Post on 05-Aug-2020
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Neuro-réanimation: coma & conscience
Prof Steven Laureys Coma Science Group Centre de Recherches du Cyclotron & Service de Neurologie Université de Liège & Centre Hospitalier Universitaire de Liège
2ème Master en sciences de la Santé publique, Finalité spécialisée Soins Intensifs et d’Urgences
www.comascience.org Demertzi et al, Ann N Y Acad Sci. 2009 (fig 3)
Coma, consciousness, self, mind & soul
1858 participants attending scientific meetings on consciousness
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Courte histoire du coma
Anoebis
cœur Maät
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Respirateur artificiel (1952)
The resuscitation greats. Bjørn Ibsen Resuscitation. 2003
Bjørn Ibsen - Copenhagen
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Pope Pius XII (1957) Consciousness | History | Death | Coma | Locked-in | Disorders of Consciousness
•! it remains for the doctor to give a definition of the “moment of death”
•! no obligation to use extraordinary means to prolong life in critically ill patients
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Coma dépassé (1959)
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Première transplantation d’un donneur en mort cérébrale (1963)
Jean Morelle & Guy Alexandre Neurology, 2005;64;1938-1942
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Christiaan Barnard (1967)
Louis Washkansky
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Définition de la mort cérébrale
Comité de Harvard 1968
Wijdicks, NEJM 2001 Bueri et al Mov Disord. 2000, 15:583-6
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Laureys, Owen and Schiff, Lancet Neurology, 2005
Conscience & éveil
NORMAL
EVEI
L
CO
NSC
IEN
CE
DE
L’EN
VIR
ON
NEM
ENT
COMA ANESTHESIE
SOMMEIL
EVEI
L
CO
NSC
IEN
CE
DE
L’EN
VIR
ON
NEM
ENT
ETAT VEGETATIF
EVEI
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NSC
IEN
CE
DE
L’EN
VIR
ON
NEM
ENT
ETAT DE CONSCIENCE
MINIMAL
EVEI
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NSC
IEN
CE
DE
L’EN
VIR
ON
NEM
ENT
LOCKED-IN SYNDROME
EVEI
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NSC
IEN
CE
DE
L’EN
VIR
ON
NEM
ENT
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L’erreur diagnostique
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Peur d’être enterré vivant (1896)
1896, Karnice-Karnicki, chamberlain of the tsar of Russia
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La mort et les medias (1980)
Transplants - Are the donors really dead ?
mort clinique ! mort
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Erreur de diagnostic et mort cérébrale
Depuis les années 50, aucun patient en mort cérébrale n’a récupéré sa conscience (test d’apnée!)
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Locked-in syndrome
Laureys et al., Progress in Brain Research, 2005
www.comascience.org Laureys et al., Progress in Brain Research, 2005
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Locked-in syndrome
www.alis-asso.fr
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unconsciousness ! “coma”
Monti, Laureys & Owen, British Med J, 2010
1972 1966 1952
2002
1994
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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What coma scale to use?
Wijdicks et al., Ann Neurol 2005
Consciousness | History | Death | Coma | Locked-in | Disorders of Consciousness
Teasdale & Jennett, Lancet 1974
GCS FOUR
Schnakers et al, Ann Neurol 2006
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives FOUR / GCS
Wijdicks et al., Ann Neurol (2005) Teasdale G, Jennett B, Lancet (1974)
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives FOUR / GCS / GLS
Wijdicks et al., (2005) Teasdale G, Jennett B, (1974) Born et al., (1985)
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Eye response
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Motor response
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Brainstem reflexes
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Respiration
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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
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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Functional MRI PET scan High-density EEG Transcranial magnetic stimulation
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Sustained 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
Automated consciousness classifier
Phillips et al, NeuroImage, 2010
“Relevance Vector Machine” on FDG-PET data in DOC
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
www.comascience.org Owen, Coleman, Boly, Davis, Laureys & Pickard, Science, 2006
Signs of consciousness on fMRI
“He’s not in coma… he’s playing tennis!”
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
ms -200 50 300 550 800 1050 1300
-5 -10 -15 -20 -25
5 10 15 20 25
Pz (!V)
Count TARGET (own name)
Coma or total locked-in syndrome?
21-y old woman basilar artery thrombosis - day 49
Other names PASSIVE
Count TARGET (other name)
Own name PASSIVE
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
Schnakers et al, Neurology, 2008 Schnakers et al, Neurocase, 2009
www.decoderproject.eu
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vegetative state
ATYPICAL ‘HIGH LEVEL’ CORTICAL ACTIVATION
Di et al, Neurology, 2007
ACTIVATION TO THE OWN NAME
fMRI predictor of outcome? Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
PUBLISHED DATA (n=48 patients) 6 fMRI (n=17) & 8 PET studies (n=32)
“low level” or absent activation •! low level activation 84% no recovery
•! no cortical activation 100% no recovery
“high level” activation •! 82% recovery (93% specificity 69% sensitivity)
Di et al, Clinical Medicine, 2008
www.comascience.org Bruno et al, Prog Brain Res, 2011 Tshibanda et al, Neuroradiology, 2010
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Multimodal imaging Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Traitement "…le cerveau (d’une femme) est un mystère...
est encore plus dans cet état là"
www.comascience.org Schnakers et al, JNNP 2008
Traitement pharmacologique
www.comascience.org Schiff et al., Nature, 2007 Laureys, De Ridder, Schiff et al., European DBS study in EMCS
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Stimuler le cerveau
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PRONOSTIQUE
www.comascience.org Eisenberg NEJM 2001 Laureys et al, Nature Clinical Practice 2008
Outcome after cardiac arrest EMERGENCE
MINIMALLY CONSCIOUS STATE
BRAIN DEATH
functional communication
VEGETATIVE STATE
COMA
brainstem reflexes
voluntary movements or command following
eye opening only reflex movements
CARDIAC ARREST
Hemodynamic stabilisation
20-50% >80%
77-98%
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Clinical outcome markers
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Circumstances surrounding CPR
•! Time between collapse and CPR > 5 min (FPR 20%; 95% CI 14-25)
•! Duration CPR > 20 min (FPR 23%; 95% CI 17-29)
•! Asystole or electro-mechanic dissociation versus ventricular fibrillation or tachycardia
(FPR 27 %; 95% CI 21-33) •! Cause of the cardiac arrest (cardiac vs noncardiac)
Rogove et al Crit Care Med 1995;23:18–25 (N=774; class I study)
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Hyperthermia
•! each °C > 37° (tympanic thermometry < 48h) -> 2 x more likely to die or remain VS after 6m
Zeiner et al Arch Intern Med 2001;161:2007–2012 (class II study)
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Clinical examination
•! at 72 hours: GCS motor score <=2 or absence of pupillary & corneal reflexes (FPR 0%; 95% CI 0 to 3)
•! Myoclonus status epilepticus (repetitive, generalized myoclonus; not single seizures or sporadic focal myoclonus)
(FPR 0%; 95% CI 0 to 8.8)
Wijdicks et al Neurology 2006 (analysis of 3 class I, 2 class II, 5 class III studies)
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Electroencephalography
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Electroencephalography
1929 Hans Berger
50 "V
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Generalized slowing baseline activity
Cerebral blood flow < 25 ml/100g/min
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EEG: burst supression
FPR= 3%, 95% CI: 0.9 à 11
Wijdicks et al 2006 1 class II 4 class III studies
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EEG: isoelectrical
Cerebral blood flow < 15 ml/100g/min
BRAIN DEATH
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Evoked potentials
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Somatosensory evoked potentials
FPR = 0.7%; 95% CI: 0.1 - 3.7
Carter Intensive Care Med, 2005 (25 studies) Zanbergen et al, Lancet 1998
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Visual evoked potentials
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Auditory brainstem evoked potentials
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N 1 0 0 s t d N 1 0 0 d e v
M M N
1 0 0 m s
1 µ V -
+
d e v i a n t n = 1 4 1 s t a n d a r d n = 7 2 6
d i f f = d e v - s t d
Mismatch negativity
Fischer et al, Crit Care Med, 2006 Naccache et al, Clin Neurophysiol 2005
presence of MMN -> outcome better than VS
n=64; 100% specificity
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Biochemical markers
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Biochemical markers
•! NSE : neuron specific enolase < neurons & neuroectodermal cells
>33 "g/l at D 1 to 3 (1 class I 4 class III and 1 class IV studies)
(FPR = 0%; 95% CI: 0 – 3) •! time-consuming >24h •! hemolysis increases values (NSE < platelets) •! cutoff points for a 0 FPR vary from 20 to 65 "g/l •! NSE is lower in induced hypothermia
•! S100 protein : calcium-binding astroglial protein (1 class I 4 class III and 1 class IV studies) values measured <D2 : poor prognostic indicator
•! Creatine kinase brain isoenzyme (CKBB) < neurons & astrocytes (6 class III studies) poor prognostic ability
•! Neurofilament in CSF (1 class IV study) FPR of 10%.
Wijdicks et al Neurology 2006
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Pronostic coma anoxique Kirsch et al, Revue Médicale de Liège 63 (2008) 263-268
DON D’ORGANES
DON D’ORGANES CŒUR NON-BATTANTS
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Epidemiology Consecutive admissions CHU ICU (26 beds) over 5 y : n=5908
631 disorder of consciousness on admission (11%)
! 356 vegetative state (56%) 227 non-traumatic (64%) 129 traumatic (36%)
" 101 died
" 200 emerged from VS 118 obeyed command & oriented (59%) 68 disoriented or inappropriate words (34%) 14 only localised pain (7%)
" 55 remained VS at discharge
Ledoux, Piret, Damas, Moonen & Laureys, in preparation
VS
28%
56% 16%
died
trauma
non- trauma
emerged
# 36% recover # 70% recover
Consciousness | History | Death | Coma | Locked-in | Disorders of Consciousness
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Chronic disorders of consciousness
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Outcome
Ledoux et al, Belgian federal project on VS
! "! #! $! %! &! '! (! )! *!
"!!
" $ ' "#
Minimally conscious state (n=84)
n=35
%
! "! #! $! %! &! '! (! )! *!
"!!
" $ ' "# n=49
%
! "! #! $! %! &! '! (! )! *!
"!!
" $ ' "# +,+-.+/0+1 ,02 3456 72
Vegetative state (n=116)
Trau
mat
ic
n=52
%
! "! #! $! %! &! '! (! )! *!
"!!
" $ ' "#
Non
-tra
umat
ic
n=64
%
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Ethical & social challenges
Consciousness | Neural correlates | Diagnosis | Prognosis | Treatment | Ethics | Conclusion
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Cognition & quality of life Cognitive and behavioral changes in 20-50%
long-term memory, executive function impairment, focal cognitive deficits •! O’Reilly et al Resuscitation 2003;58:73—9 •! Nunes et al Resuscitation 2003 57:287—97. •! Drysdale et al Resuscitation 2000 47:27—32 •! Grubb et al Stroke 2000;31:1509—14 •! Grubb et al BMJ 1996 313:143—6 •! Roine et al J Am Med Assoc 1993 269:237—42
Posttraumatic stress disorder in 20-25% (more in younger patients) •! Griffiths et al Yearbook of IC & EM 2008: 891-905 •! Gamper et al Crit Care Med 2004 32:378—83 •! O’Reilly et al Br J Clin Psychol 2004 43:83—95 •! Ladwig et al Am J Psychiatry 1999 156:912—9
Preserved health related quality of life •! Horsted et al Resuscitation. 2007 72:214-8 •! Bunch et al Crit Care Med. 2004 32:963-7 •! van Alem et al Am J Cardiol. 2004 93:131-5 •! Granja et al Resuscitation. 2002 55:37-44 •! Nichol et al Acad Emerg Med 1999 6:95—102
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Ethical issues
Demertzi et al, J Neurology 2011
2,475 medical professionals
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
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Ethics
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Ethical conclusions
•!What is meaningful outcome? •!What is acceptable probability?
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EVALUER LA DOULEUR
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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Pain without words ?
Pain is a subjective first-person experience which has to be communicated to be accurately assessed
Only motor response considered indicative of conscious perception is localization to noxious stimulation
Laureys & Boly What is it like to be vegetative or minimally conscious?
Curr Opin Neurol 20 (2007) 609-13
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No brain, no pain
Laureys, 2005
NORMAL BRAIN DEATH COMA VEGETATIVE STATE
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Motor response without pain
Bueri et al Mov Disord. 2000, 15:583-6
Spinal reflexes 75%
extension-pronation plantar responses muscle stretch reflexes abdominal reflexes undulating toe flexion sign “Lazarus’ sign
BRAIN DEATH
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No cortex, no pain
Consciousness in congenitally decorticate children: developmental vegetative state as self-fulfilling prophecy
Shewmon et al Dev Med Child Neurol. 1999
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Some cortex, some pain?
Laureys, 2005
NORMAL BRAIN DEATH COMA VEGETATIVE STATE
www.comascience.org Laureys et al., Current Opinion in Neurology, 2005
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives
Pain after coma?
COGNITIVE CAPACITY
MO
TO
R R
ES
PO
NS
IVEN
ES
S
coma
VEGETATIVE/UNRESPONSIVE
MINIMALLY CONSCIOUS
severe disability
arousal = eye opening
Communication ?
moderate disability
good recovery
live independently
professional reinsertion
Awareness ? = response to command or non-reflex movements
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 Pain in the vegetative state?
Demertzi et al, Prog Brain Res, 2009
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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
Brain activation to pain
Low level disconnected cortical activation
Noxious electrical stimulation
www.comascience.org Boly et al Lancet Neurology, 2008
disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Pain in minimally conscious state
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Assessing pain
Kappesser and Williams, Pain 2010
overestimation
agreement
underestimation
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Standardized assessment
Schnakers et al, Pain 2010
Standardized stimulation
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Pain in infants & demented
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Nociception coma scale
Checklist of Non-verbal Pain Indicators
NO
CIC
EPTI
ON
CO
MA S
CALE
Schnakers et al, Pain 2010
<4
4-7
>7
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Nociception coma scale
UNCONSCIOUS VEGETATIVE
MINIMALLY CONSCIOUS
NO
CIC
EPTI
ON
CO
MA S
CALE
Schnakers et al, Pain 2010
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Nociception Coma Scale
•! New “pain scale” for disorders of consciousness after coma
•! Assesses motor, verbal (vocal), visual (ocular), and facial responses on scales from 0 (no response) to 3 (total scores 0 – 12) to a quantified standard stimulus
•! Brief time required (1–5 min) to conduct and rate the examination
•! More sensitive compared with 4 other “pain” scales
•! Permits detect, communicate & follow non-communicative patient’s behaviors and their management
•! Allows monitoring treatment avoiding sedative effects & under-uses of analgesics
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EXPERIENCES PROCHE DE LA MORT
www.comascience.org 86
NDE (1975)
Van Lommel 2001 WCEI scale 41 (12%) Parnia 2001 Greyson scale 4 (6%) Schwaninger 2002 Greyson scale 7 (13%) Greyson 2003 Greyson scale 27 (2%) Charland 2011 Greyson scale 17 (10%)
Sensations, illusions, hallucinations, emotional or mystical feelings classically following life-threatening situations:
Cardiac arrest, perioperative or post-partum complications, septic or anaphylactic shock, electrocution, coma TBI, CVA, hypoglycaemia
? -> Neural correlate of NDE
www.comascience.org 87
Clinical death ! death
« …defined clinical death (independent of neuro- logical data) as a period of unconsciousness caused by insufficient blood supply to the brain because of inadequate blood circulation, breathing, or both. »
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Brain death = death
Transplants - Are the donors really dead ?
Clinically dead ! dead !
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Misdiagnosis of death ?
Since the 50s, no single patient showing the clinical signs of brain death ever recovered consciousness (apnea test !)
Laureys, Nature Reviews Neuroscience, 2005
1896, Karnice-Karnicki, chamberlain of the tsar of Russia
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NDE dimensions
NDE >7 Greyson Scale Greyson, B. (1985). A typology of near-death experiences. Am J Psychiatry
(n=17 ; 10% of cardiac arrest)
Out of Body Experience (Paranormal) 15 Well-Being (Affective) 13 Light (Affective) 9 Sense of a presence (Transcendental) 6 Life Review (Cognitive) 2
Charland et al, unpublished
www.comascience.org 91
NDE = false memories ? Memory Characteristics Questionnaire (Johnson, M.K., et al., J Exp Psychol Gen, 1988)
Thonnard et al, submitted
www.comascience.org 92
NDE characteristics ! dreams
Thonnard et al, submitted
Memory Characteristics Questionnaire Johnson, M.K., et al., J Exp Psychol Gen, 1988 qualitatively different
from dreams or drug-induced hallucinations
‘For many years, it was the most real thing that ever happened to me. Yes, far more real and vivid than any real-life incident. It was so real, detailed and so vivid and consistent ...; in fact, so totally un-dream- like!’
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NDE characteristics ! dreams
Thonnard et al, submitted
Memory Characteristics Questionnaire Johnson, M.K., et al., J Exp Psychol Gen, 1988
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Demertzi et al, Ann N Y Acad Sci. 2009 (fig 3)
NDE = proof of the soul ?... 1858 participants attending scientific meetings on consciousness
www.comascience.org 95
… no evidence for that hypothesis
2009 Yearbook - Towards a neuro-scientific explanation of Near-Death Experiences?
www.comascience.org 96
Light optic radiation
Ammermann et al. 2007 Els et al. 2004
DWI ADC T2
T1
Hieronymus Bosch 1500s
www.comascience.org 97
Flashback mesiotemporal
Britton and Bootzin 2004
www.comascience.org 98
Presence left temporoparietal
Arzy, S., et al. (2006) Nature 443:287 Induction of an illusory shadow person.
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OBE right temporoparietal
Blanke et al Stimulating illusory own-body perceptions. Nature, 2002 (6904)269-70 De Ridder et al Visualizing out-of-body experience in the brain. N Engl J Med, 2007 (357) 1829-1833
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NDE = happening in the brain
NDE dimension Neural substrate OBE Right temporoparietal junction
Tunnel & light occipital & optic radiation (tunnel vision & foveal light)
Life review, memory flashback, enhanced emotions
Hippocampus/amygdala
Meeting of spirits Left temporoparietal junction
Painlessness, wellbeing Anterior cingulate cortex Time distortion Cortico-striatal Mystical & transcendental – oneness, cosmic unity
Biparietal
steven.laureys@ulg.ac.be