Vegetative Brain

8/13/2019 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

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

Prognosis

Emergence or Recovery


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Vegetative State

Recovery of Consciousness

Aetiology Trauma > non-trauma

Duration of

Unconscious

(current)

Shorter > longer

Age Younger vs. older


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Vegetative State

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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Vegetative State

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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Vegetative State

Principles of Rx

Prevent 2ComplicationsProvideEnvironmentfor RecoveryTreatmentModify Patient

ModifyEnvironmentSupport FamilyChangeSociety


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Vegetative State

The Vegetative Person

Brain

Body

Medically

Vulnerable

Complex

Neurological

Complications

Environment

Physicallydependent

Family in

Crisis

Cognitively

Impaired


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Vegetative State

Cognitively Impaired

Remove Factors InhibitingMedications

Infections

Toxic states

Medical


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Vegetative State


PostureAscending Reticular Activating System

Scattered Nuclei in Brain stem

Arousal and maintain consciousness

Receive stimulation from sensory

modalities including posture


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Vegetative State


PharmacologicalAnti-Parkinsonian

L-dopa

Amantidine

BromocriptineAnti-depressants

Amphetamines

Modafanil

Zolpidem


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Vegetative State

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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Vegetative State

Modafinil

Narcolepsy

Helps daytime sleepiness, fatigue

Improved attention, cognitive benefits Better encouragement with therapists

No major side effects


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Vegetative State

Cholinergicagent(onTBI)

Speedof

mental

processing,

increased

learningandattention

Improves

general

Neufunctional

outcome

KhatebA.Eurorol.2005.

Donepezil


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Vegetative State

Hydrocephalus


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Vegetative State

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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Vegetative State

Multimodal Imaging

Functional MRI, EEG, PET, Diffusion

Tensor Imaging


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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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Vegetative State

Treatment

AIM: Improve function/hygiene

: Reduce pain

: Reduce carer burden

: Improve ADL

: Prevent Complications -

contractures, sores: Improve body image


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Vegetative State

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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Vegetative State

Anti-Spasticity Drugs

Baclofen

Dantrolene

Tizanidine

Benzodiazapines

Gabapentin Cannabinoids

Tolperisone (AV650)

(Research)

I j ti


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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

Orthopedic Surgery

Tenotomy

Neurectomy

Tendon tranfer

Tendon lengthening

Joint fusion

Osteotomy

Medical Vulnerability


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Vegetative State

Medical Vulnerability

Brain

Body

ChestinfectionsKidney/bladderStones

Urinary tractinfections

Nutritionalstate

PressuresoresOther traumae.g

Environment for Recovery


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Vegetative State

Environment for Recovery

Health

Nutrition

Physical

Sensory

Professional

Social

Societal

Modify Environment


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Vegetative State

Modify Environment

Structured stimulation

Special seating

Bed aids

Bath trolleys

Hoists

Standing frames

SUMMARY


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Vegetative State

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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Vegetative State

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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Vegetative State

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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Vegetative State

43

54

48

56

VSPatientsHealthy

Volunteers

[Coleman,Davis,Rodd,Robson,Ali,Owen,Pickard.Brain2009;132:25412552]

Sedated Volunteers: Speech Comprehension


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Vegetative State

SOUND SPEECH

PERCEPTION

SPEECH

COMPREHENSIO

N

[Davis,Colemanetal.PNAS,2007;104(41):1603216037]

Patient results: Prognosis


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Vegetative State

rs=0.81p


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Vegetative State

Patient results: fMRI Volition task

23 year old female


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Vegetative State

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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Vegetative State

Motorimagery SpatialNavigation

[Owen,Colemanetal.Science2006;313:1402]

Patient

Controls


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Vegetative State

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 State


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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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Vegetative State

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

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Vegetative Brain