Gastrointestinal Symptoms and Dopamine Transporter Asymmetry in Early Parkinson's Disease.

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.

Diagnostic value of micrographia in Parkinson's disease: a study with [123I]FP-CIT SPECT.

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 [123I]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 [123I]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).

Diagnostic accuracy of glabellar tap sign for Parkinson's disease.

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) [123I]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.

Floating door sign does not differentiate Parkinson's disease from essential tremor.

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.

Fecal microbiome alterations in treatment-naive de novo Parkinson's disease.

Gut microbiota alterations in Parkinson's disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.