Background Genome-wide association studies (GWASs) in Parkinson's disease (PD) have increased the scope of biological knowledge about the disease over the past decade. We sought to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into disease etiology. Methods We performed the largest meta-GWAS of PD to date, involving the analysis of 7.8M SNPs in 37.7K cases, 18.6K UK Biobank proxy-cases (having a first degree relative with PD), and 1.4M controls. We carried out a meta-analysis of this GWAS data to nominate novel loci. We then evaluated heritable risk estimates and predictive models using this data. We also utilized large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type and biological pathway enrichments for the identified risk factors. Additionally we examined shared genetic risk between PD and other phenotypes of interest via genetic correlations followed by Mendelian randomization. Findings We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of PD depending on prevalence. Integrating methylation and expression data within a Mendelian randomization framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested PD loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes, smoking status, and educational attainment. Mendelian randomization between cognitive performance and PD risk showed a robust association. Interpretation These data provide the most comprehensive understanding of the genetic architecture of PD to date by revealing many additional PD risk loci, providing a biological context for these risk factors, and demonstrating that a considerable genetic component of this disease remains unidentified. Funding See supplemental materials (Text S2). lead to earlier detection and refined diagnostics, which may help improve clinical trials (4). The generation of copious amounts of public summary statistics created by this effort relating to both the GWAS and subsequent analyses of gene expression and methylation patterns may be of use to investigators planning follow-up functional studies in stem cells or other cellular screens, allowing them to prioritize targets more efficiently using our data as additional evidence. We hope our findings may have some downstream clinical impact in the future such as improved patient stratification for clinical trials and genetically informed drug targets.

Background: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. Methods: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. Results: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [123I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. Conclusions: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role ...

Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.

Mutations in the gene encoding the dopamine-synthetic enzyme GTP cyclohydrolase-1 (GCH1) cause DOPA-responsive dystonia (DRD). Mencacci et al. demonstrate that GCH1 variants are associated with an increased risk of Parkinson's disease in both DRD pedigrees and in patients with Parkinson's disease but without a family history of DRD.

Background and purpose: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. Incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. Methods: A 17-question on-line survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on April 9 th , 2020.Results: By April 27 th, 2020, proper data were collected from 2,343 responders (out of 4,199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of .The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%), and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19, they were most commonly recognized in patients with multiple general symptoms, and occurred at any time during infection. Conclusion:Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Parkinson=Plus. C.H.W.-G. has received honoraria from Lundbeck and consultancy payments from Modus Outcomes and Evidera. C.T. is supported by EU Grant Horizon 2020/propag-ageing and the MJFF. C.K. serves as a medical advisor to Centogene for genetic testing reports in the fields of movement disorders and dementia, excluding Parkinson's disease.

BackgroundThe objective of this study was to investigate factors affecting health-related quality of life (HRQoL) among Estonian persons with Parkinson’s disease (PD).Methods268 persons with PD were evaluated using: the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS); the Hoehn and Yahr scale (HY); the Schwab and England Activities of Daily Living scale (SE-ADL); the Beck Depression Inventory (BDI); the Mini Mental State Examination (MMSE); the Parkinson’s Disease Questionnaire (PDQ-39). Additional questions on clinical and socio-demographic variables were asked during a semi-structured interview. Predictors of HRQoL were tested using multiple regression analysis.ResultsThe main predictors of low HRQoL were depression and motor and non-motor aspects of daily living. 59.9 % of the variation in the PDQ-39 summary index (SI) score was explained by the predictive variables identified in this study. None of the socio-demographic variables (age, gender, urban/rural living, marital status, living alone/with others, education level) were significant predictors of HRQoL. Prevalence of non-motor Parkinson’s symptoms were high (99.6 %); cognitive impairment, sleep and urinary problems were the most common. All non-motor symptoms correlated significantly with low HRQoL, except the features of impulse control disorders (ICDs).ConclusionsDepression and motor and non-motor daily living experiences were found to be significant and independent factors of low HRQoL in persons with PD. Depression was the strongest determinant of low HRQoL. Our results highlight the importance of recognition and management of non-motor symptoms, as these features had more impact on patients’ HRQoL than clinically assessed motor symptoms.

The lower extremity performance in elderly female patients with mild to moderate Parkinson's disease (PD; n = 12) and controls (n = 16) was compared. Isometric dynamometry and force-plate measurements were used. PD patients had lower (p < .05) bilateral (BL) maximal isometric leg-extension force (MF), BL isometric MF relative to body mass, and maximal rate of isometric force development than control participants. BL strength deficit was greater (p < .05) in PD patients than in controls. A significantly longer chair-rise time and lower maximal rate of vertical-ground-reaction-force development while rising from a chair was found in PD patients than in controls. These findings suggest that elderly women with PD have lowered voluntary isometric force-generation capacity of the leg-extensor muscles. Reduced BL leg-extension strength might contribute to the difficulty of individuals with PD to rise from a chair.