White matter injury

Incidence: The incidence of WMI has been difficult to quantify: PVL has been shown to be present in 75% of autopsies and diagnosed in 9% of live infants using cranial ultrasound. With the increased use of MRI more accurate assessment of the incidence of WMI can be made.

Aetiology: The periventricular white matter in the preterm infant is susceptible to a variety of insults resulting in focal necrotic lesions (periventricular leucomalacia) or more diffuse white-matter injury.

  • Hypoxic-ischaemic injury: WMI has been associated with infants with a loss of cerebral auto-regulation and hypocarbia, which reduces cerebral blood flow.
  • Inflammation: developing oligodendrocytes appear to be susceptible to the presence of proinflammatory cytokines, particularly TNF and Il-6 is associated with WMI as well as free radical  damage.

Neuropathology: Focal PVL results from coagulative necrosis with the formation of microcavities which coalesce to form macroscopic cavities. Diffuse WMI injury is associated with loss of oligodendroglia resulting in the loss of white matter volume and mild ventriculomegaly.

Diagnosis: WMI injury is often clinically silent. Cranial ultrasound screening will diagnose cystic PVL, but may not be apparent until at least 6 weeks after birth.

Currently there is no specific therapy to prevent brain injury in the preterm infant; however good general care is the best basis for helping to minimise injury:

  • Antenatal steroids.
  • Early effective resuscitation.
  • Surfactant treatment.
  • Good control of blood gases (avoid hypoxia, hypocarbia and hypercarbia).
  • Maintain the blood pressure.
  • Aim for synchronous ventilation if possible – sedate if necessary.
  • Avoid tight headgear and positioning the head too far over to one side.
  • Give drugs (indomethacin) and plasma etc. slowly (to reduce effects on cerebral blood flow).

 

Periventricular leukomalacia

The most serious white matter lesion in the preterm infant is periventricular leukomalacia (PVL). There is increasing evidence that perinatal infection often plays an important role in the pathophysiology of this lesion. The combination of chorioamnionitis and ischaemia may be particularly malignant in the evolution of PVL.

The earliest abnormality seen is an abnormally echodense area within the periventricular region or flare. This may be relatively faint and easily confused with normal appearances. In order to distinguish from normal, the following diagnostic criteria are required:

  • The echodensity is at least as bright as the choroid plexus.
  • It is visible in 2 planes.
  • It involves the white matter adjacent to the lateral ventricle, usually in the occipito-parietal or frontal region.
  • There is no detectable haemorrhage within the ventricle.
  • The echodense region is usually not well demarcated, compared to haemorrhagic infarcts, which are usually clearly demarcated and wedge-shaped.
  • The brighter the echodensity, the more confident the diagnosis and the more significant the lesion is likely to be. Periventricular echodensities may either disappear or become cystic. If in doubt, reserve your opinion about the prognosis and observe the progression of events over the next few weeks. The rate of progression to periventricular cysts varies from one baby to another, and cysts may take from 10 days to about 6 weeks to appear.

Periventricular cystic lesions identified within the first few days of life must therefore be antenatal in origin. Conversely, in an infant who is thought to be at risk of PVL from events occurring around the time of birth, a reassuring prognosis cannot be given until the scan has remained normal for 6 weeks. The affected region may go through an isodense phase before cysts appear.

The most common ante-natal events associated with PVL are:

  • Ante-partum haemorrhage
  • Chorioamnionitis
  • Maternal trauma (e.g. RTA) or severe maternal illness
  • Embolic phenomena from a dead twin
  • Maternal drug abuse (rare)

Postnatal events associated with PVL include:

  • Any cause of profound hypotension or cardiovascular collapse
  • Inadvertent hypocarbia due to hyperventilation

Periventricular cysts or periventricular leukomalacia (PVL) can be recognised by the following characteristics:

  • The cyst appears echolucent with a surrounding rim of echodense tissue.
  • The cysts are nearly always discrete, small and separate from the ventricle, unlike haemorrhagic infarcts which lead to porencephalic cysts which are larger and continuous with the ventricle.

In infants at risk of PVL, scans must be repeated regularly. As PVL may take up to 6 weeks to appear, never be too reassuring about a normal scan in the early weeks. Once cysts appear the prognosis is variable and depends on the site of the lesion (occipito-parietal worse than frontal) and on its extent. PVL is commonly associated with spastic diplegia because of involvement of the internal capsule (leg >arm).

Occasionally isolated cystic lesions may be observed in more lateral positions within the cerebral white matter. These may be embolic in origin. They may be missed unless the entire cranial cavity is interrogated during an ultrasound scan.

N.B. It is important to distinguish between an ischaemic cyst within the parenchyma (which carries a poor prognosis) and a sub-ependymal pseudocyst (SEPC) which carries a good prognosis. The critical distinction is whether the cyst is within the brain parenchyma (white matter) or within a blood clot in the ventricle or germinal matrix.

 

Bilateral cystic periventricular leucomalacia; coronal section (left); parasagittal (right)