Periventricular Leukomalacia

Question 1

Primary cause

Vulnerable age and why

Answer 1

Diffuse injury to developing oligodendrocytes and subsequent hypomyeliantoin

Primary cause = perinatal hypoxia-ischaemia - ischaemia between 24-32 weeks is selective for white matter damage

24-32 weeks = subcortical white matter is populated predominately by pre-OLs

Pre-OLs are more vulnerable to OGD and oxidative stress due to expression of AMPARs + kainate receptors

*** Pre-OLs also have mGluR5 (Gq) = during OGD these try to reduce excitotoxic shock by activating astrocytic glutamate uptake (via EAAT1/2)
BUT the cryodestructive effects of AMPARs/kainate receptors outweigh the cryoprotective effects of mGluR5

Question 2

Pathophysiology

Answer 2

Focal (vacuole) = necrotic component deep in periventricular white matter

• Can evolve to form multiple cystic lesions
• Can visualise with ultrasound

Diffuse component = astriogliosis + microgliosis occur

• Vulnerable pre-OLs are targeted
• Increase in OPCs
• OPCs = do not have the full capacity for remyelination, therefore hypomyelination occurs with ventriculomyegaly

Question 3

Therapies

Answer 3

Xenon

Hypothermia

Preclinical study = topimerate (AED) administered post-insult

• Protective against selective hypoxic-ischaemic white matter injury
• Decreased neuromotor deficits
• Attenuates AMPA-kainate receptor mediated cell death and Ca influx

Question 4

Animal Model

Answer 4

Rodent on P7

Carotid ligation followed by hypoxia (1 hour) causes selective white matter injury

BUT

• Rodents = 10% white matter
• Humans = 40% white matter

Therefore not very representative - lacks construct validity