Kernicterus

A term used pathologically to describe BILIRUBIN staining of the BASAL GANGLIA; BRAIN STEM; and CEREBELLUM and clinically to describe a syndrome associated with HYPERBILIRUBINEMIA. Clinical features include athetosis, MUSCLE SPASTICITY or hypotonia, impaired vertical gaze, and DEAFNESS. Nonconjugated bilirubin enters the brain and acts as a neurotoxin, often in association with conditions that impair the BLOOD-BRAIN BARRIER (e.g., SEPSIS). This condition occurs primarily in neonates (INFANT, NEWBORN), but may rarely occur in adults. (Menkes, Textbook of Child Neurology, 5th ed, p613)

Also Known As:

Networked: 631 relevant articles (22 outcomes, 59 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hyperbilirubinemia
2.	Jaundice (Icterus)
3.	Glucosephosphate Dehydrogenase Deficiency
4.	Birth Weight (Birth Weights)
5.	Hemolytic Anemia

Experts

1.	Bhutani, Vinod K: 16 articles (12/2022 - 05/2003)
2.	Shapiro, Steven M: 16 articles (01/2022 - 11/2002)
3.	Watchko, Jon F: 14 articles (12/2020 - 02/2005)
4.	Tiribelli, Claudio: 13 articles (12/2018 - 07/2003)
5.	Brites, Dora: 12 articles (01/2016 - 01/2002)
6.	Slusher, Tina M: 10 articles (01/2020 - 06/2004)
7.	Ahlfors, Charles E: 7 articles (01/2020 - 05/2003)
8.	Wennberg, Richard P: 7 articles (01/2020 - 10/2004)
9.	Kaplan, Michael: 7 articles (06/2011 - 04/2002)
10.	Vreman, Hendrik J: 6 articles (01/2020 - 06/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Kernicterus:

1.	BilirubinIBA 10/01/1985 - "Thus, in the undamaged rat brain, bilirubin is rapidly cleared, in contrast to its persistence in autopsy-proven human kernicterus. " 01/01/2006 - "Lapses in care have been attributed as root causes for kernicterus in an era when there should be no barriers to safe and effective bilirubin reduction strategies. " 04/28/2018 - "DHA did not reduce the bilirubin in the serum of neonatal rats with bilirubin encephalopathy, but did reduce the damage caused by bilirubin with decreased NSE and apoptosis rate as well as improved neuron morphology. " 01/01/2021 - "The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). " 12/01/2017 - "This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.55 mg/dL). "
2.	Phenobarbital (Luminal)FDA Link 11/01/2017 - "Type I is more severe and results in kernicterus if left untreated, and Type II is less severe and responds to phenobarbital. " 02/01/2016 - "The patient presented with kernicterus and phenobarbital treatment was ineffective. " 09/01/1987 - "After an episode of kernicterus in childhood he was treated with phenobarbital with a resultant marked decrease in his serum bilirubin concentration. " 04/28/2021 - "Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus." 01/01/1969 - "Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus."
3.	Glucosephosphate Dehydrogenase (Glucose 6 Phosphate Dehydrogenase)IBA 05/01/2007 - "We aimed to investigate the rate of kernicterus, and physical and laboratory examination findings in hyperbilirubinemic infants with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. " 07/01/1998 - "Prevention of kernicterus in full term infants is based on the detection of neonates at risk for developing hyperbilirubinaemia, and can be accomplished with simple tests performed on umbilical cord blood such as blood type, Rh, Coombs' test and glucose-6-phosphate dehydrogenase, in order to detect haemolytic diseases. " 01/01/1988 - "A simplified method for the detection of glucose-6-phosphate dehydrogenase activity in hair follicles that would allow health service workers in the field to determine the carrier status of pregnant women might form the basis for a future kernicterus prevention programme." 08/01/1973 - "An Iraqi Jewish family with a new red cell glucose-6-phosphate dehydrogenase variant (GD-Bagdad) and kernicterus." 06/01/2011 - "Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, a commonly occurring genetic condition, is associated in neonates with severe hemolytic episodes, extreme hyperbilirubinemia, and bilirubin encephalopathy. "
4.	Topiramate (Topamax)FDA LinkGeneric 01/01/2021 - "Darbepoetin alpha or topiramate administration ameliorates bilirubin induced neurological dysfunction in experimental model of kernicterus." 01/01/2021 - "The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus. "
5.	belnacasanIBA 01/01/2021 - "Most importantly, VX-765 improved both the short-term and long-term neurological functions of kernicterus model rats. " 01/01/2021 - "This study demonstrated that pyroptosis was involved in the pathogenesis of kernicterus through caspase-1 activation, which could be inhibited by VX-765, exerting a neuroprotective effect in kernicterus model rats."
6.	bilirubin glucuronoside glucuronosyltransferaseIBA 12/01/2001 - "Because the liver architecture is not disturbed in CN-1 and partial correction of bilirubin-UDP-glucuronosyltransferase (UGT1A1) activity is expected to be sufficient for protection against kernicterus, cell and gene therapies are being developed using the Gunn rat as an animal model of the disease. " 01/01/1991 - "Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. " 05/01/1995 - "Crigler-Najjar syndrome type I (CN-I) is a congenital hepatic metabolic deficiency in bilirubin UDP-glucuronosyltransferase activity which leads to profound jaundice and death from kernicterus. " 01/01/1984 - "For example, in Type I Crigler-Najjar syndrome, absence of hepatic bilirubin glucuronyl transferase activity causes severe unconjugated hyperbilirubinemia which invariably leads to death from kernicterus. "
7.	bucolomeIBA 08/01/1982 - "When kernicterus was induced in jaundiced rats by an injection of bucolome, the NSE level in cerebrospinal fluid was elevated up to more than 30-fold the control, together with a significantly higher level of alpha gamma form in blood plasma are helpful in detecting neuronal damage in the central nervous system." 11/26/1977 - "Induction of kernicterus by bucolome in rats." 06/01/1978 - "It is suggested that bucolome displaces bilirubin from albumin, transferring bilirubin from blood into tissues including the brain, and resulting in kernicterus. "
8.	Bile Acids and Salts (Bile Acids)IBA 01/01/2022 - "In addition, findings suggest that all the three bile acids would be equally beneficial in models of Huntington's disease, whereas UDCA and TUDCA would be more beneficial in models of Parkinson's disease and Alzheimer's disease, while GUDCA in models of bilirubin encephalopathy and TUDCA in models of depression. " 03/01/1997 - "The best parameters of the univariate analysis (encephalopathy, bilirubin, alkaline phosphatase, cholinesterase and bile acids) and their 25th and 75th percentiles were included in an additive new score which turned out to be superior to the five other scores. "
9.	ursodoxicoltaurineIBA 01/01/2022 - "In addition, findings suggest that all the three bile acids would be equally beneficial in models of Huntington's disease, whereas UDCA and TUDCA would be more beneficial in models of Parkinson's disease and Alzheimer's disease, while GUDCA in models of bilirubin encephalopathy and TUDCA in models of depression. " 11/01/2012 - "We hypothesized that the antioxidants taurourosdeoxycholic acid (TUDCA), 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), and minocycline (MNC) inhibit oxidative stress and block BIND in hyperbilirubinemic j/j Gunn rat pups that were given sulfadimethoxine to induce bilirubin encephalopathy. "
10.	MetalloporphyrinsIBA 01/01/2003 - "There is no evidence to support or refute the possibility that treatment with a metalloporphyrin decreases the risk of neonatal kernicterus or of long-term neurodevelopmental impairment due to bilirubin encephalopathy. " 01/01/2003 - "1. To determine the efficacy of metalloporphyrins in reducing bilirubin levels, reducing the need for phototherapy or exchange transfusion and reducing the incidence of bilirubin encephalopathy in neonates with unconjugated hyperbilirubinemia when compared to placebo, phototherapy or exchange transfusion. "

Therapies and Procedures

1.	Phototherapy (Light Therapy) 04/01/2013 - "Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. " 01/01/1982 - "It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. " 06/01/2011 - "In addition, effective phototherapy is crucial if we are to make kernicterus a "never-event." Finally it is essential that we conduct appropriate population-based studies to accurately elucidate the magnitude of the problem. " 02/01/2009 - "Including only cases with a procedure code for phototherapy or exchange transfusion resulted in 2.7 per 100000 diagnosed with kernicterus over the entire study period. " 06/01/1994 - "Kernicterus in premature infants: current prevalence and relationship to NICHD Phototherapy Study exchange criteria."
2.	Therapeutics 03/01/2022 - "Prediction of haemolytic disease of the foetus and newborn (HDFN) caused by maternal anti-A/-B enables timely therapy, thereby preventing the development of kernicterus spectrum disorder. " 05/01/2011 - "The management of hyperbilirubinaemia in preterm infants is not uniform in Italy and would benefit from shared national guidance together with establishment of a kernicterus registry to guide therapy." 09/01/2009 - "In spite of advances made in the use of phototherapy, and in order to avoid kernicterus, the treatment of these jaundices can require one or several exchange transfusions (ET), a therapy which is not devoid of risk. " 03/15/2005 - "Current therapy relies on phototherapy to prevent kernicterus, but liver transplantation presently is the only permanent cure. " 03/03/2005 - "Therapy is given because pronounced jaundice carries a risk for brain damage (kernicterus). "
3.	Liver Transplantation 08/01/1996 - "In 2 patients, ages 22 and 23 years, early signs of bilirubin encephalopathy could be reversed, in 1 by prompt medical intervention followed by liver transplantation and in the other by prompt liver transplantation. " 05/01/2006 - "While patients await liver transplantation for CND, hyperbilirubinemia can be managed safely and effectively to prevent kernicterus. " 03/15/2005 - "Current therapy relies on phototherapy to prevent kernicterus, but liver transplantation presently is the only permanent cure. " 09/01/1993 - "Crigler-Najjar syndrome type 1 (CN-1) is a familial disorder characterized by severe unconjugated hyperbilirubinemia and jaundice and leads to kernicterus, neurological damage, and eventual death unless treated with liver transplantation. " 11/01/2000 - "To save patients with the acute onset type of bilirubin encephalopathy, sufficient bilirubin adsorption followed by liver transplantation appears to be the most recommended therapeutic approach."
4.	Patient Readmission 01/01/2012 - "These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. " 07/01/2002 - "Prospective cohort studies on the effectiveness of the technology in the reduction of hospital readmission, and using the incidence of morbidity and mortality from kernicterus as clinical endpoints, would be useful." 01/01/2020 - "We maintain that the improved understanding generated by this project will be a step toward new evidence-based strategies for reducing ER visits and hospital readmissions for jaundice treatment and preventing bilirubin encephalopathy." 01/01/2020 - "Evidence-based progress is needed to define less invasive, less expensive, uniform, and safe methods to reduce ER visits and hospital readmissions for jaundice treatment and bilirubin encephalopathy. " 09/01/2006 - "Compared with term infants, late-preterm infants have higher frequencies of respiratory distress, temperature instability, hypoglycemia, kernicterus, apnea, seizures, and feeding problems, as well as higher rates of rehospitalization. "
5.	Plasma Exchange 09/01/2019 - "To describe the successful management of acute bilirubin encephalopathy in a dog with immune-mediated hemolytic anemia (IMHA) treated with therapeutic plasma exchange (TPE) in conjunction with conventional medical management. " 09/01/2019 - "Successful management of acute bilirubin encephalopathy in a dog with immune-mediated hemolytic anemia using therapeutic plasma exchange." 07/01/2017 - "The use of therapeutic plasma exchange to reduce serum bilirubin in a dog with kernicterus." 07/01/2017 - "To describe the use of a manual method of therapeutic plasma exchange to reduce total serum bilirubin, manage kernicterus, and halt progression of neurological dysfunction in a dog with immune-mediated hemolytic anemia (IMHA). "