Chapter 7 - Cerebellar networks and neuropathology of cerebellar developmental disorders

Abstract

The cerebellar system is a series of axonal projections and synaptic circuits as networks, similar to those of the limbic system and those subserving the propagation and spread of seizures. Three principal cerebellar networks are identified and cerebellar disease often affects components of the networks other than just the cerebellar cortex. Contemporary developmental neuropathology of the cerebellum is best considered in the context of alterations of developmental processes: embryonic segmentation and genetic gradients along the three axes of the neural tube, individual neuronal and glial cell differentiation, migration, synaptogenesis, and myelination. Precisely timed developmental processes may be delayed or precocious rhombencephalosynapsis and pontocerebellar hypoplasia exemplify opposite gradients in the horizontal axis. Chiari II malformation may be reconsidered as a disorder of segmentation rather than simply due to mechanical forces upon normally developing hindbrain structures. Cellular nodules in the roof of the fourth ventricle are heterotopia of histologically differentiated but architecturally disoriented and disorganized neurons and glial cells; they often are less mature immunocytochemically than similar cells in adjacent normal folia. Cell rests are nodules of undifferentiated neuroepithelial cells. Both are frequent in human fetuses and neonates. Axonal projections from heterotopia to adjacent cerebellar folia or nuclei are few or absent, hence these nodules are clinically silent despite neuronal differentiation.