An Overview of Kernicterus: Clinical Stages and Consequences

Kernicterus

Kernicterus is a chronic neurologic condition caused by the neurotoxic effects of bilirubin on the brain tissues of neonates. This occurs when bilirubin, a byproduct of the breakdown of red blood cells, is present in abnormally elevated levels in the newborn. Kernicterus is preventable as jaundice, the term used to describe the clinical presentation of yellow skin and eye sclera, can be treated. Additionally, risk factors for development of this devastating neurologic condition can be identified and should prompt close surveillance of total bilirubin levels in the serum of the infant who is at risk for development of one of the acute clinical phases of neurologic damage that comprise the syndrome of bilirubin induced neurologic dysfunction.

Kernicterus is a relatively rare cause of severe lifelong disability in infants who are otherwise normal, but it can be prevented. Severe or extreme levels of bilirubin in the serum cause an encephalopathy and bilirubin has been long recognized as a neurotoxin that results in the death and destruction of brain cells.

Acute Bilirubin Encephalopathy

Acute bilirubin encephalopathy is characterized by elevated bilirubin that has crossed the blood-brain barrier. When diagnosed clinically, the presentation of symptoms is wide-ranging and includes feeding problems, lethargy, hypo-or hypertonia, opisthotonus, fever, seizures, a high-pitched cry and spasmodic torticollis.
Acute bilirubin encephalopathy has three clinical phases that each has distinct characteristics. The first phase occurs with a few days after birth and symptoms include stupor, hypotonia, and poor sucking. The second phase is characterized by hypertonia, with arching of the trunk (opisthotonos) or retrocollis, which is backward arching of the neck. Infants who reach this stage develop chronic bilirubin encephalopathy. The third phase occurs after a week and the hypertonia disappears. There is rigidity of the muscles, paralysis of upward gaze, periodic oculogyric crisis, and, in the terminal phase, irregular respirations are prominent. At this third phase, four percent of affected infants die.

Chronic Bilirubin Encephalopathy

Chronic bilirubin encephalopathy is also known as kernicterus. The term refers to the lifelong disability resulting from bilirubin induced neurologic dysfunction. Kernicterus is characterized by poor feeding in the first year. A high-pitched cry is another characteristic of kernicterus.

Infants with kernicterus will have hypotonia but will retain good deep tendon reflexes. There is presence of a tonic neck reflex and righting reflex. Motor skills are delayed, with some children walking at age 5.

After the first year of life, clinical features that are prominent in children with chronic bilirubin encephalopathy include extrapyramidal disorders such as tremors, dysarthria, athetosis and ballismus. There is damage to the cochlear nuclei in the brainstem that results in hearing loss, and there is usually a limitation of upward gaze. Athetosis usually develops at sometime between the age of 18 months and 8 years. Some children only experience hearing loss and have no other symptoms.

Imaging Studies in Diagnosis of Kernicterus

When kernicterus is investigated, high serum bilirubin levels are present in most cases. Imaging studies that are most useful are MRI. On magnetic resonance imaging, there is often increased signal intensity in the globus pallidus.

How Common is Kernicterus?

In the United States, there is a voluntary kernicterus registry and 90 cases were reported during the time period from 1984 to 2001. Since all cases are not reported, the true incidence is not known.

Kernicterus is Preventable

Kernicterus is very preventable when high-risk infants are closely monitored and treated aggressively. Without treatment, however, jaundice from elevated bilirubin can result in permanent brain damage and some children may develop cerebral palsy, dental enamel hypoplasia and mental retardation as a result. Unfortunately, although neonatal jaundice is common, extreme hyperbilirubinemia is less common and the assessment of this condition has frequently been inadequate.

Recommendations by JCAHO in their Sentinal Event Alert of 2001

JCAHO is the Joint Commission on Accreditation of Healthcare Organizations and in April of 2001 they issued a ‘Sentinel Event Alert’ on kernicterus. They compiled a root cause analysis and identified four patient care processes that failed in cases that resulted in the development of kernicterus. These included:
– Patient assessment
– Continuum of care
– Patient and family education
– Treatment

With respect to patient assessment, JCAHO noted the failure to measure bilirubin levels in jaundiced infants within the first 24 hours, failure to recognize jaundice or its severity based upon visual assessment, and unreliability of visual assessment of jaundice in newborns with dark skin. The continuum of care was inadequate in cases of discharge before 48 hours without follow up within 1 to 2 days, particularly in infants less than 38 weeks gestation. Failure to provide early follow-up and physical assessment of infants with jaundice prior to discharge and failure to provide continuing lactation support to maintain adequacy of intake in breast fed newborns were also identified as problems in the continuum of care. Patient and family education was found inadequate in cases when appropriate information was not provided to parents about jaundice and when physicians failed to respond to parental concerns about a jaundiced newborn, problems with lactation or changes in the activity and behavior of the newborn. Treatment failures occurred by failure to recognize, evaluate and treat total bilirubin levels that were rapidly rising and by failure to treat severe hyperbilirubinemia aggressively and quickly with intensive phototherapy or exchange transfusion.

Recommendations of the American Academy of Pediatrics

The Clinical Practice Guideline Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was published in Pediatrics in 2004 and key recommendations included support of successful breastfeeding, establishment of protocols within the nursery for identification and evaluation of hyperbilirubinemia, measurement of total serum bilirubin or transcutaneous bilirubin levels in infants who present with jaundice within the first 24 hours of life, and recognition that visual assessment is inadequate. Additionally, the Academy recommended that all bilirubin levels be interpreted using a nomogram which allowed an interpretation based upon the hours of life, that infants born at less than 38 weeks’ gestation were at higher risk of development of severe hyperbilirubinemia and that those infants who were breastfed were at higher risk. The Academy recommended that a systematic assessment should be performed on all infants before discharge to determine the risk of severe hyperbilirubinemia and that parents be provided with both written and verbal information about neonatal jaundice. Follow-up should be arranged at the time of discharge and risk assessment and newborns should be promptly treated when treatment indications are evident, using phototherapy or exchange transfusion.

Conclusion

Adherence to these clinical practice guidelines can prevent lifelong disability and although kernicterus is relatively rare, newborn jaundice is common and should be thoroughly assessed in light of risk factors and measurement of total serum bilirubin or transcutaneous bilirubin. Prompt treatment is essential.