Neonatal hypoxic-ischemic encephalopathy

Global hypoxic-ischaemic brain injury in the neonate results in neonatal hypoxic-ischaemic encephalopathy (HIE).  Periventricular leukomalacia (PVL) is considered end stage HIE in premature infants.

It is important to remember that neonatal encephalopathy may result from a variety of conditions and hypoxic-ischaemic brain injury is one of them. 

Epidemiology

Hypoxic-ischaemic encephalopathy is one of the most common causes of cerebral palsy and other severe neurologic deficits in children, occurring in 2-9 of every 1000 live births.

Clinical presentation

The encephalopathic neonate may have low Apgar scores at delivery and metabolic acidosis documented in the cord blood. Within the first 24 hours of life, the infant may develop symptoms of apnea and seizures with abnormal electroencephalographic (EEG) results.

Pathophysiology

The lack of sufficient blood flow, in conjunction with decreased oxygen content in the blood (perinatal asphyxia) leads to loss of normal cerebral autoregulation and diffuse brain injury. The exact nature of the injury depends on the severity of hypotension and the degree of brain maturation. In term infants myelinated areas are more metabolically active and express more glutamate receptors (NMDA receptors) which makes them more vulnerable to HII due to excitotoxicity.

Clinical presentation

The encephalopathic neonate may have low Apgar scores at delivery and metabolic acidosis documented in the cord blood. Within the first 24 hours of life, the infant may develop symptoms of apnea and seizures with abnormal electroencephalographic (EEG) results.

Radiographic features

Pattern of injury is deferentdifferent in term and premature infants:

In premature infants blood flow is ventriculopetal hence mild to moderate HIE causes , germinal matrix haemorrhage, intraventricular haemorrhage, and periventricular leukomalacia (PVL). In severe cases thalami, brain stem, and cerebellum can also be affected. End stage shrunken and flattened cortex, usually in parasagittal watershed zones, is called ulegyria (case 3).

In term infants blood flow is ventriculofugal and changes are mainly like older children in watershed-border zones; namely parasagittal grey matter and subcortical white matter. Profound HIE in term babies results in thalami and basal ganglia as well as sensorimotor cortex (perirolantic region) injury.

Ultrasound

Sonography is sensitive for the detection of haemorrhage, periventricular leukomalacia (PVL), and hydrocephalus. Resistive index (RI) of the middle cerebral arteries, if correlated with gestational age, can add more information. Severe HIE results in loss of autoregulation and increased RI.

CT

CT is the least sensitive modality for evaluation of HIE because of poor parenchymal contrast resolution in neonatal brain due to the high water content of the parenchyma and high protein content of the CSF.

MRI

Is the most sensitive and specific imaging technique for examining infants with suspected hypoxic-ischemic brain injury. Conventional sequences can help exclude other causes of encephalopathy such as haemorrhage, cerebral infarction, neoplasms, or congenital malformations.

• hypoxic-ischemic injury to grey matter (deep grey matter, cortex) demonstrates characteristic T1 hyperintensity and variable T2 intensity, depending on the time at imaging and the dominant underlying pathologic condition, such as haemorrhage or gliosis
• injury to white matter generally results in T1 hypointensity and T2 hyperintensity particular in posterior limb of internal capsule due to ischaemia-induced oedema
• diffusion-weighted MR imaging performed between 24 hours and 8 days of life is more sensitive for the detection of cytotoxic oedema, as it reveals restricted diffusion earlier than the signal intensity abnormalities are evident on conventional T1 or T2 weighted images. Pseudonormalisation occurs at the end of first week

Treatment and prognosis

Increased severity of encephalopathy is indicated by the presence of cortical and basal ganglia abnormalities on conventional MR images, on diffusion-weighted MR images, and at MR spectroscopy. Severe EEG abnormalities also portend a poor outcome.

Although term infants with mild encephalopathy generally make a full recovery, 20% of affected infants die in the neonatal period and another 25% develop significant neurologic sequelae. For preterm infants, compared with term infants, the overall prognosis is worse.

Studies estimate a short therapeutic window of 2-6 hours during which interventions may be efficacious in reducing the severity of ultimate brain injury; thus, early identification of a neonate who has sustained a hypoxic-ischaemic insult is a paramount objective for optimal management and treatment.