Predictors of falls in Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy: a retrospective study

Introduction. Recurrent falling is a major clinical milestone in Parkinsonian syndromes. It has a detrimental impact on quality of life, further prognosis, and life expectancy.Aim of the study. To improve fall management and prevention, we aimed at identifying clinical parameters predicting fall frequency. To this end, we retrospectively analysed records of fall events of patients with Parkinson’s disease (PD), or progressive supranuclear palsy (PSP), or multiple system atrophy (MSA), during their two-week inpatient stay at the Parkinson-Klinik Ortenau, Wolfach, Germany. This data served as an objective proxy for patients’ fall frequency and allowed us to estimate the impact of several demographic and clinical variables on the occurrence of falling.Material and methods. Of 2,111 patients admitted to our hospital, 1,810 presented with PD, 191 with PSP, and 110 with MSA. We employed a multiple (quasi-) poisson regression analysis to model the fall frequency as a function of various demographic variables (age at diagnosis, gender) and clinical variables (disease duration and sub-type, motor and cognitive impairment, autonomic dysfunction).Results. Statistically significant predictors for falls in PD were cognitive impairment, motor impairment, and autonomic dysfunction. In PSP, significant predictors for falls were motor and autonomic dysfunction, while in MSA only disease duration predicted falls, but with only marginal statistical significance.Conclusions. Our results stress the importance of different factors in predicting falls in the different types of Parkinsonian syndrome. Preventive interventions should address these disease-specific targets for optimal success

Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia

To determine if NMDA receptor alterations are present in the cerebellum in schizophrenia, we measured NMDA receptor binding and gene expression of the NMDA receptor subunits in a post-mortem study of elderly patients with schizophrenia and non-affected subjects. Furthermore, we assessed influence of genetic variation in the candidate gene neuregulin-1 (NRG1) on the expression of the NMDA receptor in an exploratory study. Post-mortem samples from the cerebellar cortex of ten schizophrenic patients were compared with nine normal subjects. We investigated NMDA receptor binding by receptor autoradiography and gene expression of the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D by in situ hybridization. For the genetic study, we genotyped the NRG1 polymorphism rs35753505 (SNP8NRG221533). Additionally, we treated rats with the antipsychotics haloperidol or clozapine and assessed cerebellar NMDA receptor binding and gene expression of subunits to examine the effects of antipsychotic treatment. Gene expression of the NR2D subunit was increased in the right cerebellum of schizophrenic patients compared to controls. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of the NR2C subunit in the right cerebellum, compared to individuals homozygous for the T allele. Correlation with medication parameters and the animal model revealed no treatment effects. In conclusion, increased NR2D expression results in a hyperexcitable NMDA receptor suggesting an adaptive effect due to receptor hypofunction. The decreased NR2C expression in NRG1 risk variant may cause a deficit in NMDA receptor function. This supports the hypothesis of an abnormal glutamatergic neurotransmission in the right cerebellum in the pathophysiology of schizophrenia

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Dementia with Lewy bodies

Dementia with Lewy bodies is characterized histopathologically by the deposition of alpha-synuclein in inclusion bodies. Clinical diagnosis is based on progressive cognitive deficits, cognitive fluctuations, early visual hallucinations, REM sleep disorders and symptoms of Parkinsonism. On the basis of the new criteria published in 2017, better differentiation from other neurodegenerative diseases with dementia should be possible. Therapy concepts include treatment of loss of motor and cognitive performance as well as psychological and behavioral symptoms. At present, only a few studies are available on this clinical picture so that evidence-based therapy approaches are only possible to a limited extent

Recommendation for the differentiated use of nuclear medical diagnostic for parkinsonian syndromes

Zusammenfassung Die vorliegende Arbeit gibt einen uberblick uber die verschiedenen nuklearmedizinischen Verfahren in der Diagnostik bei neurodegenerativen Parkinson-Syndromen sowie ihre Evidenzlage und soll praxistaugliche Entscheidungshilfen in der Anwendung und Interpretation der Methoden und Befunde ermoglichen. Die Wertigkeit der Verfahren unterscheidet sich erheblich in Bezug auf die beiden relevanten diagnostischen Fragestellungen. Dies ist zum einen die Frage, ob uberhaupt ein neurodegeneratives Parkinson-Syndrom vorliegt, zum anderen die Frage, welches. Wahrend zur Beantwortung der ersten Frage das DAT-SPECT unter Berucksichtigung gewisser Parameter in der Praxis unbestritten die Methode der Wahl ist, eignet sich dieses Verfahren nicht zur Beantwortung der zweiten Fragestellung. Zur Unterscheidung der Parkinson-Syndrome in idiopathisch oder atypisch werden im klinischen Alltag mit der MIBG-Szintigraphie und dem FDG-PET verschiedene Verfahren angewendet. Wir legen dar, warum das FDG-PET von diesen Methoden nicht nur die geeignetste ist, um ein idiopathisches Parkinson-Syndrom von einem atypischen Parkinson-Syndrom abzugrenzen, sondern auch ausreichend valide ermoglicht, die verschiedenen atypischen neurodegenerativen Parkinson-Syndrome (d.h. MSA, PSP und CBD) voneinander zu unterscheiden, und deshalb in den Leistungskatalog der GKV aufgenommen werden sollte. Abstract The present work provides an overview of the various nuclear medicine methods in the diagnosis of neurodegenerative parkinsonian syndromes and their respective evidence and is intended to enable practical decision-making aids in the application and interpretation of the methods and findings. The value of the procedures differs considerably in relation to the two relevant diagnostic questions. On the one hand, it is the question of whether there is a neurodegenerative parkinsonian syndrome at all, and on the other hand the question of which one. While the DAT-SPECT is undisputedly the method of choice for answering the first question (taking certain parameters into account), this method is not suitable for answering the second question. To categorise parkinsonian syndromes into idiopathic (i.e. Parkinson ' s disease) or atypical, various procedures are used in everyday clinical practice including MIBG scintigraphy, and FDG-PET. We explain why FDG-PET currently is not only the most suitable of these methods to differentiate an idiopathic parkinsonian syndrome, from an atypical Parkinson's syndrome, but also enables sufficiently valid to distinguish the various atypical neurodegenerative Parkinson's syndromes (i.e. MSA, PSP and CBD) from each other and therefore should be reimbursed by health insurances