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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.

Background and Objectives: Autoantibodies against α3-subunit-containing nicotinic acetylcholine receptors (α3-nAChRs), usually measured by radioimmunoprecipitation assay (RIPA), are detected in patients with autoimmune autonomic ganglionopathy (AAG). However, low α3-nAChR antibody levels are frequently detected in other neurologic diseases with questionable significance. Our objective was to develop a method for the selective detection of the potentially pathogenic α3-nAChR antibodies, seemingly present only in patients with AAG., Methods: The study involved sera from 55 patients from Greece, suspected for autonomic failure, and 13 patients from Italy diagnosed with autonomic failure, positive for α3-nAChR antibodies by RIPA. In addition, sera from 52 patients with Ca 2 + channel or Hu antibodies and from 2,628 controls with various neuroimmune diseases were included. A sensitive live cell-based assay (CBA) with α3-nAChR-transfected cells was developed to detect antibodies against the cell-exposed α3-nAChR domain., Results: Twenty-five patients were found α3-nAChR antibody positive by RIPA. Fifteen of 25 patients were also CBA positive. Of interest, all 15 CBA-positive patients had AAG, whereas all 10 CBA-negative patients had other neurologic diseases. RIPA antibody levels of the CBA-negative sera were low, although our CBA could detect dilutions of AAG sera corresponding to equally low RIPA antibody levels. No serum bound to control-transfected cells, and none of the 2,628 controls was α3-CBA positive., Discussion: This study showed that in contrast to the established RIPA for α3 - nAChR antibodies, which at low levels is of moderate disease specificity, our CBA seems AAG specific, while at least equally sensitive with the RIPA. This study provides Class II evidence that α3-nAChR CBA is a specific assay for AAG., Classification of Evidence: This study provides Class II evidence that an α3-nAChR cell-based assay is a more specific assay for AAG than the standard RIPA., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Human-Computer Interaction (HCI) and games set a new domain in understanding people's motivations in gaming, behavioral implications of game play, game adaptation to player preferences and needs for increased engaging experiences in the context of HCI serious games (HCI-SGs). When the latter relate with people's health status, they can become a part of their daily life as assistive health status monitoring/enhancement systems. Co-designing HCI-SGs can be seen as a combination of art and science that involves a meticulous collaborative process. The design elements in assistive HCI-SGs for Parkinson's Disease (PD) patients, in particular, are explored in the present work. Within this context, the Game-Based Learning (GBL) design framework is adopted here and its main game-design parameters are explored for the Exergames, Dietarygames, Emotional games, Handwriting games, and Voice games design, drawn from the PD-related i-PROGNOSIS Personalized Game Suite (PGS) (www.i-prognosis.eu) holistic approach. Two main data sources were involved in the study. In particular, the first one includes qualitative data from semi-structured interviews, involving 10 PD patients and four clinicians in the co-creation process of the game design, whereas the second one relates with data from an online questionnaire addressed by 104 participants spanning the whole related spectrum, i.e., PD patients, physicians, software/game developers. Linear regression analysis was employed to identify an adapted GBL framework with the most significant game-design parameters, which efficiently predict the transferability of the PGS beneficial effect to real-life, addressing functional PD symptoms. The findings of this work can assist HCI-SG designers for designing PD-related HCI-SGs, as the most significant game-design factors were identified, in terms of adding value to the role of HCI-SGs in increasing PD patients' quality of life, optimizing the interaction with personalized HCI-SGs and, hence, fostering a collaborative human-computer symbiosis., Competing Interests: Authors Hugo Silva and Gonçalo Telo were employed by the company PLUX, Wireless Biosignals. Moreover, Konstantinos Filis, Elina Theodoropoulou, and George Lyberopoulos were employed by the company COSMOTE Kinites Tilepekoinonies AE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dias, Diniz, Konstantinidis, Savvidis, Zilidou, Bamidis, Grammatikopoulou, Dimitropoulos, Grammalidis, Jaeger, Stadtschnitzer, Silva, Telo, Ioakeimidis, Ntakakis, Karayiannis, Huchet, Hoermann, Filis, Theodoropoulou, Lyberopoulos, Kyritsis, Papadopoulos, Depoulos, Trivedi, Chaudhuri, Klingelhoefer, Reichmann, Bostantzopoulou, Katsarou, Iakovakis, Hadjidimitriou, Charisis, Apostolidis and Hadjileontiadis.)

Fine-motor impairment (FMI) is progressively expressed in early Parkinson's Disease (PD) patients and is now known to be evident in the immediate prodromal stage of the condition. The clinical techniques for detecting FMI may not be robust enough and here, we show that the subtle FMI of early PD patients can be effectively estimated from the analysis of natural smartphone touchscreen typing via deep learning networks, trained in stages of initialization and fine-tuning. In a validation dataset of 36,000 typing sessions from 39 subjects (17 healthy/22 PD patients with medically validated UPDRS Part III single-item scores), the proposed approach achieved values of area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval: 0.80-0.96) with sensitivity/specificity: 0.90/0.83. The derived estimations result in statistically significant ([Formula: see text]) correlation of 0.66/0.73/0.58 with the clinical standard UPDRS Part III items 22/23/31, respectively. Further validation analysis on 9 de novo PD patients vs. 17 healthy controls classification resulted in AUC of 0.97 (0.93-1.00) with 0.93/0.90. For 253 remote study participants, with self-reported health status providing 252.000 typing sessions via a touchscreen typing data acquisition mobile app (iPrognosis), the proposed approach predicted 0.79 AUC (0.66-0.91) with 0.76/0.71. Remote and unobtrusive screening of subtle FMI via natural smartphone usage, may assist in consolidating early and accurate diagnosis of PD.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with the non-motor symptoms preceding the motor impairment that is needed for clinical diagnosis. In the current study, an angle-based analysis that processes activity data during sleep from a smartwatch for quantification of sleep quality, when applied on controls and PD patients, is proposed. Initially, changes in their arm angle due to activity are captured from the smartwatch triaxial accelerometry data and used for the estimation of the corresponding binary state (awake/sleep). Then, sleep metrics (i.e., sleep efficiency index, total sleep time, sleep fragmentation index, sleep onset latency, and wake after sleep onset) are computed and used for the discrimination between controls and PD patients. A process of validation of the proposed approach when compared with the PSG-based ground truth in an in-the-clinic setting, resulted in comparable state estimation. Moreover, data from 15 early PD patients and 11 healthy controls were used as a test set, including 1,376 valid sleep recordings in-the-wild setting. The univariate analysis of the extracted sleep metrics achieved up to 0.77 AUC in early PD patients vs. healthy controls classification and exhibited a statistically significant correlation (up to 0.46) with the clinical PD Sleep Scale 2 counterpart Items. The findings of the proposed method show the potentiality to capture non-motor behavior from users' nocturnal activity to detect PD in the early stage.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder worldwide, causing both motor and non-motor symptoms. In the early stages, symptoms are mild and patients may ignore their existence. As a result, they do not undergo any related clinical examination; hence delaying their PD diagnosis. In an effort to remedy such delay, analysis of data passively captured from user's interaction with consumer technologies has been recently explored towards remote screening of early PD motor signs. In the current study, a smartphone-based method analyzing subjects' finger interaction with the smartphone screen is developed for the quantification of fine-motor skills decline in early PD using Convolutional Neural Networks. Experimental results from the analysis of keystroke typing in-the-clinic data from 18 early PD patients and 15 healthy controls have shown a classification performance of 0.89 Area Under the Curve (AUC) with 0.79/0.79 sensitivity/specificity, respectively. Evaluation of the generalization ability of the proposed approach was made by its application on typing data arising from a separate self-reported cohort of 27 PD patients' and 84 healthy controls' daily usage with their personal smartphones (data in-the-wild), achieving 0.79 AUC with 0.74/0.78 sensitivity/specificity, respectively. The results show the potentiality of the proposed approach to process keystroke dynamics arising from users' natural typing activity to detect PD, which contributes to the development of digital tools for remote pathological symptom screening.

People with spinal cord injuries (SCI), and particularly with high level lesions, can potentially lose the ability to effectively operate computers. The Multimedia Authoring and Management using your Eyes and Mind (MAMEM) project aims to design and produce a novel assistive device to support computer use by individuals with SCI and other disabilities. The solution harnesses eye tracking and brain waves, as measured by encephalography (EEG), to manipulate common computer functions. This paper describes the first step in the project, during which we defined clinically related requirements of the assistive device. These definitions were based on data from three sources: (1) a narrative review; (2) a focus group of SCI rehabilitation professionals; and (3) structured questionnaires administrated to potential computer users with SCI, addressing computer-use habits, barriers, and needs. We describe both the collection of data from each source and the clinically related requirements extracted. The novel three-source requirement assessment method is discussed, and the advantages and disadvantages of each data source are reported. In conclusion, we suggest that this approach makes it possible to organize, discuss, and prioritize the requirements, and to create a work program while planning the device. This increases our level of certainty that the efficacy and adequacy of the assistive device will be maximized, in terms of the clinical needs of users., Competing Interests: The authors have declared that no competing interests exist.

Wide comprehension of genetic features of cerebral cavernous malformations (CCM) represents the starting point to better manage patients and risk rating in relatives. The causative mutations spectrum is constantly growing. KRIT1, CCM2 , and PDCD10 are the three loci to date linked to familial CCM development, although germline mutations have also been detected in patients affected by sporadic forms. In this context, the main challenge is to draw up criteria to formulate genotype-phenotype correlations. Clearly, genetic factors determining incomplete penetrance of CCM need to be identified. Here, we report two novel intronic variants probably affecting splicing. Molecular screening of CCM genes was performed on DNA purified by peripheral blood. Coding exons and intron-exon boundaries were sequenced by the Sanger method. The first was detected in a sporadic patient and involves KRIT1 . The second affects CCM2 and it is harbored by a woman with familial CCM. Interestingly, molecular analysis extended to both healthy and ill relatives allowed to estimate, for the first time, a penetrance for CCM2 lower than 100%, as to date reported. Moreover, heterogeneity of clinical manifestations among those affected carrying the same genotype further confirms involvement of modifier factors in CCM development.

Mutations in the α-synuclein gene are a rare cause of Parkinson's disease. We investigated, by single-pulse TMS, the cortical excitability profile of nine α-synuclein patients in comparison with 24 idiopathic PD patients, subdivided into "akinetic" (n=17) and "tremor-dominant" (n=7) subgroups. The comparative assessment of rest motor threshold, active MEP and Silent Period Input/Output curves indicated that the cortical excitability of α-Synuclein patients is similar to patients with the "akinetic" form of PD. Both groups of patients exhibited differences in excitatory and inhibitory brain circuits from "tremor-dominant" patients indicating that varying clinical phenotypes are associated with differential profiles of corticospinal excitability., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

We present a dataset that combines multimodal biosignals and eye tracking information gathered under a human-computer interaction framework. The dataset was developed in the vein of the MAMEM project that aims to endow people with motor disabilities with the ability to edit and author multimedia content through mental commands and gaze activity. The dataset includes EEG, eye-tracking, and physiological (GSR and Heart rate) signals collected from 34 individuals (18 able-bodied and 16 motor-impaired). Data were collected during the interaction with specifically designed interface for web browsing and multimedia content manipulation and during imaginary movement tasks. The presented dataset will contribute towards the development and evaluation of modern human-computer interaction systems that would foster the integration of people with severe motor impairments back into society.

Cerebral cavernous malformations are vascular lesions that usually involve brain micro-vessels. They can occur both in a sporadic form and familial one. Causes of familial forms are mutations at three loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. Here, we describe a novel CCM3 missense mutation (c.422T>G) detected in two Greek brothers showing multiple lesions at magnetic resonance imaging; to date, only the youngest is symptomatic. Bioinformatics tools showed this novel variant causes a loss of function in Pdcd10 protein due to its localization in the eighth helix and, particularly, affects Leu141, a highly conserved amino acid. Roles of Pdcd10 in angiogenesis regulation and its association with early development of cerebral cavernous malformations were also considered.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

In a recent web based genome-wide association study (GWA) the rs6812193 polymorphism was identified as a new risk factor for Parkinson's disease (PD). The purpose of our study was to examine the association of the rs6812193 polymorphism with Parkinson's disease (PD) in case-control association study of Greek individuals. We studied a total of 343 individuals, 210 Greek patients with sporadic PD and 133 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We found no differences in genotype or allele frequencies between PD patients and controls (P=0.795 and P=0.892, respectively), suggesting that the rs6812193 polymorphism does not increase susceptibility to PD in the Greek population. Additional studies further investigating the association of the rs6812193 polymorphism with PD are needed in order to clarify the role of this polymorphism in different ethnicities., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Parkinson's disease (PD) is a complex, heterogeneous neurodegenerative disorder, affecting approximately 1% of the population over 60 years of age. The molecular and cellular mechanisms underlying PD pathogenesis are still unknown. Clathrin-mediated endocytosis (CME) is a procedure closely related to the intracellular trafficking of multiple molecules in the cell, including proteins, lipids, and neurotransmitters. Recently, variations in the gene encoding the phosphatidylinositol binding clathrin assembly protein (PICALM) has been associated with Alzheimer's disease (AD), suggesting a possible role of CME in the pathogenesis of neurodegenerative diseases. In this study, we examined for the first time the potential role of the PICALM rs3851179 polymorphism in PD. We studied the PICALM rs3851179 polymorphism in 191 Greek patients with sporadic PD and 118 control subjects, using a PCR-RFLP method. Our results do not provide evidence that the PICALM rs3851179 polymorphism increase susceptibility of PD, in the Greek population.

Mechanisms that mediate inflammatory responses may be crucial in Parkinson's disease (PD) pathogenesis. In the brain, the chemokine receptor CX3CR1 is exclusively expressed in microglia, selectively mediating microglia-neuron interaction in response to its ligand, the chemokine fractalkine. Two functional single nucleotide polymorphisms, V249I and T280M, in the coding sequence of the CX3CR1 receptor have been found to alter ligand-receptor affinity. The aim of this study was to investigate the genetic role of CX3CR1 in sporadic PD. We examined the V249I and T280M CX3CR1 polymorphisms in a case-control study of 176 sporadic PD patients and 115 controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed for the detection of the studied CX3CR1 genotypes. This is the first study that tests CX3CR1 gene polymorphisms in patients with PD. We found no differences in genotype or haplotype frequencies between PD patients and controls, suggesting that CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to PD. Additional studies should further investigate the CX3CL1-CX3CR1 axis in PD.

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 (123)I-FP-CIT [(123)I-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 (123)I-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.

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 © 2011 Elsevier Ltd. All rights reserved.)

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 © 2009 Elsevier Inc. All rights reserved.)

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/m(2) 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 (V(max)), as well as maximum acceleration (AC(max)) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, AC(max) 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.

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.

Mutations in beta-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.

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.

Sleep apnea-hypopnea syndrome (SAHS) causes serious symptoms and may induce patients' quality of life impairment. The aim of this study was to assess health related quality of life (HRQOL) in Greek patients with various severity SAHS before and after CPAP implementation in comparison with conservative therapy and Greek population normative data. In 180 patients (152 males, 28 females) with SAHS (apnea-hypopnea index, AHI 56 +/- 25.4/h), daytime sleepiness was assessed with the Epworth sleepiness scale (ESS) and measurements of health status were performed using the short form-36 health survey (SF-36) questionnaire and the General Health Questionnaire (GHQ-30). One hundred and thirty five patients underwent CPAP treatment and 45 were assigned to a conservative therapy. After 3 months the measurements were repeated in 105 patients under CPAP treatment and in 15 patients from the conservative group. HRQOL in all patients was lower than Greek normative data before any treatment. In patients with CPAP therapy the ESS decreased (p<0.01) and a significant improvement was observed in SF-36 dimensions (p<0.01). The improvement was more obvious in patients with severe SAHS (p<0.05) than in patients with moderate disease severity. In the majority of patients (60.9%), GHQ-30 score was high and it was negatively related to some SF-36 dimensions and positively to ESS. In patients under conservative therapy, no significant changes were observed in any measure. HRQOL in patients with SAHS at the time of diagnosis was low and reached general population levels in patients treated with CPAP. The improvement was greater in those with severe syndrome.

In the study described here we attempted to evaluate the personality profiles of 25 patients with juvenile myoclonic epilepsy (JME) at the time of diagnosis, before treatment, and to explore a potential relationship between behavioral aspects and clinical outcome. For this purpose we employed a standardized and objective instrument, the Minnesota Multiphasic Personality Inventory (MMPI), and found that patients with JME have a personality profile similar to that of the control group, which corresponds to the 3,1 code type MMPI profile. We also noted that the characteristics of this personality type include those described in patients with long-duration JME by previous researchers. Consequently, we conclude that personality aberrations are not a feature of this syndrome. Furthermore, we observed that under treatment, EEGs normalized in patients who had exhibited "psychotic tendencies" pretreatment. The credibility of our results is supported by the fact that assessment of the personality profile was not confounded by medication or the longitudinal burden of epileptic seizures.

Autosomal dominant familial Parkinson's disease (PD) due to the alpha-synuclein (G209A) mutation shares similar clinical characteristics with sporadic PD. Pathological studies however indicate more widespread neuronal degeneration in the familial form. We performed (123)I-FP-CIT SPET (DaTSCAN) study in nine patients with familial PD carrying the alpha-synuclein (G209A) mutation and fifteen matched patients with sporadic disease. Both groups had equal radioligand reduction uptake in the striatum but the alpha-synuclein patients showed less asymmetry and increased putamen to caudate ratio. Our findings indicate that there are minor differences in DAT SPET parameters between alpha-synuclein and sporadic PD patients insufficient to provide differential diagnosis.

Background: Chronic obstructive pulmonary disease (COPD) profoundly impacts patients' functional status, especially in the advanced stages, when long-term oxygen therapy (LTOT) is implemented., Objective: To determine the health-related quality of life (HRQOL) in patients with COPD and using LTOT, and assess the relationship of socioeconomic characteristics and pulmonary function test results to HRQOL scores., Methods: We studied a group of 85 patients with COPD and hypoxemia who were on LTOT, and a control group of 48 patients with stable COPD but without hypoxemia. All subjects were asked to rate their dyspnea on the Modified Medical Research Council dyspnea scale, and to take the Medical Outcomes Study Short Form (SF-36), the General Health Questionnaire (30 questions), and a questionnaire (which we developed for this study) to measure their independence in activities of daily living (ADL). We also conducted pulmonary function tests and arterial blood gas analyses, and recorded socioeconomic characteristics., Results: The subjects' socioeconomic status was moderate to low. HRQOL was impaired in patients on LTOT, especially in the physical function domain, and most of the examined dimensions correlated with the severity of dyspnea and psychological status. There was a significant association between ADL score and SF-36 score in the vitality and physical domains, but there was no significant association between HRQOL score and spirometry or blood gas values., Conclusions: HRQOL in patients with COPD and on LTOT is low and is influenced by dyspnea, mental status, and incapacity, rather than by physiological variables. We recommend a multidimensional therapeutic approach that targets symptom-control and ADL support to improve the patient's overall HRQOL.

Background: Sleep-disordered breathing (SDB) and especially obstructive sleep apnea (OSA) are associated with daytime sleepiness and an increased risk for motor vehicle crashes. Previous studies have assessed the prevalence of OSA among professional drivers, but no study so far has focused on railway drivers. The aim of this study was to assess the prevalence of SDB among Greek railway drivers, and correlate it with daytime sleepiness, quality of life, and symptoms., Methods: The following three different questionnaires were anonymously answered by 226 train drivers: a general questionnaire on their demographics and sleep habits; the Greek version of the Epworth sleepiness scale (ESS); and the Medical Outcomes Study 36-item short form (SF-36). Of the 226 drivers, 50 underwent a sleep study, a physical examination, and an assessment of their respiratory function., Results: Participants were all men, had a mean (+/-SD) age of 46.9+/-3.9 years, were overweight (mean body mass index [BMI], 28.7+/-3.7 kg/m2), and were smokers (59.7%). Snoring was reported by 69.9% of them, and apneas by 11.5%. The mean ESS score was 5.4+/-3.2. SF-36 scores were similar to those of the Greek population. The mean apnea-hypopnea index (AHI) was 11+/-14 events per hour, and the mean pulse oximetric saturation was 93.2+/-2.5%. According to AHI severity, they were divided into the following three groups: group 1, normal breathing function in sleep (n=19; AHI, <5 events per hour); group 2, mild OSA (n=20; AHI, 5.1 to 15 events per hour); group 3, moderate/severe OSA (n=11; AHI, >15 events per hour). The three groups differed in terms of BMI, and neck, waist, and hip circumferences. No difference was detected, though, in ESS and SF-36 scores., Conclusion: The majority of the Greek railway drivers are overweight and smokers. The most common reported symptom in the questionnaires is snoring, without significant daytime impairment, while sleep studies show a potentially higher prevalence of OSA., Trial Registration: Democritus University of Thrace Identifier: 2979/5-2003., Trial Registration: Union of the Greek Railway Drivers Identifier: 536/10-2003.

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.

We compared the distribution of the Tau H1 haplotype and related subhaplotypes in a group of clinically diagnosed Parkinson's disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% CI: 1.03-2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinson's disease is influenced by ethnic variation., ((c) 2006 Movement Disorder Society.)

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.

The aim of the present study was to evaluate the use of the radiopharmaceutical 123I-ioflupane in the diagnosis and differential diagnosis of Parkinsonism (P) and essential tremor (ET). Forty-three consecutive patients, aged 35-72 years, presenting symptoms and signs compatible with P, plus 11 normal volunteers, aged 40-60 years, were enrolled for the study. The radiopharmaceutical was injected iv in a dose of 185 MBq and tomographic acquisition in a single-headed Pegasys gamma-camera (ADAC, USA), 3-4 hours post injection was performed in order to evaluate the activity of the presynaptic nigro-striatal dopaminergic transporter. After reconstruction and reorientation, semiquantitative analysis was performed evaluating counts/pixel: a) in the striatum and its parts (caudate nucleus and putamen) of both hemispheres and b) in the visual cortex representing non specific binding. According to our results, all 21 individuals with ET were correctly evaluated with this method, whilst 21/22 patients were diagnosed as having P. No statistical difference concerning the binding of the radioligand to the striatum and its parts was found between normal volunteers and patients with ET. Based on the present results in 21 of our patients, the diagnosis and treatment procedure were changed, while in the remaining 22 patients diagnosis and treatment were confirmed. According to our data, as well as to the data from others, molecular imaging (SPET) with 123I-ioflupane can properly differentiate individuals with ET from those having P, in order to avoid an unnecessary use of drugs that may even cause side effects. All our patients were re-examined after eight months. At that time the above results and the treatment that was given to them meanwhile, were positively evaluated.

We studied the effects of higher mental activity on the EEG, i.e., neuropsychological EEG activation (NPA), in patients with juvenile myoclonic epilepsy (JME). Thirty patients with JME underwent a conventional EEG recording and EEG recording during performance of a battery of twelve neuropsychological tasks, which involved decision making, reading, calculations, constructive activities and drawing. Twenty-three JME patients (76.6%) responded (i.e., showed EEG activation) to at least one neuropsychological task (p = 0.003). Four neuropsychological tasks, two involving the use of the hands and two without manual involvement, were associated with a high frequency of EEG activation (40-60% of JME patients), although statistical analysis did not reveal any one test as the most significant for NPA activation. Neuropsychological EEG activation, using a variety of tasks both manual and non-manual, is a useful tool in evaluating patients with JME.

Various instruments with good psychometric properties have been developed for the assessment of health-related quality of life (HRQoL) in Parkinson's disease, (PD); however, in everyday practice a brief questionnaire is needed for quick screening of patients. We present the process of development and validation of the Greek version of PD questionnaire-8 (PDQ-8(GrV)), which is an 8-item scale derived from a well-known measure for the evaluation of HRQoL in PD, the PD questionnaire (PDQ-39). PDQ-8 (GrV) was applied to 228 nondemented Greek PD patients. Data from PDQ-39 were also collected from these patients for comparisons between the total scores of the two scales. Detailed statistical analysis showed that PD-8(GrV) has psychometric properties analogous to its parent questionnaire., (Copyright 2003 Movement Disorder Society)

The purpose of this study was to evaluate the effect of amantadine sulfate infusion on the N30 component of the median nerve short-latency somatosensory evoked potentials (SSEPs) in patients with Parkinson's disease (PD). Twenty patients with advanced PD and severe motor fluctuations received a 6-day course of amantadine sulfate infusion (400 mg/day) plus their usual levodopa medication. Patients were assessed clinically by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III and -IV). SSEPs to median nerve stimulation were recorded from the parietal and frontal regions before and after the 6-day course of amantadine infusion. Mean UPDRS motor score during the ON and OFF phase improved after amantadine infusion, as did motor fluctuations. SSEP changes resulting from amantadine sulfate treatment were observed in the P20-N30 amplitude as follows: Mean P20-N30 amplitudes before and after treatment were 2.15 +/- 1.11 microV and 3.06 +/- 1.19 microV respectively (p = 0.000), whereas mean N30-P40 amplitude increased from 2.7 +/- 1.6 microV to 3.9 +/- 1.3 microV after treatment (p = 0.000). Our results indicate that coincident to its clinical impact, amantadine infusion in patients with PD affects electrophysiologic parameters as well.