Hypothesis: By-products of vascular disruption carried in the CSF affect prenatal brain development.

Prenatal CNS disruptions can be associated with physically separate findings. Examples include cognitive issues in septo-optic dysplasia and sporadic and WNT1-related unilateral cerebellar hypoplasia, and physical findings such as thinning of the corpus callosum, ventriculomegaly, hippocampal abnormalities, olfactory tract and bulb hypoplasia, and distant cortical dysplasias with schizencephaly. Similar effects to toxicities with intraventricular hemorrhage in prematurity could occur earlier in development. CSF transportation of disruption by-products would provide access to vulnerable areas through inflammatory effects on blood-brain barrier permeability. Outcomes are influenced by location and volume of byproducts in the CSF, timing, transport, and inflammatory responses. A particular association of vermis disruption with cognitive issues may be related to CSF flow distortions that avoid toxin dilutions in the third ventricle. Symmetrical contralateral cortical dysplasia with schizencephaly may reflect immunovascular field-related vulnerabilities seen in situations such as vitiligo.