Microgyria and cytomegalic inclusion disease in infancy.

Many different malformations of the central nervous system can now be produced in the offspring of animals exposed during pregnancy to x rays, drugs, and dietetic deficiency or excess of vitamins, but proof of environmental causation of analogous human conditions is understandably scarce. Occasional neural, somatic, or gonadal maldevelopment has been reported after the administration to pregnant women of aminopterin maternal rubella and ionizing radiation remain the only widely known extrinsic causes of human embryopathy. Hence the importance of the suggestion that another, probably infective, condition, cytomegalic inclusion disease, may be also responsible for neural malformation (Diezel, 1954). It has been known for some time that the brain is one of the organs which may display the characteristic inclusions of cytomegalic inclusion disease. Haymaker, Girdany, Stephens, Lillie, and Fetterman (1954) collected seven such cases in the literature and added one of their own. In addition to the inclusions, some of these brains showed hydrocephalus, periventricular calcifica-tion, focal softening, haemorrhages, astrocytic proliferation, perivascular inflammatory infiltration , and ependymal granulations. These are, of course, evidence of neural disease, but not necessarily of malformation. Diezel was the first to report the association of cytomegalic inclusion disease with microgyria, or micropolygyria. Microgyria is a true cerebral malformation characterized by an excess of small abnormally formed gyri (Crome, 1952). Histological and embryological considerations suggest that the cause of this condition operates before the sixth month of foetal development. The patient described by Diezel was an infant weighing 2,500 g. at birth who developed neonatal jaundice, ascites with hepatomegaly, and splenomegaly, and died at 24 days. Inclusion bodies were found in the kidneys, liver, and brain. The brain weighed 130 g. and showed microgyria of the neocortical areas. Necrosis was present in the medial basal regions of both temporal lobes and in the cerebellum. The optic nerves were atrophic, there was marked hydrocephalus, and the corpus callosum was thin. On microscopy, the necrotic areas showed infiltration by lymphocytic and plasma cells with many compound granular corpuscles, macrophages, and calcified particles. The olfactory nerves were the seat of marked inflammatory change. Typical inclusions of cytomegalic inclusion disease were seen in the leptomeninges, ependymal, and glial cells, as well as in some of the undifferentiated matrix cells arranged in numerous dense periventricular foci. The only mature neurons to show inclusions were a few Purkinje cells, found after prolonged search. Architectonically, the palaeocortex and archicortex were normal and the …