Hypoxic-Ischaemic Brain Injury

Hypoxic-ischaemic damage in older children (i.e. not neonates) and adults, also known as global hypoxic-ischaemic injury, is seen in a number of settings and often has devastating neurological sequelae.
For a discussion of neonatal hypoxia, refer to neonatal hypoxic-ischaemic encephalopathy.
Epidemiology
Hypoxic-ischaemia cerebral injury occurs at any age, although the aetiology is significantly different:
older children: drowning and asphyxiation remain common causes
adults: more often a result of cardiac arrest or cerebrovascular disease, with secondary hypoxemia 1,3
Clinical presentation
Patients typically present to hospital following an acute event (near-drowning, asphyxia, cardiac/respiratory arrest). They are usually intubated and have a history of prolonged resuscitation.
Pathology
Severe global hypoxic-ischemic injury in this population primarily affects the gray matter structures:
basal ganglia
thalami
cerebral cortex (in particular the sensorimotor and visual cortices, although involvement is often diffuse)
cerebellum
hippocampi
This predominance of gray matter injury is related to the fact that gray matter contains most of the dendrites where postsynaptic glutamate receptors are located. They are therefore the sites most susceptible to the effects of glutamate excitotoxicity (i.e damage to nerve cells by excessive stimulation by glutamate). As a result of synaptic activity, gray matter is also more metabolically active than white matter. Although cerebellar injury can be seen in neonates, it tends to be more common in older patients. The reason for this predilection is not entirely clear, but it has been suggested that the relative immaturity of Purkinje cells (which are normally exquisitely sensitive to ischemic damage) in neonates somehow protects the cerebellar cortex1.
Radiographic features
CT
diffuse oedema with effacement of the CSF-containing spaces
decreased cortical gray matter attenuation with loss of normal gray-white differentiation
decreased bilateral basal ganglia attenuation
reversal sign: reversal of the normal CT attenuation of grey and white matter, demonstrated  within the first 24 hours in a small number of these patients
it has been proposed that this finding is due to the distention of deep medullary veins secondary to partial obstruction of venous outflow from the elevated intracranial pressure caused by diffuse oedema
the end result is that the cerebral white matter is of higher attenuation than the cortical gray matter
white cerebellum sign: has been described in at least one study as a component of the reversal sign and in which there is diffuse oedema and hypoattenuation of the cerebral hemispheres with sparing of the cerebellum and brainstem, resulting in apparent high attenuation of the cerebellum and brainstem relative to the cerebral hemispheres
linear hyperdensity outlining the cortex as well as linear cortical enhancement (later and less evident signs), correspond to cortical laminar necrosis
falx cerebri and tentorium cerebelli can appear hyperdense to ischaemic brain parenchyma and is one of the causes of pseudo-subarachnoid haemorrhage
Both the reversal sign and the white cerebellum sign indicate severe injury and a poor neurologic outcome 1,3.
MRI
Diffusion-weighted MR imaging is the earliest imaging modality to become positive, usually within the first few hours after a hypoxic-ischemic event due to early cytotoxic edema. During the first 24 hours, there may be restricted diffusion in the cerebellar hemispheres, basal ganglia, or cerebral cortex (in particular, the perirolandic and occipital cortices) 1,3. The thalami, brainstem or hippocampi may also be involved. Diffusion-weighted imaging abnormalities usually pseudo-normalize by the end of the 1st week 1.
As in younger patients, conventional T1 and T2 weighted images are often normal or demonstrate only very subtle abnormalities. In the early subacute period (24 hours–2 weeks), conventional T2 weighted images typically become positive and demonstrate increased signal intensity and swelling of the injured gray matter structures1.
T1 hyperintensities signaling cortical laminar necrosis become evident after two weeks. This hyperintense signal does not represent hemorrhage, it's believed to be caused by the accumulation of denatured proteins in dying cells. This hyperintensity can be seen also within a few days on FLAIR 3.