Cerebral Perfusion and Motor Deficits in Drug-Induced Parkinsonism: A Dual-Phase ¹⁸F-FP-CIT PET Study

Drug-induced parkinsonism (DIP) is the second most common cause of parkinsonism after Parkinson disease (PD). It is crucial to diagnose DIP in patients presenting with parkinsonian symptoms because discontinuation of the offending drug can improve parkinsonism. However, the detailed pathophysiology of parkinsonism related to striatal dopamine receptor blockade and disease-specific cerebral changes remains unclear.

In this cross-sectional study, we recruited patients with DIP who underwent the Unified Parkinson's Disease Rating Scale (UPDRS) assessment, brain MRI, and dual-phase ¹⁸F-FP-CIT PET. The offending drugs were gastrointestinal prokinetics (DIP_GI) and antipsychotics (DIP_AP). In addition, we enrolled early and drug-naïve patients with PD and healthy controls (HCs). We compared early-phase ¹⁸F-FP-CIT uptakes between DIP, PD, and HC groups and investigated its association with the UPDRS part III total score. We calculated the DIP-related perfusion patterns using W-scores, compared their expression among groups, and analyzed their diagnostic performance. Age at PET scan, sex, and vascular risk factors were included as covariates.

Compared with patients with PD (n = 160, mean age 68.9 ± 7.9 years; 74 men), the DIP group (n = 72, mean age 67.9 ± 12.9 years; 25 men) exhibited more profound hyperperfusion in the motor-related brain circuit and prominent hypoperfusion in widespread brain regions except for the occipital cortex than HCs (n = 62, mean age 66.9 ± 9.0 years; 25 men). In particular, the DIP_GI group (n = 23) showed relative hypoperfusion in the lateral prefrontal, insular, inferior parietal, and cingulate cortices. In the DIP group, UPDRS part III total score was not correlated with striatal dopamine deficits but was associated with the degree of relative perfusion in the prefrontal, insular, and cingulate cortices. By contrast, the UPDRS part III total score in the PD group was not correlated with cerebral perfusion but was associated with striatal dopamine depletion, especially in the posterior putamen. The DIP-related cerebral perfusion pattern effectively discriminated patients with DIP from HCs and patients with PD.

Blockage of dopamine receptors by drugs is associated with characteristic cerebral perfusion patterns that are distinct from those in patients with PD and correlate with symptom severity.