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Évaluation de la conscience aux soins intensifs

Steven LaureysComa Science GroupService de Neurologie &Centre de Recherches du CyclotronUniversité de Liège

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Disorders of consciousness Behavioural evaluation Electrophysiology Neuroimaging Ethics & quality of life

Terry Schiavo °1963, vegetative 1990, † 2005

Overviewdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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A brief history of coma

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Bjørn Ibsen (1952)

The resuscitation greats. Bjørn IbsenResuscitation. 2003

Rigshospitalet Copenhagen

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Pius XII (1957)

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Coma dépassé (1959)

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Jean Morelle & Guy Alexandre (1963)

The first organ transplant from a brain-dead donorNeurology, 2005;64;1938-1942

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Christiaan Barnard (1967)

Louis Washkansky

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Ad Hoc Committee Harvard (1968)

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Disorders of consciousness

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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QUESTIONS (répondez par OUI ou NON)

Age / Sexe (F-M) / Nationalité / Profession

1. L’esprit et le cerveau sont deux entités séparées

2. L’esprit est une entité purement physique

3. Une part spirituelle de nous-même survit après la mort

4. Chacun de nous a une âme qui est séparée de notre corps

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Mind brain beliefs

Zeman 2005 in The Boundaries of Consciousness (Ed) Laureys

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys, Owen and Schiff, Lancet Neurology, 2005

Consciousness: arousal & awareness

NORMALCONSCIOUSNESS

AR

OU

SAL

AW

AR

ENES

SCOMA

AR

OU

SAL

AW

AR

ENES

S

VEGETATIVESTATE

AR

OU

SAL

AW

AR

ENES

S

MINIMALLYCONSCIOUS

STATE

AR

OU

SAL

AW

AR

ENES

S

LOCKED-INSYNDROME

AR

OU

SAL

AW

AR

ENES

S

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Clinical evaluation

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

The absence of proof isn’t proof of the absenceAnonymous

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Brain death criteria

Wijdicks, NEJM 2001

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Motor activity in brain death

Lazarus' sign in brain deathBueri et al Mov Disord. 2000, 15:583-6

www.comascience.orgLaureys et al., Current Opinion in Neurology, 2005

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Reflex versus voluntary

COGNITIVE CAPACITY

MO

TO

R R

ES

PO

NS

IVEN

ES

S

coma

VS

MCS

severe disability

eye opening

communication

moderate disability

goodrecovery

live independently

professional reinsertion

voluntary behavior

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Glasgow Coma Scale

4. Spontaneous

3. To speech

2. To pain

1. None

AROUSAL

E - eye opening

PAIN

PAIN

HELLO

C. Not assessable

Laureys et al., Yearbook of Intensive Care Medicine, 2002

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Teasdale & Jennett, Lancet, 1974

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Glasgow Coma Scale

AWARENESS

V - verbal response

A.C. CidentICU Liège,March 2002

WHERE AM I ?

STUPID !!! … OFF !?

GROAN

…

5. Oriented conversation

4. Confused speech

3. Inappropriate words

2. Incomprehensible sounds

1. None

T. Not assessable

Laureys et al., Yearbook of Intensive Care Medicine, 2002

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Teasdale & Jennett, Lancet, 1974

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Glasgow Coma Scale

AWARENESS

M - motor response

5. Localizes pain

4. Withdraws (normal flexion)

3. Stereotyped flexion

2. Stereotyped extension

1. None

6. Obeys simple commands CLOSE YOUR EYES

PAIN

PAIN

PAIN

PAIN

PAIN

Laureys et al., Yearbook of Intensive Care Medicine, 2002

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Teasdale & Jennett, Lancet, 1974

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

FOURdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Wijdicks et al, 2005

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

FOURdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Wijdicks et al, 2005

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Blink and you live

Laureys et al., Progress in Brain Research, 2005

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Pensez-vous que5. Le patient en état végétatif ressent la douleur? 6. Le patient en état de conscience minimale ressent la douleur?7. Le patient en locked-in syndrome ressent la douleur?

Être en état végétatif chronique est pire que la mort8A. du point de vue du patient? 8B. du point de vue de la famille?

Être en état de conscience minimale chronique est pire qu’être en état végétatif

9A. du point de vue du patient? 9B. du point de vue de la famille?

Être en locked-in syndrome est pire qu’être en état végétatif ou en état de conscience minimale

10A. du point de vue du patient?10B. du point de vue de la famille?

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Coma recovery scaledisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Fear for misdiagnosis

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Andreas Vesalius (1514-1564)

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Fear of being buried alive (1896)

1896, Karnice-Karnicki, chamberlain of the tsar of Russia

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Death and the media (1980)

Transplants - Are the donors really dead ?

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Misdiagnosis of brain death

Over last 50 years no single recovery recorded if properly declared brain death

(apnea test!)

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Misdiagnosis of vegetative state

n=103 post-comatose patients

45 clinical consensus diagnosis of “vegetative state”

27 Coma Recovery Scale diagnosis(Coma Recuperatie Schaal)

40% misdiagnosis38% Schnakers et al Ann Neurol ´06 Schnakers et al, submitted37% Childs et al Neurology ´9343% Andrews et al BMJ ´96

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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How to assess eye tracking ?

Vanhaudenhuyse et al, JNNP 2008

n=52

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Blinking to threat

n=91 VS patients 46 (51%) blinking to visual threat 17 (37%) recovered to MCS

11/45 without blink recovered MCS (24%)

blinking is no sign of consciousness

Schnakers, Giacino et al, submitted

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Electrophysiology

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgGosseries et al, in preparation

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

EEG entropydisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

MCS(n=15)

VS(n=15)

CONTROL(n=15)

tim

e-fr

eque

ncy

bala

nced

spe

ctra

l ent

ropy

75% sensitivity75% specificity

www.comascience.orgLaureys, Perrin et al., Neurology, 2004

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Cognitive evoked potentialsdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

minimally conscious stateµV

0.0

-2.5

-5.0

-7.5

-10.0

2.5

5.0

7.5

10.0

OTHER NAMES

N1

ms100 300 500 800 1000 1300200 400 600 700 900 1100 1200 15001400

P3

OWN NAME

Perrin et al, Archives in Neurology, 2006

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Functional neuroimaging

The map is not the territoryAlfred Korzybski (1879-1950)

disorders of consciousness | clinical evaluation | neuroimaging | ethics & quality of life | future | conclusion

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resting metabolismactivation studies

passive active

disorders of consciousness | clinical evaluation | neuroimaging | ethics & quality of life | future | conclusion

www.comascience.orgLaureys, Owen & Schiff, Lancet Neurology, 2004 (sleep data from Pierre Maquet; anesthesia data from Mike Alkire)

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Resting metabolismdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

“Awareness network”disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

n=60

Laureys et al, NeuroImage 1999

www.comascience.orgVoss, … Schiff, Journal of Clinical Investigation, 2006

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

“miracle” recovery from MCS

Terry Wallis wakes from 19-year MCS

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Lancet, 2000

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Thalamo-cortical modulationdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgSchiff et al., Nature, 2007

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Thalamic stimulationdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgSchnakers et al, JNNP 2008

Amantadine in MCSdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

amantadine amantadine

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Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

resting brain functionbrain activation studies

passive paradigmsactive paradigms

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Pensez-vous que11. on peut arrêter le traitement (nutrition et hydratation) chez le patient en état

végétatif chronique ?

12. on peut arrêter le traitement chez le patient en état de conscience minimale chronique ?

13. on peut arrêter le traitement chez le patients locked-in chronique?

Souhaiteriez-vous de continuer à vivre si vous étiez :

14. en état végétatif chronique

15. en état de conscience minimale chronique

16. en locked-in syndrome chronique

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Do they feel pain ?disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

GRIMACINGNO RESPONSE AWAKENING

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys et al., Neuroimage, 2002Laureys, Nature Reviews Neuroscience, 2006

Vegetative is not apallicdisorders of consciousness | clinical evaluation | neuroimaging | ethics & quality of life | future | conclusion

Low level disconnected cortical activation

Painful stimulation

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"…a (wo)men’s brain is a mystery...and even more so in this state."

Hable con Ella

Pedro Almodóvar

www.comascience.orgLaureys et al., Neurology, 2004

Emotional processingdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

resting brain functionbrain activation studies

passive paradigmsactive paradigms

www.comascience.orgOwen, Coleman, Boly, Davis, Laureys and Pickard, Science, 2006

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Active fMRI paradigmsdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Boly et al, NeuroImage 2007

www.comascience.orgDi et al, Neurology, 2007

fMRI precedes the clinic vegetative minimally conscious

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Ethics &quality of life

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Progress in Brain Research, 2005

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Locked-in syndrome (LIS)disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgBruno, Pellas… Laureys, in preparation

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Quality of life in LISdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

QUESTION 17.Anamnestic Comparative Self Assessment (Bernheim et al)

X

X Locked-in patients n=70

X

X Matched healthy controls n=70QUESTION 18.Êtes-vous croyant : Non-Oui (quelle religion / pratiquant ?)

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Conclusions

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Conclusions

• Diagnosis• misdiagnosis of VS (40%) • behavioral evaluation (CRS-R)• need for objective markers of consciousness

• Vegetative state• disconnection syndrome with impaired

fronto-parietal neuronal “workspace”

• Minimally conscious state• preserved emotional & pain perception

• Locked-in syndrome• right to communicate, right to die, right to live

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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also thanks to

Gustave Moonen MD PhDChristophe Phillips PhD IngQuentin Noirhomme PhD IngPierre Maquet MD PhD

Frédéric Pellas MD (Nîmes) Adrian Owen PhD (Cambridge)Louis Puybasset MD (Paris)Fabien Perrin PhD (Lyon)Haibo Di PhD (Zhejiang)Joe Giacino PhD, Nico Schiff MD (NY)

thanks to

Melanie Boly MDDidier Ledoux MDCaroline SchnakersAudrey VanhaudenhuyseMarie-Aurélie BrunoOlivia GosseriesVictor CologanPierre Boveroux MDAthena Demertzi

the patients & families

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion