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jake-head-shot.jpgJake Young is a MD/PhD student at Mount Sinai School of Medicine in NYC getting a PhD in Behavioral Neuroscience. He holds a BS and MS in Biological Sciences from Stanford University. If a volcano were to erupt Pompei-style in Central Park, his body would be preserved in a scoliotic posture over his lab desk. Archeaologists would later conclude that he spent most of his day training rats to perform tricks, until he went blind building electrical equipment by hand using a dissecting microscope. But, still, he died happy...because science is cool.

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Recovery = Probably Not a Persistent Vegetative State

Category: Neurological disease
Posted on: March 6, 2009 1:51 PM, by NotoriousLTP

I caught this story (with an accompanying video) over at Mind Hacks and Neuron Culture about this poor woman from the UK who fell unconscious from a viral infection in her brain stem. Using fMRI, a doctor at Cambridge named Adrian Owen showed that she still had residual brain functions such as response to light. The woman has since recovered from her condition and can interact, though she still faces substantial impairment.

The thing is that people are continuing to use the term persistent vegetative state to describe her condition. I think this is misusing the term. A better description would be that she was probably mis-diagnosed and now has gone through a partial recovery.

Check out the video first:

A very sad story, and I wish Kate the best in her recovery.

However, I do have a comment about how this story is being presented.

Some people are likely to frame this case as a recovery from a persistent vegetative state. I want to make clear that I don't think that is what happened here. Rather, the much more likely event is that she was mis-diagnosed as being in a persistent vegetative state when she was in fact in a minimally conscious state (more on this in a second). Part of that misdiagnosis has to do with limitations in our ability to get an accurate diagnosis -- something Dr. Owen is trying to address.

First thing, you have to understand the diagnostic criterion for different types of unconscious states. The table below is from here. It compares the different symptoms of various unconscious states (click to enlarge).



chart.jpg

Note that neurologists draw a clear distinction between minimally conscious (MC) and persistent vegetative states (PVS). Partly, this distinction rests on different clinical findings. For example, to what degree does the patient track different visual stimuli? To what degree does the patient respond to noxious (painful) stimuli? These are the types of clinical findings that a neurologist would look for in a clinical exam to differentiate between the two states.

Partly, and more important in relation the patient shown above, this distinction rests are the relationship between clinical findings and whether we think the patient is completely unconscious (PVS) or only intermittently or partially conscious (MC). However, the relationship between clinical findings and consciousness isn't clear cut. There isn't a clear relationship between the responsiveness to pain and the existence of consciousness. It is something that we have to infer. Because we don't have access to what the patient is thinking (or not thinking) it is really hard to tell whether they are conscious or not.

This is in part a problem with the term PVS. Neurologists are often loath to use it because it basically rests on the failure of the patient to get better. Because the vegetative state persists, we call it PVS. Unfortunately, at present we really don't have a better system.

Thus, without justifying what may well have been physician error, I can see how this patient may have been mis-diagnosed. She says in the video above that she could perceive pain and did have intermittent consciousness of what was happening to her. This means that she was not in a PVS as I understand the term. The problem is that even a very good diagnostician may have missed the signs of that intermittent consciousness.

This is why Dr. Owen's research is so important. (More on his research here.) In using fMRI to determine whether the activity associated with consciousness is present in these patients, he is giving us a much more powerful diagnostic test. Before, we had EEGs and clinical exam, but if you can do an fMRI or a PET scan and show that conscious-like activity exists, we can be much more certain about the patients diagnosis. And this is not a trivial problem in a couple of isolated cases. Some estimate that as many as 40% of these patients are diagnosed as being in PVS when they are in fact in MC.

The distinction between PVS and MC is also critical in terms of prognosis. I never want to say never, but it is exceedingly rare to see some with PVS recover. In fact, I might go so far as to argue that one of the clinical criterion for PVS is the near impossibility of recovery. PVS is generally caused by anoxic brain injuries where nothing remains intact but the housekeeping functions of the brain -- breathing, orienting to light, sleep cycles, etc. There is nothing left of the higher functions to recover. By contrast, MC (which is much more commonly caused by trauma or infectious disease) can spare a greater deal of the brain. What is impaired is often the reticular activating system (RAS) -- a sort of neurological on-off switch without which none of these higher centers can be active. (Some clinical interventions may be possible to reactivate the RAS, using drugs or deep-brain stimulation, which is why you sometimes read about coma "recoveries." Whenever you read that, I want you to remember that the patient was probably in a MC rather than a PVS).

These are rough distinctions. Individual patients are rarely clear cut with these issues. But the take home is that PVS patients will probably never get better and MC patients -- though they are likely to have significant continuing impairment -- might.

The take-home that I want you take away from this story is not that a PVS patient recovered. I do not think that she had PVS. The important point is that scientists are working to help us distinguish between patients who have a very bad prognosis and those that have a slightly better one.

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Comments

1

It will be interesting to see how euthanasia advocates spin this. Your blog entry gives us an indication of an argument they may use.

Posted by: Mike | March 6, 2009 3:11 PM

2

Excellent analysis, dude. It is very important that you are making this distinction clear. Kudos.

Posted by: Comrade PhysioProf | March 6, 2009 3:23 PM

3

...and if the suspected witch drowns they weren't a witch. The impossibility of recovery is just such a test. There are so many problems in logic with this it makes my head hurt. Those clinical criteria were developed without any knowledge of their relationship to consciousness in these states so their predictive value is basically zero. People that woke up may not have been conscious and some who never wake up may be. Given the recent debate on what fMRI studies mean, if anything, I'm leaving my blanket instructions not to pull the plug in place.

Posted by: just doug | March 6, 2009 6:20 PM

4

Hi Jake,

People recover from PVS and there are many well documented cases reported in the literature.

A recent review reviews predictors of recovery from PVS, although despite some well known exceptions in the literature, after 1 year it is increasingly unlikely.

In the case described above, which seems to be Owen's 1998 report from the Lancet, it sounds like Kate was originally in PVS, and slowly regained awareness, consciousness, and then motor control.

However, the point of Owen's research (most explicitly his 2006 Science paper) was to show that someone who fulfils the clinical diagnosis of PVS (i.e. no external signs of conscious activity) can actually consciously respond to external stimuli.

In other words, she was not misdiagnosed - she fulfilled all the criteria of the diagnosis, but the research has demonstrated that the diagnosis lacks validity - i.e. it does not keep track of the recovery of awareness and consciousness.

Actually, I think this is the exact point your making but it's important to make the distinction between misdiagnosis and the validity of the diagnosis.

Posted by: Vaughan | March 7, 2009 2:40 PM

5

I can comment on this type of scenario first hand. My son sustained an anoxic injury at 14 months of age, and we were told that he was in a PVS and would never recover. 3 years later we now know that he is actually locked in. Doctors can only do the best with the information they have at the time of diagnosis, but the ability of the human brain (especially the plastic brain of a child) to recover is far beyond our current ability to medically comprehend.

Posted by: Alicia | March 9, 2009 10:09 AM

6

The People who are facing these problems like Persistent Vegetative State , Minimally Conscious State or Locked in Syndrome are aware of this fact that there is actually nothing for them medical science can do. They are only victims of experiences with them and that is against all the ethics.

Posted by: Anwer Kamal Pasha | March 22, 2009 6:59 PM

7

Thanks for the positive feedback about our team's research. Your analysis of the main problems in this area is incisive and your interest is much appreciated. Best regards, Adrian M. Owen

Posted by: Adrian Owen | April 8, 2009 1:52 PM

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