An 18-month-old boy is brought to the office due to abnormal limb movements and delay in achieving motor milestones. He is unable to pull up to stand or walk and recently developed stiffness in the extremities. Birth history is remarkable for readmission at age 1 week for severe, persistent jaundice due to RhD incompatibility, which required intensive phototherapy and exchange transfusion. On examination, the patient exhibits a limited upward gaze and dystonic extremity movement. MRI of the head would most likely reveal abnormal signal in which of the following areas?
Bilirubin-induced neurologic dysfunction | |
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Clinical features |
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This child with a history of severe neonatal jaundice has dystonic movements and gaze abnormalities, findings concerning for bilirubin-induced neurologic dysfunction (BIND).
Unconjugated bilirubin, a by-product of red blood cell destruction, is normally increased in all newborns and is bound to plasma albumin, preventing it from crossing the immature neonatal blood-brain barrier. However, the bilirubin concentration can dramatically rise (total bilirubin >30 mg/dL), usually in the setting of an underlying hemolytic condition (eg, RhD incompatibility, glucose-6-phosphate dehydrogenase deficiency), and can exceed the albumin binding capacity. If this happens, the excess bilirubin remains unbound and can pass beyond the blood-brain barrier. This neurotoxic bilirubin preferentially deposits in the basal ganglia and brainstem nuclei.
Initial symptoms of acute BIND occur in the neonatal period and are often subtle (eg, poor feeding) but may include inconsolability, change in tone, and apnea. Patients with prolonged, severe hyperbilirubinemia or delayed/inadequate treatment are at risk for chronic BIND (previously referred to as kernicterus), which typically develops after infancy and is irreversible. Destruction of neurons in the basal ganglia leads to abnormal movements (eg, chorea, dystonia). Similarly, upward gaze palsy and sensorineural hearing loss occur due to neuronal destruction in the gray matter of visual and auditory brainstem nuclei, respectively. Developmental delay, as seen in this patient, is also typical.
(Choice B) Abnormalities of the corpus callosum (eg, agenesis, dysgenesis) often cause gross motor delay. However, dystonia and gaze abnormalities would not be expected, and bilirubin deposition does not occur in the corpus callosum.
(Choice C) Damage to the lateral temporal cortex, which is typically spared in BIND, usually affects receptive speech (ie, Wernicke area), and gross motor delays would not be seen.
(Choice D) Thiamine deficiency in adults with Wernicke-Korsakoff syndrome is associated with mammillary body damage that causes memory impairment, not motor dysfunction. BIND is not associated with damage to this area.
(Choice E) Occipital lobe damage, which does not occur in BIND, can lead to cortical blindness but does not explain this patient's abnormal movements and tone.
Educational objective:
Excess unconjugated bilirubin in the neonatal period, often caused by increased hemolysis, can cross the blood-brain barrier and deposit in the basal ganglia and brainstem nuclei. If inadequately treated, this can lead to chronic, irreversible neurologic dysfunction, including abnormal movements (eg, chorea, dystonia) and impaired vision and hearing.