Infection and white matter damage

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Infection and white matter damage

• William Tarnow-Mordi

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Types of white matter injury

• Diffuse white matter damage
• Periventricular leukomalacia
• Intraventricular haemorrhage
• Punctate haemorrhagic/ ischaemic lesions
• Periventricular haemorrhagic infarction
  detection by ultrasound unreliable MRI
  scanning is the gold standard

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Diffuse white matter abnormality

• Most preterm babies have diffuse white matter
  abnormality on MRI scan when they reach term
  equivalent
• This has been attributed to poor nutrition,
  infection, postnatal steroids
• Associated with ?vasogenic oedema,
  oligodendrocyte dysfunction or reduced axonal
  diameter

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Periventricular leukomalacia

• Histological diagnosis with softening of the
  white matter and focal cystic degeneration
• Occurs in 3 - 9 of all preterm babies lt 30 weeks
  gestation
• Previously attributed to ischaemia, typically
  evolving 2 - 6 weeks after hypotensive insult
• Now also attributed to infection

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Periventricular leukomalacia

• On histology there is cytotoxic oedema,
  macrophage infiltration and apoptosis
  (programmed cell death)
• Also associated with delayed myelination,
  probably because of glial necrosis and
  oligodendrocyte dysfunction

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Debillon et al

• Inoculated bacterial endotoxin (lipopolysaccharide
  ) into uterus with 14 fetal rabbits at 80 of
  term pregnancy
• delivered the fetuses 12, 24 and 48 hr later
• after 48 hours, histology showed extensive
  programmed cell death (apoptosis), with
  periventricular leukomalacia and periventricular
  cyst formation

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• Furthermore, low doses of LPS that by themselves
  have no adverse effects in 7-day-old rats
  (corresponding to term human fetus), dramatically
  increase brain injury to a subsequent
  hypoxic-ischemic challenge, implicating that
  bacterial products can sensitize the immature CNS

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Volpe Pediatric Research 2003

• Three interacting, maturation-dependent factors
  predispose to PVL
• immature vascular supply to cerebral white matter
• impairment of cerebral blood flow autoregulation
• vulnerability of oligodendrocyte
• to attack by free radicals
• particularly after ischaemia-reperfusion injury

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Leviton and Gillies 1976

• Reviewed autopsies and notes of 40 infants with
  perinatal telencephalic leuco-encephalopathy
  (PTL)
• Compared with 76 infants who died without PTL
• PTL more common after
• bacterial gram negative septicaemia
• ? Endotoxin damages developing white matter

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Brain damage
Infection / inflammation is an important
proposed pathway in neonatal brain damage
Dammann Leviton, Pediatrics 1999
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