1. Coma and consciousness
A/Prof Andrew Zacest
FRACS, FFPMANZCA
Royal Adelaide Hospital

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

4. 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

5. Consciousness
• State of full awareness
of the self and one’s
relationship to the
environment
• Arousal
• Awareness

6. 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

7. CEREBRAL CORTEX
Primary Secondary
Sensory Sensory Cortex Association Association
Cortex in each Modality Cortex Cortex
LIMBIC SYSTEM
BASAL
THALAMUS FOREBRAIN
HYPOTHALAMUS
THALAMIC EXTRATHALAMIC
ASCENDING BRAIN STEM
ASCENDING
AROUSAL AROUSAL
SPINAL CORD

8. Primary Secondary
Sensory Sensory Cortex Association Association
Cortex in each Modality Cortex Cortex
THALAMUS
INTRA SENSORY ASSOCIATION
LAMINAR RELAY NUCLEI BASAL FOREBRAIN
NUCLEI NUCLEI
RETICULAR LIMBIC
NUCLEUS NUCLEI
EXTRA
THALAMIC
THALMIC AROUSAL
ASCENDING BRAIN STEM
AROUSAL ?
RETICULAR FORMATION
ACh
PEDUNCULOPONE NUCLEUS
NA
LOCUS COERULEUS
5HT
ROSTRAL RAPHE COMPLEX

9. 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

10. 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

11. 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

12. Impact force and TBI
I CONFUSION Normal consciousness without amnesia
II CONFUSION Confusion Normal
consciousness
+ Amnesia with posttraumatic
Impact III amnesia (PTA) only
or Shear
CONFUSION + AMNESIA Normal
strains
Impulse consciousness
IV with PTA + retrograde
amnesia
V COMA PARALYTIC Confusion
+ Amnesia
VI COMA Vegetative State
DEATH

13. 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

14. MECHANICAL FORCES – coma and sequelae
CONCUSSIVE SYNDROMES COMA “INSTANTANEOUS” DEATH
GCS 13-15 GCS 9-12 Moderate TBI Forces of great magnitude
Minor TBI GCS 3-8 Severe TBI as in high speed MVAs
Mild 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

15. MINIMALLY CONSCIOUS STATE
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

16. VEGETATIVE STATE
• Complete unawareness of self and
environment
• Preservation sleep-wake cycles
• Complete or partial preservation of
hypothalamic and brain stem
autonomic functions

17. "ROADSIDE DEATH" MECHANICAL INJURY
Forces of great magnitude such
as in high speed MVAs disrupting
brain tissue CONCUSSION  Death (rare)
Different spectrum of brain lesions (Grades 1 to 3)  Recovery
in 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

18. 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

19. 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

20. LOCKED-IN SYNDROME
• State of alert wakefulness
associated with paralysis of the
body and inability to speak
• Communication possible via eye
movements or eyeblinks

21. AKINETIC MUTISM
 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

22. Causes of coma in humans
• Evidence from lesions, head injury, medical
• Either extensive areas of cerebral hemisphere
or ascending reticular system
• Autopsy studies

23. Brain lesions that cause coma

25. Neuropathology

26. 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

27. 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

28. 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

29. Intracranial pressure
• ICP = cerebral venous
pressure
• CPP = MAP – ICP
• Mass lesions ↑ ICP
• ICP > 20mmHg
abnormal
• Uncontrolled ICP leads
to brain herniation and
death

30. 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

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

32. Clinical assessment - History
• History is important
• History of trauma ?
• PMH ?
• Collateral history ?
• Alcohol ?
• Drugs ?
• ? SAH ? Stroke ? Fever ?
• Prior neurological exam

33. Clinical examination
• A,B,C
• Pupil and ocular motility
• Motor response

34. Pupils and EOM

35. Motor response

36. Glasgow Coma Score
• Teasdale & Jennett
1974
• 3 components
• early assessment
• monitoring progress
• paediatric coma scale

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

38. Neuroimaging
• CT
• MRI
• fMRI
• PET
• Lesions
• Function – CBF
• Limitations
• Can they predict
outcome ?

39. Why is the patient drowsy ?

40. 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 examiner
Is infallible)

41. 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

42. 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

43. 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

44. PROGNOSIS FOR NEUROLOGIC RECOVERY
Coma
Usually recovery, persistent vegetative state, or death in 2 to 4 weeks
Brain Death
No recovery
Persistent Vegetative State
Depends on cause (acute traumatic or non-traumatic
injury, degenerative or metabolic condition, or developmental malformation)
Locked-In Syndrome
Recovery unlikely: persistent quadriplegia with prolonged
survival possible

45. 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

46. 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