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?