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Objective: A total of 48% of patients with Parkinson's disease (PD) present symptoms of gastrointestinal dysfunction, particularly constipation. Furthermore, gastrointestinal tract (GIT)-related non-motor symptoms (NMSs) appear at all stages of PD, can be prodromal by many years and have a relevant impact on the quality of life. There is a lack of GIT-focused validated tools specific to PD to assess their occurrence, progress, and response to treatment. The aim of this study was to develop and evaluate a novel, disease- and symptom-specific, self-completed questionnaire, titled Gut Dysmotility Questionnaire (GDQ), for screening and monitoring gastrointestinal dysmotility of the lower GIT in patients with PD. Methods: In phase 1, a systematic literature review and multidisciplinary expert discussions were conducted. In phase 2, cognitive pretest studies comprising standard pretests, interviews, and evaluation questionnaires were performed in patients with PD (n = 21), age- and sex-matched healthy controls (HC) (n = 30), and neurologists (n = 11). Incorporating these results, a second round of cognitive pretests was performed investigating further patients with PD (n = 10), age- and sex-matched HC (n = 10), and neurologists (n = 5). The questionnaire was adapted resulting in the final GDQ, which underwent cross-cultural adaptation to the English language. Results: We report significantly higher GDQ total scores and higher scores in five out of eight domains indicating a higher prevalence of gastrointestinal dysmotility in patients with PD than in HC (p<0.05). Cognitive pretesting improved the preliminary GDQ so that the final GDQ was rated as relevant (100/100%), comprehensive (100/90%), easy to understand concerning questions and answer options (100/90%), and of appropriate length (80/100%) by neurologists and patients with PD, respectively. The GDQ demonstrated excellent internal consistency (Cronbach's alpha value of 0.94). Evidence for good construct validity is given by moderate to high correlations of the GDQ total score and its domains by intercorrelations (rs = 0.67-0.91; p < 0.001) and with validated general NMS measures as well as with specific items that assess gastrointestinal symptoms. Interpretation: The GDQ is a novel, easy, and quick 18-item self-assessment questionnaire to screen for and monitor gastrointestinal dysmotility with a focus on constipation in patients with PD. It has shown high acceptance and efficacy as well as good construct validity in cognitive pretests. [ABSTRACT FROM AUTHOR]

Objective: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which, often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living, offers the potential for transforming disease assessment and accelerating diagnosis. Methods: A privacy-aware method for classifying patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed. Voice features from running speech signals were extracted from passively-captured recordings over voice calls. Language-aware training of multiple- and single-instance learning classifiers was employed to fuse and predict on voice features and demographic data from a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients). Results: By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. Conclusions: The proposed approach outperforms other methods proposed for language-aware PD detection considering the ecological validity of the voice data. Significance: This paper introduces for the first time a high-frequency, privacy-aware and unobtrusive PD screening tool based on analysis of voice samples captured during routine phone calls. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are important mediators of inflammatory responses by recognition of many pathogen-related molecules and endogenous proteins related to immune activation. Accumulating data have recently pointed out the role of neuroinflammation in Parkinson's disease (PD) pathogenesis. In the present study, we investigated the potential role of the TLR9 − 1237 T/C and TLR2 − 194 to − 174 del polymorphisms in PD. We studied a total of 333 individuals, 215 Greek patients with sporadic PD and 118 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism method. No statistically significant differences were found between PD patients and control subjects for the TLR9 − 1237 T/C genotypes or alleles. Regarding the TLR2 − 196 to − 174 del polymorphism, the del/del genotype and the del allele were overrepresented in the PD group compared to controls, however, this result did not reach statistical significance ( P = 0.087). Further studies investigating the TLR-inflammatory background of PD are awaited to provide important insight into the aetiology of the disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane 123I-FP-CIT [[123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and 123I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems. [ABSTRACT FROM AUTHOR]

We evaluated pupil light reflex (PLR) in patients with Parkinson's disease (PD) and normal controls by means of pupillometry and explored its possible relation to clinical characteristics in parkinsonian patients. PLR was evaluated using pupillometry in 66 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited by single flash stimuli of 24.6 candelas/m2 intensity and 20 ms duration, and six parameters were studied after full recording of pupil's movement. A significant increase in latency (T1) and significant decrease in amplitude (R1-R2), maximum constriction velocity (Vmax), as well as maximum acceleration (ACmax) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, ACmax emerged as a significant predictor for discrimination between PD patients and controls. There was no significant correlation between pupillometry parameters and clinical characteristic of patients (disease duration, stage, and the Unified Parkinson's Disease Rating motor scale). The study demonstrates PLR disorder in PD patients even without overt clinical autonomic dysfunction. Pupillometry appears to be a useful and noninvasive method for exploration of PLR alterations in PD and may prove to be useful for the early detection of subclinical autonomic nervous system dysfunction. [ABSTRACT FROM AUTHOR]

A translated version of the Mattis Dementia Rating Scale (DRS) into Greek ((DRS-GR) was applied to a sample of Greek population (N = 356) comprising normal middle-aged and elderly subjects (controls), as well as patients suffering from Parkinson's (PD) and Alzheimer's disease (AD) to test its reliability and validity. A well-known dementia screening instrument, the Mini Mental State Examination test (MMSE), and a nonverbal measure of abstract reasoning, the Raven Coloured Progressive Matrices, were employed as measures of DRS-GR concurrent validity. Reliability analysis was satisfactory with Cronbach's alpha reaching 0.82 and item to total correlations yielding high coefficients for most items. DRS-GR scores were influenced by age and education, but not by gender. Correlation between MMSE and the total DRS-GR score was significant in patients and normal controls, but correlation between DRS-GR and RCPM was significant in AD and nondemented PD only. Specificity and sensitivity for dementia screening, calculated on a Receiver Operating Characteristic curve, with a cut-off score the mean value minus two standard deviations, corrected for age and education, was 96% and 80%, respectively. Our preliminary findings show that DRS-GR is a reliable and well-adapted instrument for clinical application in the Greek population. [ABSTRACT FROM AUTHOR]

Abstract: Hyperhomocysteinemia is considered a risk factor for vascular disease causing endothelial damage and consequently atherogenesis. The purpose of this study was to investigate the effect of elevated homocysteine on certain biochemical markers of endothelial function in patients with idiopathic Parkinson’s disease (PD). Blood homocysteine levels were assessed in 57 PD patients and 40 matched normal controls. Investigation of the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) genotype was also performed in 43 PD patients. The following markers of endothelial function were assessed: superoxide dismutase (SOD), nitric oxide (NO), sICAM-1 and sE-selectin. Homocysteine levels were found mildly elevated in PD patients particularly in those treated with L-Dopa. MTHFR genotype did not influence significantly this finding. SOD activity was found reduced but it was not correlated to homocysteine levels. All other parameters measured were normal and were not related to hyperhomocysteinemia. Our findings indicate that mild hyperhomocysteinemia in PD patients was not associated with endothelial dysfunction. [Copyright &y& Elsevier]

Abstract: Subdural hematoma is a rare cause of secondary parkinsonism. We report a 65-year-old woman with reversible parkinsonism due to bilateral chronic subdural hematomas. Symmetrical parkinsonism evolved acutely 45 days after a trivial head injury. Mild pyramidal signs were also present on her left side. MRI revealed bilateral chronic subdural hematomas. The patient’s parkinsonism was completely abolished one month after successful neurosurgical evacuation of the hematomas. [Copyright &y& Elsevier]

Abstract: We describe a case with left hemiparkinsonism due to a parasagittal meningioma with surrounding edema compressing the right basal ganglia. The patient was successfully operated and his symptoms resolved completely. However 7 years later his hemiparkinsonism reappeared due to a relapse of the right parasagittal meningioma. This rare case points to the significance of neuroimaging in the evaluation of parkinsonism. [Copyright &y& Elsevier]

Abstract: Brain-derived neurotrophic factor (BDNF) enhances survival of dopaminergic neurons in the substantia nigra, whereas in patients with Parkinson’s disease (PD), the expression of BDNF mRNA is decreased, thus making BDNF a candidate gene for PD susceptibility. The association between BDNF Val66Met polymorphism and PD has been evaluated in several studies with controversial results. Thus, we determined the distribution of BDNF Val66Met polymorphism in 184 Greek patients with sporadic PD and 113 control participants using polymerase chain reaction–restriction fragment length polymorphism, and explored the association of the polymorphism with certain clinical parameters of the disease. Our results do not support a major role for the BDNF Val66Met polymorphism in PD in the Greek population. [Copyright &y& Elsevier]

Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as new causal Parkinson’s disease (PD) genes, with the VPS35 D620N and EIF4G1 R1205H mutations being identified in both autosomal dominant late-onset familial and sporadic PD patients. However, the frequencies of these two mutations among different ethnic groups vary. We studied the VPS35 D620N and EIF4G1 R1205H mutations in a total of 333 individuals, 202 Greek patients with sporadic PD and 131 control subjects, using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. None of our studied individuals carried these two mutations. Our data support that the VPS35 D620N and EIF4G1 R1205H mutations are not a common cause of PD in the Greek population. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigated the association of the rs6812193 polymorphism with Parkinson's disease. [•] SCARB2 is implicated in the lysosomal pathway recently associated with PD pathogenesis. [•] The rs6812193 polymorphism doesn’t increase susceptibility to PD in the Greek population. [•] The role of this polymorphism should be further examined in different ethnic populations. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disease, with a constantly increasing prevalence and a high global financial impact arising from direct and indirect costs. Large-scale, observational studies provide data that support the better comprehension of disease aspects, constitute a baseline reference for future studies and assist comparisons among different patient populations, allowing the recognition of distinctive characteristics and special needs. The present study is the first to depict the clinical characteristics and their interplay in a large sample of Parkinson's disease (PD) patients in Greece. Nine hundred eighty six consecutive PD outpatients were recruited from 17 centers around Greece in the time period from 8/2007 to 7/2009 and were examined and interviewed by movement disorders experts. Multiple clinical characteristics were recorded including age at diagnosis, disease severity, patients' self classification of PD symptoms and their relevance to physician's global clinical impression, smoking, alcohol consumption, presence of family history for PD, dementia, depression, hypertension, cancer and other comorbidities. Associations of high clinical significance were found between certain clinical characteristics. [ABSTRACT FROM AUTHOR]

Abstract: To determine whether polymorphisms in the microtubule-associated protein tau (MAPT) and/or glycogen synthase kinase-3β (GSK3β) genes underpin susceptibility to Parkinson''s disease (PD), we conducted a case–control association study in a Greek cohort of 196 PD cases and 163 healthy controls. In our study, the MAPT H1 haplotype was found to be significantly associated with PD, no association was detected between the intronic rs6438552 (−157 T/C) GSK3β polymorphism and PD, whereas the C/C genotype of the promoter rs334558 (−50 T/C) GSK3β polymorphism was found to exert a protective role. The C/C genotype of the rs334558 GSK3β polymorphism was also found to have an additional protective role in our MAPT H1/H1 PD subgroup. Haplotype analysis revealed that, the T–T haplotype of both GSK3β polymorphisms was over-represented in PD patients compared to controls, and this association was independent of MAPT H1 haplotype. [Copyright &y& Elsevier]

Abstract: Mutations in β-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the gene''s exons. Four mutations previously associated with Gaucher disease and/or Parkinson''s disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P =0.019, OR=4.2; 95%CI=1.28–13.82), suggesting that GBA mutations may modify age of onset for PD. [Copyright &y& Elsevier]