Periventricular Leucomalacia

Periventricular leucomalacia is injury to the cerebral white matter around the lateral ventricles in preterm infants. It ranges from cystic necrosis to diffuse white matter injury with loss of oligodendrocyte precursors and later impaired myelination.

Cystic disease has become uncommon, affecting under 5% of very preterm infants, while milder diffuse white matter injury is more frequent. The result is spastic diplegia, visual impairment and cognitive and behavioural difficulties.

Risk factors are gestation under 32 weeks, chorioamnionitis, prolonged rupture of membranes, hypotension, hypocapnia (PaCO2 under 30 mmHg), sepsis, necrotising enterocolitis, patent ductus arteriosus with diastolic steal, severe intraventricular haemorrhage and twin-to-twin transfusion.

Pathophysiology.

Pre-oligodendrocytes, abundant between 23 and 32 weeks, are highly sensitive to hypoxia ischaemia, free radicals and cytokines. The periventricular watershed zone has immature vascular autoregulation, so fluctuations of cerebral blood flow cause ischaemia.

Inflammation from maternal or neonatal infection causes microglial activation and oligodendrocyte death. The result is focal necrosis (cystic form) or diffuse injury with reactive gliosis and reduced white matter volume.

• Usually no abnormal signs in the neonatal period.
• Later: spastic diplegia (legs more than arms), or quadriplegia in severe disease, delayed motor milestones, cortical visual impairment, strabismus, epilepsy, and cognitive, attention and behavioural problems.

Red flags.

• Persistent periventricular echodensity beyond 7 days or cystic change on ultrasound.
• Absent fidgety movements on general movements assessment at 3 to 5 months.
• Asymmetric tone or early hand preference.

• Cranial ultrasound: periventricular echodensity (flare) over 7 days, then cysts at 2 to 4 weeks and ventricular enlargement.
• MRI at term equivalent age: reduced white matter volume, ventricular dilatation with irregular margins, thin corpus callosum and T2 signal abnormality. MRI is more sensitive than ultrasound for diffuse injury.
• General movements assessment at 3 to 5 months and structured neurodevelopmental review from 3 months.
• Formal vision, hearing and developmental testing.

Differential diagnosis. Haemorrhagic parenchymal infarction, posthaemorrhagic ventricular dilatation, hypoxic ischaemic injury, congenital infection (cytomegalovirus), metabolic leucodystrophies and genetic white matter disease.

Prevention.

• Antenatal corticosteroids, delayed cord clamping for 30 to 60 seconds, and transfer of mothers at risk of preterm birth to a tertiary centre.
• Magnesium sulphate for neuroprotection when delivery is expected before 30 to 32 weeks: 4 g IV over 20 to 30 minutes, then 1 g/h until delivery or for up to 24 hours.
• In the nursery, avoid hypotension, hypocapnia (keep PaCO2 over 35 mmHg) and hypoxia. Treat sepsis early and close a haemodynamically significant duct when indicated.

Established disease. No specific treatment exists. Early intervention programmes, physiotherapy and occupational therapy start in infancy.

• Spasticity: oral baclofen 0.3 mg/kg/day in 3 divided doses, increased gradually to a maximum of 2 mg/kg/day (maximum 40 mg daily under 8 years), botulinum toxin injections for focal spasticity, orthoses and orthopaedic surgery for contractures.
• Vision and hearing assessment, educational support and treatment of epilepsy.

Monitoring. Neurodevelopmental follow up to at least 2 years of corrected age and ideally school age, with growth, vision, hearing and motor assessment.

Referral and escalation. Refer early to neurodevelopmental, physiotherapy and ophthalmology services when ultrasound or MRI shows white matter injury.