Assessment of the deep gray nuclei in holoprosencephaly

BACKGROUND AND PURPOSE: Although holoprosencephaly has been known for many years, few detailed analyses have been performed in a large series of patie nts to outline the range of morphology in this disorder, particularly regar ding the deep gray nuclear structures, We reviewed a large patient cohort t o elucidate the combinations of morphologic aberrations of the deep gray nu clei and to correlate those findings with recent discoveries in embryology and developmental neurogenetics, METHODS: A retrospective review of the imaging records of 57 patients (43 M R studies and 14 high-quality CT studies) to categorize the spectrum of dee p gray nuclear malformations, The hypothalami, caudate nuclei, lentiform nu clei, thalami, and mesencephalon were graded as to their degree of noncleav age, Spatial orientation was also evaluated, as was the relationship of the basal ganglia to the diencephalic structures and mesencephalon, The extent of noncleavage of the various nuclei was then assessed for statistical ass ociation, RESULTS: In every study on which it could be accurately assessed, we found some degree of hypothalamic noncleavage. Noncleavage was also common in the caudate nuclei (96%), lentiform nuclei (85%), and thalami (67%), Complete and partial noncleavage were more common in the caudate nuclei than in the lentiform nuclei. The degree of thalamic noncleavage was uniformly less tha n that in the caudate and lentiform nuclei. Abnormalities in alignment of t he long axis of the thalamus were seen in 71% of cases, and were associated with degree of thalamic noncleavage; 27% of patients had some degree of me sencephalic noncleavage, CONCLUSION: The hypothalamus and caudate nuclei are the most severely affec ted structures in holoprosencephaly, and the mesencephalic structures are m ore commonly involved than previously thought in this "prosencephalic disor der." These findings suggest the lack of induction of the most rostral aspe cts of the embryonic door plate as the cause of this disorder.