A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy.

Abstract

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by the presence of neuronal and oligodendroglial alpha-synuclein aggregates. To investigate the relationship between the occurrence of neuronal cytoplasmic and intranuclear inclusions (NCIs and NNIs, respectively) and the progression of neuronal degeneration, we performed a quantitative analysis of the pontine and inferior olivary nuclei based on 14 cases of MSA. alpha-Synuclein immunohistochemistry revealed that NCIs and NNIs were present in both brain nuclei in all the cases. The average incidence of NCIs in the pontine and inferior olivary nuclei was 9.1% and 25.8%, respectively, and that of NNIs was 9.2% and 9.0%, respectively. The number of NNIs was strongly correlated with that of neurones in the pontine and inferior olivary nuclei. Although the number of NCIs was not correlated with the neuronal population in both nuclei, the NCI count in patients with moderate MSA was higher than in patients with mild MSA. The NNI count was much higher than the NCI count in the pontine nucleus in four patients, and was the same in the olivary nucleus in three of the four patients. Moreover, the neuronal population in the NNI-predominant cases was significantly higher than in the NCI-predominant cases. These findings suggest that NCI formation is accelerated by the progression of the disease process, and that in MSA, NNI formation is an earlier phenomenon than NCI formation.