Johan Stender1, Olivia Gosseries2, Marie-Aurélie Bruno2, Vanessa Charland-Verville2, Audrey Vanhaudenhuyse2, Athena Demertzi2, Camille Chatelle2, Marie Thonnard2, Aurore Thibaut2, Lizette Heine2, Andrea Soddu3, Mélanie Boly2, Caroline Schnakers2, Albert Gjedde4, Steven Laureys5. 1. Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. 2. Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium. 3. Brain and Mind Institute, Physics and Astronomy Department, University of Western Ontario, London ON, Canada. 4. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. 5. Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium. Electronic address: steven.laureys@ulg.ac.be.
Abstract
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 (18)F-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). (18)F-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. (18)F-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 41 (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 (18)F-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. FUNDING: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.
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 (18)F-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). (18)F-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. (18)F-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 41 (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 (18)F-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. FUNDING: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.
Authors: Jonathan Marehbian; Susanne Muehlschlegel; Brian L Edlow; Holly E Hinson; David Y Hwang Journal: Neurocrit Care Date: 2017-12 Impact factor: 3.210