Diffuse brain dysfunction
- generalised severe metabolic or toxic disorders depress overall brain function
- drug overdose
- CO poisoning, anaesthetic gases
- hypoglycaemia, hyperglycaemia
- hypoxic/ischaemic brain injury
- hypertensive encephalopathy
- severe uraemia
- hepatocellular failure
- respiratory failure with CO₂ retention
- hypercalcaemia, hypocalcaemia
- hypoadrenalism, hypopituitarism, hypothyroidism
- hyponatraemia, hypernatraemia
- metabolic acidosis
- hypothermia, hyperpyraxia
- trauma (closed head injury)
- epilepsy
- encephalitis, cerebral malaria, septicaemia
- subarachnoid haemorrhage
- metabolic disorders e.g. porphyria
- cerebral oedema from chronic hypoxia

Direct effect within brainstem
- lesion within the brainstem damages or inhibits the reticular activating system
- brainstem haemorrhage or infarction
- brainstem neoplasm
- brainstem demyelination
- Wernicke-Koraskoff syndrome
- Trauma

Pressure effect on brainstem
- mass lesion within cerebral hemisphere or cerebellum compresses brainstem
-> inhibition of reticular activating system
- hemisphere tumour, infarction, abscess, haematoma, encephalitis, trauma
- cerebellar mass lesions

- focal lesions do not affect consciousness unless they compress the brainstem
- oedema surrounding a mass lesion may contribute to its effects

Persistent vegetative state and locked-in syndrome - distinct from coma
- persistent vegetative state - loss of sentient behaviour; patient perceives little or nothing, but is apparently awake and breathes spontaneously
- locked-in syndrome - state of unresponsiveness due to massive brainstem infarction; patient is aware but cannot move or communicate except by vertical eye movement
- brainstem death - irreversible loss of the capacity for consciousness together with irreversible loss of the ability to breathe

Examination
- assess and record depth of coma according to Glasgow Coma Scale

General examination
Temperature
Skin appearance
- cyanosis, jaundice, purpura, rashes, pigmentation, injection marks, trauma
Skin texture and hydration
- coarse and dry in hypothyroidism
Breath
- alcohol, ketones, hepatic or uraemic foetor
Respiration
- depressed but regular respiration occurs in stupor and light coma
- Cheyne-Stokes respiration - alternating hyperpnoea and apnoea - occurs in bilateral cerebral dysfunction - sign of incipient coning; occurs with CO₂ retention, chronic hypoxia, normal people during sleep
- Kussmaul respiration - deep, sighing respiration seen in DKA, uraemia
- Central neurogenic hyperventilation - sustained, rapid, deep breathing seen with pontine lesions
- Ataxic respiration - shallow, halting, irregular respiration which occurs following damage to medullary respiratory centre
- Vomiting, hiccup, exercise yawning - lower brainstem lesion

Neurological examination
Head, neck and spine
- nose trauma, skull burr-holes, cranial bruits, neck stiffness
Pupils
- size, reaction to light
- dilatation of one pupil - herniation of cerebellar tonsil
- Horner's syndrome - lesions of hypothalamus
- bilateral mid-point reactive pupils (i.e. normal) - metabolic comas, CNS-depressant drugs
- bilateral light-fixed dilated pupils - brainstem death, deep coma of any cause
- bilateral pin-point, light-fixed pupils - pontine haemorrhage, opiates
- bilateral mid-position light-fixed or slightly dilated light-fixed - brainstem damage interrupts the light reflex
Fundi
- papilloedema
- retinal haemorrhage
Ocular movements
- slight divergence of eyes in most cases of coma
- slow side-to-side movements in light coma
- vestibulo-ocular reflex - doll's head reflex is lost in deep coma and in brainstem lesions
- caloric reflex - lost in brainstem lesions, used in diagnosis of brainstem death
- abnormalities of conjugate gaze - sustained conjugate lateral deviation in destructive frontal lesions; skew deviation in brainstem or cerebellar lesions; occular bobbing in pontine or cerebellar haemorrhage
- lateralizing signs - response to visual threat, facial weakness, tone of limbs, asymmetrical response to painful stimuli, asymmetry of plantar response, asymmetry of tendon reflexes, asymmetry of decerebrate/decorticate posturing

CT/MRI
- mass lesions/intracranial haemorrhage

CSF examination
- ensure no raised ICP before performing LP - CT head first

Electrophysiological tests
- EEG is valuable in diagnosis of metabolic coma and encephalitis

Long-term
- skin care - turn, remove rings, avaoidance of pressure sores or palsies
- oral hygiene - mouth washes, suction
- eye care - taping of lids, prevention of corneal damage, irrigation
- fluids - intragastric or i.v. fluids
- calories - liquid diet through fine intragastric tube - 1225 kJ/day
- sphincters - cathterisatio only when essential; avoid constipation by evacuating rectum