1. Infection and white matter damage
William Tarnow-Mordi

5. 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

6. 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

8. Periventricular leukomalacia
Histological diagnosis with “softening” of the white matter and focal cystic degeneration
Occurs in 3 - 9% of all preterm babies < 30 weeks gestation
Previously attributed to ischaemia, typically evolving weeks after hypotensive insult
Now also attributed to infection

9. 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

15. 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

18. 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

21. 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

23. 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

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