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Background: While previous imaging studies have generally shown normal striatal dopamine transporter (DAT) binding in essential tremor (ET), emerging evidence suggests a partial dopaminergic mechanism in this condition and an epidemiological link between ET and Parkinson's disease (PD). This link seems particularly meaningful in ET patients with additional neurological signs, such as slowness of movements, rigidity, or rest tremor (ET+)., Objectives: To investigate the potential dopaminergic pathophysiology of ET+ and to compare it to PD., Methods: Fourty-three ET+ patients, 115 PD patients and 40 healthy controls were studied using [ 123 I]FP-CIT SPECT imaging and clinical examinations. A median follow-up of 3.0 years was carried out to confirm the diagnoses. ET+ patients underwent an extended follow-up with a median of 7.7 years (range 4.3-9.8 years). Region-specific binding ratios of striatal DAT binding were compared among the groups and correlated with the MDS-UPDRS motor scores., Results: Bradykinesia scores were negatively associated with posterior putamen DAT binding in both the ET+ and PD groups, with the strongest correlation observed in finger tapping (F = 11.1, β = -0.10, 95%CI -0.16 to -0.04, P = 0.001). In ET+ patients, kinetic tremor asymmetry correlated with posterior putamen DAT binding asymmetry (r = 0.33, P = 0.043), indicating a relationship between more severe tremor and subtle contralateral DAT loss., Conclusions: In ET+, subtle increases in bradykinesia scores correlate with striatal dopaminergic dysfunction, while kinetic tremor asymmetry is associated with hemispheric DAT binding asymmetry. These findings support the concept of partial dopaminergic involvement in the pathophysiology of ET+., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: This study was undertaken to investigate the effects of dietary caffeine intake on striatal dopamine function and clinical symptoms in Parkinson disease in a cross-sectional and longitudinal setting., Methods: One hundred sixty-three early Parkinson disease patients and 40 healthy controls were investigated with [ 123 I]FP-CIT single photon emission computed tomography, and striatal dopamine transporter binding was evaluated in association with the level of daily coffee consumption and clinical measures. After a median interval of 6.1 years, 44 patients with various caffeine consumption levels underwent clinical and imaging reexamination including blood caffeine metabolite profiling., Results: Unmedicated early Parkinson disease patients with high coffee consumption had 8.3 to 15.4% lower dopamine transporter binding in all studied striatal regions than low consumers, after accounting for age, sex, and motor symptom severity. Higher caffeine consumption was further associated with a progressive decline in striatal binding over time. No significant effects of caffeine on motor function were observed. Blood analyses demonstrated a positive correlation between caffeine metabolites after recent caffeine intake and dopamine transporter binding in the ipsilateral putamen., Interpretation: Chronic caffeine intake prompts compensatory and cumulative dopamine transporter downregulation, consistent with caffeine's reported risk reduction in Parkinson disease. However, this decline does not manifest in symptom changes. Transiently increased dopamine transporter binding after recent caffeine intake has implications for dopaminergic imaging guidelines. ANN NEUROL 2024;96:262-275., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Gastrointestinal symptoms are common in Parkinson's disease (PD), but their neurophysiological correlates are not well understood. We recently reported that functional gastrointestinal symptoms were not associated with asymmetry per se but might be associated with lower left striatal dopamine transporter (DAT) binding. The purpose of this study was to further investigate if specific gastrointestinal symptoms associate with monoamine transporter changes in specific striatal or extrastriatal areas., Methods: Ninety PD patients, who underwent DAT ¹ 2 I-FP-CIT SPECT imaging, were assessed using the MDS-Unified Parkinson's Disease Rating Scale part III, Rome III, and Wexner constipation score. DAT binding was calculated from striatal subregions using region-to-occipital cortex ratio. Voxel-wise analysis was used to assess the relationship between gastrointestinal symptoms and striatal DAT and extrastriatal serotonin transporter (SERT) binding.3 I-FP-CIT SPECT imaging, were assessed using the MDS-Unified Parkinson's Disease Rating Scale part III, Rome III, and Wexner constipation score. DAT binding was calculated from striatal subregions using region-to-occipital cortex ratio. Voxel-wise analysis was used to assess the relationship between gastrointestinal symptoms and striatal DAT and extrastriatal serotonin transporter (SERT) binding., Results: Irritable bowel syndrome (IBS) criteria were fulfilled in 17 patients and were linked to higher ¹ 2 3 I-FP-CIT binding in the right posterior putamen and adjacent areas as compared to patients without IBS. No other significant associations between gastrointestinal symptoms and DAT or SERT binding were found., Conclusions: These findings suggest that PD patients with IBS may have higher DAT binding in the right hemisphere. This finding implicates alterations of brain neurotransmitter physiology in the gastrointestinal symptoms of PD patients., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Diagnostic usefulness of the floating door sign was tested in 144 PD patients, 41 essential tremor patients and 38 controls. There were no differences in the presence of floating door sign between PD and ET patients. The sign does not seem to be a reliable differential diagnostic tool., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Micrographia is a common symptom of Parkinson's disease (PD), and it may precede other motor symptoms. Despite the high prevalence of micrographia in PD, its neurobiological mechanisms are not known. Given that levodopa may alleviate consistent micrographia and that nondopaminergic essential tremor (ET) is not associated with micrographia, micrographia could possibly be used as an ancillary diagnostic method that reflects nigrostriatal dopamine function. We evaluated the usefulness of micrographia as a simple one-sentence writing test in differentiating PD from ET. A total of 146 PD patients, 42 ET patients and 38 healthy controls provided writing samples and were scanned with brain [ 123 I]FP-CIT dopamine transporter (DAT) SPECT imaging with ROI-based and voxelwise analyses. The diagnostic accuracy of micrographia was evaluated and compared to that of DAT binding. Compared to ET and healthy controls, PD patients showed micrographia (consistent, 25.6% smaller area of handwriting sample in PD compared to ET, p = 0.002, and 27.2% smaller area of handwriting compared to healthy controls, p = 0.004). PD patients showed 133% more severe progressive micrographia compared with ET patients (median b =  - 0.14 in PD, b =  - 0.06 in ET, p = 0.021). In early unmedicated cognitively normal patients, consistent micrographia showed 71.2% specificity and 87.5% sensitivity in PD versus ET differentiation, but micrographia had no correlation with striatal or extrastriatal [ 123 I]FP-CIT binding in patients with PD. The one-sentence micrographia test shows moderately good accuracy in PD versus ET differentiation. The severity of micrographia has no relationship with DAT binding, suggesting nondopaminergic mechanism of micrographia in PD.ClinicalTrials.gov identifier: NCT02650843 (NMDAT study)., (© 2022. The Author(s).)

Background: The neurophysiological correlates of gastrointestinal symptoms (GISs) in Parkinson's disease (PD) are not well understood. It has been proposed that in patients with a gastrointestinal origin of PD dopaminergic neurodegeneration would be more symmetric., Objectives: The aim is to assess the associations between GISs and asymmetry of nigrostriatal dopaminergic neurodegeneration in PD., Methods: Ninety PD patients were assessed using motor and GIS scales and 123 I-FP-CIT SPECT. We calculated the asymmetry index and the predominant side of motor symptoms and dopamine transporter (DAT) imaging defect and assessed their association with GISs., Results: There were no significant differences in GISs between symmetric and asymmetric dopaminergic defect. Left predominant defect was related to more GIS and higher constipation scores., Conclusions: GISs were associated with left predominant reduction in putaminal DAT binding but not asymmetry per se. It remains open whether left-sided DAT deficit is related to more pronounced GI involvement or symptom perception in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.)

Glabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson's disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [ 123 I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal). In addition, the consistency of the GR was investigated with 89 patients after a mean follow-up of 2.2 years. PD and ET patients had higher GR scores than healthy controls (p < 0.001), but there was no difference in GR between PD and ET patients (p = 0.09). There were no differences in the ratio of abnormal to normal GRs between the PD and ET groups (73% vs. 64% abnormal, respectively, p = 0.13) or in DAT binding between PD patients with abnormal and normal GRs (p > 0.36). Over follow-up, the GR changed from abnormal to normal in 20% of PD patients despite the presence of clinically typical disease. The sensitivity and specificity of GR for differentiating PD from ET were 78.3% and 36.2%, respectively. Although GR has been used by clinicians in the diagnostics of PD, it does not separate PD from ET. It also shows considerable inconsistency over time, and abnormal GR has no relationship with dopamine loss. Its usefulness should be tested for other clinical diagnostic purposes., (© 2021. The Author(s).)

Objective: To evaluate possible differences between brain dopamine transporter (DAT) binding in a group of symptomatic parkinsonism patients without dopaminergic degeneration and healthy individuals., Background: Dopaminergic neuroimaging studies of Parkinson's disease (PD) have often used control groups formed from symptomatic patients with apparently normal striatal dopamine function. We sought to investigate whether symptomatic patients can be used to represent dopaminergically normal healthy controls., Methods: Forty healthy elderly individuals were scanned with DAT [ 123 I]FP-CIT SPECT and compared to 69 age- and sex-matched symptomatic patients with nondegenerative conditions (including essential tremor, drug-induced parkinsonism and vascular parkinsonism). An automated region-of-interest based analysis of the caudate nucleus and the anterior/posterior putamen was performed. Specific binding ratios (SBR = [ROI-occ]/occ) were compared between the groups., Results: DAT binding in symptomatic patients was 8.6% higher in the posterior putamen than in healthy controls (p = 0.03). Binding correlated negatively with age in both groups but not with motor symptom severity, cognitive function or depression ratings., Conclusions: Putaminal DAT binding, as measured with [ 123 I]FP-CIT SPECT, was higher in symptomatic controls than in healthy individuals. The reason for the difference is unclear but can include selection bias when DAT binding is used to aid clinical diagnosis and possible self-selection bias in healthy volunteerism. This effect should be taken into consideration when designing and interpreting neuroimaging trials investigating the dopamine system with [ 123 I]FP-CIT SPECT., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)