Atlas of Neonatal Pathology: Kernicterus

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+ Neonatal pathology

Kernicterus

Introduction

Kernicterus is bilirubin staining of the deep gray matter nuclei of the brain and brainstem. It is an anatomic diagnosis made at autopsy. Bilirubin is neurotoxic. Kernicterus was originally described in mature infants who died of severe Rh isoimmunization (such a case is rarely seen today). Extremely premature sick infants are at higher risk of kernicterus than mature infants.

Etiology

Hyperbilirubinemia as a result of increased bilirubin production and decreased bilirubin elimination
Immature blood-brain barrier of the neonates — the barrier is less well developed in the neonatal period than in adulthood. The integrity of the barrier may be further disrupted by hypercarbia, hypoxia, acidosis, hypoglycemia, infection (meningitis).
Total serum bilirubin comprises a conjugated fraction and an unconjugated fraction. The unconjugated fraction is composed of bound bilirubin (bound to albumin) and free bilirubin. Only free bilirubin is available to cross the blood-brain barrier and cause neurotoxicity. The blood-brain low plasma albumin or displacement of bilirubin from albumin by certain drugs or lipid emulsions may increse the proportion of free bilirubin which can enter the brain.
The precise bilirubin level which causes kernicterus is unpredictable. Classic kernicterus was recognized with blood bilirubin level greater than 20 mg/dl. In premature infants the level causing neuronal damage may be considerable lower.
Well-known risk conditions
- Hemolytic disorders — Rh isoimmunization, ABO incompatibility, glucose-6-phosphate-dehydrogenase deficiency
- Birth trauma — significant bruising, cephalohematoma, subgaleal hemorrhage
- Sepsis
- Extreme prematurity
- Rare — galactosemia, congenital hypothyroidism, Crigler-Najjar syndrome (congenital defect of bilirubin conjugation)

Clinical signs

Acute bilirubin toxicity appears in the first few days of life in term infants. Preterm infants are at risk for slightly longer.

Classic kernicterus (mature infants):

Acute bilirubin encephalopathy (first week of life): decreased alerteness, hypotonia, poor feeding. Babies may also present with retrocollis or opisthotonus. Some infants have no neurologic signs.
Chronic bilirubin encephalopathy: athetosis, chorea, hearing abnormalities, delayed psychomotoric developement, cerebral palsy (in preterm babies kernicterus is just one of determining factors)
Prevention of hyperbilirubinemia and its neurotoxicity — phototherapy, exchange transfusion

Macroscopic appearance

Prominent yellow staining of specific regions: Basal ganglia, lateral thalamic nucleus, hippocampus, geniculate bodies, nuclei of brainstem and floor of the fourth ventricle, dentate nucleus, inferior olive, anterior horn of spinal cord, cuneate and gracilis nuclei.

Pictures

Kernicterus: Kernicterus, Macro, autopsy (70901) Kernicterus, Macro, autopsy (70902) Kernicterus, Macro, autopsy (70903)

Another case: Kernicterus, Macro, autopsy (70839)

Histology

Vacuolization of cytoplasm, colouration (in frozen section) — early microscopic lesions. Loss of neurons and reactive astrocytosis.