Topography of Dopamine Transporter Availability in the Cerebellar Variant of Multiple System Atrophy

Voxel-wise comparison of [¹²³I]-2β-carbomethoxy-3beta-(4-iodophenyl)tropane ([¹²³I]β-CIT) radioligand distribution measured by single-photon emission computed tomography (SPECT) revealed distinct patterns of reduced dopamine transporter (DAT) availability in the Parkinson's variant of MSA (MSA-P). The aim of this study was to identify the monoamine transporter distribution pattern in patients with the cerebellar variant of MSA (MSA-C). Additionally, monoamine transporter availability was investigated in a small cohort of patients with sporadic adult-onset ataxia (SAOA).

[¹²³I]β-CIT SPECT was performed in patients with MSA-C (n = 12), MSA-P (n = 14), SAOA (n = 5), and controls (n = 15) matched for age. Parametric images of [¹²³I]β-CIT binding potential (BP_ND) were generated and analyzed by statistical parametric mapping (SPM) and region of interest (ROI) analysis.

SPM localized significant reductions of [¹²³I]β-CIT BP_ND in the striatum, midbrain, and pons in MSA-C compared to controls. When compared with MSA-P, the striatal DAT decline was significantly less affected in MSA-C. ROI analysis revealed reductions of striatal and midbrain [¹²³I]β-CIT binding in MSA-C compared to SAOA, whereas no significant difference was apparent between the SAOA and control groups.

Midbrain and pontine monoaminergic transporter binding was severely impaired in MSA-C, matching the underlying pathological features. Striatal DAT availability was relatively less affected in MSA-C compared to MSA-P, reflecting measureable, but less-profound, degeneration of the nigrostriatal dopaminergic projections. Preliminary results of reduced striatal and midbrain [¹²³I]β-CIT binding in MSA-C, compared to SAOA, suggest that the potential of DAT-SPECT as a surrogate marker in the diagnostic workup of patients with adult-onset cerebellar ataxia should be further investigated.