eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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vol. 53
Original paper

Quantitative pathological changes in the cerebellum of multiple system atrophy

Richard A. Armstrong

Folia Neuropathol 2015; 53 (3): 193-202
Online publish date: 2015/09/29
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Multiple system atrophy (MSA) is a rare neurodegenerative disorder associated with parkinsonism, ataxia, and autonomic dysfunction. Its pathology is primarily subcortical comprising vacuolation, neuronal loss, gliosis, and -synuclein-immunoreactive glial cytoplasmic inclusions (GCI). To quantify cerebellar pathology in MSA, the density and spatial pattern of the pathological changes were studied in -synuclein-immunolabelled sections of the cerebellar hemisphere in 10 MSA and 10 control cases. In MSA, densities of Purkinje cells (PC) were decreased and vacuoles in the granule cell layer (GL) increased compared with controls. In six MSA cases, GCI were present in cerebellar white matter. In the molecular layer (ML) and GL of MSA, vacuoles were clustered, the clusters exhibiting a regular distribution parallel to the edge of the folia. Purkinje cells were randomly or regularly distributed with large gaps between surviving cells. Densities of glial cells and surviving neurons in the ML and surviving cells and vacuoles in the GL were negatively correlated consistent with gliosis and vacuolation in response to neuronal loss. Principal components analysis (PCA) suggested vacuole densities in the ML and vacuole density and cell losses in the GL were the main source of neuropathological variation among cases. The data suggest that: (1) cell losses and vacuolation of the GCL and loss of PC were the most significant pathological changes in the cases studied, (2) pathological changes were topographically distributed, and (3) cerebellar pathology could influence cerebral function in MSA via the cerebello-dentato-thalamic tract.

multiple system atrophy, cerebellum, vacuolation, -synuclein, spatial pattern

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