Distinct clinical features of predominant pre-synaptic and trans-synaptic nigrostriatal dysfunction in multiple system atrophy

Abstract

Background: The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology.

Objective: To investigate the difference in clinical features between MSA patients with predominantly pre-synaptic nigrostriatal dysfunction and those with trans-synaptic nigrostriatal dysfunction.

Methods: We retrospectively analyzed clinical data of 61 patients with MSA who underwent both [¹⁸F]FP-CIT-PET and [¹⁸F]FDG-PET within 3 months of clinical evaluation, and who had ≤3 years of disease duration. Tracer uptake of the striatum on [¹⁸F]FP-CIT-PET and glucose metabolism of the striatum on [¹⁸F]FDG-PET were analyzed using eight striatal subregional volumes-of-interest templates. The patients were classified into two subgroups according to the predominant pre-synaptic tracer uptake loss of the posterior putamen on [¹⁸F]FP-CIT-PET (MSA-SNpc, n = 21) and trans-synaptic dopaminergic dysfunction reflected by both [¹⁸F]FP-CIT-PET and [¹⁸F]FDG-PET (MSA-STR, n = 40).

Results: Parkinsonian features were significantly more severe in the MSA-STR group than in the MSA-SNpc group (P = .005) and cerebellar ataxia was significantly more severe in the MSA-SNpc group (P = .036). The cerebellar type of MSA was significantly more common in the MSA-SNpc group (P = .001). There was no difference in age at onset, disease duration at the time of study, or Mini-Mental Status Examination scores between the groups.

Conclusions: Patients with MSA showed distinct clinical features depending on whether the pattern of nigrostriatal dysfunction was predominantly pre-synaptic or trans-synaptic.

Keywords: Cerebellar ataxia; Multiple system atrophy; Nigrostriatal integrity; Orthostatic hypotension; Parkinsonism.