Role of dopaminergic neurotransmission in pathophysiology of action tremor in Parkinson's disease

Background: Rest tremor (RT), a tremor that occurs in a body part that is completely supported against gravity, is together with rigidity and bradykinesia among the core features of Parkinson’s disease (PD). In addition to classical RT, many PD patients also have action tremor (AT) occurring during sustained postures or voluntary movement. Earlier studies showed a good correlation between striatal dopamine transporter (DAT) binding, measured with [123I] FP-CIT SPET and bradykinesia. By contrast, neither rigidity nor rest tremor seems to be closely related to the degree of dopaminergic denervation as measured by DAT imaging. Little is known about the relationship, if any, between the severity of action tremor and striatal DAT binding. Subjects and Methods: A cross-sectional study was conducted in 94 patients (57 men and 37 women) with Parkinson’s disease staging 1-2 on the Hoehn-Yahr scale. Data on the severity of action tremor and other motor signs were collected using the Unified Parkinson’s Disease Rating Scale part III. DAT imaging was performed after injection of 111-185MBq of 123I-FP-CIT. Images were visualized on Workstation Xeleris 3.0 (GE Healthcare) and reconstructed with dedicated software by a nuclear physician blinded about the clinical information of patients. Spearman correlation coefficient was performed to evaluate the relationship between putamen DAT binding and severity of bradykinesia, severity of rigidity, RT and AT respectively. Multivariable logistic regression analysis was used to assess the association between age, sex, disease duration, and levodopa equivalent daily dose and investigated variables after adjusting for possible confounders. Results: In this group of patients with early PD, DAT binding in the putamen significantly correlated with the severity of bradykinesia (Spearman r=-0.35, P<0.001) but not with the severity of rigidity (Spearman r=0.02, P=0.8), RT (Spearman r=0.05, P=0.6), or AT (Spearman r=-0.03, P=0.7). The findings were confirmed by multivariable regression analysis adjusted by age, sex, disease duration, and levodopa equivalent daily dose. Conclusion: Our study confirms the good correlation between putamen DAT binding and bradykinesia and the lack of correlation between putamen DAT binding and rigidity/RT. In addition, we failed to found any significant correlation between putamen DAT binding and severity of action tremor, which suggests a contribution of non-dopaminergic mechanisms to its pathophysiology