Olivopontocerebellar pathology in multiple system atrophy

Abstract

Olivopontocerebellar atrophy (OPCA) is widely accepted as part of the neuropathological spectrum of multiple system atrophy (MSA). The distribution of affected sites in the olivopontocerebellar (OPC) system and their interrelationship remain poorly understood due to lack of quantitative studies. To further investigate the OPC pathology in MSA, we performed a morphometric analysis of 20 MSA cases and eight healthy controls. In the MSA cases, mean neuronal cell densities were significantly reduced in (medial and dorsal) accessory and principal inferior olives, pontine nuclei, cerebellar vermis (except nodulus), and hemispheres. Inferior olives and pontine nuclei were more severely affected than cerebellar Purkinje cells in most cases. Cerebellar Purkinje cells were more severely depleted in vermis rather than in hemisphere. There was a poor topographic correlation between neuronal cell loss in inferior olives and cerebellar cortex. These results suggest a primary degeneration of olivopontine nuclei and cerebellar Purkinje cells in OPCA. Inferior olives, pontine nuclei and cerebellar cortex were all significantly more severely affected in cases with a pure or predominating cerebellar syndrome (OPCA type, n = 4) compared to those with pure or predominating parkinsonism (SND type, n = 14). However, although cerebellar signs had been noted in life in only six cases, morphometry revealed OPCA in 17 of the 20 MSA brains.

Patterned Purkinje cell degeneration in mouse models of Niemann‐Pick type C disease

“…In particular, the nodular zone, and especially lobule X, is resistant to the insult and shows limited cell loss. Sparing of cell loss within the NZ has also been described in other diseases, including X-chromosome-linked copper malabsorption (Iwata et al, 1979), multiple systems atrophy (Kume et al, 1991;Wenning et al, 1996), and spinocerebellar ataxia 6 (Yang et al, 2000). This resistance may not be due to the zebrin II-immunoreactive phenotype.…”

Heat shock protein 25 expression and preferential Purkinje cell survival in the lurcher mutant mouse cerebellum

“…For example, in the acid sphingomyelinase knockout mouse, the pattern of Purkinje cell degeneration mirrors that seen in the ϩ/Lc: Purkinje cells died in the AZ and PZ and surviving Purkinje cells were seen in the CZ and NZ (MacCauley et al, 2008). Purkinje cells in the NZ also appear to be spared in disease models such as prion disease (PrP null mice: Rossi et al, 2001) and multiple system atrophy (Kume et al, 1991;Wenning et al, 1996).…”

Mapping of Purkinje Neuron Loss and Polyglucosan Body Accumulation in Hereditary Cerebellar Degeneration in Scottish Terriers

“…In humans and rodent models, some disorders have been described in which there is differential loss of Purkinje neurons in the hemispheres versus the vermis, although the reasons for this differential loss are unknown. 27,42 In Scottish Terriers, there was no evidence of differential loss of Purkinje neurons between the vermis and hemispheres, and the significance of the dorsoventral gradient of Purkinje neuronal loss is unclear. Attempts to correlate the degree of neuronal loss with the severity of neurological signs were not made because there was no opportunity to accurately quantify their neurological signs at time of euthanasia.…”