The vesicular forebrain (pseudo-aprosencephaly): a missing link in the teratogenetic spectrum of the defective brain anlage and its discrimination from aprosencephaly

Two cases out of a sample of 41 fetuses and infants with prosencephalic mal formation, observed at the Institute of Pathology and Department of Neuropa thology of the University of Heidelberg, are described here in detail. Thes e cases presented grossly with microcephaly and missing forebrain, appearin g to be cases of aprosencephaly. However, in one of these cases glio-mesenc hymal membranes with an ependymal outline, consistent with the microscopic appearance of the dorsal sac membrane in holoprosencephaly and obviously re presenting remnants of a collapsed primitive prosencephalic vesicle, could be demonstrated. In the other case only hindbrain structures, with the exce ption of the cerebellum, were present without any demonstrable remnants of a prosencephalon. We propose that the microscopic specification of a primit ive prosencephalic vesicle in the first case and similar cases does not jus tify the diagnosis of atelencephaly/aprosencephaly because the prosencephal on was not really missing (pseudo-aprosencephaly). The prosencephalic anlag e had been formed but remained vesicular without further differentiation of a holospheric brain mantle as in common holoprosencephaly ('vesicular fore brain'), We believe that pseudo-aprosencephaly represents the most primitiv e form of holoprosencephaly, in which the forebrain remains as a complete s ac, linking classical holoprosencephaly with 'true' aprosencephaly, i.e., d efective prosencephalic anlage due to developmental arrest. The 'vesicular forebrain' allows one to extend the classification of Probst by an addition al category which might be termed complete sac category, intercalated betwe en the dorsal sac category and 'true' atelencephaly/aprosencephaly.