Kernicterus This is now a rare cause of extrapyramidal motor disorder in children and adults. Such cases are the neurologic sequelae of erythroblastosis fetalis secondary to Rh and ABO blood incompatibilities or to a deficiency of the hepatic enzyme glucuronosyltransferase. The symptoms of kernicterus appear in the jaundiced neonate on the second or third postnatal day. The infant becomes listless, sucks poorly, develops respiratory difficulties as well as opisthotonos (head retraction), and becomes stuporous as jaundice intensifies. The serum bilirubin is usually greater than 25 mg/dL. In acidotic and hypoxic infants (e.g., those with low birth weight and hyaline membrane disease), the kernicteric lesions develop with much lower levels of serum bilirubin.
A proportion of infants with this disease die within the first week or two of life. Many of those who survive are developmentally delayed, deaf, hypotonic, and totally unable to sit, stand, or walk. There are exceptional patients, however, who are mentally normal or at most only slightly limited. They develop a variety of persistent neurologic sequelae—choreoathetosis, dystonia, and rigidity of the limbs—a picture not too different from that of cerebral spastic diplegia with involuntary movements. Kernicterus should always be suspected if an extrapyramidal syndrome is accompanied by bilateral deafness and paralysis of upward gaze. Later, in childhood there may be a greenish pigmentation of the dental enamel.
Neonates who die in the acute postnatal stage of kernicterus show a unique yellow staining (icterus) of nuclear masses at one time was called the “Kern nuclei” and gave the disease its name in the basal ganglia, brainstem, and cerebellum. In those surviving this postnatal insult, the pathologic changes consist of a symmetrically distributed nerve cell loss and gliosis in the subthalamic nucleus, the globus pallidus, the thalamus, and the oculomotor and cochlear nuclei; these lesions are the result of the hyperbilirubinemia. In more than 30 cases examined by R.D. Adams, the immature cerebral cortex including the hippocampus was spared. In the newborn, unconjugated bilirubin can pass through the poorly developed blood–brain barrier into these nuclei, where it is assumed to be directly toxic. Acidosis and hypoxia exacerbate the effect. Also in the newborn, the development of hyperbilirubinemia is enhanced by a transient deficiency of the enzyme glucuronosyltransferase, essential for the conjugation of bilirubin. Hereditary hyperbilirubinemia, caused by lack of this enzyme (Crigler-Najjar syndrome), may exhibit the same effects on the nervous system at a later period of infancy or childhood as hyperbilirubinemia because of Rh incompatibility.
Immunization, phototherapy, and exchange transfusions designed to prevent high levels of unconjugated serum bilirubin have been shown to protect the nervous system from the toxic effects of erythroblastosis fetalis. If the blood bilirubin level can be held to less than 20 mg/dL (10 mg/dL in premature infants), the nervous system may escape perinatal damage. The effective use of these measures has practically eradicated this disease.
Both kernicterus and ischemic état marbré must be differentiated clinically from hereditary choreoathetosis, the Lesch-Nyhan syndrome, and—later in life, from ataxia-telangiectasia and Friedreich ataxia.