Search

Introduction: Parkinson's disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants., Methods: In a selected cohort of 190 Hungarian patients with clinical signs of PD and suspected genetic risk, we performed the genetic testing of the GBA1 gene. As other genetic hits can modify clinical features, we also screened for additional rare variants in other neurodegenerative genes and assessed the APOE-ε genotype of the patients., Results: In our cohort, we identified 29 GBA1 rare variant (RV) carriers. Out of the six different detected RVs, the highly debated E365K and T408M variants are composed of the majority of them (22 out of 32). Three patients carried two GBA1 variants, and an additional three patients carried rare variants in other neurodegenerative genes (SMPD1, SPG11, and SNCA). We did not observe differences in age at onset or other clinical features of the patients carrying two GBA1 variants or patients carrying heterozygous APOE-ε4 allele., Conclusion: We need further studies to better understand the drivers of clinical differences in these patients, as this could have important therapeutic implications., (© 2023. The Author(s).)

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited., Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD., Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed., Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published., Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The median age of disease onset is around 60 years. From a genetic point of view, PD is basically considered a sporadic, idiopathic disease, however, hereditary components can be detected in 5-10% of patients. Expanding data are available regarding the targeted molecular therapy of the disease., Areas Covered: The aim of this current review article is to provide brief clinical and molecular insight into three important genetic forms (LRRK2, SNCA, GBA) of hereditary PD subtypes and to present the human clinical trials in relation to these forms of the disease., Expert Opinion: These small hereditary subgroups are crucially important in drug development, because the general trend is that clinical trials that treat PD patients as a large group, without any separation, do not meet expectations. As a result, no long term conclusions can currently be drawn regarding the effectiveness of the molecules tested in these phase 1 and 2 studies. Further precise studies are needed in the near future.

Background: Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson's disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. More and more single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known about the impact of genetic variations of the IDO on the pathogenesis of PD., Methods: SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls., Results: No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers., Conclusions: The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD., Competing Interests: Given his role as Guest Editor, Masaru Tanaka had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Graham Pawelec. The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Background: Balance impairment in Parkinson's disease is multifactorial and its changes due to subthalamic stimulation vary in different studies., Objective: We aimed to analyze the combination of predictive clinical factors of balance impairment in patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least one year., Methods: We recruited 24 patients with Parkinson's disease treated with bilateral subthalamic stimulation and 24 healthy controls. They wore an Opal monitor (APDM Inc.) consisting of three-dimensional gyroscopes and accelerometers in the lumbar region. We investigated four stimulation conditions (bilateral stimulation OFF, bilateral stimulation ON, and unilateral right- and left-sided stimulation ON) with four tests: stance on a plain ground with eyes open and closed, stance on a foam platform with eyes open and closed. Age, disease duration, the time elapsed after implantation, levodopa, and stimulation responsiveness were analyzed. The distance of stimulation location from the subthalamic motor center was calculated individually in each plane of the three dimensions. We analyzed the sway values in the four stimulation conditions in the patient group and compared them with the control values. We explored factor combinations (with age as confounder) in the patient group predictive for imbalance with cluster analysis and a machine-learning-based multiple regression method., Results: Sway combined from the four tasks did not differ in the patients and controls on a group level. The combination of the disease duration, the preoperative levodopa responsiveness, and the stimulation responsiveness predicted individual stimulation-induced static imbalance. The more affected patients had more severe motor symptoms; primarily, the proprioceptive followed by visual sensory feedback loss provoked imbalance in them when switching on the stimulation., Conclusions: The duration of the disease, the severity of motor symptoms, the levodopa responsiveness, and additional sensory deficits should be carefully considered during preoperative evaluation to predict subthalamic stimulation-induced imbalance in Parkinson's disease., Competing Interests: The authors have declared that no competing interests exist.

Parkinson's disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Considering the devastating symptoms, high prevalence, and lack of definitive diagnostic test, there is an urgent need to identify possible biomarkers and new therapeutic targets. Genes identified and/or proposed to be linked to PD encode proteins that fulfill diverse roles in cellular functions. There is a growing interest in identifying common traits which lead to the disease. Long non-coding RNAs have recently emerged as possible regulatory hubs of complex molecular changes affecting PD development. Among them, NEAT1 has attracted particular interest. It is a major component and the initiator of nuclear paraspeckles, thus regulating transcription and modifying protein functions. This review summarizes data available on the role of NEAT1 in PD. NEAT1 upregulation in PD has repeatedly been reported, however, whether this is part of a protective or a damaging mechanism is still a topic of debate. It has been proposed that NEAT1 propagates PD via its interaction with PINK1 and several micro RNAs and by modulating SNCA expression. On the other hand, findings of NEAT1 acting as a bona fide LRRK2 inhibitor argue for its protective role. These contradictory results could be due to the different disease models implemented. This calls attention to the difficulties posed by the complex patho-mechanisms of neurodegenerative disorders and the limitations of disease models. However, the potential of NEAT1 as a biomarker and as a therapeutic target for PD highly warrants further research to elucidate its exact role in this neurodegenerative disorder.

Introduction: Parkinson's disease (PD) is a progressive, chronic neurodegenerative disorder. The main neuropathological cause of the disease is the death of dopaminergic neurons in the substantia nigra. Unfortunately, there is no curative treatment yet. The gold-standard of the treatment is levodopa (LD). During the course of the disease, motor complications develop, which postulates the addition of entacapone (ENT) to the dopaminergic medication. Previous studies have suggested that patients have a better quality of life when entacapone is added in a combination with LD., Areas Covered: A systematic literature search was performed. Articles were identified through PubMed (MEDLINE), Web of Science, Ovid, and ClinicalTrials.gov databases. The following search terms were used: 'Levodopa' AND 'Carbidopa' OR 'Benserazide' AND 'Entacapone'. The search period was between 2000 and 2020. Twenty randomized and 10 non-randomized clinical trials (12,893 subjects) were included in the qualitative analysis. The systematic review was written in line with the PRISMA guideline., Expert Opinion: ENT administered in combination with LD resulted in a better quality of life compared to separate tablets. Therefore, in PD patients where impaired motor performance develops and the application of entacapone is necessary, it is suggested to be administered in a single tablet form.

Background and Purpose: The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients., Methods: The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method., Results: Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9)., Conclusion: Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Behind the symptoms there is a complex pathological mechanism which leads to a dopaminergic cell loss in the substantia nigra pars compacta. Despite the strong efforts, curative treatment has not been found yet. To prevent a further cell death, numerous molecules were tested in terms of neuroprotection in preclinical (in vitro, in vivo) and in clinical studies as well. The aim of this review article is to summarize our knowledge about the extensively tested neuroprotective agents (Search period: 1991-2019). We detail the underlying pathological mechanism and summarize the most important results of the completed animal and clinical trials. Although many positive results have been reported in the literature, there is still no evidence that any of them should be used in clinical practice (Cochrane analysis was performed). Therefore, further studies are needed to better understand the pathomechanism of PD and to find the optimal neuroprotective agent(s).

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder that poses serious burden to individuals and society as well. Although a number of PD associated genetic factors have been identified, the molecular mechanism of the disease so far has not been completely elucidated. Involvement of long non-coding RNAs (lncRNAs) in the pathology of neurodegenerative disorders is attracting increased interest because of the diverse mechanisms lncRNAs affect gene expression and cellular homeostasis at different levels. We aimed to test the feasibility of detecting alterations in lncRNA levels in easily accessible samples of PD patients by routine laboratory technique. By narrowing the number of selected lncRNAs implicated in neurodegeneration and increasing the number of PD samples included, we found one out of 41 lncRNAs readily detectable in increased level in peripheral blood of PD patients. We detected NEAT1 to be significantly up-regulated in PD patients in multiple comparisons. NEAT1 is the core element of nuclear paraspeckles and it plays role in regulation of transcription, mRNA and miRNA levels, mitochondrial and cellular homeostasis. Our finding is in accord with recent data demonstrating changes in the level of NEAT1 in neurons of PD patients and in several models of the disease. However, to our knowledge this is the first study to report NEAT1 up-regulation in blood of PD patients. Identification of altered expression of this lncRNA in the periphery might help to a better understanding of the mechanisms underlying PD, and can contribute to the identification of new therapeutic targets and disease markers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction : Parkinson's disease is a neurodegenerative disorder which is characterized by the combination of motor and non-motor symptoms. As yet, there is no curative treatment. The gold standard for symptom control is levodopa. Two years after the start of substitution therapy, around 50% of patients experience some degree of fluctuation in motor performance. Catechol-O-methyltransferase (COMT) inhibitors are important agents in treating these fluctuations. Areas covered : This article summarizes our knowledge about a new third-generation COMT inhibitor, namely opicapone (OPC) (Search period: 2016-2019). The authors detail the pharmacological profile of OPC and summarize the results of completed clinical trials. In addition, they briefly summarize the achievements of the past few years. Expert opinion : Based on clinical trials conducted so far, OPC is an effective and safe new drug. In comparison to entacapone and tolcapone, it does not require close laboratory monitoring or multiple oral administrations, which may result in better adherence. No serious adverse event was reported during the drug development phases. Dyskinesia was the most common complaint. Further comparative studies and broader trial inclusion criteria are needed to help the decision between COMT inhibitors and to expand the patient spectrum where this drug can be applied.

Introduction: Parkinson's disease is the second most common neurodegenerative disease. Lifestyle, environmental effects and several genetic factors have been proposed to contribute to its development. Though the majority of PD cases do not have a family history of disease, genetic alterations are proposed to be present in 60 percent of the more common sporadic cases., Objective: The aim of this study is to evaluate the frequency of PD related specific risk variants of LRRK2, MAPT, SNCA and PARK10 genes in the Hungarian population. Out of the ten investigated polymorphisms three are proposed to have protective effect and seven are putative risk factors., Methods: For genotyping, TaqMan allelic discrimination and restriction fragment length polymorphism method was used. LRRK2 mutations were investigated among 124 sporadic PD patients and 128 healthy controls. MAPT and SNCA variant frequencies were evaluated in a group of 123 patients and 122 controls, while PARK10 variant was studied in groups of 121 patients and 113 controls., Results: No significant difference could be detected in the frequencies of the investigated MAPT and PARK10 variants between the studied Hungarian PD cases and controls. The minor allele of the risk factor S1647T LRRK2 variant was found to be more frequent among healthy male individuals compared to patients. Moreover, in the frequency of one of the investigated SNCA variant a significant intergroup difference was detected. The minor allele (A) of rs356186 is proposed to be protective against developing the disease. In accord with data obtained in other populations, the AA genotype was significantly more frequent among Hungarian healthy controls compared to patients. Similarly, a significant difference in genotype distribution was also found in comparison of patients with late onset disease to healthy controls, which was due to the higher frequency of AG genotype among patients., Conclusion: The frequencies of different gene variants show great differences in populations. Assessment of the frequency of variants of PD related genes variants is important in order to uncover the pathomechanisms underlying the disease, and to identify potential therapeutic targets. This is the first comprehensive study focusing on these genetic variants in the population of East-Central European region. Our results extend the knowledge on the world wide occurrence of these polymorphisms by demonstrating the occurrence of specific alleles and absence of others in Hungarian PD patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The treatment of Parkinson's disease depends on the symptoms of the patients and obviously the stage of the disease. Several different approaches can be found in the literature. Based on the published data, in this review we try to summarize the different approaches to the disease stages and theirs' clinical relevance. Actually, one of the most important issue is the recognition of advanced stage and therefore we reviewed the device-aided therapies.

Background: Levodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG., Objectives: Our aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment., Methods: In this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS., Results: Non-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14-23) to 16 points (median, IQR:12-20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20-29) to 18 points (median, IQR:13-25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9-50.3) to 27.0 (median, IQR:21.3-31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36-54) to 34 (median, IQR:21-45) points (p = 0.003)., Conclusions: As far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The treatment of advanced Parkinson's disease is challenging for both physicians and caregivers. The device-aided therapies need expertise and dedicated hospital centers. In this summary we have concluded the available data and recommendation for the treatment options in advanced Parkinson's disease and adopt them to the daily care in Hungary.

Introduction: A different innervation pattern of proximal and distal muscles from the contra- and ipsilateral motor circuits raises the question as to whether bilateral, contra- and ipsilateral subthalamic stimulation may have different effects on the distal and proximal movements of the upper limb. To answer this question, we performed kinematic analyzes in patients with Parkinson's disease., Methods: Twenty-eight Parkinsonian patients treated by bilateral subthalamic stimulation were examined with an age-matched control group of 28 healthy subjects. They performed 14s of finger tapping, hand grasping and pronation-supination. The patient group performed these sessions in four conditions (BOTH ON, BOTH OFF, CONTRA ON, IPSI ON) after withdrawal of dopaminergic medication for 12h and a fifth condition after taking medication (BOTH ON-MED ON). A motion sensor with a three-dimensional gyroscope was worn on the index finger. Speed, amplitude, rhythm and decrement of movements were calculated and compared across these conditions., Results: Speed and amplitude of the more distal movements were improved similarly by contra- and bilateral stimulation. Bilateral stimulation was more effective than contralateral stimulation for the more proximal movements. Contra- and bilateral stimulation ameliorated the rhythm similarly in each movement task. Decrement of distal and proximal movements was not affected by the stimulation conditions., Conclusion: This is the first study to show that the outcome of bi- and unilateral subthalamic stimulation on proximal and distal upper limb movements should be evaluated separately postulating the different somatotopic organization of subloops in the cortico-basal ganglia motor circuits., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is the second most common neurodegenerative disorder, with cases of either familial or sporadic origin. Several polymorphisms in a number of genes have been proved to have an important role in the development of PD. Particular attention has recently been paid to genes of the glucocerebrosidase (GBA) and the vacuolar protein sorting-associated protein 35 (VPS35). In this study, the three most common mutations (L444P, N370S and R120W) of the GBA gene and the D620N mutation of the VPS35 gene were examined in 124 Hungarian patients diagnosed with sporadic PD (SPD) and 122 control subjects. The frequency of the L444P mutation of the GBA gene proved to be higher in the PD patients (2.4%) than in the controls (0%), although the difference was not statistically significant. All the patients who carried the mutant allele were in the early-onset PD (EOPD) group. However, neither the R120W nor the N370S variant of the GBA gene nor D620N mutation of the VPS35 gene were detected among the PD cases or the controls. Even though these results suggest that the studied mutations are quite rare in SPD patients, the most frequent L444P mutation of the GBA gene may be associated with the development of EOPD in the Hungarian population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In the advanced Parkison's disease (PD) the late complications of levodopa therapy have to be considered: motor and/or non-motor fluctuations with or without disturbing dyskinesias. The non-motor fluctuations often influence the quality of life (QoL) in a much more negative way compared with the motor symptoms. In the treatment of advanced PD there are several device-aided methods - deep brain stimulation, apomorphine pump, levodopa/carbidopa intestinal gel (LCIG) - to improve the symptoms, the QoL, sometimes even in an individual, tailored custom form. The LCIG therapy was introduced in Hungary in 2011. Here we summarize the data of our patients: we have tested almost 60 patients and in 43 cases we have started this treatment. We analyze the duration of illness, levodopa therapy, motor and non-motor fluctuation of patients and present our experiences with the test phase and the chronic LCIG therapy via PEG/PEJ implantation. We paid attention to the surgery and device - depending side effects. Our experiences are similar to the international data. In patients selection ,,the right treatment, to the right patient, in the right time" is of importance.

Background: The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian., Methods: Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version., Results: For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94., Conclusion: The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

The motor complications in advanced Parkinson's disease may interfere with the quality of life. To overcome this disability, a jejunal levodopa pump was developed. In this review we have summarized the published clinical data with this method.

Goals: The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-b nding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1 ,2, 4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Methods: Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography., Results: Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder with a considerable socioeconomic burden. The pathomechanism of PD clearly involves the synergistic interaction of dopaminergic and glutamatergic dysfunctioning, including maladaptive corticostriatal synaptoplasticity. Most of the available treatment options have the aim of restoration of the physiological dopaminergic activity. Currently, the most widely used treatment is L-3,4-dihydroxyphenylalanine (L-DOPA), which leads to the best symptomatic relief in PD. However, the long-term use of L-DOPA results in abnormal involuntary movements in almost all cases, the development of these dyskinetic movements also involving maladaptive corticostriatal synaptoplasticity. Perhaps chronic L-DOPA treatment has neurotoxic effects as well, but it has not yet been proved in clinical studies. Another important group of dopamine replacement therapy (DRT)-related side-effects consists of disinhibitory psychopathologies. Recent studies revealed that genetic polymorphisms affecting certain dopaminergic and glutamatergic receptors serve as independent risk factors for the development of these pathological conditions in PD patients. The available scientific data demonstrate that alterations in the kynurenine pathway of the tryptophan metabolism can be observed in PD and these alterations may contribute to the disease pathogenesis and to the occurrence of DRT-related side-effects. Therapeutic strategies that target the restoration of the kynurenine metabolism could therefore hold promise.

Parkinson's disease is a promising target of applying personalized medicine. For this purpose it is crucial to reveal the genetic and environmental factors, which contribute to the disease, also to collect epidemiologic data and to preserve the patients samples and data in a proper biobank. In our investigation we examined the prevalence of the most frequent Parkinson's disease causing LRRK2 G2019S mutation in a Hungarian Parkinson-patient group. From 120 patients, we haven't detected this substitution in anyone. Our investigation suggest that the mutation LRRK2 G2019S may be a rare cause of Parkinson disease in the Hungarian population.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder the pathomechanism of which is not yet fully known. With regard to the molecular mechanism of development of the disease, oxidative stress/mitochondrial impairment, glutamate excitotoxicity and neuroinflammation are certainly involved. Alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, can contribute to the complex pathomechanism. There are several possibilities for therapeutic intervention involving targeting of this altered metabolic route. The development of synthetic molecules that would shift the altered balance towards the achievement of neuroprotective effects would be of great promise for future clinical studies on PD.

Pramipexol retard is the newest drug for the treatment of Parkinson's disease. The prolonged release of the agent in this preparation allows a more continuous dopaminergic stimulation than previous preparations, without reducing the agent's already known and proven clinical efficiency. In addition, it has a more favourable adverse effect profile than previous preparations, and patient compliance can also be better as it needs to be taken only once daily. These benefits have been proven in recent clinical studies, of which the most important ones are reviewed here.

The triple combination of levodopa, DDCI and entacapone (Stalevo) is used to treat motor complication in patients with Parkinson's disease. In this study we summarized the clinical data of our patients treated with Stalevo for the longest period. We can concluded, that after switching to Stalevo due to wearing off, the average levodopa doses were lower then before and the motor complications were milder. After 3 years of Stalevo therapy the levodopa doses were increased but still did not reach the average doses before introducing Stalevo. After switching the patients' general well-being was improved as indicated by the visual analogue scale. In summary, the Stalevo treatment is safe and effective for long run and improves the patients' quality of life.

The authors summarized the evidence supporting neuroprotection based on the data available in the literature. In vivo and in vitro studies have indicated that many compounds can decrease neurodegeneration, excitotoxicity, oxidative stress, protein aggregation, disturbance of Ca2+ homeostasis and compensate the energy impairment. Selegiline, rasagiline, dopamine agonists and other molecules (ubiquinone, kynurenic acid, tocopherol, creatine, glatiramer acetate) exert neuroprotective effects in preclinical studies. Much less clinical data are available regarding neuroprotection in different neurological disorders. In this review, such preclinical and clinical evidences are summarized.

The triple combination of levodopa, DDCI and entacapone (Stalevo) is used to treat motor complication in Parkinsonian patients with fluctuation. An observational investigation has been conducted in Hungary to study the effects of Stalevo on the "wearing off" phenomenon and on the quality of life in patients, who are to be treated with. The introduction of Stalevo to the treatment resulted in no changes in the number of patients taking selegiline, amantadine and dopamine agonists, while the number of patients taking anticholinergic drugs were slightly increased. This treatment significantly decreased the average Hoehn-Yahr stadium, as well as the non-motor symptoms, without any remarkable side effect. Stalevo also improved the quality of life, detected by the EQ-5D questionnaire and the visual analogue scale.

Despite the levodopa is used for the treatment of Parkinson's disease for a long time, recently many questions raised about its clinical use. New issues emerged based on the clinical trials, on latest neuroimaging data and on better understanding the pathomechanism of motor complications. These observations have changed the routine clinical use of levodopa. In this review we summarize the evidences and practical implications of levodopa therapy.