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Bilirubin encephalopathy | |
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Brain MRI. Hyperintense basal ganglia lesions on T2-weighted images, showing Kernicterus bilirubin encephalopathy. | |
Specialty | Psychiatry, Neurology, Pediatrics |
Diagnostic method | physical examination of moro reflex |
Bilirubin encephalopathy, is a clinal condition in neonates caused by increased levels of billirubin that is accumulated within the brain. [1] This disease is a progression of Neonatal jaundice if it is not identified and treated. [2] Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is toxic to brain cells when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey 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.
When hyperbilirubinemia increases past a mild level, it leads to jaundice, raising the risk of progressing to Bilirubin encephalopathy. 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.
Acute bilirubin encephalopathy is the early stages of the disorder of hyperbilirubinemia during the first days of life. If it is not treated it can progress to Kernicterus which is fatal. Clinically, it encompasses a wide range of symptoms which can be divided into three phases: [3] [1]
Kernicterus, is accumulation of high levels of unconjugated bilirubin within the basal ganglia of brain which can cause neurological lesions. Reduction of bilirubin in this state will not reverse the sequelae. [4] Christian Georg Schmorl coined the term Kernicterus in 1904.
Clinically, manifestations of kernicterus include: [5]
These impairments are associated with lesions in the basal ganglia, auditory nuclei of the brain stem, and oculomotor nuclei of the brain stem. Cortex and white matter are subtly involved. Cerebellum may be involved. Severe cortical involvement is uncommon.
Subtle bilirubin encephalopathy is a chronic state of mild bilirubin-induced neurological dysfunction (BIND). Clinically, this may result in neurological, learning and movement disorders, isolated hearing loss and auditory dysfunction.[ citation needed ]
In the vast majority of cases, kernicterus is associated with unconjugated hyperbilirubinemia during the neonatal period. The blood–brain barrier is not fully functional in neonates and therefore bilirubin can cross into the central nervous system. Moreover, neonates have much higher levels of bilirubin in their blood due to:
Bilirubin is known to accumulate in the gray matter of neurological tissue where it exerts direct neurotoxic effects. It appears that its neurotoxicity is due to mass-destruction of neurons by apoptosis and necrosis.[ citation needed ]
Gilbert's syndrome and G6PD deficiency occurring together especially increases the risk for kernicterus. [6]
Naturally, all neonates are prone to jaundice development due to immaturity of the liver that cannot filter the vast amount of fetal hemoglobin that is rapidly changing to Adult hemoglobin. [7] Therefore it is recommended to assess all newborns for jaundice. [8]
Kernicterus presents as jaundice and neurological symptoms such as cerebral paresis, gaze palsy and hearing loss. Bilirubin tests needs to be done on newborns as an indirect bilirubin level above 25 mg/dl, is diagnostic for kernicterus. If a newborn's Rh is different from its mother's Rh, then there is Rh incompatibility, which increases the risk of developing kernicterus. [7]
Measuring the serum bilirubin is helpful in evaluating a baby's risk for developing kernicterus. These numbers can then be plotted on the Bhutani nomogram. In neonates with hyperbilirubinemia, light therapy may be effective in reducing the serum bilirubin level. More severe cases may require the use of exchange transfusion.[ citation needed ]
Acute bilirubin encephalopathy's treatment would be phototherapy and exchange transfusion which is essentially changing the newborns blood. [9]
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 can improve the hearing loss that can come with kernicterus (auditory neuropathy – ANSD).[ citation needed ]