Objective: To clarify how dopaminergic denervation occurs along the dorsoventral axis of the posterior putamen in the earliest stages of PD.

Background: Dopamine loss in Parkinson’s disease (PD) affects most intensely the mesostriatal system. Early in the evolution, the topography of dopaminergic striatal denervation follows a posterior‑anterior gradient, being the caudal (posterior) putamen the earliest and most depleted area. A dorso-ventral gradient for denervation has also been suggested, with predominant dorsal depletion. This would correspond mainly with the lower limb somatotopic representation and would imply that motor onset should principally be by the lower limb.

Method: Early drug‑naive PD patients (n=23) and healthy subjects (HS) (n=19) underwent fluorodopa (FD) examination in a hybrid PET‑MR system (mMR‑Biograph 3T Siemens). FD uptake rate was estimated using Patlak graphical method and averaged within task fMRI‑based subdivision for foot and hand putaminal motor activations from the Human Connectome Project dataset. Unpaired 2‑sample t‑test and paired t-test were used for between and within group statistics respectively. FD uptake rates were further averaged slice-wise in the dorsoventral direction and Z-scores were estimated for PD patients with respect to HS group.

Results: FD uptake differed between HS and PD patients for both foot and hand fMRI-based ROIs in both more affected (MAS) and less affected sides (LAS) (P<0.001). The percentage of depletion for the hand putaminal region was significantly higher than that of the foot in both MAS (68.9 vs 60.2; P<0.001) and LAS (49.0 vs 43.9; P<0.001). Slice-wise analysis revealed an overall denervation with a focal onset of depletion peaking at the center of the hand functional territory in the MAS. This pattern was also recognized, albeit less strikingly, in the LAS. FD uptake rates in upper- and lower-limbs functional areas were highly correlated (rMAS=0.87; rLAS=0.87) suggesting a similar decline for both territories. No correlations were found between the uptake rates for any putaminal somatotopically defined and the MDS-UPDRS III items.

Conclusion: The largest depletion was found in the territory corresponding to the functional representation of upper limbs. These results might indicate that there is a specific dopaminergic vulnerability for the upper‑limbs striatal representation in the early stages of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-denervation-in-de-novo-parkinsons-disease-does-functional-somatotopy-plays-a-role/