Lecture 30; Preterm brain injury 1 Flashcards

1
Q

Where does majority of injury occur in the preterm baby?

A

In the white matter structures

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2
Q

Describe the relationship between birth age, injury and death;

A
  • 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

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3
Q

How many births are preterm (32 weeks)?

A

5-13%

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4
Q

What are the most common problems associated with preterm babies?.

A
  • ~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

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5
Q

How likely is a child to have cerebral palsy instead of cancer?

A

10x

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6
Q

What are the side effects of cerebral palsy?

A
Arm and Leg Weakness
• Abnormal walking...if at all
• Limb Contractures/ Curvature of the Spine
• Swallowing/Feeding Problems
• Learning Disabilities
• Social Alienation
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7
Q

What important to know regarding brain injury?

A

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
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8
Q

What are the main causes of fetal brain injury?

A
  • Hypoxia-ischemia (reduced oxygen and blood flow to the brain) (common peri-labour insult)
  • Infection–Maternal, fetal/postnatal–Cytokine production
  • Accident/trauma
  • Teratogens
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9
Q

What are teratogens and what do they don?

A

Teratogens –Drug use, alcohol, smoking, carbon monoxide

Can cause direct effects on brain and secondary actions on oxygenation, blood flow, and nutrient provision

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10
Q

What are the main white matter injuries seen in preterm brain injury?

A

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

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11
Q

Write some notes on focal microscopic necrosis;

A
  • Pan-cellular degeneration
  • Axonal degeneration
  • Highly correlated with cerebral palsy

Many little holes filled with fluid of necrotic cells

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12
Q

Write some notes on diffuse white matter injury;

A

Reactive microglia
Reactive Astroycytes
Pre-oligodendrocyte death

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13
Q

How could impaired myelination lead to cerebral plasy? / focal necrotic cyst?

A

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.

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14
Q

What would and MRI reveal for these preterm brain injuries?

A
  • Cavitary white matter lesions
  • Diffuse white matter lesions
  • Ventriculomegaly
  • Decreased volume of white matter tracts (white matter atrophy)
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15
Q

What do preterm babies have an increased risk for?

A

Smaller brain size.

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16
Q

When is the period of risk for white matter injuries in babies?

A

Preterm birth-> 32 weeks gestational age

After this time, you can still get white matter injury but also with cortical injury.

17
Q

Define the oligiodendrocytes stages of lineage development;

A

Ol Progenitor (OPC)
Pre OL
Immature OL
Mature OL

18
Q

What is OPC and pre OL identified by?

A

Stained for PDGF b (OPC) (also migratory cell of lineage)

O4 factor. (POL)

Both of these are the proliferative cells do the oligiodendrocyte lineage

19
Q

What are Immature and mature OL identified by?

A

Immature = O1

Mature. (very complex, myelinates axons)

20
Q

What stage of oligiodendrocyte development is the target for preterm brain injury?

A

18-32 weeks
Pre OL is dominant cell type
No Immature Ols

21
Q

What happens at ~30 weeks regarding Ol?

A
  • Maturation ~30 weeks

* Differentiation of PreOLs to Immature OLs

22
Q

When does myelination occur?

A
  • Begins in PVWM
  • Extensiveby birth

28-40 weeks

23
Q

What is the target cell for preterm white matter brain injury demyelination?

A

Pre OL

Every year in Exam essay.

24
Q

What did they find when they compared pre OL populations in dead babies with and without white matter injury?

A

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

25
Q

What does MRI show regarding grey matter structures?

A

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.

26
Q

Why is the lack of grey matter injury in preterm mri confusing?

A

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

27
Q

What happens in the long term to babies with preterm brain injury regarding grey matter?

A
  • Long term reduction in grey matter growth/connectivity
    • Cortical growth, folding, complexity
    • Subcortical growth (hippocampus, thalamus, striatum and basal ganglia)

Range of associated deficits

28
Q

What are the associated deficits in preterm long term grey matter injury?

A

Cortical growth/folding: Impaired neurodevelopmental outcomes, impaired cognition / IQ outcomes into adulthood.

29
Q

When is the fastest rate of brain growth?

A

Last trimester of pregnancy

Therefore premature birth can halt this grey matter growth

30
Q

Likely to be asked;

When is the period of most susceptible brain injury? What are the two common white and grey matter injuries, why?

A

preterm birth-> 32 weeks

Diffuse white matter injury

Reduced chronic grey matter volume.

31
Q

Is there any loss of cortical neurons?

A
  • 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