September 2006

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)