Vegetative Brain
Transcript of Vegetative Brain
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Vegetative State
Low Awareness StatesVegetative and Minimally Conscious States
Dr Ashraff Ali
Consultant in RehabilitationLead Medical Consultant
Brain Injury Rehabilitation Service
Royal Hospital for Neuro-disability
London, U.K.
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Vegetative State
Recovery ContinuumComaVegetative State
Minimal Conscious StateCognitive Impaired States
(Physical)Normal
.
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Vegetative State
Vegetative State Nomenclature
Prolonged coma
Coma vigile Akinetic mutism
Apallic syndrome
Neocortical death
Post-traumatic Unawareness State
Decerebrate dementia
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Vegetative State
Vegetative State
To vegetate:
To live a merely physical life,
devoid of intellectual activity orsocial intercourse.
Oxford English Dictionary 1740
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Vegetative State
Vegetative State
An organic body capable of
growth and development butdevoid of sensation and thought.
Oxford English Dictionary 1764
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Vegetative State
Vegetative State
Definition
Preserved sleep-awake pattern, respondsonly reflexively to stimulation and shows
no evidence of meaningful response to
enviroment.
Awake but not aware
Jennett Plum
Multi-Society Task ForceRCP Working group
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Vegetative State
Diagnosis
Diagnosis
Clinical Neuro-Physiological
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Vegetative State
Preconditions
Establish cause of VSTBI, ABI, Metabolic, Infection
Exclude persisting effect ofSedatives, causative drugs,
metabolic disturbances.
Exclude treatable structural
cause. (imaging)
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Vegetative State
Spontaneous Eye opening Breathing spontaneously Sleep-awake pattern Reflex responses to
stimulation
Clinical Features of VS
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Clinical features of VS
No meaningful response
No language Brainstem Autonomic function
preserved May blink to menace
Roving eye movements Very brief tracking!!
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Problematic Presentations
Grasp Reflex Swallowing Chewing & Tongue Pumping/Thrusting Bruxism Grunts & Groans Smiles & Frowns (spontaneous) Relaxation Response
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Vegetative State
Vegetative State
Incompatible Features
Discriminative Perception
Purposeful Action
(reaching out to an object) Communicative Act or intent
Appropriate use of language
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Vegetative State
Minimally Conscious State
everely altered consciousness inwhich the patient does not meet thecriteria for coma or the vegetative state
because there is inconsistent butreproducible or sustained behavioural
evidence of self or environmentalawareness
Aspen WP 2001
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Vegetative State
Minimally Conscious State
At least one of the folloiwing must
be present Follow simple commands
Gestural or verbal yes/no
response
Intelligible communication
Purposeful behaviour
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Vegetative State
MCS - Reproducibility
CONSISTENCY
COMPLEXITY
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Vegetative State
Minimally Concious State
Emergence from MCS
Interactive Communication
Use of objects functionally
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Diagnostic distinction
Normal
ConsciousnessComa Vegetative
State
Minimally
Conscious
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Vegetative State
SMART
Sensory Modality Assessment Rehab Technique
Observed responses to sensory stimulation i.e.: Visual,
Tacti le, Auditory, Olfactory, Gustatory, Wakefulness,
Functional Motor and Communicative Capacity 5 Levels.
1) No response
2) Reflexive response
3) Withdrawal response
4) Localising response
5) Discriminatory response
- 43% of patients referred to RHN as VS are misdiagnosed
(K. Andrews)
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Vegetative State
JFK Coma Recovery Scale
SMART 2008
AUDITORY FUNCTION SCALE
4 - Consistent Movement to Command *
3 - Reproducible Movement to Command *
2 - Localization to Sound
1 - Auditory Startle0 - None
VISUAL FUNCTION SCALE
5 - Object Recognition *
4 - Object Localization: Reaching *
3 - Visual Pursuit *
2 - Fixation *1 - Visual Startle
0 - None
MOTOR FUNCTION SCALE
6 - Functional Object Use t
5 - Automatic Motor Response *
4 - Object Manipulation *3 - Localization to Noxious Stimulation *
2 - Flexion Withdrawal
1 - Abnormal Posturing
0 - None/Flaccid
OROMOTOR/VERBAL FUNCTION
SCALE
3 - Intelligible Verbalization *
2 - Vocalization/Oral Movement
1 - Oral Reflexive Movement0 - None
COMMUNICATION SCALE
2 - Functional: Accurate t
1 - Non-Functional: Intentional *
0 - None
AROUSAL SCALE3 - Attention
2 - Eye Opening w/o Stimulation
1 - Eye Opening with Stimulation
0 Unarousable
Total score (maximum = 23)
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Differential Diagnosis (1)Condition Coma Veg. State Min. Cons
StateLocked-inSyndrome
Self Awareness - - Partial Full
Cyclical EyeOpening - + + +
Motor function Reflex &Postural
Postures orwithdraws.Occasional
non-purpose
Localises.Reach forobjects.
Automaticmovements
Quadriplegic.Vertical eyemovement
Experience pain No No ? Yes
Respiratory
Function
Depressed or
varied
Normal Normal Normal
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Differential Diagnosis (2)
Condition Coma Veg. State Min. ConsState
Locked-inSyndrome
AuditoryFunction None Startle. Brieforientation Localise.Inconsistcommands-following
Preserved
Visual
Function
None Startle.
Brieforientation
Sustained
visual fix.Sustainedpursuit.
Preserved.
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Differential Diagnosis (3)
Condition Coma Veg. State Min. ConsState
Locked-inSyndrome
Communication None None Contingentvocalisat/n.Inconsist
verbal/n orgesture
Aphonic/anarthric.Verical eye
movement andblinking
Emotion None None or reflexsmiling crying
Contingentsmiling or
crying
Preserved
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Prognosis
Emergence or Recovery
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Recovery of Consciousness
Aetiology Trauma > non-trauma
Duration of
Unconscious
(current)
Shorter > longer
Age Younger vs. older
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Age v Reach Independence -VS 1 m
02
4
6
8
10
12
1416
18
20
40
Age
%I
ndependent1yr
Braakman 1988
Jennett 1990
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VS Outcome Adults VS 1/12
0
10
20
30
40
50
60
70
80
90
100
0 3 6 9 12
Months
%
0
10
20
30
40
50
60
70
80
90
100
0 3 6 9 12
Months
%
Traumatic Non-Traumatic
VS
VS
Conscious Conscious
DeadDead
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Vegetative StateSMART 2010
Medical Management
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Vegetative State
Complexity of Presentation
Physical/motor
Sensory
Cognitive/
behavioural
Communication
Psychosocial &Emotional
Medical
FamilyDynamics
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Principles of Rx
Prevent 2ComplicationsProvideEnvironmentfor RecoveryTreatmentModify Patient
ModifyEnvironmentSupport FamilyChangeSociety
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The Vegetative Person
Brain
Body
Medically
Vulnerable
Complex
Neurological
Complications
Environment
Physicallydependent
Family in
Crisis
Cognitively
Impaired
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Cognitively Impaired
Remove Factors InhibitingMedications
Infections
Toxic states
Medical
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Cognitively Impaired
PostureAscending Reticular Activating System
Scattered Nuclei in Brain stem
Arousal and maintain consciousness
Receive stimulation from sensory
modalities including posture
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Cognitively Impaired
PharmacologicalAnti-Parkinsonian
L-dopa
Amantidine
BromocriptineAnti-depressants
Amphetamines
Modafanil
Zolpidem
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Awakening Agents
Psychostimulants
Zolpidem
Methylphenidate
Siddall et al. Literature search
Cochrane Register Ten clinical trials in TBI: improvement in memory,
attention concentration, mental processing
2008 Australia Monash University
Randomised crossover Double BlindPlacebo controlled trial TBI
MPH enhances information processing speed
Pharmacological Agents
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Modafinil
Narcolepsy
Helps daytime sleepiness, fatigue
Improved attention, cognitive benefits Better encouragement with therapists
No major side effects
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Cholinergicagent(onTBI)
Speedof
mental
processing,
increased
learningandattention
Improves
general
Neufunctional
outcome
KhatebA.Eurorol.2005.
Donepezil
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Hydrocephalus
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Interventions
Sensory stimulation
Wood et al 1992 structured control stimulation avoiding over stimulation
improved level of arousal, used GCS Scale (insensitive).
SMART and WHIM more sensitive
Posture Median nerve stimulation improved reawakening.
Cooper EB et al, Neuropsychological Rehabilitation 2005
Deep brain electrical stimulation to improve arousal and cognition.
Schiff NB et al
Lumbar infusion studies (Ventriculomegaly)Picard JD et al
Intrathecal Baclofen Pump for spasticity
Cell therapy for brain repair (Parkinsons and Huntingtons
Disease)
Phillips W, Barker RA et al
Multimodal Imaging
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Multimodal Imaging
Functional MRI, EEG, PET, Diffusion
Tensor Imaging
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Vegetative StateSMART 2010
Interventions
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Vegetative State
Spasticity
Velocity dependant
Resistance to musclelengthening or stretching
Shortened muscles contractures
soft tissue changes
Impairment of attempted
movements
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Vegetative State
Spasticity
Aggravating Factors:
Nociceptive stimuli
Bladder, ureteric stones
Catheter blockage, constipation
Pressure sores Tight leg bags
UTI
Heterotrophic ossification
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Treatment
AIM: Improve function/hygiene
: Reduce pain
: Reduce carer burden
: Improve ADL
: Prevent Complications -
contractures, sores: Improve body image
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Spasticity Management
Identify aim and goal of treatment
Line of action: MDT decision, 24 hour Mn1. Avoid, prevent noxious stimuli
2. PT/OT/Physicalmodalities/casting/splinting, positioning
3. Oral medication
4. Injections: Botulinum toxin, alcohol, LA, Phenol(perineural, motor pt.)5. Intrethecal Baclofen pump
6. Neurosurgical procedure
7. Orthopedic surgery
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A i S i i D
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Anti-Spasticity Drugs
Baclofen
Dantrolene
Tizanidine
Benzodiazapines
Gabapentin Cannabinoids
Tolperisone (AV650)
(Research)
I j ti
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Injections
Local anaesthetics +/- adrenaline Diagnostic
Prior to casting/splinting
Reversible quickly
Perineural, motor point block
Ethyl Alcohol Reduces spasticity by months-years
Denatures protein, precipitates protoplasm
Pain, phlebitis, dysesthesia Peripheral neural palsy
Intoxication
Ph l
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Phenol
4-6% aqueous phenol, 1-10 mls
Any form of spasticity
Botulinum toxin sparing use
Perineurally Motor point block
Denatures protein, necrosis
Long term effect Reverses when nerves regenerates
S.E: Pain, dysesthesia, oedema, DVT, vascularinjury, sensory loss, weakness
Early onset, longer effect (BTX) Cheap, repeatable (technique needs expertise)
B t li T i
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Botulinum Toxin
BOTOX, DYSPORT, MYOBLOC,XEOMIN
Reduces spasticity variety of causes
Functional benefit gait, UL function
Mechanism: Blocks neuromusculartransmission by inhibit ing acetylcholinerelease reversible denervation
7 serotypes: A to G (similar mode ofaction)
Only A and B are commercially available
Type A SNAP-25 substrate Type B Synaptobrevin
I t th l B l f P
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Intrathecal Baclofen Pump
Refractory Spasticity or side effects
SCI, cerebral, CP, MS
Dystonia Effective for leg spasticity more than arm
Can improve gait
Can help bladder management
Constipation worsens Mechanism same as oral but much lower dose
S.E: drowsiness, hypotension, dizziness, weakness,headache
Overdose respiratory depression, coma (reversible) Withdrawal effect MOD death
Protocol (test dose etc.)
Neurosurgical Ablation
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Neurosurgical Ablation
Rhizotomy
Spinal roots severed Radio frequency
Selective surgical Spastic CP (better gait, increases ROM)
Sensations preserved
S.E: sensory impairment, hypotonia, weakness,bladder dysfunction
Myelotomy
Cordotomy, DREZOTOMY
Orthopedic Surgery
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Orthopedic Surgery
Tenotomy
Neurectomy
Tendon tranfer
Tendon lengthening
Joint fusion
Osteotomy
Medical Vulnerability
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Medical Vulnerability
Brain
Body
ChestinfectionsKidney/bladderStones
Urinary tractinfections
Nutritionalstate
PressuresoresOther traumae.g
Environment for Recovery
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Environment for Recovery
Health
Nutrition
Physical
Sensory
Professional
Social
Societal
Modify Environment
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Modify Environment
Structured stimulation
Special seating
Bed aids
Bath trolleys
Hoists
Standing frames
SUMMARY
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SUMMARY
Prevent 2ComplicationsProvideEnvironmentfor RecoveryTreatmentModify Patient
ModifyEnvironment
Support FamilyChangeSociety
fMRI: Hierarchal Approach
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Vegetative State
Speech Perception
Sound Perception
Speech Comprehension
Volition
C
OGNITIV
ECOMPLEXITY
fMRI Auditory task: Hierarchal paradigm
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Ambiguous
sentence
Unambiguous
sentence
Signal
correlated
noise
Scan Scan
Time(seconds)
Theshellwasfiredtowardsthetank
(Highambiguity,atleast2ambiguouswords)
Theirholidaywasquiteshortandwouldendsoon
(Lowambiguity,
matched
for
length,
syntactic
complexity,
word
frequency,
etc.,)
Scan
Silence
fMRI Auditory task: Volunteer results
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Left Right
Level1 Sound Silence(auditorystimulusvs.silence)Level2 Sentences Signalcorrelatednoise(intelligiblespeechvsunintelligble)Level3 Retrievalofsemanticinformation(highvs.lowambiguouswords)
MRI Scan: White matter tractography
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Vegetative State[TemporalLobe][VegetativePatient] [Control]
Right
Left
Patient results: Sound Perception
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Vegetative State[Coleman,Davis,Rodd,Robson,Ali,Owen,Pickard.Brain2009;132:25412552]
Patient results: Speech Perception
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Vegetative State[Coleman,Davis,Rodd,Robson,Ali,Owen,Pickard.Brain2009;132:25412552]
Patient results: Speech Comprehension
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43
54
48
56
VSPatientsHealthy
Volunteers
[Coleman,Davis,Rodd,Robson,Ali,Owen,Pickard.Brain2009;132:25412552]
Sedated Volunteers: Speech Comprehension
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SOUND SPEECH
PERCEPTION
SPEECH
COMPREHENSIO
N
[Davis,Colemanetal.PNAS,2007;104(41):1603216037]
Patient results: Prognosis
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rs=0.81p
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Patient results: fMRI Volition task
23 year old female
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23 year old female
Diagnosis: Diffuse axonal injury following RTA
Over 6 months, assessed by a multidisciplinary team employing repeated standardized
assessments.
Behaviours observed were consistent with the International classification of the vegetative
state.During the period of investigation the patient opened her eyes spontaneously, but showed
no evidence of tracking using either visual or auditory stimuli.
No response to command was observed.
Underwent fMRI
Presented with spoken words vs. Matched noise
Speech specific activity observed bilaterally in middle andsuperior temporal gyri (similar to healthy volunteers)
Ambiguous words additional activity in left inferior frontal
region (same as healthy volunteers)
Patient results: fMRI Volition task
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Motorimagery SpatialNavigation
[Owen,Colemanetal.Science2006;313:1402]
Patient
Controls
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Second fMRI study with mental imagery
1) Playing game of tennis activation of
supplementary motor area2) Visiting all of the rooms in her house activity
in parahippocampal gyrus, posterior parietalcortex, lateral premotor cortex (similar to healthy
volunteers)Conclusion: Diagnosed VS clinically but patient
retained abil ity to understand spoken commandAND respond through brain activity
therefore conscious awareness present.Future Development: Brain Computer Interface
Brain Computer Interface
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Vegetative StateSMART 2008
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Discussion semantic conditioning / learning
DOC patients may have partially preserved conscious processing, which cannot
be exhibited overtly via vountary behavioral markers (intentional movement or
verbal responses).
Alternatively, this results may imply that trace conditioning can indeed be
acquired in the absence of consciousness
Learning seems to be heralding recovery.
This method can potentially become a bedside test for awareness in DOC.
While extremely speculative it is important to investigate whether training the
circuits involved in associative learning (awareness?) may help the recovery of
consciousness. (T bekinschtein)
Semantic conditioning
Conclusion
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Terminology to be used VS and
MCS Optimisation of general condition
Behaviour observation assessment
Multimodal assessment objectives maybe commonly used in future
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Vegetative State
Dr Ashraff Ali
Royal Hospital for Neuro-disability
Email: [email protected]
www.rhn.org.uk/institute