Coma & related states · 11h30-12h00 : Evaluation de la spasticité – Aurore THIBAUT 12h00-13h00 : Don d’organes – Didier LEDOUX 13h00-13h30 : Lunch 13h30-14h00 : Transcranial

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

[email protected]

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)


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.


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)


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


Programme

Vendredi 01/02

Centre de Recherches du Cyclotron

10h00 : Mot de clôture et discussion – Audrey VANHAUDENHUYSE


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


Reducing awareness to 2D

Boly et al, Ann NY Acad Sci 2009

Vanhaudenhuyse & Demertzi et al, J Cogn Neursoci 2011



Laureys et al., Lancet Neurology, 2004

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives Consciousness ≠ global brain function



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


Laureys et al, Neuroimage 1999


Laureys, Trends in Cognitive Sciences, 2005

Consciousness ≈ frontoparietal



Frontoparietal “global workspace”

Baars, Ramsoy, Laureys, Trends in Neurosciences 2003

no arousal no awareness

preserved arousal no awareness



Laureys et al, Lancet Neurology, 2004


Precuneus ≈ hub in the network


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


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




Two awareness networks

Laureys, Scientific American 2007 Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011


EXTERNAL or SENSORY

AWARENESS

INTERNAL or SELF

AWARENESS



Two awareness networks


EXTERNAL or SENSORY

AWARENESS

INTERNAL or SELF

AWARENESS

0.05 Hz ≈ 20s

Laureys, Scientific American 2007 Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011



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)




Modulation by hypnosis

Demertzi et al, Prog Brain Res 2011

N D H N D H N D H

Normal wake

Distraction

Hypnosis




Consciousness ≠ primary cortex

Laureys et al, Brain, 2000

Boly et al, Archives of Neurology, 2004


“VEGETATIVE” UNRESPONSIVE

MINIMALLY RESPONSIVE



Consciousness ≈ top-down

Boly, Garrido, Gosseries, Bruno, Schnakers, Massimini, Litvak, Laureys, Friston, Science, 2011




Disorders of consciousness

Bruno et al, J Neurology, 2011

VEGETATIVE/UNRESPONSIVE



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

[email protected]



Eye tracking : use a mirror!

Vanhaudenhuyse et al J Neurol Neurosurg Psychiatry 2008

n=52



A new name for « vegetative »

Laureys et al, BMC Medicine 2011

“There’s nothing we can do… he’ll always be a vegetable.”




Monti & Vanhaudenhuyse, Coleman, Boly, Pickard, Tshibanda, Owen, Laureys New England J Med 2010

Yes-No communication with fMRI




EEG-based Brain Computer Interfaces


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%)



EEG-based Brain Computer Interfaces


Schnakers et al, Neurology, 2008 Schnakers et al, Neurocase, 2009

Fellinger et al Clin Neurophysiol, 2011

theta synchronization

theta synchronization



Aphasia as a confound


Bruno et al, J Neurology, 2012



Automated consciousness classifier

Phillips et al, NeuroImage, 2011

“Relevance Vector Machine” on FDG-PET data in DOC



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

Thibaut et al, J Rehabil Med 2012



Visual fixation is a reflex

Bruno et al, BMC Neurology 2010




Consciousness ≈ connectivity

EEG-TMS

Rosanova and Gosseries et al, Brain 2012




“Resting state” default brain activity

PCC

MFC

Boly et al, Human Brain Mapping 2009


0.05 Hz ≈ 20s



Functional MRI in “resting state”


Jox, Bernat, Laureys, Racine, Lancet Neurology 2012



Should we trust the machine?





False positives / false negatives

Soddu et al Hum Brain Mapp. 2012


“resting state” default mode fMRI studies

BOLD

motion



Default connectivity in anesthesia

Boveroux et al, Anesthesiology 2010

WAKE ANESTHESIA




“Resting” default mode connectivity

Vanhaudenhuyse et al, Brain 2010

Functional connectivity

in "

defa

ult n

etw

ork

"

locked-in syndrome

MCS > VS/UWS




EEG entropy

Gosseries et al, Functional Neurology, 2011



vegetative state

ATYPICAL ‘HIGH LEVEL’ CORTICAL ACTIVATION

Di et al, Neurology, 2007

ACTIVATION TO THE OWN NAME

Predicting outcome in chronic DOC


Di et al, Clinical Medicine, 2008

Perrin et al Arch Neurol 2006

Qin et al, Neurosci Lett 2008


Landnes and Bruno et al, Brain, 2011

Understanding plasticity


Homeostatic decline SWA ≈ plasticity (Tononi)

256 HD video sleep EEG


Tshibanda et al, Prog Brain Res, 2009 Tshibanda et al, Neuroradiology, 2010


MRI: DTI & spectroscopy




Nociception and pain

Demertzi et al, Prog Brain Res, 2009


Schnakers et al, Pain, 2010, JNNP 2012

Nociception Coma Scale –R

Total score >3 / 9 = analgesic treatment



Laureys et al, Neuroimage, 2002

Laureys, Nature Reviews Neuroscience, 2005

Do they feel pain ?

Low level disconnected cortical activation

Noxious electrical stimulation



Boly et al Lancet Neurology, 2008


Pain in minimally conscious state



Curative treatment: amantadine

Schnakers et al J Neurol Neurosurg Psychiatry 2008




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



Ethical framework

Fins et al, Am J BioEthics 2008



End-of-life issues

Demertzi et al, J Neurology 2011

2,475 medical professionals


66% 82%

28%

67%

N o r t h

S o u t h

C e n t r a l


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



Burnout in caregivers

51

568 health care workers (Maslach Burnout Inventory)

Gosseries, Demertzi et al, Brain Injury 2012



Quality of life

Bruno et al, BMJ Open, 2011



Bruno et al, Prog Brain Res, 2011

Erik Ziegler, Cyclotron Art Committee

Conclusion



Results of additional diagnostic testing and

their possible ethically relevant effects


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



New knowledge, new nosology

Bruno, Vanhaudenhuyse et al J Neurology, 2011



AWARENESS COMMUNICATION

Conclusion

Laureys & Boly, Nature Clinical Practice, 2008 Laureys & Schiff, NeuroImage, 2012 Sanders et al, Anesthesiology, 2012


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


Slides on website

[email protected]

Documents

Coma & related states · 11h30-12h00 : Evaluation de la spasticité – Aurore THIBAUT 12h00-13h00 : Don d’organes – Didier LEDOUX 13h00-13h30 : Lunch 13h30-14h00 : Transcranial