Coma and consciousness

A/Prof Andrew ZacestFRACS, FFPMANZCA

Royal Adelaide Hospital

Overview• Why is this important ?• Historical considerations • Normal consciousness • Impairment of consciousness and coma• Pathology• Clinical assessment• Neuroimaging• Treatment• Outcome• Future

Consciousness - historical

• Greeks – impaired consciousness = brain failure • Philosphers – Aristotle, Descartes, John Locke• 1800s – cerebral hemispheres – consciousness• 1890 – Wernicke’ s – periventricular lesions • 1916 – encephalitis lethargica - autopsy• 1917 – von Economo - proposed arousal circuit from midbrain• 1929 – Berger – EEG in humans• 1935 – Bremer – EEG in animals with lesions• 1949 – Moruzzi - RAS lesions in animals• 1951 – Starzl – electrical stim of RAS in animals

Consciousness

• State of full awareness of the self and one’s relationship to the environment

• Arousal • Awareness

NORMAL CONSCIOUSNESS

• Arousal wakefulness–Thalamic ascending system–Extrathalamic ascending system

• Awareness–Distributed neuronal networks–Modular organization–Thalamo-cortical-thalamic circuitry

• Awareness requires wakefulness but wakefulness can be present without awareness

CEREBRAL CORTEX

PrimarySensory Cortex

SecondarySensory Cortexin each Modality

Association Cortex

Association Cortex

THALAMUS

LIMBIC SYSTEM

HYPOTHALAMUS

BRAIN STEM

SPINAL CORD

BASAL FOREBRAIN

THALAMICASCENDINGAROUSAL

EXTRATHALAMICASCENDINGAROUSAL

THALAMUS

INTRA SENSORY ASSOCIATIONLAMINAR RELAY NUCLEINUCLEI NUCLEI

RETICULAR LIMBICNUCLEUS NUCLEI

BRAIN STEM

RETICULAR FORMATION

PEDUNCULOPONE NUCLEUS

LOCUS COERULEUS

ROSTRAL RAPHE COMPLEX

BASAL FOREBRAIN

EXTRATHALAMICAROUSAL

PrimarySensory Cortex

SecondarySensory Cortexin each Modality

Association Cortex

Association Cortex

ACh

NA

5HT

THALMICASCENDINGAROUSAL ?

Disorders of consciousness

• DOC• Continuum• Unique definitions and

criteria• Require detailed and

sometimes repeated examination

• Prognostic implications• Differential diagnosis

Bernat et al Annu Rev Med 60 :2009

Mild TBI- concussion

• Most common form of TBI 22:1

• Does not require LOC• Evidence of head

impact• GCS 13-15• Neurosurgical

intervention not required

• Common in sport• Cumulative effect

Axonal injury in mild TBI

• 5 patients with mild TBI• Death from other cause• Autopsy• APP -axonal injury• No fracture-hematoma• Axonal injury in all cases• Fornix injured in all• Reticular system injury

Blumbergs P, Scott G. Lancet 334 :1994

Impact

or

Impulse

CONFUSION Normal consciousness without amnesia

CONFUSION Confusion Normal consciousness

+ Amnesia with posttraumatic

amnesia (PTA) only

CONFUSION + AMNESIA Normal consciousness

with PTA + retrograde amnesia

COMA PARALYTIC Confusion + Amnesia

COMA Vegetative State

DEATH

Shearstrains

III

I

II

IV

V

VI

Impact force and TBI

Coma - definition

• Gk – deep sleep• Unresponsiveness• Eyes closed• Does not respond to

stimuli• No awareness of

outside or self• Graduation in depth of

coma but no arousal cycle

MECHANICAL FORCES – coma and sequelae

CONCUSSIVE SYNDROMES COMA “INSTANTANEOUS” DEATH

GCS 13-15 GCS 9-12 Moderate TBI Forces of great magnitudeMinor TBI GCS 3-8 Severe TBI as in high speed MVAsMild TBI disrupting neural tissue

Different spectrum of brain lesions in this forensic population

Recovery Mild Moderate Severe Vegetative Minimal Death Disability Disability Disability State (VS) Conscious (spectrum State psychologic & neurologic Persistent VS dysfunction) Permanent VS

Spectrum Spectrum Spectrum Spectrum Spectrum Spectrum focal + focal > focal + diffuse > diffuse >

focal + diffuse diffuse diffuse focal focal

diffuse injury injury injury injury injury injury

Patients who are unable to follow instructions

reliably or communicate, but who demonstrate

inconsistent but reproducible behavioural

evidence of self-awareness or awareness of

the environment.

American Congress of Rehabilitation Medicine, 1995

MINIMALLY CONSCIOUS STATE

VEGETATIVE STATE

• Complete unawareness of self and

environment

• Preservation sleep-wake cycles

• Complete or partial preservation of

hypothalamic and brain stem

autonomic functions

"ROADSIDE DEATH" MECHANICAL INJURYForces of great magnitude suchas in high speed MVAs disruptingbrain tissue CONCUSSION Death (rare)Different spectrum of brain lesions (Grades 1 to 3) Recoveryin this forensic population Postconcussion syndrome

COMA Death(Grades) Brain death

Recovery Spectrum of neurologic and psychologic

disability including minimally conscious state

VEGETATIVE STATE Death Recovery with spectrum of neurologic and

psychologic disability Minimally conscious state

PERSISTENT VEGETATIVE STATE Death Recovery with spectrum of neurologic and

psychologic disability Minimally conscious state

PERMANENT VEGETATIVE STATE Death ? Recovery disability

PERMANENT VEGETATIVE STATE

• Implies an irreversible state

• A patient in a persistent vegetative state becomes permanently vegetative when the diagnosis of irreversibility can be established with a high degree of clinical certainty

• Based on probabilities, not absolutes

BRAIN DEATH

Permanent absence of all brain functions (including brain stem)

Brain-dead patients are irreversibly comatose and apnoeic and have lost all brain stem reflexes and cranial-nerve functions

LOCKED-IN SYNDROME

• State of alert wakefulness associated with paralysis of the body and inability to speak

• Communication possible via eye movements or eyeblinks

Marked diminution in drive (global inertia) with complete or near-

complete loss of spontaneity and reduced action, ideation, speech

and emotion

Well-preserved smooth pursuit eye movements, coupled with

occasional speech and movement to command

Intact sleep-wake cycles (normal arousal)

Bilateral lesions of orbito-mesial frontal cortex, limbic system

including the septum and anterior cingulum and paramedian meso-

diencephalic reticular formation

AKINETIC MUTISM

Causes of coma in humans

• Evidence from lesions, head injury, medical• Either extensive areas of cerebral hemisphere

or ascending reticular system• Autopsy studies

Brain lesions that cause coma

Neuropathology

TBI – vegetative state

• Recovery of arousal in unresponsive patient• Autopsy of 49 patients, 35 blunt TBI, 14 non

TBI• Diffuse axonal injury most common (71%)• Thalamus abnormal in 80% -96%• Ischaemic damage, haematomas • Non TBI ischaemia in 64%, thalamus always• Either subcortical white or thalamic lesions

J Adams, Graham D, Jennett B Brain 123 2000

Clinical approach to reduced level of consciousness

• Brain failure• What is the cause ? History ?• Structural or metabolic ?• What investigations are necessary ?• What emergency measures are necessary ?• Time is important

Structural causes (surgical)

• Supratentorial mass lesion impairing diencephalon

• Infratentorial lesion damaging arousal system• History may be limited• Clinical diagnosis depends on recognition of

signs of injury to arousal pathways• Neurological signs tends to progress as

intracranial pressure ↑ and brain herniation

Intracranial pressure

• ICP = cerebral venous pressure

• CPP = MAP – ICP• Mass lesions ↑ ICP• ICP > 20mmHg

abnormal• Uncontrolled ICP leads

to brain herniation and death

Brain herniation

• Arises from compensatory shifts of brain due to raised ICP

• Vicious cycle leading to death • ↑ ICP → ↓ CPP → hypoxia → edema → ↑ ICP

→ death

Diagnosis of Stupor and Coma. Plum and Posner 2007

Herniation syndromes

• Uncal – pupil dilatation then oculomotor failure• Central – diencephalic - ↓ alertness - midbrain – oculomotor failure - posturing (extensor) - pontine – flaccid - medulla – autonomic failure

Clinical assessment - History

• History is important• History of trauma ?• PMH ?• Collateral history ?• Alcohol ?• Drugs ?• ? SAH ? Stroke ? Fever ?• Prior neurological exam

Clinical examination

• A,B,C• Pupil and ocular motility• Motor response

Pupils and EOM

Motor response

Glasgow Coma Score

• Teasdale & Jennett 1974

• 3 components• early assessment• monitoring progress• paediatric coma scale

Investigations

• Electrolytes, LFT, glucose, creatinine• Blood gas, CXR,ECG• Lumbar puncture• Toxicology• CT/MRI

Neuroimaging

• CT• MRI• fMRI• PET• Lesions• Function – CBF• Limitations• Can they predict

outcome ?

Why is the patient drowsy ?

Medical causes of coma Often multifactorial• Hypoxia Ischaemia Hyper/hypothermia Metabolic Drugs/alcohol Organ failure Infection Epilepsy Head injury Psychogenic Locked in syndrome

Don’t delay imaging if in doubt(Neither the neurological exam or examinerIs infallible)

Differential characteristics of Coma

• Supratentorial mass lesions Focal dysfunction early, progression, localising neurological deficit,

assymetry

• Infratentorial mass lesions History of brainstem dysfunction, immediate coma, pupil,

oculomotor, respiratory abnormality

• Metabolic/diffuse Delirium common, motor signs symmetric, pupils often normal,

seizures

• Psychogenic Lids actively closed, inconsistent but normal exam

Management of Coma

• Identify cause of coma if possible• A,B,C – stabilise patient and get help• Assume a structural cause until proven otherwise• Control glucose, treat seizures, electrolyte and temp

disturbance, give thiamine, treat infection• Control agitation• Surgical - call neurosurgical registrar• Metabolic/Stroke – medical registrar

Prognosis

• Depends on diagnosis• Coma after TBI – 15% PVS - 45% moderately disabled - 7% good recovery - <1% chance of awareness > 1yr• Coma after anoxic-ischaemic injury - 53% dead - 32% PVS - 15% awakened - <1% chance of awareness > 3mo

PROGNOSIS FOR NEUROLOGIC RECOVERY

ComaUsually recovery, persistent vegetative state, or death in 2 to 4 weeks

Brain DeathNo recovery

Persistent Vegetative StateDepends on cause (acute traumatic or non-traumaticinjury, degenerative or metabolic condition, or developmental malformation)

Locked-In Syndrome Recovery unlikely: persistent quadriplegia with prolonged survival possible

Interventions for DOC

• Systemic review of literature• At least 6 mos (T), 3 mos (NT) for MCS, VS• 16 of 5852 papers eligible for review• Levodopa, amantadine, zolidepm• PNS, SNS (124), ECS, DBS (1), ITB• Heterogeneity, methodology problems• Schiff et al 2007 – DBS- central thalamus target• Investigational therapies

Georgiopoulos et al Stereotact Func Neurosurg 88 : 2010

Conclusions

• Impaired consciousness is brain failure• Longer coma exists the poorer the prognosis• Prompt diagnosis is important• Clinical assessment can expedite diagnosis and

treatment• Prompt treatment gives the best chance of

recovery