Lecture 30; Preterm brain injury 1 Flashcards
Where does majority of injury occur in the preterm baby?
In the white matter structures
Describe the relationship between birth age, injury and death;
- Most hospitals treat from 23 weeks onwards
- Injury and death statistics decrease as the birth age gets older
Note
- 32 weeks survival near 100% (use to be lower until corticosteroids were developed for use in prem lungs surfactant), also huge reduction in risk of severe disability
How many births are preterm (32 weeks)?
5-13%
What are the most common problems associated with preterm babies?.
- ~15% develop cerebral palsy (severe motor neuron loss)
- ~25-50% with cognitive and learning disabilities at childhood and adolescence i.e ADHD low IQ
These are life long consequences and cost $, productivity to the state
How likely is a child to have cerebral palsy instead of cancer?
10x
What are the side effects of cerebral palsy?
Arm and Leg Weakness • Abnormal walking...if at all • Limb Contractures/ Curvature of the Spine • Swallowing/Feeding Problems • Learning Disabilities • Social Alienation
What important to know regarding brain injury?
When it occured
Prior to birth? During birth? After birth?–
Determine the cause of brain injury–Potential interventions/treatment strategies
- Historically, all newborn brain injury thought to occur during birth or shortly after birth–E.g. prolonged labor, cord problems, blood pressure instability
- With new imaging technologies, determined that injury/injurious events can occur well before birth
What are the main causes of fetal brain injury?
- Hypoxia-ischemia (reduced oxygen and blood flow to the brain) (common peri-labour insult)
- Infection–Maternal, fetal/postnatal–Cytokine production
- Accident/trauma
- Teratogens
What are teratogens and what do they don?
Teratogens –Drug use, alcohol, smoking, carbon monoxide
Can cause direct effects on brain and secondary actions on oxygenation, blood flow, and nutrient provision
What are the main white matter injuries seen in preterm brain injury?
Focal Cystic Necrosis (Necrotic cells form fluid, cyst)
Focal Microscopic Necrosis
More common now;
Diffuse white matter injury
Diffus myelination failure
Loose all cellular elements in cyst formation
Write some notes on focal microscopic necrosis;
- Pan-cellular degeneration
- Axonal degeneration
- Highly correlated with cerebral palsy
Many little holes filled with fluid of necrotic cells
Write some notes on diffuse white matter injury;
Reactive microglia
Reactive Astroycytes
Pre-oligodendrocyte death
How could impaired myelination lead to cerebral plasy? / focal necrotic cyst?
Oligodendrocytes create myelin sheath around axons.
- Improves signal transduction
This can occur on motor neurons. Impairs signalling.
Cysts in the brain can also do this.
What would and MRI reveal for these preterm brain injuries?
- Cavitary white matter lesions
- Diffuse white matter lesions
- Ventriculomegaly
- Decreased volume of white matter tracts (white matter atrophy)
What do preterm babies have an increased risk for?
Smaller brain size.
When is the period of risk for white matter injuries in babies?
Preterm birth-> 32 weeks gestational age
After this time, you can still get white matter injury but also with cortical injury.
Define the oligiodendrocytes stages of lineage development;
Ol Progenitor (OPC)
Pre OL
Immature OL
Mature OL
What is OPC and pre OL identified by?
Stained for PDGF b (OPC) (also migratory cell of lineage)
O4 factor. (POL)
Both of these are the proliferative cells do the oligiodendrocyte lineage
What are Immature and mature OL identified by?
Immature = O1
Mature. (very complex, myelinates axons)
What stage of oligiodendrocyte development is the target for preterm brain injury?
18-32 weeks
Pre OL is dominant cell type
No Immature Ols
What happens at ~30 weeks regarding Ol?
- Maturation ~30 weeks
* Differentiation of PreOLs to Immature OLs
When does myelination occur?
- Begins in PVWM
- Extensiveby birth
28-40 weeks
What is the target cell for preterm white matter brain injury demyelination?
Pre OL
Every year in Exam essay.
What did they find when they compared pre OL populations in dead babies with and without white matter injury?
Significant PreOL death in the babies with white matter injury.
O4 cell.
Hyp; Chronic WMI myelination failure is due to selective loss of pre OL
Diffuse pattern of injury
What does MRI show regarding grey matter structures?
Acutely there appears to be no grey matter injury in MRI in preterm babies
Term babies are at a far higher risk of developing grey matter brain injury.
Why is the lack of grey matter injury in preterm mri confusing?
Up to 50% incidence of unexplained cognitive and learning deficits in later life?
- functions primarily related to grey matter structure not white matter.
•No acute damage to grey matter structures
What happens in the long term to babies with preterm brain injury regarding grey matter?
- Long term reduction in grey matter growth/connectivity
- Cortical growth, folding, complexity
- Subcortical growth (hippocampus, thalamus, striatum and basal ganglia)
Range of associated deficits
What are the associated deficits in preterm long term grey matter injury?
Cortical growth/folding: Impaired neurodevelopmental outcomes, impaired cognition / IQ outcomes into adulthood.
When is the fastest rate of brain growth?
Last trimester of pregnancy
Therefore premature birth can halt this grey matter growth
Likely to be asked;
When is the period of most susceptible brain injury? What are the two common white and grey matter injuries, why?
preterm birth-> 32 weeks
Diffuse white matter injury
Reduced chronic grey matter volume.
Is there any loss of cortical neurons?
- Autopsy cases with severe necrotic WMI (cystic (PVL) injury)
- 38% reduction in density of layer 5 pyramidal neurons
But very little evidence for loss of cortical neurons in babies with diffuse white matter injury
