive statements.

It should be noted that finding the ability to communicate with an individual formerly misdiagnosed as being in PVS is rare, even when some degree of awareness is found it is not usually a guarantee that they fully understand everything that is going on around them. It is possible that somebody who can communicate in a scanner may also not be fully aware of what condition they are in, though they may even falsely believe themselves to be, but what this offers, even at its most basic, is access to more facts upon which assumptions about a brain may be based. At its best it gives a patient a voice, though possibly not a say, in decisions over how they should be treated.

Looking into the future, these discoveries may help to provide rehabilitation techniques to those people in minimally conscious states who cannot react with the outside world in a consistent way. Current rehabilitation techniques need something to hook onto,  a consistent physical response, such as a finger that the patient will almost always move when requested. fMRI is still a relatively rare and very expensive facility, but it offers that ‘something’ to hook onto in patients who have a reaction that shows up in the scanners imaging, and that means that either by using fMRI scanning regularly as part of a rehabilitation programme, or by finding other ways to detect the responses that using fMRI scanning has uncovered, the potential exists for a greater number of individuals who fall into a minimally conscious state to embark upon a programme of rehabilitation.

The Undiscovered Brain

There have been two encouraging items in the press recently about patients diagnosed as being in a persistent vegetative state (PVS), a condition where it is believed the brain has no awareness of the world around it but is able to support basic life functions such as breathing.

In Cambridge a group of scientists used a special scanning technique (called fMRI) to discover that a 23 year old woman could hear and that her brain responded to requests to imagine activities in exactly the same way as the brains of healthy volunteers did. On Tuesday this week The Guardian printed a detailed article updating a story they first told in May this year about the effects a sleeping drug called Zolpidem has been having on patients in the same persistent vegetative state, as well as on other patients with brain related problems. Beyond these recently reported findings there are also interesting results to be found from people using a drug called Levodopa which is commonly used by people suffering from Parkinson’s disease and there are the interesting scans and testimonies of people who have come out of long term states of reduced consciousness which add to the weight of information which has serious implications over what assumptions can be made for the “unconscious” brain.

As the husband of a woman in a state of impaired consciousness I have a first hand perspective of the assumptions that are made about people in this kind of condition and why these discoveries are important.

There are two main areas of interest that these discoveries have an impact upon, they are the understood level of awareness of the unconscious brain and implications for continuing care and treatment.

There are several classifications that are often given to people in a reduced state of consciousness, in addition to the persistent vegetative state there is also the minimally conscious state (MCS) where there is some identifiable awareness of the environment around and the Locked-In state where the individual is thought to have all their cognitive functioning in place but is unable to move or communicate but for, possibly, the blink of an eye. These are basic summaries rather than scientific descriptions.

In reality even people who are diagnosed as being in PVS will often have relatives and/or carers who are sure that they see regular signs of awareness. What the research in Cambridge has shown is that in at least one of these cases there was some awareness which would have remained undetected using standard methods of testing.

To understand the importance of this discovery you have to know what happens to patients who are in any form of unconscious state where awareness is difficult to detect, and to their relatives. Here I can use Ladan as an example, though I have also come into contact with a few more patients and their families over the last couple of years.

When Ladan was unconscious after her first haemorrhage in November 2004 she quickly recovered to a point where she was able to obey simple commands and track with her eyes, though sometimes she would be more asleep than at other times. A Registrar Neurologist spoke to me and other members of Ladan’s family while Ladan was in this state and on a bed in front of us. He told us that Ladan was not aware of anything, she could not hear anything, she could not tell that her family was around her and that it was unlikely that she ever would have such awareness again. He told us that it is common for family members to imagine such awareness exists when it does not and that we should accept that we were just seeing what we would like to see. Stood there, in front of Ladan, he asked us to confirm that we understood what he was telling us. A couple of days later that same registrar’s face was a beacon of happiness as he himself witnessed Ladan following everything he asked her to do with her eyes and face. He had seen much less evidence than we had seen, but until he had seen it for himself he was convinced that we were imagining it.

Now imagine if, at that earlier moment, Ladan not only heard everything that the registrar had told us but that it was followed by us saying “well, I guess that’s it then”, and leaving her to be by herself for the most part of her life from that moment on. Thankfully I knew myself to be of sound enough mind to be sure that what I had been seeing was real and I immediately leaned over and said several reassuring words in Ladan’s ear as soon as he left her side to assure her that I knew she was aware, could hear, and would not be left alone.

This is just the first stage at which this assumption, that an outward lack of signs of awareness is evidence that a patient cannot really see, hear or have awareness of their environment, might have a serious impact on their future care and support.

Because people in a reduced state of consciousness are able to live with minimal assistance (such as being fed and cleaned) they are generally kept in a care environment where there is a strong likelihood that they will pick up serious infections or develop other complications, sometimes related to how well they are looked after, which will require identification and treatment. Relatives are often asked if they would like their loved one to be treated in the event of serious infection or left to deteriorate, and this decision is often made on the basis of an assessment that the patient has no awareness of their environment, no ability to tell that loved ones are there, no ability to see or hear, no perception whatsoever. Even if one close relative, most likely the one who spends most time with the patient, is certain that they are seeing real signs of awareness there, it is still likely that other relatives will hear what the doctor is saying and attempt to convince the closest relative that they are imagining everything and should focus on their own life more instead of holding out hope for somebody who, they are told, is all but dead. So although an assumption of zero awareness does not affect whether somebody lives or dies in the earliest stages of their continuing care, this belief can have a major impact on how long the patient will continue to live once they start picking up infections from the hospital or care home environment.

The recent study in Cambridge should ideally sound as a trumpet blast to doctors who boldly state that patients cannot hear and have no awareness, and make neuro-specialists much more careful in the way they describe a patient’s condition. Ladan’s two neuro-specialist consultants have always been very open minded in their words and actions.

There are a number of patients who recover from long or short term loss of consciousness with at least some memories of their time when they were theoretically unaware of anything around them, but these memories are often vague or inaccurate and are therefore probably dismissed too easily. Although the study in Cambridge may not seem to prove very much it does remind everyone that any current diagnosis of PVS is an assumption based on tests which, it is known, cannot give a full picture of what the brain may or may not be doing.

There may be a lot more loving and optimistic care and support for patients if these assumptions were stated as the assumptions that they really are and not presented to families as scientific facts, and with more support, and more to live for, more people who were thought to lack awareness might even find the strength to improve to at least some greater degree.

Beyond the implications on how infections are dealt with and how a patient would be communicated with and supported with a more open-minded assessment being given to relatives, the discoveries that are being made with Zolpidem and from newer scanning techniques with recently improved patients may have important implications for the way that patients with reduced levels of consciousness are looked after and treated.

There are now several reported cases of people who have had severe brain damage showing areas of brain as ‘dead’ on a scan and then, after some unexpected future improvement, had a scan which shows activity in those locations. This has always been considered impossible as the brain is thought to be an organ that cannot regenerate to repair itself. The trials of the drug Zolpidem in South Africa have uncovered scan results of this nature and have raised the suggestion that brain tissue might be able to hibernate rather than die. Such a suggestion raises questions over what potential exists for recovery following brain damage.

Zolpidem and Levodopa are two drugs that have had very unexpected results on patients with reduced levels of consciousness. Zolpidem is a sleeping pill which was discovered to have amazing results when a brain damaged patient who could not communicate was agitated and given the sleeping pill to calm him down, shortly after administration of the drug the patient turned to the nurse and seemed to focus on her, the nurse asked the man if he could hear her and he replied “yes”. It is not yet known for sure why the drugs have positive effects on a large number of people but there is a theory that the traumatized brain develops an increased sensitivity to a neurotransmitter in the brain called GABA, GABA inhibits responsiveness and is thought to be part of the brains mechanism for dealing with pain, the theory is that Zolpidem is stopping this oversensitivity to GABA and so allowing the brain to become more responsive. This theory falls nicely in line with the observations that Levodopa has an impact on people in reduced states of consciousness. Levodopa increases a neurotransmitter called dopamine in the brain, which is important for movement and cognitive function, dopamine neurons are known to be suppressed by GABA. Beyond the obvious hope that success stories relating to these drugs brings to the table it also may raise some questions over the fairly common use in PVS and similar patients of a drug called Gabapentin which is designed to imitate GABA neurons in the brain and is used to reduce a patient’s responses to pain or agitation, it may even be prescribed for use instead of handling the patient in a comfortable fashion. If there is truth to the theory that reducing sensitivity to GABA is the key to Zolpidem’s success, and it is seen that continued use of Zolpidem has a cumulative positive effect on patients, then it might be that using drugs like Gabapentin is having a negative long term impact on any chance of recovery.

While this blog entry may be too specialized for many of you who come here for updates on how Ladan is doing, I hope it will be encouraging for the steps that are being made, however small, toward better understanding the states of reduced consciousness that people fall into. The articles below, particularly the Guardian’s G2 article, make for interesting reading.

Further Reading:
G2 Article on Zolpidem
BBC News – Vegetative Patient Communicates (with video)