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Neonatal Brain Injury:Mechanism, Management and
Prognosis
Charlotte Patterson4th Year Medical Student
Contents• Why choose this SSC?•What is Birth Asphyxia and HIE?•Prognosis•Treatment and Management
• Conservative & Supportive• New therapies:
- Hypothermia- Chemical Therapy- Cellular Therapy
• Evidence Based Medicine?•Disability, Disadvantage and Diversity•Ethics, Law and Medicine•References
What is Birth Asphyxia and HIE?
Birth Asphyxia: The result of a critical reduction in O2 delivery to the fetus either antenatally, during labour and/or delivery that is sufficient to produce a lactic acidosis and render the infant in distress at birth.
Hypoxic-Ischaemic Encephalopathy (HIE) describes the clinical manifestation of brain injury starting immediately or up to 48hrs post-asphyxia.
Pattern of Injury in HIE
Miller et. al, (2005) Journal of Paediatrics
Neuro-imagery in HIE
Normal HIE
Clinical Presentation and Prognosis
Mild: - Irritable- Excessive response to stimulation- Hyperventilation- Impaired feeding
Moderate:- Marked abnormality: tone and movement
- Cannot feed- Seizures
Severe:- No normal spontaneous movements/ response to
pain.- Limb tone fluctuation- Seizures prolonged- Multi-organ failure
Complete recovery
Variable Recovery
Mortality: 30-40%Disability: 80%
Pathophysiology:Neuronal Injury
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
Management: Supportive
• Resuscitation• Respiratory Support• Seizure Management
• Fluid Restriction• Hypotension Management
• Treat and Monitor Hypoglycaemia• Restore electrolyte Balance
- Anticonvulsants- Continuous Amplitude Integrated EEG (aEEG)
-Inotropes-IV Fluids
Treatment
1. Hypothermia
2. Chemical Therapy
3. Cellular Therapy
1. HypothermiaReduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
1. Hypothermia
Mechanism• Modifies cells programmed for apoptosis• Reduces cerebral metabolic rate, therefore production of toxic NO
and Free Radicals.Who is treated?• Neonates with an abnormal aEEG- fairly predictiveWhat happens?• Aims to lower basal ganglia temperature 32-34°c• Whole body or Just headDisadvantages• Little benefit if severe brain damage• Not yet trialled in pre-term infants
1. Hypothermia
Wachtel et. al 2011
1. Hypothermia
2. Chemical TherapyReduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
2. Chemical Therapy
Agents that inhibit glutamate release, uptake, or blockage of glutamate receptors
Blockade of free radical generation or removal- free radical inhibitor
Blockade of downstream effects and inhibitors of inflammatory effects
Magnesium Xenon
Deferoxamine Allupurinol
Indomethacin
Erythropoetin
3. Cellular Therapy
Stem cells that may help repair ischaemic neuronal tissue• Neural Stem cells• Multi-potent adult progenitor stem cells• Mesenchymal Stem cells (MSCs)• Human Umbilical Cord Stem Cells
MSCs can differentiate into neurones and oligodendrocytes, therefore help repair ischaemic neural tissue.
May also help with restoration of functional networks via axonal sprouting and synaptogenesis.
3. Cellular Therapy• 9 day old mice• HIE artificially induced with R common carotid artery
occlusion.• MSCs injected into mice: 1st dose 3d, 2nd dose 10d.
Velthoven et al. 2010 Journal of Neuroscience
Ethics and Lawwww.topbraininjurylawyers.com
Legal Action..
Thank you- any questions?