Low Awareness States

Vegetative and Minimally Conscious States

Dr Ashraff Ali
Consultant in Rehabilitation Lead Medical Consultant Brain Injury Rehabilitation Service Royal Hospital for Neuro-disability London, U.K.
Vegetative State

Recovery Continuum .
Coma Vegetative State Minimal Conscious State Cognitive Impaired States
(Physical)

Normal
Vegetative State

Vegetative State Nomenclature Prolonged coma Coma vigile Akinetic mutism Apallic syndrome Neocortical death Post-traumatic Unawareness State Decerebrate dementia
Vegetative State

Vegetative State To vegetate: To live a merely physical life, devoid of intellectual activity or social intercourse. Oxford English Dictionary 1740
Vegetative State

Vegetative State

An organic body capable of growth and development but devoid of sensation and thought. Oxford English Dictionary 1764
Vegetative State

Vegetative State Definition

Preserved sleep-awake pattern, responds only reflexively to stimulation and shows no evidence of meaningful response to enviroment. Awake but not aware Jennett Plum Multi-Society Task Force RCP Working group
Vegetative State

Diagnosis

Clinical

Diagnosis

Neuro-Physiological

Vegetative State

Vegetative State Preconditions Establish cause of VS

TBI, ABI, Metabolic, Infection

Exclude persisting effect of Sedatives, causative drugs, metabolic disturbances. Exclude treatable structural cause. (imaging)
Vegetative State

Clinical Features of VS Spontaneous Eye opening Breathing spontaneously Sleep-awake pattern Reflex responses to stimulation
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!!
Vegetative State

Problematic Presentations
Grasp Reflex Swallowing Chewing & Tongue Pumping/Thrusting Bruxism Grunts & Groans Smiles & Frowns (spontaneous) Relaxation Response
Vegetative State

Vegetative State Incompatible Features

Discriminative Perception Purposeful Action (reaching out to an object) Communicative Act or intent Appropriate use of language

Vegetative State

Minimally Conscious State

Severely altered consciousness in

which the patient does not meet the criteria for coma or the vegetative state because there is inconsistent but reproducible or sustained behavioural evidence of self or environmental awareness
Aspen WP 2001
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
Vegetative State

MCS - Reproducibility

CONSISTENCY

COMPLEXITY

Vegetative State

Minimally Concious State Emergence from MCS

Interactive Communication Use of objects functionally

Vegetative State

Diagnostic distinction
Normal Consciousness Coma Vegetative State Minimally Conscious

Vegetative State

SMART
Sensory Modality Assessment Rehab Technique Observed responses to sensory stimulation i.e.: Visual, Tactile, 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)
Vegetative State

JFK Coma Recovery Scale

AUDITORY FUNCTION SCALE 4 - Consistent Movement to Command * 3 - Reproducible Movement to Command * 2 - Localization to Sound 1 - Auditory Startle 0 - 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
SMART 2008

OROMOTOR/VERBAL FUNCTION SCALE 3 - Intelligible Verbalization * 2 - Vocalization/Oral Movement 1 - Oral Reflexive Movement 0 - None COMMUNICATION SCALE 2 - Functional: Accurate t 1 - Non-Functional: Intentional * 0 - None AROUSAL SCALE 3 - Attention 2 - Eye Opening w/o Stimulation 1 - Eye Opening with Stimulation 0 Unarousable Total score (maximum = 23)

Vegetative State

Differential Diagnosis (1)

Condition S elf Awarenes s Cyclical Eye Opening Motor function Coma Reflex & Postural Veg. S tate + Postures or withdraws. Occasional non-purpose No Normal Min. Cons S tate Partial + Localises. Reach for objects. Automatic movements ? Normal Locked-in S yndrome Full + Quadriplegic. Vertical eye movement

Experience pain Res piratory Function

No Depressed or varied

Yes Normal

Vegetative State

Differential Diagnosis (2)

Condition Auditory Function Coma None Veg. S tate S tartle. Brief orientation Min. Cons S tate Localise. Inconsist commandsfollowing S ustained visual fix. S ustained pursuit. Locked-in S yndrome Preserved

Vis ual Function

None

S tartle. Brief orientation

Preserved.

Vegetative State

Differential Diagnosis (3)

Condition Communication Coma None Veg. S tate Min. Cons S tate None Contingent vocalisat/n. Inconsist verbal/n or gesture None or reflex Contingent smiling crying smiling or crying Locked-in S yndrome Aphonic/ anarthric. Verical eye movement and blinking Preserved

Emotion

None

Vegetative State

Prognosis Emergence or Recovery

Vegetative State

Recovery of Consciousness
Aetiology Trauma > non-trauma

Duration of Shorter > longer Unconscious (current) Age Younger vs. older

Vegetative State

Age v Reach Independence -VS 1 m

20 18 16 % Independent 1 yr 14 12 10 8 6 4 2 0 <20 20-40 Age >40
Vegetative State
Braakman 1988 Jennett 1990

VS Outcome Adults VS 1/12

100 90 80 70 60 50 40 30 20 10 0 0

Traumatic
Dead

Non-Traumatic
100 90 80 70 60 50 40 30 20 10 0 0

VS
%

Dead

VS

Conscious
3 6 Months 9 12

Conscious
3 6 Months 9 12

Vegetative State

Medical Management

SMART 2010

Vegetative State

Complexity of Presentation
Sensory Physical/motor Medical

Family Dynamics Psychosocial & Emotional Cognitive/ behavioural

Vegetative State

Communication

Principles of Rx
Prevent 2 Complications Provide Environment for Recovery Treatment Modify Patient
Vegetative State

Modify Environment Support Family Change Society

The Vegetative Person

Cognitively Impaired Brain Complex Neurological Complications

Physically dependent Medically Vulnerable

Body Family in Crisis Environment

Vegetative State

Cognitively Impaired Remove Factors Inhibiting Medications Infections Toxic states Medical
Vegetative State

Cognitively Impaired Posture Ascending Reticular Activating System

Scattered Nuclei in Brain stem Arousal and maintain consciousness Receive stimulation from sensory modalities including posture
Vegetative State

Cognitively Impaired Pharmacological Anti-Parkinsonian Anti-depressants Amphetamines Modafanil Zolpidem

Vegetative State

L-dopa Amantidine Bromocriptine

Pharmacological Agents
Awakening Agents Psychostimulants Zolpidem Methylphenidate Siddall et al.

Literature search Cochrane Register Ten clinical trials in TBI: improvement in memory, attention concentration, mental processing Randomised crossover Double Blind Placebo controlled trial TBI MPH enhances information processing speed
Vegetative State

2008 Australia Monash University

Modafinil
Narcolepsy Helps daytime sleepiness, fatigue Improved attention, cognitive benefits Better encouragement with therapists No major side effects

Vegetative State

Donepezil
Cholinergicagent(onTBI) Speedofmentalprocessing,increased learningandattention ImprovesgeneralNeufunctionaloutcome
KhatebA.Eurorol.2005.

Vegetative State

Hydrocephalus

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

Vegetative State

Multimodal Imaging
Functional MRI, EEG, PET, Diffusion Tensor Imaging

Vegetative State

Interventions

SMART 2010

Vegetative State

Spasticity Velocity dependant Resistance to muscle lengthening or stretching

Shortened muscles contractures soft tissue changes

Impairment of attempted movements

Vegetative State

Spasticity
Aggravating Factors: Nociceptive stimuli Bladder, ureteric stones Catheter blockage, constipation Pressure sores Tight leg bags UTI Heterotrophic ossification
Vegetative State

Treatment AIM: Improve function/hygiene : Reduce pain : Reduce carer burden : Improve ADL : Prevent Complications contractures, sores : Improve body image
Vegetative State

Spasticity Management
Identify aim and goal of treatment Line of action: MDT decision, 24 hour Mn
1. 2.

3. 4.

Avoid, prevent noxious stimuli PT/OT/Physical modalities/casting/splinting, positioning Oral medication Injections: Botulinum toxin, alcohol, LA, Phenol
(perineural, motor pt.)

5. 6. 7.

Intrethecal Baclofen pump Neurosurgical procedure Orthopedic surgery

Vegetative State

Physical Treatment
Mainstay throughout course Other modalities adjunctive Serial casting especially contractures

Increases sarcomere numbers Decreases sensory (cutaneous) input Increases ROM, avoid further loss ROM Best time for casting? Increase in ROM, maintain ROM Increase in function Increase in comfort Less pain Maintain muscle length Joint integrity preservation Increase alignment Decrease tone

Orthotics/splinting

Seating and positioning

Vegetative State

Anti-Spasticity Drugs
Baclofen Dantrolene Tizanidine Benzodiazapines Gabapentin Cannabinoids Tolperisone (AV650)

(Research)
Vegetative State

Injections
Local anaesthetics +/- adrenaline

Diagnostic Prior to casting/splinting Reversible quickly Perineural, motor point block Reduces spasticity by months-years Denatures protein, precipitates protoplasm Pain, phlebitis, dysesthesia Peripheral neural palsy Intoxication
Vegetative State

Ethyl Alcohol

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, vascular injury, sensory loss, weakness Early onset, longer effect (BTX) Cheap, repeatable (technique needs expertise)
Vegetative State

Botulinum Toxin
BOTOX, DYSPORT, MYOBLOC,XEOMIN Reduces spasticity variety of causes Functional benefit gait, UL function Mechanism: Blocks neuromuscular transmission by inhibiting acetylcholine release reversible denervation 7 serotypes: A to G (similar mode of action) Only A and B are commercially available Type A SNAP-25 substrate Type B Synaptobrevin
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.)
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
Vegetative State

Orthopedic Surgery Tenotomy Neurectomy Tendon tranfer Tendon lengthening Joint fusion Osteotomy

Vegetative State

Medical Vulnerability
Nutritional state Chest infections Kidney/bladder Stones Brain Urinary tract infections Pressure sores Other trauma e.g #

Body

Vegetative State

Environment for Recovery

Health Nutrition Physical Sensory Professional Social Societal

Vegetative State

Modify Environment Structured stimulation Special seating Bed aids Bath trolleys Hoists Standing frames

Vegetative State

SUMMARY
Prevent 2 Complications Provide Environment for Recovery Treatment Modify Patient
Vegetative State

Modify Environment Support Family Change Society

fMRI: Hierarchal Approach

Volition

COGNITIVE COMPLEXITY

Speech Comprehension

Speech Perception

Sound Perception

Vegetative State

fMRI Auditory task: Hierarchal paradigm

Ambiguous sentence
Scan

Unambiguous sentence
Scan

Signal correlated noise

Scan

Silence

Time(seconds)

Theshell wasfiredtowardsthetank
(Highambiguity,atleast2ambiguouswords)

Theirholidaywasquiteshortandwouldendsoon
Vegetative State (Lowambiguity,matchedforlength,syntacticcomplexity,word frequency,etc.,)

fMRI Auditory task: Volunteer results

Left Right

Level1 Sound Silence(auditorystimulusvs.silence) Level2 Sentences Signalcorrelatednoise(intelligiblespeechvsunintelligble) Level3 Retrievalofsemanticinformation(highvs.lowambiguous words) Vegetative State

MRI Scan: White matter tractography

Left

Right

[TemporalLobe][VegetativePatient]

Vegetative State
[Control]

Patient results: Sound Perception

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

Patient results: Speech Perception

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

Patient results: Speech Comprehension

HealthyVolunteers VSPatients

48

43

56

54

Vegetative State

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

Sedated Volunteers: Speech Comprehension

SOUND SPEECH PERCEPTION SPEECH COMPREHENSIO N

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

Patient results: Prognosis

rs =0.81p<0.001

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

fMRI Volition task: A measure of awareness

Vegetative State

Patient results: fMRI Volition task

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 and superior temporal gyri (similar to healthy volunteers) Ambiguous words additional activity in left inferior frontal region (same as healthy volunteers) Vegetative State

Patient results: fMRI Volition task

Motorimagery SpatialNavigation

Patient

Controls

Vegetative State
[Owen,Colemanetal.Science2006;313:1402]

Second fMRI study with mental imagery 1) Playing game of tennis activation of supplementary motor area 2) Visiting all of the rooms in her house activity in parahippocampal gyrus, posterior parietal cortex, lateral premotor cortex (similar to healthy volunteers) Conclusion: Diagnosed VS clinically but patient retained ability to understand spoken command AND respond through brain activity therefore conscious awareness present. Future Development: Brain Computer Interface
Vegetative State

Brain Computer Interface

Vegetative State

SMART 2008

Vegetative State

SMART 2008

Vegetative State

Vegetative State

Discussion semantic conditioning / learning

DOC patients may have partially preserved conscious processing, cannot Semantic which conditioning 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)
Vegetative State

Conclusion Terminology to be used VS and MCS Optimisation of general condition Behaviour observation assessment Multimodal assessment objectives may be commonly used in future

Vegetative State

Conclusions Many advances in recent years Conclusive Evidence is Lacking Meanwhile prevent secondary brain injury as soon as medical assistance reaches patients. Commence Rehabilitation from day 1 of hospitalisation and not after reaching Rehab units.
Vegetative State

Dr Ashraff Ali
Royal Hospital for Neuro-disability

Email: aali@rhn.org.uk www.rhn.org.uk/institute

Vegetative State