Kernicterus

[Lola Maroun]

Kernicterusis a bilirubin-induced brain dysfunction.[1] The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey matter of the central nervous system, potentially causing irreversible neurological damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death.

ABE is an acute state of elevated bilirubin in the central nervous system. Clinically, it encompasses a wide range of symptoms. These include lethargy, decreased feeding, hypotonia or hypertonia, a high-pitched cry, spasmodic torticollis, opisthotonus, setting sun sign, fever, seizures, and even death. If the bilirubin is not rapidly reduced, ABE quickly progresses to chronic bilirubin encephalopathy.[citation needed]

CBE is a chronic state of severe bilirubin-induced neurological lesions. Reduction of bilirubin in this state will not reverse the sequelae. Clinically, manifestations of CBE include: [citation needed]

These impairments are associated with lesions in the basal ganglia, auditory nuclei of the brain stem, and oculomotor nuclei of the brain stem. Cortex and white matter are subtly involved. Cerebellum may be involved. Severe cortical involvement is uncommon.

SBE is a chronic state of mild bilirubin-induced neurological dysfunction (BIND). Clinically, this may result in neurological, learning and movement disorders, isolated hearing loss and auditory dysfunction.[citation needed]

Bilirubin is known to accumulate in the gray matter of neurological tissue where it exerts direct neurotoxic effects. It appears that its neurotoxicity is due to mass-destruction of neurons by apoptosis and necrosis.[citation needed]

Measuring the serum bilirubin is helpful in evaluating a baby's risk for developing kernicterus. These numbers can then be plotted on the Bhutani nomogram. In neonates with hyperbilirubinemia, light therapy may be effective in reducing the serum bilirubin level. More severe cases may require the use of exchange transfusion.[citation needed]

Kernicterus, or bilirubin encephalopathy, is bilirubin-induced neurological damage, which is most commonly seen in infants. It occurs when the unconjugated bilirubin (indirect bilirubin) levels cross 25 mg/dL in the blood from any event leading to decreased elimination and increased production of bilirubin. The unconjugated bilirubin can cross the blood-brain barrier as it is lipid-soluble, unlike the water-soluble conjugated bilirubin. It gets deposited in the brain tissue, mainly the basal ganglia. This activity reviews the evaluation and management of kernicterus and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.

Objectives:Identify the etiology of kernicterus.Outline the components of the evaluation of kernicterus.Summarize the management options available for kernicterus.Identify interprofessional team strategies for improving care coordination and outcomes in neonates with kernicterus.Access free multiple choice questions on this topic.

Kernicterus, or bilirubin encephalopathy, is bilirubin-induced neurological damage, which is most commonly seen in infants. It occurs when the unconjugated bilirubin (indirect bilirubin) levels cross 25 mg/dL in the blood from any event leading to decreased elimination and increased production of bilirubin. The unconjugated bilirubin can cross the blood-brain barrier as it is lipid-soluble, unlike the water-soluble conjugated bilirubin. It gets deposited in the brain tissue, mainly the basal ganglia. The neurotoxicity of unconjugated bilirubin leads to various neurologic sequelae.[1]

In the United States kernicterus registry, 56% had abnormalities known to increase the bilirubin concentration in the blood. Glucose-6-phosphate dehydrogenase deficiency was diagnosed in 21.3%, severe hemolytic processes were recognized in 20.5%, birth trauma was identified in 15%, and other causes such as galactosemia, Crigler-Najjar syndrome, and sepsis were diagnosed in 7%. However, no etiology was identified in 43.4% of the infants.[8]

The condition occurs primarily in children, mostly African Americans and South Asians, and is slightly more common in males than females. The incidence of kernicterus is not exactly known in the United States. Asian, Hispanic, Native American, and Eskimo infants have a higher production of bilirubin than white infants. Black infants, on the other hand, have lower production levels. Preterm infants are at a higher risk of kernicterus than term infants.[9] Male infants have a higher level of serum bilirubin than female infants. The prevailing risk of chronic kernicterus is about one in seven in infants with total serum bilirubin greater than 30 mg/dL.[10] Kernicterus also occurs in infants with bilirubin levels less than 25 mg/dL, but the population risk of this occurrence is unknown.[11]

The pathophysiology is dependent upon the underlying condition causing a buildup of unconjugated bilirubin. Crigler-Najjar syndrome, Gilbert syndrome, hemolytic disorders, and decreased ability to conjugate bilirubin in neonates are the most common conditions.[6]

The circulating unconjugated bilirubin, which is lipid-soluble, passes the blood-brain barrier and enters neuronal and glial membranes. In the brain, bilirubin has a special affinity for the globus pallidus, the hippocampus, and the subthalamic nucleus. Many other structures, including the striatum, thalamus, cranial nerve nuclei, inferior olives, and dentate nuclei of the cerebellum, are less frequently affected. Bilirubin attaches to cell membranes and is toxic to neurons and oligodendroglia. It damages the mitochondria, inhibits oxidative phosphorylation, and causes calcium release promoting apoptosis. It also affects axonal and dendritic growth in the central nervous system.[12]

The case history should begin by asking about the onset and duration of jaundice. The onset of jaundice within 24 hours of life is always pathological, whereas it can be physiological after 24 hours of life.[13] The presence of neurologic symptoms like altered mental status, hypotonia, and decreased reflexes, especially in a preterm infant, should arouse the suspicion of kernicterus. The infants can also present with non-specific symptoms like reduced feeding from the inability to suck efficiently. The onset and duration of the symptoms should also be noted to assess the reversibility of neurologic damage. The risk factors for hemolytic diseases are one of the most important clues for determining the underlying cause of kernicterus.

It is essential to ask about any family history of anemia or jaundice since birth or in adulthood. This history gives an idea about conditions like Gilbert syndrome, Crigler-Najjar syndrome, G6PD deficiency, sickle cell disease, and spherocytosis.[14] A family history of metabolic disorders like urea cycle disorders and fatty acid metabolism disorders should be ruled out as these disorders can also have a similar presentation. The mother should be asked about any similar presentations in a previously born child to rule out Rh incompatibility.[3] It may also indicate that the mother might have 20% to 40% more beta-glucuronidase enzyme, leading to hyperbilirubinemia in babies.

A detailed social history should be asked, outlining any harmful practices in the mother, such as alcoholism or drug use. Antenatal history should be noted down to determine any pre-existing conditions in the mother, like TORCH infections or diabetes mellitus.

Congenital infections in infants can present with jaundice due to decreased glucuronidation or increased hemolysis. A baby born to a mother with diabetes is usually large for gestational age, which indicates a higher number of red blood cells with an increased rate of turnover leading to jaundice.

A detailed history is a stepping stone to diagnosing the etiology of kernicterus as it aids in eliminating the cause of hyperbilirubinemia, thus alleviating the symptoms and the resulting neurologic damage.

The physical exam should be comprehensive, with special attention to the neurological exam. The child's level of consciousness should be assessed. The presence of icterus and yellowish discoloration of the body might be evident. The infants are usually not febrile. Vital signs may be significant for tachycardia, dyspnea, and impaired oxygen saturation. The fontanelles should be examined to check for any increase in intracranial pressure. Increased intracranial pressure leads to bulging fontanelles with the separation of suture lines. The setting sun sign is also an indication of increased intracranial pressure. The enlarged third ventricle puts pressure on the upward gaze center in the midbrain, causing a tonic downward eye deviation.

The neurologic abnormalities associated with hyperbilirubinemia are known as bilirubin-induced neurologic dysfunction (BIND).[15] They are classified as acute and chronic based on their period of evolution.

Neonatal jaundice contains a wide spectrum of causes.[25] The neonates are naturally prone to developing jaundice due to the replacement of fetal hemoglobin with adult hemoglobin, and the inability of the immature liver to keep up. However, physiologic jaundice should be a diagnosis of exclusion. It is of utmost importance to rule out other serious diseases as they can have disabling sequelae. As kernicterus presents with jaundice and neurologic symptoms, other diseases that cause either of the symptoms should also be considered and evaluated. A few differential diagnoses to keep in mind are:

Constipation (and inability to pass meconium in neonates) can lead to the increased enterohepatic circulation of bilirubin, causing hyperbilirubinemia and jaundice. Accelerated meconium evacuation through glycerin suppositories has been proposed in the management of hyperbilirubinemia. However, there was no effect on the total bilirubin levels in the patients, though it helped in an earlier passage of meconium.

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