Hypoxic Ischemic Encephalopathy

Original Editor - User Name
Top Contributors - Lauren Heydenrych and Manisha Shrestha

This article or area is currently under construction and may only be partially complete. Please come back soon to see the finished work! (16/08/2023)

Introduction

Hypoxic Ischemic Encephalopathy (HIE) is an injury to the brain, occurring in the neonatal period (under 28 days old) in which there is a deprivation of oxygen supply to the brain, also termed an anoxic brain injury. It is a common cause of neonate mortality and developmental psychomotor disorders in the pediatric population worldwide. HIE is one of the major causes of cerebral palsy.

Attributing neonatal encephalopathy to perinatal hypoxic–ischemic injury requires combinations of parameters indicative of metabolic acidosis in the first postnatal hours with low cord pH (<7.0), base deficit of over 12, and evidence of a need for respiratory support also starting in the first minutes, with low Apgar scores at and beyond 5 min.

Epidemiology

• The incidence of HIE is ~1–8 per 1,000 live births in technically advanced countries and is up to 10-20 per 1,000 live births in less developed countries.In a study done in a teaching hospital in Uganda fatality rates of HIE were documented at 26%. Between 10-60% was cited in this article as the incidence rate in more developed countries, with 25% of survivors having adverse long-term neurodevelopmental outcomes.

Etiology

Maternal factor

Fetal factor

Delivery condition

Mechanism of Injury / Pathological Process

Various conditions, both prenatally and postnatally can cause an hypoxic-ischemic (HI) event. This includes pre-eclampsia, umbilical cord knotting, shoulder dystocia and placental abruption. In these events, there is an impairment in blood flow to the fetal brain which results in decreased oxygen and glucose delivery to the brain.

If there is moderate decreased blood flow, the cerebral arteries will shunt blood flow from the anterior circulation to the posterior circulation. This is in order to preserve those areas of the brain necessary for survival - brainstem, cerebellum and basal ganglia. This limits damage to the cerebral cortex and watershed areas of the cerebral hemispheres. Damage to the basal ganglia and thalami occurs when there is acute hypoxia and an abrupt decrease in cerebral blood flow.

Decreased cerebral perfusion sets in motion a cascade of events, starting with a depletion of energy for the cells involved. This energy crisis or primary energy failure starts an 'ischemic cascade' - which then goes on to cause a simultaneous disruption in the blood-brain barrier, neuronal cell loss and inflammatory response. These in turn, then feed into five events of an HI injury, which are influenced by each other and by the preceding events.

These 5 events are described by Greco et al (2020) as:

• Oxidative stress
• Intracellular calcium accumulation
• Mitochondrial dysfunction
• Excitotoxicity
• Inflammation

Greco et al.also describes an HI injury occuring in 3 phases:

1. First immediate phase = Primary neuronal death.
2. Second phase = Latent phase
3. Third phase = Secondary energy failure/ delayed neuronal death.

The first phase occurs during the initial insult, with primary energy failure, which results in oxidative metabolism failure, cytotoxic oedema and the accumulation of cerebral circulation.

The second phase occurs about six to fifteen hours after the primary insult and with the restoration of cerebral blood flow. In this phase, there is clinical deterioration in the severely affected neonate. Seizures also typically occur in this phase

The third phase can occur days after the initial HI insult. It is associated with encephalopathy and increased seizure activity. In this phase excitotoxicity, apoptosis and microglial activation are described. It is generally far more extensive in damage.

Clinical Presentation/manifestation

The following can be observed with an HIE insult:

• Depression in the level of consciousness
• Respiratory depression
• Abnormality of muscle tone and power
• Disturbances in cranial nerve function
• Seizures
• In neurologic dysfunction, low APGAR scores and metabolic acidosis must also be present.
• There can also be damage to other organs including the liver, kidneys, and heart, all observed by the relevant markers in the blood.

Fetal asphysia:

Meconium stained liquor:

APGAR score

Seizure

tone

Diagnostic considerations

Diagnosis of HIE is based on clinical presentation as above as well as:

• MRI - the preferred imaging choice which has found consistent long-term prognostic value.
• and aEEG.
• Sarnat staging

These however, cannot always be performed, owing to the physiological stability of the infant or hyperthermia treatment which depress the aEEG readings.

Other diagnostic tests include:

• Biomarkers
• Placental analysis - considering any abnormalities

Sarnat staging system

This classification divides HIE into 3 distinct classes:

1. Stage 1: Mild
2. Stage 2: Moderate
3. Stage 3: Severe

The Sarnat staging system was the first time a systematic approach was applied to neonatal encephalopathy and has endured more than 44 years. The system itself is based on clinical signs and electroencephalogram (EEG) changes. Some modifications have been applied in trials relating to therapeutic hypothermia.

Thompson scoring

In 1997, Thompson et al. tested a numeric scoring system with fewer clinical assessment-based items in 45 neonates with HIE. In contrast to the Sarnat scale, the Thompson score did not require categorization of severity of encephalopathy but rather relied on a simple numeric score to describe the peak severity of encephalopathy.

By design, the Thomspon score did not require specific training or depend on the availability of advanced technologies (e.g., magnetic resonance imaging, computed tomography, cerebral function monitoring).

The score consisted of clinical assessment of nine signs: tone, level of consciousness, seizures, posture, Moro, grasp, suck, respiratory pattern, and fontanelle findings. Each sign was scored from 0 to 3, making highest score of 27 and lowest score of 0.

It has performed daily until a score of 0 was achieved or the infant was discharged from the hospital.

Limitations:

• Unclear inclusion criteria for infants (“if clinical signs of hypoxic–ischemic encephalopathy developed after birth”)
• A small sample size.

Management / Interventions

Medical Management

• Therapeutic hypothermia
  • Hypothermia is the current standard of care for infants with HIE. Recommendations stipulated are cooling the whole body to a core temperature of 33.5°C for 72 hours starting 6 hours after birth. This method of treatment, however, is not completely effective and there is often a high prevalence of complications and even mortality.

• Various neuroprotective treatments are being studied which are targeted at the ischemic cascade. These include Magnesium Sulphate, Argon, Xenon, Melatonin Erythropoietin (EPO), Allopurinol, and even stem cells and cord blood mononuclear cells.
• Antiseizure medication
• General systemic support is an important consideration in infants who have undergone an HI event as this aids in the restoration of cerebral blood flow.

This support includes:

• Respiratory support
• Cardiovascular support
• Fluids, electrolyte and Nutritional support.

Prognosis

Depending upon the severity of brain damage and medical treatment, usally:

Mild or moderate cases could be cured completely, but severe cases represent poor prognosis with high mortality or cerebral complications such as mental retardation and cerebral palsy.

Overall mortality: 20%

Overall incidence of sequel: 30%

Mild: 100% good prognosis

Moderate: 80% normal

Severe: 50 5 death , 50% sequel

Presence of seizure increases chance of cerebral palsy by 50-70 times

Prevention

• Better obstetric care
• Skilled resuscitation teams and neonatal facilities

Resources

add appropriate resources here