Inflammatory pathogenesis of cortical polymicrogyria: an autopsy study

Polymicrogyria, a cortical abnormality usually classified among neuron migration disorders, is characterized by different etiologies and pathogeneses. Recently, it has been proposed that polymicrogyria could be acquired as a consequence of a lasting damage to the developing brain. In this study, we test the hypothesis that an infection in the fetal adnexa may give rise to distant brain defects and eventually polymicrogyria. Thirty-two fetuses spontaneously aborted for extensive ascending chorioamnionitis at 15-26 wk of gestation were evaluated. Control subjects were represented by 8 fetuses aborted at 15-24 wk of gestation. A complete autopsy was carried out between 4 and 12 h after fetal expulsion. We found different histologic alterations in the primitive cortical architecture, both isolated and combined (undulation of the cortical ribbon, untimely cortical folding/molecular layer fusion, and neuronal loss). A total of 25 cases presented one or more of the above-described morphologic alterations in the brain (78%). On the contrary, similar alterations were never observed in any of the control brains (p=0.019). Our findings indicate that chorioamnionitis significantly impairs brain cortex morphogenesis. Such neuron damage may be caused by an unspecific, indirect mechanism of injury to the developing cortex involving hypoxia and free radical generation. The reported brain abnormalities may even evolve into polymicrogyria in surviving fetuses.