Dopaminergic pathway and primary visual cortex are involved in the freezing of gait in Parkinson’s disease: a PET-CT study

Background: Freezing of gait (FOG) could be partly alleviated by dopaminergic drugs but the mechanism still needs to be elucidated. The purpose of this study is to explore the mechanisms of FOG by vesicular monoamine transporter VMAT2 distribution with the (18)F-AV133 tracer and 18-fludeoxyglucose positron emission tomography–computed tomography ((18)F-FDG PET-CT). Methods: Clinical material and PET-CT data were collected from 20 patients with FOG and 147 patients without FOG from November 1, 2017 to October 31, 2018. Brain scans of all participants were acquired over an approximately 20-min period, 120 min after injection of approximately 250 MBq (18)F-AV133. The mean uptake ratios of different regions were identified by NeuroQ software of (18)F-FDG PET-CT. Data analysis included variance, chi-square analysis, covariance analysis, and logistic regression. Results: Our data showed that patients with FOG were provided with greater doses of dopaminergic drugs (p<0.05). The frequency of FOG was 11.98% and increased as Parkinson’s disease progressed. FOG was more common in the elderly and strongly associated with the duration. Cognitive impairments were obvious, assessed by Mini-Mental State Examination and Montreal Cognitive Assessment (p<0.05). The VMAT2 distribution with (18)F-AV133 was decreased significantly in the caudate nucleus and lentiform nucleus while the metabolism of these areas was elevated, determined by (18)F-FDG PET-CT (p<0.05). The metabolism of the primary visual cortex decreased obviously in patients with FOG compared with those without FOG (p<0.05). Conclusion: FOG mainly occurred in the advanced stage, and was strongly associated with the duration and larger dose of dopaminergic drugs. The dopamine level of the nigrostriatal system decreased significantly and the uptake ratios of the primary visual cortex dropped obviously in the FOG group compared with the non-FOG group. Our study suggests that both the dopaminergic pathway and the primary visual cortex are involved in the pathogenesis of FOG.