KERNICTERUS
Kernicterus is the rare but most severe complication of bilirubin toxicity in indirect hyperbilrubinenia, characterized by acute neurological signs mainly involving extrapyramidal system, with high mortality or long-term sequelae.
The term “Bilirubin encephalopathyquot; or “Bilirubin- induced neurological dysfunctionquot; (BIND) is also used to encompass wider range of clinical presentations of bilirubin toxicity, including kernicterus.
Etiopathogenesis: Bilirubin is neurotoxic. However, following factors determine risk of kernicterus:
• Severity of bilirubinemia: Kernicterus develops only after a critical serum bilirubin level has reached.
• Type of bilirubin: Conjugated bilirubin is not neurotoxic, as it is water-soluble and does not cross BBB. In contrast, unconjugated bilirubin is fat-soluble and readily crosses the BBB, to cause neurological damage.
• Albumin binding of unconjugated bilirubin: In plasma, unconjugated bilirubin is circulated in free form
Fig. 12.17: Kernicterus.
as well as albumin-bind form. Only free-form is neurotoxic.
• Integrity of BBB, which may be damaged by hypoxia, acidosis and sepsis to permit bilirubin crossing at lower serum levels and development of kernicterus.
Pathology: Entry of free unconjugated bilirubin into brain leads to selective and irreversible destruction of neuronal cells. Basal ganglia is the primary site of bilirubin staining/toxicity, apart from dentate nucleus, auditory nucleus and hippocampus.
Clinically, kernicterus presents with following features in a deeply icteric baby:
• Early kernicterus (stage I) during first 24-48 hours, with poor sucking, lethargy and high-pitched shrill cry. These features indicate impending bilirubin encephalopathy and need for exchange transfusion, irrespective of bilirubin levels.
• Established kernicterus (stage II) with generalized hypotonia/rigidity, depressed Moro's and other neonatal reflexes, sun-set sign (visible upper sclera due to persistent downward gaze), opisthotonus and seizures (Fig. 12.17).
• Terminal kernicterus (stage III) with generalized hypotonia, absence of cry and stupor in deeply icteric baby.
Mortality and risk of long-term neurological damage is very high in stage II/III disease, despite exchange transfusion, as irreversible neurological damage has already occurred.
Late complications of kernicterus include—(a) cerebral palsy, usually of choreo-athetoid or extra-pyramidal type,
(b) sensory-neural deafness, and (c) mental retardation or learning disabilities. Brownish discoloration of teeth is common in severe neonatal hyperbilirubinemia.
Management: Prevention is the key of management in kernicterus with early phototherapy and exchange transfusion in indirect hyperbilirubinemia and prompt treatment of BBB impairing factors. However, once the neurological damage has developed, it is irreversible and management aims to improve quality of life.