Objective: To evaluate the progression of posterior putamen dopaminergic denervation in relation to motor progression in the less affected and more affected side of the body (LAS and MAS) in early-stage Parkinson’s disease (PD).

Background: In PD, striatal dopaminergic denervation, quantifiable with 6-[18F]-fluoro-L-dopa (FDOPA) PET follows a posterior-to-anterior gradient, with the most significant deficit in the posterior putamen, contralateral to the MAS.

Method: Untreated PD patients with focal motor signs aged under 65 years, within the first year of diagnosis, were evaluated with the MDS-UPDRS III and FDOPA PET. Follow-up assessments were conducted at 2 and 5 years.

In the FDOPA PET, the Ki values of the posterior putamen corresponding to the MAS and LAS were quantified for each patient.

The MAS and LAS clinical involvement of each patient were calculated with the lateralized score of the MDS-UPDRS III. 

All comparisons were made using the Wilcoxon test.

We investigated the DaTscan results of the Parkinson’s Progression Markers Initiative (PPMI) database as an external validation of our results.

Results: Fifty-four patients were recruited, with 23 and 8 patients completing follow-up visits at 2 and 5 years, respectively.

Both sides showed a decline in posterior putamen Ki values over time. While MAS and LAS had different values at baseline and at the 2-year follow-up (p-values<0.001 and 0.04, respectively), at the 5-year follow-up, LAS and MAS were similar (p-value=0.16). Also, LAS at the 5-year follow-up had a greater denervation compared to MAS baseline levels (p-value=0.047).

Similar trends were observed in the PPMI database.

MDS-UPDRS III scores for MAS and LAS increased over time, with LAS scores remaining lower than MAS scores, even when comparing LAS at 5 years with MAS at baseline (p-value<0.001).

Conclusion: While the clinical manifestations of PD are thought to be mainly and directly related to the degree of dopaminergic striatal denervation, our results show a clinico-dopaminergic mismatch, where, despite similar or greater dopaminergic denervation, LAS showed less clinical progression compared to MAS. This phenomenon needs further investigation to understand its underlying mechanisms, that could be due to different selective vulnerability between the 2 hemispheres, or to more efficient compensatory mechanisms.

Further validation through comparison with the PPMI database is underway.

MDS-UPDRS III and Posterior Putamen (MAS & LAS)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-denervation-and-focal-motor-progression-in-early-parkinsons-disease-a-5-year-longitudinal-study/