Changes in globus pallidus with (pre)term kernicterus

OBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest means of diagnosis and prevention. METHODS: Charts and MR and ultrasound images of 5 preterm infants and 3 term infants with suspected bilirubin-associated brain damage were reviewed. Included were preterm infants with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150, the diagnosis was confirmed during the neonatal period. The others were picked up as outpatients and scanned at 12 or 22 months' corrected age. Three instances of term kernicterus were included for comparison of serial MRI in the neonatal period and early infancy: they were caused by glucose-6-phosphate dehydrogenase deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase deficiency. RESULTS: Five preterm infants of 25 to 29 weeks' gestational age presented with total serum bilirubin (TSB) levels below exchange transfusion thresholds commonly advised. Mixed acidosis was present in 3 infants around the TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of displacing drugs. All failed to pass bedside hearing screen tests and had severe hearing loss on auditory brain response testing. Symmetrical homogeneous hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus pallidus was hyperintense on T1-weighted MR images in this child. The other infants presented with severe developmental delay as a result of dyskinetic quadriplegia and hearing loss. Globus pallidus was normal on T1- but hyperintense on T2-weighted MR images at 12 or 22 months' corrected age. Subthalamic involvement was documented in coronal fluid attenuated inversion recovery MRI in 2 infants. The term infants with classical clinical presentation in the neonatal period had MR behavior similar to the preterms, but pallidal injury was not recognized with targeted sonographic examination. Their neonatal MR images demonstrated pallidal T1 hyperintensity and mild T2 hyperintensity. CONCLUSION: Acidotic very low birth weight preterm infants with low serum albumin levels develop MR-confirmed pallidal injury and hearing loss facing "accepted" TSB levels. Serial MRI documents a shift from acute mainly T1 hypersignal to permanent T2 hypersignal in globus pallidus within the late neonatal period. Subthalamic and not thalamic involvement helps to differentiate from ischemic or metabolic disorder. As newborns, these infants are rigid and have severe apnea, before developing hypertonic quadriplegia in infancy.