Objective: The aim of the present study is to clarify correlation between motor deficits and dopaminergic neuronal loss in advanced Parkinson’s disease (PD).

Background: Series of clinical studies in PD reported that loss of dopaminergic terminals in the dorsal putamen correlate with motor symptoms. However, pathological findings demonstrated that dopamine fibers in the dorsal putamen are almost absent by 4-5 years post-diagnosis while motor symptoms still continue to deteriorate beyond that period. Here, we investigate clinical correlation between neuronal loss and motor deficits in patient with advanced PD. The loss of striatal dopaminergic terminals were evaluated using presynaptic dopamine transporter tracer, 123I-FP-CIT. The density of nigral dopaminergic cell bodies were also assessed by neuromelanin MRI imaging becausepost-mortem findings showed loss of nigral melanized neurons lags behind the loss of dopaminergic markers in the dorsal putamen, with more gradual loss in the first decade and thereafter.

Method: We recruited 45 patients with advanced PD (disease duration ≧5 years: age 66.5±8.2). Motor symptoms were measured by MDS-UPDRS part Ⅲ score during practically defined off state. The binding ratio of 123I-FP-CITwas quantified by DaTQUANT software. Neuromelanin MRI imaging was acquiredand the contrast-to-noise ratio (CNR) of the substantia nigra (SN) and pontine region was calculated. Regression analysis was performed to evaluate the associations of MDS-UPDRS part Ⅲ score ofwith the binding ratioof striatal123I-FP-CIT uptake and withCNR of the SN.

Results: Correlation between the MDS-UPDRSpart Ⅲscore (41.7 ± 14.3) andthe binding ratioof striatal123I-FP-CITuptake (0.69 ± 0.21)did not reach significant level (r = 0.24, P = 0.09). Negative correlation between MDS-UPDRS part Ⅲ score and CNR of the SN(1.19 ± 0.03) was significant (r= 0.37, P < 0.05).

Conclusion: These results suggest that severity of motor symptoms in advanced PD is associated with the degree of damage in nigral dopaminergic cell bodies assessed by neuromelanin MRI imaging rather than the degree of loss of striatal dopaminergic terminals evaluated with presynaptic dopamine transporter tracer.

References: Jeffrey H. Kordower, C. Warren Olanow, Hemraj B. Dodiya et al. Brain.2013:136 2419-2431.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/imaging-biomarker-for-progression-of-motor-symptoms-in-advanced-parkinsons-disease/