Midline cerebral dysgenesis, dysfunction of the hypothalamic-pituitary axis, and fetal alcohol effects
C. L. Coulter, R. W. Leech, G. B. Schaefer, B. W. Scheithauer and R. A. Brumback
Department of Neurology, Creighton University, Omaha, NE 68131.
OBJECTIVE--Neuropathologic evaluation was performed on an infant with fetal
alcohol effects. DESIGN--Coronal brain sections and representative tissue
blocks stained with hematoxylin-eosin, silver stain, and immunocytochemical
stains for hypothalamic and pituitary hormones were evaluated for
neuropathologic abnormalities. PATIENT--A 2.5-month-old American Indian
girl who had been exposed to first-trimester maternal binge alcohol abuse
died after persistent problems of growth failure, sodium imbalance,
aberrant temperature regulation, respiratory distress, and seizures.
RESULTS--Autopsy revealed severe microcephaly, hypertelorism, midfacial
hypoplasia, a high-arched palate, shortened palpebral fissures, and a small
brain. The frontal lobes were fused anteriorly; olfactory bulbs and tracts
were absent; and optic nerves were hypoplastic. An enlarged and bulbous
hypothalamus obscured the pituitary gland. The thalamus and caudate nuclei
were fused across the midline. Posteriorly, the single ventricle split to
form rudimentary lateral horns. The anterior corpus callosum, septum
pellucidum, fimbria, and fornices could not be identified. The anterior
commissure and supraoptic nuclei were microscopically present. Many
Purkinje cells were horizontally positioned, with abnormal dendritic
structure. The posterior pituitary lobe was absent, and the infundibulum
was flanked by a hypoplastic adenohypophysis and a large subarachnoid
heterotopia. Immunocytochemical studies identified only vasopressin and
neurophysin in the hypothalamus and only growth hormone and prolactin in
the pituitary gland. CONCLUSION--To our knowledge, an association between
fetal alcohol effects and a complex cerebral anomaly with features of
incomplete holoprosencephaly and septo-optic dysplasia has not previously
been reported and suggests a possible common pathogenesis needing further
study.
