1 – Kernicterus
Ranck and Windle (1959) noted the major difference
between the brainstem damage they found and
kernicterus was the absence of jaundice in the infant
monkeys and lack of bilirubin pigment in the brain
lesions.

High levels of bilirubin are thought to cause
kernicterus, but yellow staining is not uniform
throughout the brain in children with kernicterus.  Why
the characteristic pattern of yellow pigmentation
affects only specific nuclei in the brainstem still seems
not to be understood; though the experiments by
Lucey et al (1964) extended those of Ranck and
Windlle, and would appear to provide an explanation.  
It should be noted that Windle was a principal
collaborator in the experiments of Lucey et al.

Lucey et al induced hyperbiliruninemia in fourteen
newborn monkeys by injecting a solution of bilirubin
into the bloodstream every six hours.  Bilirubin levels
of 20 to 35 mg were maintained for up to 96 hours.  
"Six healthy full-term monkeys were asphyxiated at
birth.  A rubber bag filled with saline solution was
placed over the fetal head as it was delivered from the
uterus before the first breath.  The umbilical cord was
then clamped and asphyxiation carried out for 10 or
12 minutes" (p45).  Hyperbilirubinemia was then
induced in the asphyxiated monkeys as in the
fourteen control animals.

Lucey et al described the monkeys made
hyperbilirubinemic as showing marked yellow
coloration of skin and mucous membranes.  Those not
asphyxiated became slightly lethargic but none
developed signs of neurological impairment.  Monkeys
subjected to asphyxia before induction of
hyperbilirubinemia developed tremors, seizures, and
prolonged periods of opisthotonus (a postural state
with arched back and neck).  Figure 1 is from the
article by Lucey et al and shows a newborn monkey
with kernicterus during an opisthotonic seizure.  
Between seizures the monkeys were weak and flaccid
with intermittent hyperirritability.  The
hyperbilirubinemic asphyxiated monkeys also had
abnormal EEGs.

"Hyperbilirubinemia alone did not result in selective
staining of nuclei in the brain, such as is associated
with human kernicterus … the brains had a diffuse,
faint to moderate, yellow color, but no extravascular
bilirubin was seen" (p50).

On the other hand, all of the monkeys asphyxiated
prior to induction of hyperbilirubinemia exhibited
selective canary-yellow staining of nuclei in the
brainstem.  The most striking color was seen in the
basal ganglia, thalamus, subthalamic and inferior-
collicular nuclei, cranial nerve nuclei, cuneate nuclei,
superior and inferior olivary complexes, dentate and
roof nuclei and vermis of the cerebellum.

Individual variation was also seen in which some
nuclei were more affected in some animals and less in
others.  Lucey et al compared this with the variation
found in human cases.  Lucey et al viewed asphyxia
as just one of a number of agents acting in
combination with various other factors that can cause
damage within the brain.  However, it is puzzling that
although kernicterus had been known for nearly a
hundred years as a particular form of cerebral palsy,
and its association with sensorineural deafness had
been recognized, brainstem damage continued to be
viewed as "minimal."

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