what is the cause of kernicterus

Full Answer

What causes kernicterus bilirubin?

Kernicterus, or bilirubin encephalopathy, is bilirubin-induced neurological damage, which is most commonly seen in infants. It occurs when the unconjugated bilirubin (indirect bilirubin) levels cross 25 mg/dL in the blood from any event leading to decreased elimination and increased production of bilirubin.

Why are infants at risk for kernicterus?

It happens when babies build up too much of a chemical called bilirubin in their blood. Normally, this condition goes away on its own. It's only when the bilirubin level stays too high and isn't treated that jaundice becomes kernicterus and causes brain damage.

When does kernicterus develop?

In most cases, the syndrome characteristic of kernicterus develops by three to four years of age.

Why kernicterus occurs in newborn?

Kernicterus is a rare but serious complication of untreated jaundice in babies. It's caused by excess bilirubin damaging the brain or central nervous system.

What drugs cause kernicterus?

Certain drugs — particularly antibiotics — have also been linked to kernicterus. Sulfonamides (also called sulfa drugs) are a group of antibiotics that kill bacteria. One common antibiotic combines the sulfonamide sulfamethoxazole with trimethoprim (SMX-TMP) to treat bacterial infections.

Who is at risk for kernicterus?

Infants born to mothers of blood type O negative are at greatest risk, with one series of 249 infants with severe hyperbilirubinemia reporting an odds ratio of 48.6 for infants with Rh incompatibility.

How can kernicterus be prevented?

Early diagnosis and treatment of jaundice can prevent kernicterus. If you're concerned that your baby might have jaundice visit your baby's doctor right away. Ask for a jaundice bilirubin test.

What are the stages of kernicterus?

In phase 1, the infant demonstrates decreased alertness, hypotonia, and poor feeding. This is followed by a phase of hypertonia of the extensor muscles. Progress to this phase invariably leads to long-term neurologic deficits. Phase 3 usually occurs in infants aged >1 week, and they typically demonstrate hypotonia.

Why does bilirubin increase in babies?

Newborns produce more bilirubin than adults do because of greater production and faster breakdown of red blood cells in the first few days of life. Normally, the liver filters bilirubin from the bloodstream and releases it into the intestinal tract.

How common is kernicterus?

Kernicterus only affects about 1 in 44,000 newborns in developed countries because jaundice is usually treated before it becomes dangerous. Symptoms of kernicterus include excessive sleepiness, high-pitched crying, muscle spasms and arching in the neck and back.

Can adults get kernicterus?

Kernicterus in an adult is very rare. In this case, extracorporeal charcoal-column perfusion treatment led repeatedly to severe depletion of fibrinogen, with extensive hemorrhages.

What can happen to babies with jaundice?

If a baby with very high levels of bilirubin is not treated, there's a risk they could develop permanent brain damage. This is known as kernicterus.

What is kernicterus in infants?

Kernicterus, or bilirubin encephalopathy, is bilirubin-induced neurological damage, which is most commonly seen in infants. It occurs when the unconjugated bilirubin (indirect bilirubin) levels cross 25 mg/dL in the blood from any event leading to decreased elimination and increased production of bilirubin. The unconjugated bilirubin can cross the blood-brain barrier as it is lipid-soluble, unlike the water-soluble conjugated bilirubin. It gets deposited in the brain tissue, mainly the basal ganglia. This activity reviews the evaluation and management of kernicterus and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.

What are the warning signs of kernicterus?

They should be educated to seek medical attention when any warning signs like decreased activity, altered mental status, and poor suckling reflex are present. Pearls and Other Issues. Traditionally, kernicterus is defined by neurologic damage due to excessive unconjugated bilirubin deposition in the brain tissue.

Can a CT scan diagnose kernicterus?

Head ultrasound, CT, and MRI - not routinely used to diagnose kernicterus. They are indicated only when lab results are inadequate or inconclusive. They may aid in ruling out other causes of encephalopathy.

Is kernicterus more common in males or females?

The condition occurs primarily in children, mostly African Americans and South Asians, and is slightly more common in males than females. The incidence of kernicterus is not exactly known in the United States. Asian, Hispanic, Native American, and Eskimo infants have a higher production of bilirubin than white infants.

Why does kernicterus occur randomly?

Causes. Some cases of kernicterus occur randomly, for no apparent reason (sporadically). According to the medical literature, excess levels of bilirubin (hyperbilirubinemia) alone is not sufficient to produce kernicterus. Potential causes may include Rh disease and/or unknown factors.

When is Kernicterus suspected?

In most cases, persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice) is apparent within the first few days of life.

How to treat kernicterus durint?

Treatment for Kernicterus focuses on decreasing the amount of unconjugated bilirubin in the blood. Early treatment is imperative in the attempt to prevent the symptoms and physical findings associated with kernicterus durint the first months of life. Such treatments may include exchange blood transfusions in which small amounts of blood are withdrawn repeatedly and replaced with blood from a donor until most of the blood has been exchanged. In another procedure known as plasmapheresis, unwanted substances (toxins, metabolic substances and plasma parts) are removed from the blood. During this procedure, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma and the blood is transfused into the affected individual.

What is the name of the disease that causes bilirubin to accumulate in the brain?

Kernicterus is a rare neurological disorder characterized by excessive levels of bilirubin in the blood (hyperbilirubinemia) during infancy. Bilirubin is an orange-yellow bile pigment that is a byproduct of the natural breakdown of hemoglobin in red blood cells (hemolysis). Toxic levels of bilirubin may accumulate in the brain, potentially resulting in a variety of symptoms and physical findings. These symptoms may include lack of energy (lethargy), poor feeding habits, fever, and vomiting. Affected infants may also experience the absence of certain reflexes (e.g., Moro reflex, etc.); mild to severe muscle spasms including those in which the head and heels are bent backward and the body bows forward (opisthotonus); and/or uncontrolled involuntary muscle movements (spasticity). In some cases, infants with kernicterus may develop life-threatening complications.

Why is phototherapy used for kernicterus?

This helps to speed up the excretion of bilirubin from the skin and aids in its decomposition. As an affected individual ages, body mass increases and the skin thickens; phototherapy becomes less effective against preventing the symptoms and physical findings associated with kernicterus. Therefore, liver transplantation may be performed. Some researchers believe that liver transplantation should be performed at an early age, before brain damage potentially associated with kernicterus can develop.

How long does it take for kernicterus to appear?

In some cases, symptoms and physical findings of kernicterus appear two to five days after birth. Within the first few days of life, affected infants develop abnormally high levels of bilirubin in the blood (hyperbilirubinemia) and persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).

What is kernicterus type 1?

In some rare cases, kernicterus may result from a rare disorder known as Crigler-Najjar Syndrome Type I. (For more information on this disorder, choose “Crigler Najjar” as your search term in the Rare Disease Database.)

Signs and Symptoms

Jaundice usually appears first on the face and then moves to the chest, belly, arms, and legs as bilirubin levels get higher. The whites of the eyes can also look yellow. Jaundice can be harder to see in babies with darker skin color. The baby’s doctor or nurse can test how much bilirubin is in the baby’s blood.

Diagnosis

At a minimum, babies should be checked for jaundice every 8 to 12 hours in the first 48 hours of life. It is important for your baby to be seen by a nurse or doctor when the baby is between 3 and 5 days old, because this is usually when a baby’s bilirubin level is highest.

Risk Factors

About 60% of all babies have jaundice. Some babies are more likely to have severe jaundice and higher bilirubin levels than others. Babies with any of the following risk factors need close monitoring and early jaundice manage­ment:

Why is kernicterus more common in babies?

Babies with a darker skin color are more likely to develop kernicterus because jaundice is more difficult to identify. That means that jaundice may go undiagnosed and untreated, which is a leading reason why the condition progresses into kernicterus.

How to diagnose kernicterus?

To diagnose kernicterus, your doctor will carefully assess your baby and their symptoms. General guidelines for postnatal care include monitoring and checking the baby’s bilirubin level via a blood test. Babi es with higher than 25 milligrams of total serum bilirubin in their blood will be treated, often in the hospital, until bilirubin levels decrease. Kernicterus can occur in babies with a bilirubin level below 25 mg, so it is important that doctors carefully examine and monitor the baby. Bilirubin levels alone are generally not enough to make a complete diagnosis. Your doctor must consider blood tests, symptoms and the child’s overall health. Immediate diagnosis and treatment can prevent brain damage from occurring.

How Does Kernicterus Affect Children?

Along with the aforementioned symptoms, Kernicterus can lead to a number of neurological disorders, some slight such as minor learning disabilities, and some as serious as athetoid cerebral palsy. Other risks and complications include complete hearing loss, and even death.

What is the brainstem affected by kernicterus?

Brain damage caused by kernicterus often affects parts of the brain responsible for hearing, movement and other motor functions. Primarily, this includes the brainstem and the basal ganglia. Kernicterus is linked to hearing loss, vision problems, athetoid cerebral palsy and intellectual disabilities.

What is kernicterus in babies?

Kernicterus, also known as Hyperbilirubinemia or bilirubin encephalopathy, is a rare neurological disorder that occurs when hyperbilirubinemia damages the brain. Whereas with jaundice treatment reduces bilirubin levels and the baby recovers, kernicterus means that bilirubin levels are toxic. Excess levels of bilirubin in the baby’s blood can enter brain tissue and cause damage. This occurs in around 5% of babies who have jaundice – or around one in every 44,000 newborns. Generally, jaundice is treated before bilirubin levels get too high and there is a risk of brain damage. Unfortunately, not all babies are diagnosed and treated quick enough to prevent kernicterus.

How long does it take for a baby to show signs of kernicterus?

Symptoms of Kernicterus. Kernicterus symptoms will greatly depend upon if it’s in an early or later stage of the disorder. Generally, symptoms begin two to five days after the baby is born. The most notable symptom is, of course, the yellowing of the baby’s skin, whites of the eyes and mucous membranes.

Can Kernicterus be Prevented?

Since 60-80% of newborns have some level of jaundice, the best way to prevent kernicterus is to recognize the risk and take measures to diagnose and treat jaundice quickly. Although in many cases, there is no known way to discern which infant will develop jaundice severe enough to cause Kernicterus, there are some risk factors that increase the risk of a baby developing kernicterus. These include:

What are the symptoms of kernicterus?

Limpness or stiffness of the whole body. Unusual eye movements. Muscle spasms or reduced muscle tone. Other symptoms of kernicterus can develop as a child gets older: Seizures or convulsions. Unusual motor development and movement. Muscle spasms and/or writhing. Hearing and other sensory problems.

What is the rarest brain damage that can happen in newborns with jaundice?

Kernicterus is a rare kind of preventable brain damage that can happen in newborns with jaundice. Jaundice is a yellow coloring of the skin and other tissues that affects about 60%-80% of infants in the United States.

Can jaundice cause kernicterus?

Most cases of jaundice don’ t require treatment, but if it goes on too long, complications can occur and it can lead to kernicterus. Symptoms of kernicterus can vary, but may include: Drowsiness or lack of energy. Uncontrollable or very high-pitched/shrill crying. Fever.

What is the diagnosis of Kernicterus?

Kernicterus is reserved for a diagnosis with a combination of clinical features and MRI findings. The classic diagnosis includes a tetrad of features: (1) dystonia and/or athetosis; (2) hearing impairment or deafness; (3) lack of upward gaze; and (4) dental enamel dysplasia, along with abnormal MRI findings in the globus pallidus and subthalamic nuclei. Other less common accompanying symptoms may include hypotonia or sensorimotor abnormalities, and oculomotor abnormalities may vary and include strabismus or other misalignment of the eyes 34).

What are the long term effects of kernicterus?

Long-term outcomes of infants with kernicterus vary widely based on severity as well as a variety of risk factors described previously. Increased incidence of dyskinetic cerebral palsy occurs following high bilirubin exposure in full-term infants or low–moderate levels of bilirubin exposure in preterm infants 38). Cerebral palsy was most recently defined by an international committee as “a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain 39). The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, behavior, by epilepsy, and by secondary musculoskeletal problems” 40).

What is yellow staining in kernicterus?

Original autopsy studies of kernicterus identified yellow staining and necrosis of the basal ganglia, specifically in the globus pallidus, indicative of “unbound bilirubin” crossing the blood–brain barrier (BBB). Other regions noted to have cellular damage after hyperbilirubinemia include the substantia nigra reticulata, subthalamic nuclei, vestibular and oculomotor nuclei, hippocampus, and cerebellar Purkinje cells. Loss of neurons, decreased myelination, and gliosis can be observed in the internal and external globus pallidus and subthalamic nuclei. These regions all have functions related to movement, balance, and posture regulation and appear to be selectively vulnerable. The globus pallidus may also serve to integrate inputs from multiple systems including somatosensory and motor pathways; thus, integration of this information may be damaged in patients with kernicterus 17). By contrast, regions such as the striatum and thalamus generally appear to be spared following hyperbilirubinemia. This specific pattern of brain injury helps distinguish bilirubin-induced neurologic dysfunction from injury following hypoxic–ischemia, in which the caudate, putamen, posterior limb of the internal capsule, and cortex are more vulnerable. One theory for the selective vulnerability of the globus pallidus and subthalamic nuclei is their relatively high resting levels of neuronal activity observed in the neonatal brain, compared to nearby regions. Johnston et al. 18) observed that regions with higher neuronal activity are more vulnerable to oxidative stressors or toxins such as bilirubin. Lesions in these regions are observed in infants with classic athetotic cerebral palsy. One hypothesis for the connection between globus pallidus injury and athetosis is that reduced activity of the globus pallidus results in decreased inhibitory input to the thalamus, resulting in its “dys-inhibition” and increased motor activity, consistent with athetosis 19).

What is the term for the abnormality of the brain that results from high levels of bilirubin in?

Kernicterus is a rare but irreversible brain damage that can result from high levels of bilirubin in a baby’s blood being deposited in baby’s brain tissue. Kernicterus is usually seen only in infants with untreated jaundice, and it very rarely occurs in adults. Kernicterus is the pathological finding of deep-yellow staining ...

What is the condition where babies have uncontrollable movements in the arms, legs, face and other body parts?

Athetoid cerebral palsy. Babies with this condition have uncontrollable movements in the arms, legs, face and other body parts.

How to predict hyperbilirubinemia?

Therefore, the best available method for predicting severe hyperbilirubinemia appears to be the use of a timed total serum bilirubin measurement analyzed in the context of the infant’s gestational age . Infants of less than 38 weeks’ gestation whose total serum bilirubin concentration is greater than the 75th percentile have a greater than 10% risk of developing severe hyperbilirubinemia; similarly, infants of 39 to 40 weeks’ gestation whose total serum bilirubin concentration is above the 95th percentile have a greater than 10% risk 74).

How does UCB affect the brain?

When UCB starts to leave the blood and go into brain tissue, it starts to cause neurological signs and symptoms. Early on it’s hard to tell when symptoms start, it may just be increased sleepiness. But then lethargy, abnormal decreased and/or increased muscle tone, abnormal high-pitched (high-sounding cry), backward arching of the trunk and spine (opisthotonus), download deviation of the eyes (sun-setting sign), and even worse – seizures and cardiovascular collapse. I’ve described the worst case scenario, a progression of worsening signs and symptoms that progresses to become a neurological emergency requiring immediate treatment. But, we talk more about in this website in the section title Acute Bilirubin Encephalopathy (ABE) also called Acute Kernicterus.

What is the yellow staining of the deep nuclei of the brain called?

Kernicterus refers to the yellow staining of the deep nuclei (i.e., the kernel) of the brain namely, the basal ganglia. Kernicterus involves a specific part of the basal ganglia, the globus pallidus. It also includes lesions (damage) to brainstem nuclei in auditory (hearing), oculomotor (eye movement), and vestibular (balance) ...

How to prevent kernicterus in a baby?

The only effective way at preventing kernicterus is to lower the serum bilirubin levels either by phototherapy or exchange transfusion. Visual inspection is never sufficient; therefore, it is best to use a bilimeter or blood test to determine a baby's risk for developing kernicterus. These numbers can then be plotted on the Bhutani nomogram.

What is unconjugated hyperbilirubinemia?

Unconjugated hyperbilirubinemia during the neonatal period describes the history of nearly all individuals who suffer from kernicterus. It is thought that the blood–brain barrier is not fully functional in neonates and therefore bilirubin is able to cross the barrier. Moreover, neonates have much higher levels of bilirubin in their blood due to:

Why do people get jaundice?

When this happens in adults, it is usually because of liver problems . Newborns are especially vulnerable to hyperbilirubinemia-induced neurological damage, because in the earliest days of life, the still-developing liver is heavily exercised by the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the blood–brain barrier is not as developed. Mildly elevated serum bilirubin levels are common in newborns, and neonatal jaundice is not unusual, but bilirubin levels must be carefully monitored in case they start to climb, in which case more aggressive therapy is needed, usually via light therapy but sometimes even via exchange transfusion .

What is the cause of death in newborns?

Although the severe hemolytic disease of the newborn is usually the cause of death, many children who barely survive the anemia exhibit permanent mental impairment or damage to motor areas of the brain because of precipitation of bilirubin in the neuronal cells, causing destruction of many, a condition called kernicterus.

Can G6PD cause kernicterus?

Gilbert's syndrome and G6PD deficiency occurring together especially increases the risk for kernicterus .

Does kernicterus cause intellectual disability?

In the past it was thought that kernicterus (KI) often cause an intellectual disability. This was assumed due to difficulty with hearing, that is typically not detected in a normal audiogram accompanied by impairments of speech, with choreoathetosis. With advances in technology, this has proven to not be the case as those living with KI have repeatedly demonstrated their intelligence using Augmentative Communication devices. Although most individuals with kernicteric cerebral palsy have normal intelligence, some children with mild choreoathetosis develop dull normal intelligence or mild intellectual disability even without auditory dysfunction.

Can kernicterus be treated?

Currently no effective treatment exists for kernicterus. Future therapies may include neuroregeneration. A handful of patients have undergone deep brain stimulation, and experienced some benefit. Drugs such as baclofen, clonazepam, gabapentin, and artane are often used to manage movement disorders associated with kernicterus. Proton pump inhibitors are also used to help with reflux. Cochlear implants and hearing aids have also been known to improve the hearing loss that can come with kernicterus (auditory neuropathy – ANSD).

Signs and Symptoms

Diagnosis

Treatment

Risk Factors

• About 60% of all babies have jaundice. Some babies are more likely to have severe jaundice and higher bilirubin levels than others. Babies with any of the following risk factors need close monitoring and early jaundice manage­ment: Preterm Babies Babies born before 37 weeks, or 8.5 months, of pregnancy might have jaundice because their liver is not...

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