The Harder Problem: Functional PET Scanning and Prognosis in the Vegetative State

Cardiac arrest or very severe head injuries are most often fatal, but what of when they are not? Often in such cases we find a person in deep coma, yet one with signs, such as preserved pupillary reflexes, facial movement, or remaining breathing efforts, that they are not brain dead. When this state is prolonged, we may call it the "vegetative state."

Many people who enter the vegetative state never regain consciousness, but others, especially those whose brain injury is from head trauma rather than cardiac arrest, do recover at least some some level of waking consciousness. Prediction of who will recover would be useful in counseling families regarding decisions on how long to maintain artificial means of life support such as mechanical ventilation.

In the Lancet this week, a study has been published which found that functional PET imaging may improve the accuracy of clinical predictions of the potential of waking from a vegetative state.The method seemed more accurate than fMRI in those patients.

Chalmers famously asked the hard problem:  Given a complete materialist description of a thinking, feeling, behaving human, why should those physical processes we have described so completely be accompanied by subjective consciousness? Of course, when engaged in honest conversation with another person, we do not doubt that he is thinking and feeling; the fact that he possesses subjective consciousness is more obvious to us than any physicalist philosophy of mind could ever be!

But what of the person who is vegetative? Here common sense intuitions may fail. This is the harder problem: to find a way of seeing as partially conscious (or denying such) with those who show no outward signs of consciousness.

Related questions for which I have no fixed answers yet:  if one who appears comatose shows partial functional PET signs of conscious awareness, is it correct to say that the patient is in some sense conscious?  If so, where lie our ethical duties? If not, where have we drawn the line, and why?

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ABSTRACT

The Lancet, Early Online Publication, 16 April 2014

doi:10.1016/S0140-6736(14)60042-8Cite or Link Using DOI

This article can be found in the following collections: Neurology (Head injury)

Copyright © 2014 Elsevier Ltd All rights reserved.

Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study

Johan Stender MD a c †, Olivia Gosseries PhD a †, Marie-Aurélie Bruno PhD a, Vanessa Charland-Verville MSc a, Audrey Vanhaudenhuyse PhD a, Athena Demertzi PhD a, Camille Chatelle PhD a, Marie Thonnard MSc a, Aurore Thibaut MSc a, Lizette Heine MSc a, Andrea Soddu PhD b, Mélanie Boly PhD a, Caroline Schnakers PhD a, Prof Albert Gjedde PhD c, Prof Steven LaureysPhD a 

Summary

Background

Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI).

Methods

For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale—Revised (CRS—R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS—R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale—Extended.

Findings

We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). 18F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30—61) and had lower overall congruence with behavioural scores (63%, 51—73) than PET imaging. 18F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness.

Interpretation

Cerebral 18F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate.