The symptoms depend on the stage of kernicterus.

Early stage:

Extreme jaundice

Absent startle reflex

Poor feeding or sucking

Extreme sleepiness (lethargy)

Mid stage:

High-pitched cry

Arched back with neck hyperextended backwards

Bulging fontanel (soft spot)

Seizures

Late stage (full neurological syndrome):

High-frequency hearing loss

Intellectual disability

Muscle rigidity

Speech difficulties

Seizures

Movement disorder

Pathophysiology

Kernicterus is a bilirubin-induced brain dysfunction. Bilirubin is a highly neurotoxic

substance that may become elevated in the serum, a condition known as hyperbilirubinemia.
Hyperbilirubinemia may cause bilirubin to accumulate in the gray 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. Neonates are especially vulnerable to hyperbilirubinemia-induced neurological
damage
Bilirubin staining can be noted on autopsy of fresh specimens in the regions of the basal ganglia,
hippocampus, substantia nigra, and brainstem nuclei. Such staining can occur in the absence of

severe hyperbilirubinemia; in this situation, factors influencing permeability of the blood-brain

barrier (eg, acidosis, infection) and the amount of unbound (versus albumin-bound) bilirubin may
play a role.
Characteristic patterns of neuronal necrosis leading to the clinical findings consistent with chronic
bilirubin encephalopathy are also essential in the pathophysiology of this entity. Bilirubin staining
of the brain without accompanying neuronal necrosis can be observed in babies who did not
demonstrate clinical signs of bilirubin encephalopathy but who succumbed from other causes.
This staining is thought to be a secondary phenomenon, dissimilar from the staining associated
with kernicterus

Acute bilirubin encephalopathy (ABE)[edit]

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
encepalopathy.

Kernicterus (Bilirubin encephalopathy) is an acquired metabolic encephalopathy of

the neonatal period. Its etiology and pathogenesis overlap to some extent with HIE.
Kernicterus is caused by unconjugated hyperbilirubinemia that develops either as a
result of hemolytic disease (Rh incompatibility, hereditary spherocytosis, other
hemolytic disorders) or because of inability of the liver to conjugate bilirubin. The latter
is seen in a rare defect of glucuronyl transferase, the Crigler-Najjar syndrome, and in
premature babies in whom this enzyme is not fully functional. Unconjugated (indirect)
bilirubin in serum is bound to albumin. Unbound, unconjugated, circulating
bilirubin crosses the blood-brain barrier and, because it is lipid soluble, it
penetrates neuronal and glial membranes. Hypoalbuminemia, low pH, which weakens
the albumin-bilirubin bond, and drugs (salicylates, sulfonamides) that compete with
bilirubin for albumin binding, increase the amount of unconjugated unbound bilirubin.
Prematurity and low birth weight are the greatest risk factors for bilirubin-induced brain
injury.

High T2 signal in
globus pallidus
Kernicterus

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. In the hippocampus, kernicterus involves the CA2-CA3 sectors of the
pyramidal layer, unlike HIE, which affects CA1. The reason for the topography of the
lesions are not known. In severe kernicterus, affected structures have a bright yellow
color (kernicterus means nuclear jaundice). Microscopically, they show neuronal
necrosis (eosinophilic neurons similar to HIE) and, in burned-out cases, neuronal loss,
gliosis and atrophy. Bilirubin binds to cell membranes and is toxic to neurons and
oligodendroglia. It damages mitochondria, inhibits oxidative phosphorylation, and
causes calcium release promoting apoptosis. It also stunts axonal and dendritic growth.
The acute toxic injury is aggravated by inflammatory reactions of microglia and
astrocytes.

Immaturity of the blood-brain barrier probably plays a role in kernicterus. Infusion of

bilirubin in experimental animals, after "opening" of the barrier by injecting
hypertonic solutions, causes bilirubin staining. Bilirubin encephalopathy affects
parts of the brain that are also involved in perinatal HIE. According to one school of
thought, kernicterus is simply due to leakage of bilirubin in areas where the bloodbrain barrier has been damaged by HIE.