Patterns of dopamine transporter imaging in subtypes of multiple system atrophy

Acta Neurol Scand. 2018 Aug;138(2):170-176. doi: 10.1111/ane.12932. Epub 2018 Mar 24.

Abstract

Objectives: To investigate the differences in the pattern of striatal (caudate and putamen) dopamine transporter (DAT) loss in a multiple system atrophy (MSA) cohort, based on the clinical variants parkinsonian subtype (MSA-P) and cerebellar subtype (MSA-C) via (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11 C-CFT) positron emission tomography (PET) imaging.

Materials and methods: One hundred and six subjects (forty-one patients with probable MSA-P; forty patients with probable MSA-C; twenty-five healthy controls) underwent 11 C-CFT PET. Subregional 11 C-CFT uptake of bilateral caudate, anterior putamen, and posterior putamen was calculated respectively to measure the striatal dopaminergic function.

Results: Significant decrease in DAT binding in striatum was revealed in patients with MSA-C and MSA-P compared to normal controls (all regions, MSA-C vs controls, P < .0001; MSA-P vs controls, P < .0001). DAT reduction was more pronounced in MSA-P patients than that in MSA-C patients (all regions, P < .0001). Eleven of forty MSA-C patients displayed no DAT loss, whereas striatal DAT loss was evident in all MSA-P patients. MSA-P subtype showed a more obvious anteroposterior gradient of DAT loss and more asymmetric dopaminergic dysfunction compared to MSA-C patients.

Conclusion: The subtypes of MSA studied here show significantly different spatial/anatomic patterns of striatonigral degeneration which may provide insights into their disease pathophysiology. Specifically, MSA-P patients exhibit an uneven and much greater pronounced loss of dopamine innervation, while a relatively uniform pattern is revealed in patients with the MSA-C. Furthermore, the typical reduction in DAT 11 C-CFT binding in striatum is not present in all MSA-C patients, with a minority of cases showing normal DAT binding.

Keywords: 11C-CFT PET; dopamine transporters; multiple system atrophy; subtype.

MeSH terms

  • Adult
  • Aged
  • Carbon Radioisotopes
  • Corpus Striatum / diagnostic imaging*
  • Corpus Striatum / metabolism
  • Dopamine Plasma Membrane Transport Proteins / analysis*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple System Atrophy / diagnostic imaging*
  • Multiple System Atrophy / metabolism
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals

Substances

  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • SLC6A3 protein, human