Hypoxic-Ischaemic Encephalopathy ✅ Flashcards
What is the incidence of HIE?
1-1.5 per 1000 live births
What % of cases of cerebral palsy are caused by HIE?
30%
How much higher is the incidence of HIE in low-income countries?
Up to 10x
What does perinatal hypoxia mean?
Lack of oxygen to the fetus and newborn
What does perinatal ischaemia mean?
Lack of blood flow to the fetus and newborn
What does perinatal asphyxia mean?
Lack of gas exchange to the fetus and newborn
What is more damaging, ischaemia or hypoxia?
Ischaemia
Why is ischaemia more damaging than hypoxia?
It also leads to glucose depletion, which is important in the causation of neuronal injury
What results from impaired respiratory gas exchange in asphyxia?
Hypoxia and hypercarbia
What is the result of hypercarbia produced from asphyxia?
- Acidosis
- Reduced cerebral blood flow
What is HIE?
A specific type of encephalopathy due to low oxygen and blood delivery to the brain
What are the categories of causes of neonatal encephalopathy?
- Hypoxic-ischaemic
- Infection
- Trauma and haemorrhage
- Metabolic
- Neuronal migration defects
- Congenital myotonia
- Neonatal stroke
What are the haemorrhagic cases of neonatal encephalopathy?
- Subgaleal
- Extradural
- Subdural
What are the metabolic causes of neonatal encephalopathy?
- Non-ketotic hyperglycinaemia
- Mitochondrial myopathies
- Aminoacidaemias
Give a neuronal migration defect that can cause neonatal encephalopathy
Lissencephaly
Give 3 congenital myotonias that can cause neonatal encephalopathy?
- Myasthenia gravis
- Peroxisomal disorders
- Prader-Willi syndrome
What are the infectious causes of neonatal encephalopathy?
- Neonatal sepsis
- Meningitis
- Herpes meningoencephalitis
When should a clinical diagnosis of HIE be made?
In the presence of all criteria;
- Evidence of intrapartum asphyxia, such as a sentinel event
- Respiratory depression at delivery
- Encephalopathy in the immediate postnatal period
Give 7 sentinel events during labour and delivery which may cause an acute brain injury
- Cord prolapse
- Uterine rupture
- Abruption of placenta
- Amniotic fluid embolism
- Acute maternal haemorrhage
- Maternal circulatory failure
- Acute neonatal haemorrhage
Give 3 causes of acute neonatal haemorrhage
- Vasa praevia
- Acute loss from cord
- Feto-maternal haemorrhage
What features might indicate intrapartum asphyxia and respiratory depression at birth?
- Apgar score ≤5 at 10 minutes after birth
- Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
- Acidosis within 60 minutes of birth
- Base deficit ≥16mmol/L within 60 minutes of birth
What is acidosis within 60 minutes of birth defined as?
Umbilical cord, arterial, or capillary pH of <7.0
What samples can base deficit be measured in to detect intrapartum asphyxia?
Umbilical cord or any blood sample
What might indicate moderate to severe neonatal encephalopathy?
- Early onset seizures
- Altered sensorium
- Abnormal tone
- Abnormal primitive reflexes
What is meant by altered sensorium?
Reduced or absent response to stimulation
How might tone be abnormal in moderate to severe neonatal encephalopathy?
Hypotonia or flaccidity
What primitive reflexes might be abnormal in moderate to severe neonatal encephalopathy?
Weak or absent suck or Moro reflex
What is used to determine which cases require treatment/intervention for HIE?
- Clinical assessment
- Cerebral function monitoring (aEEG)
What finding on aEEG might indicate a need to intervene in HIE?
Moderate or severe abnormalities in the background electrical activity
What are the indicators for intrapartum asphyxia?
- Abnormal CTG
- Reduced fetal movements
- Cord pH ≤7.0
- Base deficit ≥16mmol/L
Is the presence of indicators for intrapartum asphyxia without moderate to severe encephalopathy an indication for intervention?
NO
Why is the adherence to criteria for intervention in HIE important medico-legally?
Has potential consequences in relation to maternal care during labour and delivery
In how many phases does hypoxic-ischaemic injury lead to neuronal death?
Two
What are the phases in which hypoxic-ischaemic injury leads to neuronal death?
- Primary neuronal necrosis
- Delayed neuronal death
What causes primary neuronal necrosis in HIE?
Cellular hypoxia and primary energy failure following depletion of cellular high-energy compounds
How long after the insult does primary neuronal necrosis occur in HIE?
May occur immediately
How can primary neuronal necrosis in HIE be treated?
It can’t - it is not amenable to nay treatment or intervention
When does delayed neuronal death occur in HIE?
Usually following a latent period of at least 6 hours
What causes delayed neuronal death in HIE?
- Repercussion and hyperaemia
- Cytotoxic oedema
- Programmed apoptotic cell death
- Mitochondrial failure
- Free radical damage
- Accumulation of excitotoxins
- Nitric oxide synthesis
- Cytotoxic actions of microganglia
What is the delayed neuronal death in HIE associated with?
- Seizures
- Encephalopathy
What is the clinical significance of the delayed phase of neuronal damage in HIE?
The latent period before secondary neuronal necrosis offers a ‘therapeutic window of opportunity’
Why does the latent period before delayed neuronal damage in HIE offer a therapeutic window?
Because delayed neuronal damage leads to large proportion of the neuronal necrosis following a severe and global insult, so is an opportunity to prevent this
What intervention can be useful before the delayed phase of neuronal damage?
Cooling (moderate hypothermia)
How does moderate hypothermia have its neuroprotective actions?
- Decreased number of apoptotic but not necrotic cells
- Reduction in cerebral metabolic rate and oxygen consumption
- Attenuation of excitatory amine release such as glutamate
- Improving update of glutamates in neuronal cells
- Reduction in the synthesis of toxic nitric oxide and free radicals
What are the main patterns of brain injury in HIE?
- Basal ganglia and thalamus (BGT)
- Watershed pattern
- Global pattern
What is a BGT brain injury associated with?
A sentinel event
Why are the basal ganglia and thalamus often differentially affected when there is a sentinel event causing HIE?
These structures are more susceptible to hypoxic-ischaemic type injury
Why are the basal ganglia and thalamus more susceptible to a hypoxic-ischaemic type injury?
Because of their high metabolic rate and high concentration of NMDA receptors
What is a BGT HIE often accompanied by?
- Brainstem injury
- Involvement of posterior limb of internal capsule
Where are lesions found in brainstem injuries associated with a BGT HIE?
- Midbrain
- Pons
- Cerebellar vermis
How severe are BGT HIE injuries?
Vary, from mild-focal to involving the whole of the BGT area
What is the prognosis of BGT HIE injury?
- 50% die in 2-3 years
- Range of impairments in survivors
What impairments might be present in survivors of BGT HIE injuries?
- Cerebral palsy
- Speech and language difficulty
- Visual and hearing impairment
What % of survivors of BGT HIE injuries develop cerebral palsy?
75%
What is the best predictor of motor problems in HIE?
BGT lesions
What is the best predictor for an inability to walk at 2 years in HIE?
Posterior limb of internal capsule (PLIC) involvement
What is the watershed pattern of HIE also known as?
Parasagittal cerebral injury
What causes a watershed pattern HIE?
Mainly chronic partial hypoxia
What can produce similar lesions to watershed HIE?
- Hypertension
- Infection
- Hypoglycaemia
Where are the areas of necrosis found in watershed HIE?
Border zones between major cerebral arteries
What impairment might watershed HIE lead to?
Communication problems
What part of the pain is affected in global pattern HIE?
Subcortical white matter and cortex
When is global pattern HIE seen?
In severe neonatal encephalopathy
What is the prognosis of global pattern HIE?
Usually fatal
What scoring systems can be used in HIE?
- Sarnat stages
- Thompson scoring system
What is the advantage of Sarnat stages?
- Brief
- Objective
- Good correlation with outcomes
What is Sarnat stage 1 characterised by?
- Irritability
- Lethargy or hyperalertness
- Hyper-reflexia
- Tachycardia
- Dilated pupils
- Abnormal tone
Improves with 24-48 hours
What is the prognosis of Sarnat stage 1 HIE?
Mild encephalopathy with no risk of death or significant disability
What is Sarnat stage 2 characterised by?
- Seizures
- EEG abnormaliites
- Abnormal tone
- Proximal weakness
- Loss of consciousness
What is the mortality of Sarnat stage 2 HIE?
5%
What is the chance of neurodisability in Sarnat stage 2 HIE?
25%
What is Sarnat stage 3 HIE characterised by?
- Deep coma and unresponsiveness
- Flaccid tone
- Areflexia
- Abnormal EEG
What is found on EEG in Sarnat stage 3 HIE?
Discontinuous background electrical activity or burst suppression pattern
What is the mortality of Sarnat 3 HIE?
80%
What is the chance of neurodisability in survivors of Sarnat 3 HIE?
Most survivors have severe disability
What are the advantages of the Thompson scoring system for HIE?
- Objective
- Can be used for monitoring
- Simpler to use
What is scored in the Thompson HIE score?
- Tone
- LOC
- Seizures
- Posture
- Moro
- Grasp
- Suck
- Respiration
- Fontanelle
How is tone scored in the Thompson HIE score?
0 - Normal
1 - Hyper
2 - Hypo
3 - Flaccid
How is LOC scored in the Thompson HIE score?
0 - Normal
1 - Hyper alert, stare
2 - Lethargic
3 - Comatose
How is seizures scored in the Thompson HIE score?
0 - None
1 - Infrequent, <3/day
2 - Frequent, >2/day
How is posture scored in the Thompson HIE score?
0 - Normal
1 - Fisting, cycling
2 - Strong distal flexion
3 - Decerebrate
How is Moro scored in the Thompson HIE score
0 - Normal
1 - Partial
2 - Absent
How is grasp scored in the Thompson HIE score?
0 - Normal
1 - Poor
2 - Absent
How is suck scored in the Thompson HIE score?
0 - Normal
1 - Poor
2 - Absent/bites
How is respiration scored in the Thompson HIE score?
1 - Normal
2 - Hyperventilation
3 - Brief apnoea
4 - Apnoea
How is fontanelle scored in the Thompson HIE score?
0 - Normal
1 - Full, not tense
2 - Tense
What is the limitation of scoring systems in HIE?
- Difficult to measure some clinical parameters
- Many infants have intermediate signs between stages
- Assessment is complicated by interventions
In what situations might it be more difficult to measure some clinical parameters when scoring HIE?
- Soon after birth
- Sedated or ventilated infants
What therapies might make it more difficult to score an infant with HIE?
- Anti-convulsant therapies
- Paralytic agents
- Co-morbidities
What investigations may be useful in HIE?
- Amplitude modulated EEG (aEEG) or cerebral function monitor
- Cranial ultrasound
- Magnetic resonance imaging
What is aEEG/cerebral functioning monitoring useful for?
- Clinical assessment at the bedside
- Grading the severity of encephalopathy
- Seizure detection
- Identifying patients suitable for therapeutic hypothermia
What are the advantages of aEEG/cerebral function monitoring?
- Easy to obtain a trace and interpret
- Robust and objective
- Excellent correlation with neurodevelopment abnormality
What findings on aEEG/cerebral function monitoring are associated with poor neurodevelopment outcome?
Severely abnormal patterns persisting for more than about 48 hours after birth
What % of infants with severely abnormal patterns on aEEG/cerebral function monitoring will have a poor neurodevelopmental outcome?
70%
What is a normal aEEG within 6 hours of birth a good predictor of?
Normal outcome
What is cranial ultrasound useful for?
- Exclude other causes of encephalopathy
- Detecting calcification and cysts
- Detecting atrophy
- Detecting cerebral haemorrhage
Give 2 other causes of encephalopathy that can be excluded with cranial ultrasound?
- Metabolic causes
- Structural malformations
What are calcification and cysts on cranial ultrasound suggestive of?
Viral infection
What is atrophy on cerebral ultrasound suggestive of?
Longstanding damage
What are Doppler cerebral flow velocity indices used for?
- Markers of cerebral perfusion
- Assessing severity of HIE and predicting long-term outcome
What is the preferred imaging modality in HIE?
MRI
Why is MRI the preferred imaging method in HIE?
- It’s sensitivity for detecting HIE
- Can provide information about the timing of the injury
- Can identify other causes
When is the optimal time to do a MRI in HIE?
Between 5-14 days
Why should MRI ideally not be done before 5 days in HIE?
Injury may be underestimated if performed during the first few days after birth
What form of imaging can provide useful prognostic data about HIE in the first week?
MRS (magnetic resonance spectroscopy)
What findings on MRS correlate with later neurological problems?
Reduction in N-acetylaspartate (NAA)
What does a reduction of NAA on MRS reflect?
Neuronal injury and elevation of lactate (indicating tissue ischaemia and hypoxia)
What does supportive treatment in HIE include?
- Maintaining cardiorespiratory stability
- Maintaining biochemical parameters
- Management of renal failure
- Management of deranged clotting
- Seizure control
- Initial fluid restriction
What biochemical parameters should be maintained in supportive management for HIE?
- Glucose
- Electrolytes
- Blood gases
Why are fluids initially restricted in HIE?
To prevent cerebral oedema
What ethical concerns arose when conducting RCTs into the benefit of therapeutic hypothermia in infants with HIE?
- Concerns about ethics of significant early intervention in a newborn infant with a severe, unexpected condition
- Concern that intervention reduced death at expense of worsening neurodisability
What infants with HIE were excluded from studies looking at the benefits of therapeutic hypothermia?
- Infants with mild HIE
- Infants with the most extensive brain injuries that needed palliative care
Why do infants with HIE not need therapeutic hypothermia?
They have excellent prognosis without it
What ‘dose’ of therapeutic hypothermia has been shown to be effective in reducing death and neurodisability at 18 months in patients with HIE?
Mild hypothermia (33-34 degrees C) started within 6 hours and continued for 72 hours
What is the number needed to treat for therapeutic hypothermia in HIE?
7
What proportion of infants with moderate/severe HIE have a normal outcome at 2 years of age with cooling?
6 out of 10
What did the UK TOBY study show regarding therapeutic hypothermia for HIE?
- Significant reduction in risk of cerebral palsy and moderate-severe disability at 7 years with cooling
- Significantly improved survival
What is the rate of death or moderate-severe disability in infants with moderate to severe HIE?
46%
What drugs are being researched to see if they can produce an improvement in HIE?
- Magnesium sulphate
- Melatonin
- N-acetylcysteine
- Erythropoietic
- Xenon inhalation
