coma & related states - coma science group webpage
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www.comascience.org
1
Coma & related states
Steven Laureys MD PhD Coma Science Group Cyclotron Research Centre & Neurology Dept University & University Hospital of Liège Belgium
coma@ulg.ac.be
www.comascience.org 2
Programme
Lundi 28/01
Arrivée au Centre de Recherches du Cyclotron
10h00-11h00 : Présentation globale des travaux du Coma Science Group (partie 1) – Steven LAUREYS
11h00-11h30 : Pause café
11h30-12h15 : Présentation globale des travaux du Coma Science Group (partie 2) – Steven LAUREYS
12h15-13h00 : Visite du Centre – Audrey VANHAUDENHUYSE
13h00-14h00 : Lunch
14h00 : Départ pour le CHU (+/-5 minutes du Cyclotron) 14h30-16h30 : Visite du CHU – Audrey VANHAUDENHUYSE :
Département de Neurologie (Tahar Bakay)
Département d’Imagerie Médicale (Jacques Trenteseaux, Laurent Hermoye)
www.comascience.org 3
Programme
Mardi 29/01
10h00-16h00
Visite du Centre Neurologique et de Réadaptation Fonctionnelle de Fraiture – Vanessa CHARLAND
(Adresse : Champ des Alouettes 30 4557 Fraiture +/-30 minutes de Liège)
Présentation des différentes installations dédiées aux patients en état de conscience altérée (salle « snoezelen », bain thérapeutique, kiné, logopédie, etc.) et présentation du fonctionnement du centre par le Dr Laurence PIRNAY.
www.comascience.org 4
Programme
Mercredi 30/01
10h00-13h00
Visite des cliniques de l’IPAL – Aurore THIBAUT
Présentation des différentes installations dédiées aux patients en état de conscience altérée et présentation du fonctionnement du centre par le Dr Alioun DIOH.
(Adresse : Montagne Sainte-Walburge 4, 4000 Liège +/-15 minutes du centre de Liège)
15h00-16h00
Visite d’un patient au domicile – Aurore THIBAUT (Adresse : rue du cimetière 7, 1450 Gentinnes +/-1h de Liège)
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Programme
Jeudi 31/01
Centre de Recherches du Cyclotron
10h00-10h30 : Evaluation clinique – Audrey VANHAUDENHUYSE
10h30-11h00 : EEG & Interfaces Cerveau-ordinateur Quentin NOIRHOMME
11h00-11h30 : Pause café
11h30-12h00 : Evaluation de la spasticité – Aurore THIBAUT
12h00-13h00 : Don d’organes – Didier LEDOUX
13h00-13h30 : Lunch
13h30-14h00 : Transcranial direct-current stimulation – Aurore THIBAUT
14h00-14h30 : Présentation du projet fédéral belge – Marie-Aurélie BRUNO 14h30-16h00 : Discussion
www.comascience.org 6
Programme
Vendredi 01/02
Centre de Recherches du Cyclotron
10h00 : Mot de clôture et discussion – Audrey VANHAUDENHUYSE
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Laureys, Trends in Cognitive Sciences, 2005
Reducing consciousness to 2D
Coma
General Anesthesia
Locked-in syndrome
Minimally Responsive
-command following MCS+
- non-reflex movements MCS-
“Vegetative” unresponsive
Conscious Wakefulness
Drowsiness
St I-II Sleep
St III-IV Sleep
Lucid
Dreaming
REM Sleep
Epilepsy Sleepwalking
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
= necessary but not sufficient
www.comascience.org 8
Reducing awareness to 2D
Boly et al, Ann NY Acad Sci 2009
Vanhaudenhuyse & Demertzi et al, J Cogn Neursoci 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 9
Laureys et al., Lancet Neurology, 2004
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Consciousness ≠ global brain function
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Consciousness ≈ frontoparietal
Areas systematically dysfunctional in “vegetative” state
Areas recovering metabolism after recovery from “vegetative” state
Laureys et al, J Neurol Neurosurg Psychiatry, 1999
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Laureys et al, Neuroimage 1999
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Laureys, Trends in Cognitive Sciences, 2005
Consciousness ≈ frontoparietal
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 12
Frontoparietal “global workspace”
Baars, Ramsoy, Laureys, Trends in Neurosciences 2003
no arousal no awareness
preserved arousal no awareness
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Laureys et al, Lancet Neurology, 2004
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Precuneus ≈ hub in the network
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Terry Wallis wakes from 19-year coma
Voss et al, J Clin Invest, 2006
www.comascience.org Vogt and Laureys, Prog Brain Res, 2005 Vogt, Vogt and Laureys, NeuroImage, 2006
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Precuneus ≈ hub in the network
ANESTHESIA
Activity in P
CC/p
recuneus
loss of command following
WAKE
DROWSY
SEDATION
ANESTHESIA
WAKE
SLEEP Activity in PCC/precuneus
WAKE STAGE 2 STAGE 3-4 REM SLEEP Activity in P
CC/p
recuneus
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Two awareness networks
Laureys, Scientific American 2007 Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
EXTERNAL or SENSORY
AWARENESS
INTERNAL or SELF
AWARENESS
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Two awareness networks
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
EXTERNAL or SENSORY
AWARENESS
INTERNAL or SELF
AWARENESS
0.05 Hz ≈ 20s
Laureys, Scientific American 2007 Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
External and internal awareness
Boly et al, PNAS 2007
EXTERNAL (SENSORY) AWARENESS (laser stimulation)
Perrin et al, Neuropsychologia 2005 Qin et al, Human Brain Mapping, 2010
INTERNAL (SELF) AWARENESS (own name)
perceived (433±23 mJ) > unperceived (438±21 mJ)
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Modulation by hypnosis
Demertzi et al, Prog Brain Res 2011
N D H N D H N D H
Normal wake
Distraction
Hypnosis
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Consciousness ≠ primary cortex
Laureys et al, Brain, 2000
Boly et al, Archives of Neurology, 2004
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
“VEGETATIVE” UNRESPONSIVE
MINIMALLY RESPONSIVE
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Consciousness ≈ top-down
Boly, Garrido, Gosseries, Bruno, Schnakers, Massimini, Litvak, Laureys, Friston, Science, 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Disorders of consciousness
Bruno et al, J Neurology, 2011
VEGETATIVE/UNRESPONSIVE
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Diagnostic error
n=103 post-comatose patients – 45 clinical consensus diagnosis ‘vegetative state’
– 18 signs of awareness (Coma Recovery Scale)
40% potential misdiagnosis
Schnakers et al, BMC Neurology 2009
coma@chu.ulg.ac.be
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Eye tracking : use a mirror!
Vanhaudenhuyse et al J Neurol Neurosurg Psychiatry 2008
n=52
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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A new name for « vegetative »
Laureys et al, BMC Medicine 2011
“There’s nothing we can do… he’ll always be a vegetable.”
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Monti & Vanhaudenhuyse, Coleman, Boly, Pickard, Tshibanda, Owen, Laureys New England J Med 2010
Yes-No communication with fMRI
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
EEG-based Brain Computer Interfaces
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
SCIENCE GROUP
COMA
Cruse et al, Lancet 2012
3/16 VS/UWS (19%) - 2/5 traumatic (40%) - 1/11 non-traumatic (9%) Cruse et al, Neurology 2012
7/23 MCS (30%) - 7/15 traumatic (49%) - 0/8 non-traumatic (0%)
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
EEG-based Brain Computer Interfaces
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Schnakers et al, Neurology, 2008 Schnakers et al, Neurocase, 2009
Fellinger et al Clin Neurophysiol, 2011
theta synchronization
theta synchronization
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Aphasia as a confound
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Bruno et al, J Neurology, 2012
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Automated consciousness classifier
Phillips et al, NeuroImage, 2011
“Relevance Vector Machine” on FDG-PET data in DOC
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Frontoparietal global workspace
Thibaut et al, J Rehabil Med 2012
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Visual fixation is a reflex
Bruno et al, BMC Neurology 2010
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Consciousness ≈ connectivity
EEG-TMS
Rosanova and Gosseries et al, Brain 2012
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
“Resting state” default brain activity
PCC
MFC
Boly et al, Human Brain Mapping 2009
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
0.05 Hz ≈ 20s
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Functional MRI in “resting state”
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Jox, Bernat, Laureys, Racine, Lancet Neurology 2012
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Should we trust the machine?
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Jox, Bernat, Laureys, Racine, Lancet Neurology 2012
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
False positives / false negatives
Soddu et al Hum Brain Mapp. 2012
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
“resting state” default mode fMRI studies
BOLD
motion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Default connectivity in anesthesia
Boveroux et al, Anesthesiology 2010
WAKE ANESTHESIA
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
“Resting” default mode connectivity
Vanhaudenhuyse et al, Brain 2010
Functional connectivity
in "
defa
ult n
etw
ork
"
locked-in syndrome
MCS > VS/UWS
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
EEG entropy
Gosseries et al, Functional Neurology, 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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vegetative state
ATYPICAL ‘HIGH LEVEL’ CORTICAL ACTIVATION
Di et al, Neurology, 2007
ACTIVATION TO THE OWN NAME
Predicting outcome in chronic DOC
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Di et al, Clinical Medicine, 2008
Perrin et al Arch Neurol 2006
Qin et al, Neurosci Lett 2008
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Landnes and Bruno et al, Brain, 2011
Understanding plasticity
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Homeostatic decline SWA ≈ plasticity (Tononi)
256 HD video sleep EEG
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Tshibanda et al, Prog Brain Res, 2009 Tshibanda et al, Neuroradiology, 2010
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
MRI: DTI & spectroscopy
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Nociception and pain
Demertzi et al, Prog Brain Res, 2009
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Schnakers et al, Pain, 2010, JNNP 2012
Nociception Coma Scale –R
Total score >3 / 9 = analgesic treatment
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Laureys et al, Neuroimage, 2002
Laureys, Nature Reviews Neuroscience, 2005
Do they feel pain ?
Low level disconnected cortical activation
Noxious electrical stimulation
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 45
Boly et al Lancet Neurology, 2008
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Pain in minimally conscious state
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Curative treatment: amantadine
Schnakers et al J Neurol Neurosurg Psychiatry 2008
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 47
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Consciousness ≈ thalamo-cortical
Intralaminar nuclei “reconnections” in spontaneous recovery from
“vegetative” unresponsive state
Laureys et al, Lancet 2000 Schiff et al, Nature 2007
Intralaminar nuclei stimulation induces “recovery” from
minimally responsive state
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Ethical framework
Fins et al, Am J BioEthics 2008
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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End-of-life issues
Demertzi et al, J Neurology 2011
2,475 medical professionals
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
66% 82%
28%
67%
N o r t h
S o u t h
C e n t r a l
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Treatment can be stopped in chronic...
Do not feel pain Feel pain
Demertzi & Racine et al, Neuroethics 2012
Ag
ree
me
nt
(%)
Ag
reem
en
t
MCS VS/UWS
(n=2259)
Attitudes towards pain & end-of-life
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 51
Burnout in caregivers
51
568 health care workers (Maslach Burnout Inventory)
Gosseries, Demertzi et al, Brain Injury 2012
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Quality of life
Bruno et al, BMJ Open, 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 53
Bruno et al, Prog Brain Res, 2011
Erik Ziegler, Cyclotron Art Committee
Conclusion
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org 54
Results of additional diagnostic testing and
their possible ethically relevant effects
Jox, Bernat, Laureys, Racine, Lancet Neurology 2012
Results of Tests Beneficial Effects Harmful Effects
Tests show less brain activity than neurological examination
Relatives may better cope with the decision to withdraw life- sustaining treatment
Relatives may lose hope, purpose, and meaning in life
Tests show more brain activity than neurological examination
Clinical management may be intensified by the chance of further recovery
False hopes may be nurtured, leading to long-term harm, disappointment & suffering
Tests show the same level of brain activity as neurological examination
Clinicians and relatives may be affirmed in their decision about the level of treatment
Clinicians and relatives may be disappointed & treatment cost/effectiveness may be poor
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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New knowledge, new nosology
Bruno, Vanhaudenhuyse et al J Neurology, 2011
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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AWARENESS COMMUNICATION
Conclusion
Laureys & Boly, Nature Clinical Practice, 2008 Laureys & Schiff, NeuroImage, 2012 Sanders et al, Anesthesiology, 2012
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Human conscious awareness ≈ emergent property of collective
critical neural network dynamics, involving a frontoparietal global workspace
Diagnostic use ≈ 40% misdiagnosis Prognostic use multimodal imaging
Therapeutic use pain treatment / deep brain stimulation thalamus
Ethical issues
www.comascience.org 57
Slides on website
coma@ulg.ac.be
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