Links Between Abnormal Brain Structure and Cognition in Holoprosencephaly

Abstract

Converging information on medical issues, motor ability, and cognitive outcomes is essential when addressing long-term clinical management in children with holoprosencephaly. This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance. Additionally, a cognitive profile was described using the Carter Neurocognitive Assessment, an experimental diagnostic instrument designed specifically for young children with severe neurodevelopmental dysfunction. Findings indicated that nonseparation of the deep gray nuclei was significantly associated with the cognitive construct of vocal communication, but not with the cognitive constructs of social awareness, visual attention, or auditory comprehension. Importantly, motor skill deficits did not significantly affect performance on the Carter Neurocognitive Assessment. This study is the first investigation to provide a descriptive overview of specific cognitive skills in this group of children. The results also strongly suggest that this feature of the brain's structure does not predict all aspects of neurodevelopmental function. These findings contribute a critical component to the growing body of knowledge regarding the medical and clinical outcomes of children with holoprosencephaly.

Microcephaly with simplified gyral pattern

“…Further, abnormal configuration of the basal ganglia is a well-established associated brain anomaly in holoprosencephaly. 23,24 In our sample, it is interesting to note that all infants with an abnormal pons also had an abnormal cerebellum, which might be explained by smaller pontocerebellar tracts. None of the associated abnormalities were present in the control infants, whereas they were found in 10 of 12 patients, underlining the ability of our scoring system to reliably distinguish normal from abnormal.…”

Holoprosencephaly: A guide to diagnosis and clinical management

“…The severe motor impairment observed in alobar and semilobar holoprosencephaly is less frequently seen in the lobar type and the middle interhemispheric variant; patients with the latter forms may walk with assistance, adequately control their limbs, and even speak words or sentences [37]. The enhanced vocal communication in these patients may be explained by more complete separation of the deep gray nuclei, but because separation of the deep gray nuclei does not appear to correlate with social awareness, visual attention, and auditory comprehension, differences in those constructs may be caused by structural changes in different regions [38]. The Carter Neurocognitive Assessment (CNA) may be useful to clinicians for assessing cognitive function in children with more severe impairment [38].…”

“…The enhanced vocal communication in these patients may be explained by more complete separation of the deep gray nuclei, but because separation of the deep gray nuclei does not appear to correlate with social awareness, visual attention, and auditory comprehension, differences in those constructs may be caused by structural changes in different regions [38]. The Carter Neurocognitive Assessment (CNA) may be useful to clinicians for assessing cognitive function in children with more severe impairment [38]. …”

Audiological chronological findings in children with congenital anomalies of the central nervous system

“…SIX3 has been found to be associated with HPE. Most children with HPE have severe motor impairment and little expressive language ability [16][17][18][19]. Antoneli et al showed that patients with alobar HPE had abnormalities in ABRs represented by increased interwave latencies in addition to those with absent waves, whereas patients with lobar HPE had normal ABRs [20].…”