Kernicterus
Encyclopedia
Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin
. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin
, which circulates in the blood and causes jaundice
. Alternatively, Rh incompatibility between mother and fetus may cause hemolysis
of fetal red blood cells, thereby releasing unconjugated bilirubin into the fetal blood. Since the fetal blood brain barrier is not fully formed, some of this released bilirubin enters the brain and interferes with normal neuronal development.
Kernicterus may also be found in infants as a symptom of Crigler-Najjar syndrome
type I, a hereditary hyperbilirubinemia resulting in a decreased ability to excrete bilirubin that is fatal within 18 months of life. Other inherited genetic disorders that can contribute to the development of hyperbilirubinemia are Gilbert's syndrome
and G6PD deficiency, especially if they are present concurrently.
In adults and older children, jaundice is harmless in and of itself. However, the tissues protecting the brain (the blood-brain barrier
) are immature in newborns. Bilirubin penetrates the brain and is deposited in cell bodies (gray matter), especially the basal ganglia
, causing irreversible damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage
and even death.
Some medications, such as the antibiotic co-trimoxazole
(a combination of trimethoprim
/sulfamethoxazole
) may induce this disorder in the baby, either when taken by the mother or given directly to the baby, due to displacement of bilirubin
from binding sites on serum albumin
. The bilirubin
is then free to pass into the Central Nervous System
, because the baby's blood-brain barrier
is not fully developed.
The only effective way at preventing kernicterus is to lower the serum bilirubin levels either by phototherapy or exchange transfusion
.
Symptoms of kernicterus in infants include abnormalities of tone, including hypertonia
or hypotonia
, lethargy, a distinct, high-pitched cry, and arching of the back (retrocollis or opisthotonus
). In children and adults, mild kernicterus manifests through movement and language processing disorders. Furthermore, it mimics autism-spectrum disorders and is often misdiagnosed as such.
The word originates from the German kern, nucleus, kernel, and the Greek
ikterus, jaundice.
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, which circulates in the blood and causes jaundice
Neonatal jaundice
Neonatal jaundice or Neonatal hyperbilirubinemia is a yellowing of the skin and other tissues of a newborn infant. A bilirubin level of more than 85 umol/l manifests clinical jaundice in neonates whereas in adults a level of 34 umol/l would look icteric...
. Alternatively, Rh incompatibility between mother and fetus may cause hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
of fetal red blood cells, thereby releasing unconjugated bilirubin into the fetal blood. Since the fetal blood brain barrier is not fully formed, some of this released bilirubin enters the brain and interferes with normal neuronal development.
Kernicterus may also be found in infants as a symptom of Crigler-Najjar syndrome
Crigler-Najjar syndrome
Crigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in...
type I, a hereditary hyperbilirubinemia resulting in a decreased ability to excrete bilirubin that is fatal within 18 months of life. Other inherited genetic disorders that can contribute to the development of hyperbilirubinemia are Gilbert's syndrome
Gilbert's syndrome
Gilbert's syndrome , often shortened to GS, also called Gilbert-Meulengracht syndrome, is the most common hereditary cause of increased bilirubin and is found in up to 5% of the population...
and G6PD deficiency, especially if they are present concurrently.
In adults and older children, jaundice is harmless in and of itself. However, the tissues protecting the brain (the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
) are immature in newborns. Bilirubin penetrates the brain and is deposited in cell bodies (gray matter), especially the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, causing irreversible damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
and even death.
Some medications, such as the antibiotic co-trimoxazole
Co-trimoxazole
Trimethoprim/sulfamethoxazole or co-trimoxazole is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections.The name co-trimoxazole is the British Approved Name, and has been marketed worldwide...
(a combination of trimethoprim
Trimethoprim
Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors...
/sulfamethoxazole
Sulfamethoxazole
Sulfamethoxazole is a sulfonamide bacteriostatic antibiotic.It is most often used as part of a synergistic combination with trimethoprim in a 5:1 ratio in co-trimoxazole , also known under trade names such as Bactrim, Septrin, or Septra; in Eastern Europe it is marketed as Biseptol...
) may induce this disorder in the baby, either when taken by the mother or given directly to the baby, due to displacement of bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
from binding sites on serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
. The bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
is then free to pass into the Central Nervous System
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, because the baby's blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
is not fully developed.
The only effective way at preventing kernicterus is to lower the serum bilirubin levels either by phototherapy or exchange transfusion
Exchange transfusion
An exchange transfusion is a medical treatment in which apheresis is used to remove one person's red blood cells or platelets and replace them with transfused blood products...
.
Symptoms of kernicterus in infants include abnormalities of tone, including hypertonia
Hypertonia
Hypertonia a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. It is caused by lesions to upper motor neurons in the central nervous system, which carry information from the central nervous system to the muscles and control posture, muscle...
or hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, lethargy, a distinct, high-pitched cry, and arching of the back (retrocollis or opisthotonus
Opisthotonus
Opisthotonus or opisthotonos, from Greek roots, opistho meaning "behind" and tonos meaning "tension", is a state of a severe hyperextension and spasticity in which an individual's head, neck and spinal column enter into a complete "bridging" or "arching" position...
). In children and adults, mild kernicterus manifests through movement and language processing disorders. Furthermore, it mimics autism-spectrum disorders and is often misdiagnosed as such.
The word originates from the German kern, nucleus, kernel, and the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
ikterus, jaundice.