Failure of prosencephalic unfolding and neuronal migration in acardia

Acardia is a fatal complication of twin pregnancy. It is caused by a retrograde flow of arterial blood from a "pump" into an acardiac twin through placental arterial and venous connections. The heart function of the recipient twin is either blocked or insufficient to support perfusion of the upper body. Severe developmental anomalies ensue. While most acardiacs are anencepahalic, a few twins with a rudimental heart ("hemicardiac") are able to support a variably complex brain. Here we report three cases of hemicardiac twinning with neuronal migrational defects. The most severe abnormalities affected the supratentorial compartment. They can be conceptually divided in two groups. The first, which we tentatively linked to agenesis of the choroid plexus, can be described as a failure of prosencephalic unfolding. The resulting defects included collapsed neocortex, agenesis of the hippocampi and scrambled basal ganglia and diencephalon. The second group of lesions can be theoretically deduced to a result of disruption of the glia-pial boundary with subsequent formation of leptomeningeal heterotopia and zona cerebrovasculosa. Our observations highlight that even in the milieu of a normal genetic background, severe restriction of brain perfusion could lead to neuronal migration defects. Our data also show that adequate unraveling of the brain architecture is crucially dependent on both the parenchymal vascularization and production of the cerebrospinal fluid by the choroid plexus.