Hyperbilirubinemia: Subcortical Mechanisms of Cognitive and Behavioral Dysfunction

Are the neuromotor disabilities of bilirubin-induced neurologic dysfunction disorders related to the cerebellum and its connections?

“…1) and cerebellar roof nuclei, is an equally consistent feature of kernicterus [4,5]. With few exceptions [13,17], however, cerebellar lesions have not featured prominently in discussions of bilirubin-induced neurodevelopmental sequelae; their involvement, under-recognized perhaps because injury to other regions dominate the neurophenotype in classic kernicterus. As suggested by Koziol et al [13], and further detailed below, this may not be the case in BIND.…”

“…Isolated disturbances of central auditory processing are also included in the spectrum of BIND [1,2]. A putative association between postnatal hyperbilirubinemia and an increased risk of cognitive dysfunction (e.g., lower intelligence quotient) and a range of neuropsychiatric syndromes, including attention deficit-hyperactivity disorder, autism, and schizophrenia, has also been alleged [1,2,6,[9][10][11][12][13]. As such, these conditions might also be manifestations of BIND [2,9,13].…”

“…A putative association between postnatal hyperbilirubinemia and an increased risk of cognitive dysfunction (e.g., lower intelligence quotient) and a range of neuropsychiatric syndromes, including attention deficit-hyperactivity disorder, autism, and schizophrenia, has also been alleged [1,2,6,[9][10][11][12][13]. As such, these conditions might also be manifestations of BIND [2,9,13]. However, as with subtle kernicterus, the linkage between hyperbilirubinemia and their genesis remains uncertain and a source of continued study and debate [1,2,6,[9][10][11][12][13][14][15][16][17][18][19].…”

“…As such, these conditions might also be manifestations of BIND [2,9,13]. However, as with subtle kernicterus, the linkage between hyperbilirubinemia and their genesis remains uncertain and a source of continued study and debate [1,2,6,[9][10][11][12][13][14][15][16][17][18][19].…”

“…Investigators have hypothesized a range of subcortical neuropathologies in the genesis of cognitive and behavioral dysfunctions associated with moderate hyperbilirubinemia [13,17]. Koziol et al [13] provide a masterful, comprehensive summary of this topic. The current review builds on this line of speculation with a focus on the cerebellum and its connections in the development of the subtle neuromotor disabilities of BIND.…”