An Unusual Malformation of the Forebrain and Concomitant Destructive Encephalopathy with Calcifications

Abstract

A 9-year old boy with profound mental retardation and severe neurologic deficit presented an unusual malformation of the forebrain distinguished by the following features: 1) microtelencephalon, alobulation, afissuration, and abnormal convolutional pattern; 2) persistence of hippocampal formation at its embryonic site in the dorsomedial wall of the telencephalon; 3) hypoplasia and abnormal configuration of ventricles; 4) agenesis of cerebral commissures; and 5) abnormal location and orientation of gray structures. Important concomitant findings characterized by severe destructive lesions, massive calcification, granular ependymitis, and low grade inflammation were suggestive of late sequelae of an infectious process, possibly congenital. Transplacental transmission of an unidentified pathogen with teratogenic properties was hypothesized as the probable cause. The teratogenic insult started in an early embryonic period and affected primarily the development of the neopallium in the telencephalic wall. The arrested development of the neopallium disrupted the chain of interdependent developmental events; consequently characteristic morphological modifications normally induced by the continuous growth and differentiation of the neopallium failed to occur or took an abnormal course. The name architelencephalon (Greek: arche, beginning; telencephalon, cerebral hemispheres) proposed for this particular malformation of the forebrain indicates its resemblance both to the human brain at early stages of development and also to mammalian brains on a lower level of phylogeny. Associated anomalies included an unilateral microphthalmia with cataract, severe stenosis of the aqueduct of Sylvius and macrocephaly. The microphthalmia was either a developmental anomaly or was infectious in origin. The stenosis of the aqueduct was attributed to granular ependymitis. Tearing of the thin dorsal diencephalic plate and arachnoid membrane and escape of the cerebrospinal fluid into the subdural space probably accounted for the macrocephaly.