Vertical Gaze Palsy in Kernicterus

Vertical gaze palsy, together with extrapyramidal abnormalities, neurosensorial hearing loss, and dental enamel dysplasia, is a core feature of kernicterus spectrum disorders (KSD).[1] However, gaze disturbances in children with KSD have been rarely documented in literature.[2] We report a 12-year-old boy with neonatal hyperbilirubinemia (gestational age 37 weeks, maximum bilirubin level 410.4 µmol/L at 5 days of life), who developed a dyskinetic cerebral palsy with mild intellectual disability. The boy presents a vertical saccade palsy mainly affecting upward gaze, with minor involvement of vertical smooth pursuit movements ([Video 1]). Brain magnetic resonance imaging (MRI; performed at 3 years) revealed mild signal changes in the globi pallidi ([Fig. 1]). Brainstem auditory evoked potentials’s (BAEPs) alteration suggested auditory neuropathy.

Video 1.

Ocular motility examination. Vertical smooth pursuit movements are partially limited in upward direction. Both verbally-guided and visually-guided saccades are impaired in the vertical plane, especially in the upward direction. To facilitate the initiation of saccades, synkinetic blinking is used as an adaptive strategy.

Fig. 1 Mild signal hyperintensity in axial (A) and coronal (B) T2-weighted brain MRI. White arrows indicate globi pallidi. Symmetric hyperintense signal abnormalities of globi pallidi and subthalamic nuclei on T1-weighted images are the typical neuroimaging findings of acute neonatal bilirubin encephalopathy. These abnormalities usually disappear 1 to 3 weeks after the acute event. In the chronic phase, T2- and FLAIR-hyperintensities of the globi pallidi are the most frequent finding.[5] FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging.

Brainstem nuclei are especially vulnerable to bilirubin neurotoxicity,[3] while vertical gaze palsy is expected to be the consequence of an injury of the rostral interstitial nucleus of the median longitudinal fascicle, in the upper pole of the red nucleus, located in the rostral midbrain.[4]

The nonprogressive course and normality of metabolic workup (plasma oxysterols, lysosphingolipids, amino acids, acylcarnitine, creatine and guanidine acetate, and urinary organic acids) argue against different etiologies.

Vertical gaze disturbances are a diagnostic clue in patients with dyskinetic cerebral palsy, strongly suggesting KSD.

• References

• 1 Przekop A, Sanger TD. Birth-related syndromes of athetosis and kernicterus. Handb Clin Neurol 2011; 100: 387-395
• 2 Hoyt CS, Billson FA, Alpins N. The supranuclear disturbances of gaze in kernicterus. Ann Ophthalmol 1978; 10 (11) 1487-1492
• 3 Le Pichon J-B, Riordan SM, Watchko J, Shapiro SM. The Neurological Sequelae of Neonatal Hyperbilirubinemia: Definitions, Diagnosis and Treatment of the Kernicterus Spectrum Disorders (KSDs). Curr Pediatr Rev 2017; 13 (03) 199-209
• 4 Yilmaz Y, Alper G, Kiliçoglu G, Celik L, Karadeniz L, Yilmaz-Değirmenci S. Magnetic resonance imaging findings in patients with severe neonatal indirect hyperbilirubinemia. J Child Neurol 2001; 16 (06) 452-455
• 5 Bosemani T, Anghelescu C, Boltshauser E. , et al. Subthalamic nucleus involvement in children: a neuroimaging pattern-recognition approach. Eur J Paediatr Neurol 2014; 18 (03) 249-256