Kernicterus

In newborn infants or neonates, the immature blood-brain-barrier (BBB) allows bilirubin in its conjugated form to reach the central nervous system (CNS) and exert toxic effect on neuronal cells and affect various metabolic processes (apoptosis, utilization of energy, and mitochondrial function) in the basal ganglia and the brainstem [1] [2]. Thus, signs of bilirubin-mediated toxicity may start during the first several weeks of life, in which case the term acute bilirubin encephalopathy is used [2] [3]. Jaundice as the most prominent finding, together with lethargy, feeding difficulties, and hypotonia followed by hypertonia are some of the earliest symptoms seen in acute disease, whereas abnormal extension of the neck (retrocollis), generalized aching and opisthotonus, fever, convulsions, and a very high-pitched cry are manifestations encountered of more severe intoxications [2] [4] [5]. In some cases, brainstem damage can induce life-threatening apnea due to diminished responses of the respiratory center to CO2 concentrations [4] [5]. Bilirubin encephalopathy may take a chronic course, and the term kernicterus is sometimes used to describe the long-term complications of this disorder. Disturbances in auditory function (total hearing loss is a possibility), dysplasia of deciduous teeth, inability to sustain an upward vertical gaze and persistent abnormalities of muscle tone and control are seen [2] [3] [5] [6]. Intellectual deficits, although being an uncommon finding, is one of the more debilitating sequelae of chronic bilirubin encephalopathy [3].

Because of the complications that may arise from bilirubin encephalopathy, all newborn babies must be carefully monitored in their first several days of life in order to make an early diagnosis. In fact, guidelines advocate that physicians should check for jaundice every 8-12 hours [2], thus illustrating the importance of a proper physical examination and adequate clinical suspicion, perhaps the two most important components of the workup. If jaundice does appear, bilirubin encephalopathy must be ruled out, which can be done by measuring the total serum and total conjugated bilirubin (TSB and tcB, respectively) in blood [2]. These values must be interpreted according to the age of the newborn (in hours), and a value exceeding the 95% percentile yields solid evidence to make a presumptive diagnosis [2]. Since cholestasis, glucose-6-phosphate dehydrogenase (G6PD) deficiency (for newborns who received phototherapy), and hypothyroidism can be the underlying cause of bilirubin encephalopathy, a comprehensive laboratory workup encompassing these entities must be carried out [2]. Imaging studies of the endocranium, such as magnetic resonance imaging (MRI), are highly useful for determining the extent of damage caused by bilirubin [7]. Typical findings include high intensity of the subthalamic nuclei and globus pallidus on T1-weighed studies, but the use of more advanced methods - MR spectroscopy (MRS), and diffusion-weighted imaging (DWI) is advocated in order to recognize the ailment early on [7].

1. Ostrow JD, Pascolo L, Shapiro SM, Tiribelli C. New concepts in bilirubin encephalopathy. Eur J Clin Invest. 2003;33(11):988-997.
2. AAP Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297–316.
3. Connolly AM, Volpe JJ. Clinical features of bilirubin encephalopathy. Clin Perinatol. 1990;17(2):371-379.
4. Amin SB, Bhutani VK, Watchko JF. Apnea in Acute Bilirubin Encephalopathy. Semin Perinatol. 2014;38(7):407-411.
5. Arnolda G, Nwe HM, Trevisanuto D, et al. Risk factors for acute bilirubin encephalopathy on admission to two Myanmar national paediatric hospitals. Matern Health Neonatol Perinatol. 2015;1:22.
6. Shapiro SM. Chronic bilirubin encephalopathy: diagnosis and outcome. Semin Fetal Neonatal Med. 2010;15(3):157-163.
7. Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF. Magnetic Resonance Imaging of Bilirubin Encephalopathy: Current Limitations and Future Promise. Semin Perinatol. 2014;38(7):422-428.