The Human Cerebellum as a Semaphore for Neuropathology

The cerebellum has intricate connections either directly or indirectly with most levels of the brain. While many of these are functionally relevant, prominent neuropathologic changes that reflect the underlying anatomy arise from injury to a few major pathways. Identifying these pathologic sequelae can help to identify the cells involved in the underlying disease. The cerebellum has two distinct components: the aesthetically pleasing cortical dendritic folia and the deep nuclei. The uniform and monotonous cerebellar cortex contains molecular, Purkinje, and granular layers. Several deep nuclei are the main efferent projections from the cerebellum. Key neuron types relevant to cerebellar pathology include the cortical excitatory granular input and inhibitory Purkinje output neurons, the deep nuclear excitatory projection neurons, as well as key afferent nuclei (eg, inferior olivary, pontine, and sensory neurons) and efferent targets (eg, red nucleus, thalamus). Pathologic processes that affect one or more of these neuron groups lead to stereotypic anatomical changes, which in turn signal the existence of those processes. This article first reviews key aspects of human cerebellar anatomy and histology, then discusses some key connections, and finally presents a selection of cases from humans that illustrate these interconnections.