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Objective: The caudal zona incerta (cZI) is a promising, clinically beneficial target for deep brain stimulation (DBS) in Parkinson’s disease (PD). To assess whether DBS of the cZI affects the rate of dopamine terminal dysfunction, PD patients with and without DBS were followed prospectively with ¹²³I FP-Cit single photon emission tomography from the first diagnosis and up to 8 years.

Methods: Six patients underwent DBS of the cZI during the survey period. Twenty-two PD patients only on pharmacotherapy served as controls. ¹²³I FP-Cit and clinical assessment were performed at baseline and after 1, 3 and 5 years in all patients. Ten patients also underwent a ¹²³I FP-Cit after 8 years. Image data were evaluated semiquantitatively. Mixed-model analysis was used to assess the relative change in ¹²³I FP-Cit uptake and comparison between surgically and conservatively treated PD patients.

Results: The relative decrease in ¹²³I FP-Cit uptake was more pronounced in DBS-treated patients than in controls in the more affected caudate (P=0.037) and putamen (P=0.013). The annual decrease rates were higher in the less affected than the more affected putamen, and were slightly greater in DBS-treated patients (4.8%, 95%confidence interval: 8.5–2.2%) than in controls (4.0%, 95% confidence interval: 5.1–3.1%).

Conclusion: This long-term prospective study confirms that the underlying dopaminergic dysfunction continues despite clinical improvement in PD patients with DBS of the cZI. A slightly faster rate of decrease in ¹²³I FP-Cit uptake in these patients compared with conservatively treated PD patients may reflect a more aggressive form of PD.