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Parkinson Disease: HELP
Articles by Claudia Trenkwalder
Based on 74 articles published since 2008
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Between 2008 and 2019, C. Trenkwalder wrote the following 74 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial What would Dr. James Parkinson think today? The 21st Annual Congress of the International Parkinson's disease and movement disorders society. 2017

Obeso, Jose A / Trenkwalder, Claudia. ·HM CINAC, HM Puerta del Sur, and CEU-San Pablo University, Madrid. CIBERNED, Institute Carlos III, Spain. · Department of Neurosurgery, University Medical Center, Goettingen, and Paracelsus-Elena Hospital, Kassel, Germany. ·Mov Disord · Pubmed #28712120.

ABSTRACT: -- No abstract --

2 Review Pain in Parkinson's disease: facts and uncertainties. 2018

Antonini, A / Tinazzi, M / Abbruzzese, G / Berardelli, A / Chaudhuri, K R / Defazio, G / Ferreira, J / Martinez-Martin, P / Trenkwalder, C / Rascol, O. ·University of Padua, Padua. · University of Verona, Verona. · University of Genoa, Genoa. · University of Rome, Rome. · IRCCS NEUROMED, Isernia, Italy. · Kings College London, London, UK. · University of Cagliari, Cagliari, Italy. · Hospital de Santa Maria, Lisbon, Portugal. · National Center of Epidemiology and CIBERNED, Madrid, Spain. · University Medical Center Goettingen, Goettingen, Germany. · Université de Toulouse, Toulouse, France. ·Eur J Neurol · Pubmed #29520899.

ABSTRACT: Pain is one of the most common and troublesome non-motor symptoms of Parkinson's disease (PD). It can appear at any time during the disease and is often present before diagnosis. However, there is little or no consensus on its definition. An expert group of clinicians with relevant research experience met to review the existing evidence and to identify gaps in our understanding leading towards AUTHOR: 'understanding towards' has been changed to 'understanding leading towards'. Please check and confirm that this is appropriate an optimized therapy of pain in PD. Key findings from epidemiologic, neurophysiologic, neuroimaging and clinical studies are reviewed. In each case, the evidence base is limited by wide variations in the definitions of pain applied, study methodologies and populations evaluated. Disease-related and medical conditions trigger spontaneous pain in patients with PD, which is then abnormally processed and results in painful manifestations in specific body parts. Dopaminergic medications, such as rotigotine, as well as opiate analgesics, such as oxycodone, have shown positive results but future studies with more detailed pain characterization at inclusion are warranted.

3 Review Getting a good night sleep? The importance of recognizing and treating nocturnal hypokinesia in Parkinson's disease. 2018

Bhidayasiri, Roongroj / Trenkwalder, Claudia. ·Chulalongkorn Center of Excellence on Parkinson Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand; Department of Rehabilitation Medicine, Juntendo University, Tokyo, Japan. Electronic address: rbh@chulapd.org. · Department of Neurosurgery, University Medical Center Gottingen, Paracelsus Elena Hospital, Kassel, Germany. ·Parkinsonism Relat Disord · Pubmed #29336905.

ABSTRACT: When Parkinson's disease (PD) patients are asked about the quality of their sleep, their answers are dominated by difficulties associated with impaired mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70% of PD patients, and contributes to poor sleep quality, and increased carer burden. Here we explore four areas of nocturnal hypokinesia that are relevant to clinical practice, namely: manifestations and definition; clinical assessment and objective monitoring; etiologies and contributing factors; and evidence-based therapeutic approaches. In addition, we provide an operational definition of what constitutes nocturnal hypokinesia and outline different methods of assessment, ranging from clinical interviews and rating scales to objective night-time monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in PD begins with recognizing its manifestation by inquiring about cardinal symptoms and contributing factors from, not only patients, but also carers, followed by formal assessment, and the application of individualized evidence-based treatment. Night-time dopaminergic treatment is the primary therapy; however, careful clinical judgment is required to balance the benefits with the potential adverse events related to nocturnal dopaminergic stimulation. Future studies are needed to explore the practicality of home-based objective assessment of nocturnal hypokinesia, new therapeutic options not limited to dopaminergic medications, and non-pharmacologic approaches, including training on compensatory strategies and bedroom adaptations.

4 Review [Pharmacotherapy of Parkinson's disease : Aspects of drug safety]. 2017

Müller-Rebstein, S / Trenkwalder, C / Oertel, W H / Culmsee, C / Eckermann, G / Höglinger, G U. ·Klinik für Neurologie, Klinikum rechts der Isar, Technische Universität München und Lehrstuhl für Translationale Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE) München, Feodor-Lynen Str. 17, 81377, München, Deutschland. · Institut für Pharmakologie und Klinische Pharmazie, Philipps-Universität Marburg, Marburg, Deutschland. · Paracelsus Elena-Klinik Kassel, Klinik für Neurochirurgie, Universitätsmedizin Göttingen, Göttingen, Deutschland. · Klinik für Neurologie, Philipps-Universität Marburg, Marburg, Deutschland. · Institut für Neurogenomik, Helmholtz Zentrum für Gesundheit und Umwelt München, München, Deutschland. · Fachkrankenhaus für Psychiatrie, Psychotherapie, Psychosomatik und Neurologie, Bezirkskrankenhaus Kaufbeuren, Kaufbeuren, Deutschland. · Klinik für Neurologie, Klinikum rechts der Isar, Technische Universität München und Lehrstuhl für Translationale Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE) München, Feodor-Lynen Str. 17, 81377, München, Deutschland. Guenter.Hoeglinger@tum.de. ·Nervenarzt · Pubmed #28497256.

ABSTRACT: BACKGROUND: This overview focuses on the aspects of the pharmacotherapy of Parkinson's disease, which is one of the most common disorders of the nervous system. This article presents the complexity of the pharmacotherapy of geriatric patients with neurological diseases. OBJECTIVES: Information about the potential risk factors and aspects of drug safety in the pharmacotherapy of Parkinson's disease. MATERIALS AND METHODS: Selective literature search using PubMed and the scientific-clinical experience of the authors. RESULTS: Patients with Parkinson's disease are usually geriatric patients with concomitant diseases. As a result they are often treated with comedication which leads to a complex medication regime with more than five drugs. Such polypharmacy increases the risk of adverse drug events due to the rising number of possible interactions and contraindications. To control this risk and maintain a safe therapy, certain measures should be considered. This implies additional need for educational work in order to create awareness regarding potential adverse drug events. In certain cases of diagnosed comorbidities or relevant drug prescriptions in the medication regime, follow-up examinations should be conducted. CONCLUSION: Specific parameters of Parkinson's disease, the health-related quality of life of affected patients and the quality of pharmacotherapeutic drug safety can be improved by targeted monitoring of the medication regime. As a result, the overall drug safety can be increased.

5 Review Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations. 2015

Trenkwalder, Claudia / Chaudhuri, K Ray / García Ruiz, Pedro J / LeWitt, Peter / Katzenschlager, Regina / Sixel-Döring, Friederike / Henriksen, Tove / Sesar, Ángel / Poewe, Werner / Anonymous6190836 / Baker, Mary / Ceballos-Baumann, Andres / Deuschl, Günther / Drapier, Sophie / Ebersbach, Georg / Evans, Andrew / Fernandez, Hubert / Isaacson, Stuart / van Laar, Teus / Lees, Andrew / Lewis, Simon / Martínez Castrillo, Juan Carlos / Martinez-Martin, Pablo / Odin, Per / O'Sullivan, John / Tagaris, Georgios / Wenzel, Karoline. ·Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurosurgery, University Medical Centre, Goettingen, Germany. Electronic address: trenkwalder@pk-mx.de. · National Parkinson Foundation Centre of Excellence, Kings College Hospital, Denmark Hill Campus, London, UK. · Movement Disorders Unit, Department of Neurology, Fundacion Jimenez Diaz, Madrid, Spain. · Wayne State University School of Medicine, Parkinson's Disease and Movement Disorders Program, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, USA. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital, Vienna, Austria. · Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurology, Philipps-University, Marburg, Germany. · Movement Disorder Clinic, Bispebjerg Hospital, Copenhagen, Denmark. · Department of Neurology, Hospital Clínico Universitario, Santiago de Compostela, Spain. · Department of Neurology, Medical University of Innsbruck, Austria. ·Parkinsonism Relat Disord · Pubmed #26189414.

ABSTRACT: Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation.

6 Review Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. 2013

Ferreira, J J / Katzenschlager, R / Bloem, B R / Bonuccelli, U / Burn, D / Deuschl, G / Dietrichs, E / Fabbrini, G / Friedman, A / Kanovsky, P / Kostic, V / Nieuwboer, A / Odin, P / Poewe, W / Rascol, O / Sampaio, C / Schüpbach, M / Tolosa, E / Trenkwalder, C / Schapira, A / Berardelli, A / Oertel, W H. ·Laboratory of Clinical Pharmacology and Therapeutics and Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. ·Eur J Neurol · Pubmed #23279439.

ABSTRACT: OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

7 Review Lewy body and parkinsonian dementia: common, but often misdiagnosed conditions. 2010

Mollenhauer, Brit / Förstl, Hans / Deuschl, Günther / Storch, Alexander / Oertel, Wolfgang / Trenkwalder, Claudia. ·Paracelsus-Elena-Klinik, Kassel, Germany. brit.mollenhauer@pk-mx.de ·Dtsch Arztebl Int · Pubmed #20963199.

ABSTRACT: BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are the two most common types of dementing neurodegenerative disease after Alzheimer's disease (AD). Both of these conditions are often diagnosed late or not at all. METHODS: Selective literature review. RESULTS: The severe cholinergic and dopaminergic deficits that are present in both DLB and PDD produce not only motor manifestations, but also cognitive deficits, mainly in the executive and visual-constructive areas, as well as psychotic manifestations such as visual hallucinations, delusions, and agitation. The intensity of these manifestations can fluctuate markedly over the course of the day, particularly in DLB. Useful tests for differential diagnosis include magnetic resonance imaging and electroencephalography; in case of clinical uncertainty, nuclear medical procedures and cerebrospinal fluid analysis can be helpful as well. Neuropathological studies have revealed progressive alpha-synuclein aggregation in affected areas of the brain. In DLB, beta-amyloid abnormalities are often seen as well. CONCLUSION: DLB should be included in the differential diagnosis of early dementia. If motor manifestations arise within one year (DLB), dopaminergic treatment should be initiated. On the other hand, patients with Parkinson's disease should undergo early screening for signs of dementia so that further diagnostic and therapeutic steps can be taken in timely fashion, as indicated. Cholinesterase inhibitors are useful for the treatment of cognitive deficits and experiential/behavioral disturbances in both DLB (off-label indication) and PDD (approved indication).

8 Review Quantification of α-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. 2010

Mollenhauer, Brit / El-Agnaf, Omar M A / Marcus, Katrin / Trenkwalder, Claudia / Schlossmacher, Michael G. ·Paracelsus-Elena-Klinik, Kassel, Klinikstrasse 16, 34128 Kassel, Germany. brit.mollenhauer@pk-mx.de ·Biomark Med · Pubmed #20945981.

ABSTRACT: The pursuit of laboratory tests that allow for the reliable and inexpensive identification of subjects with parkinsonism represents a hot topic in translational neuroscience. This unmet need affects the counseling of presymptomatic, at-risk subjects and delays the accurate diagnosis of already symptomatic individuals. The absence of validated markers that are closely linked to the pathological disease process also compromises the objective monitoring of therapeutic interventions in clinical trials. Typical Parkinson's disease represents a heterogenous syndrome (but the majority of patients suffer from neurodegeneration) that is linked to the misprocessing of α-synuclein (α-Syn). The identification of α-Syn as a bona fide constituent of human cerebrospinal fluid and its quantification in early cross-sectional studies represent the beginning of a new chapter in Parkinson's disease research. It will determine what role, if any, cerebrospinal fluid α-Syn plays as a biomarker candidate in Lewy inclusion-positive forms of parkinsonism. This article focuses on the progress that has been made in seven recently published papers and highlights the challenges that lie ahead. We also provide specific information regarding standardized operating procedures for cerebrospinal fluid collection in PD biomarker research efforts.

9 Review Scales to assess sleep impairment in Parkinson's disease: critique and recommendations. 2010

Högl, Birgit / Arnulf, Isabelle / Comella, Cynthia / Ferreira, Joaquim / Iranzo, Alex / Tilley, Barbara / Trenkwalder, Claudia / Poewe, Werner / Rascol, Olivier / Sampaio, Cristina / Stebbins, Glenn T / Schrag, Anette / Goetz, Christopher G. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. birgit.ho@i-med.ac.at ·Mov Disord · Pubmed #20931631.

ABSTRACT: There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). A variety of scales have been applied to the evaluation of PD sleep and wakefulness, but only a small number have been assessed specifically for clinimetric properties in the PD population. The movement disorder society has commissioned this task force to examine these scales and to assess their use in PD. A systematic literature review was conducted to explore the use of sleep scales in PD and to determine which scales qualified for a detailed critique. The task force members, all of whom have extensive experience in assessing sleep in PD reviewed each of the scales using a structured proforma. Scales were categorized into recommended, suggested and listed according to predefined criteria. A total of 48 potential scales were identified from the search and reviewed. Twenty-nine were excluded because they did not meet review criteria or were variations of scales already included, leaving 19 scales that were critiqued and rated by the task force based on the rating criteria. Only six were found to meet criteria for recommendation or suggestion by the task force: the PD sleep scale (PDSS) and the Pittsburgh sleep quality index (PSQI) are recommended for rating overall sleep problems to screen and to measure severity, the SCOPA-sleep (SCOPA) is recommended for rating overall sleep problems both to screen and to measure severity, and for rating daytime sleepiness; the Epworth sleepiness scale (ESS) is recommended for rating daytime sleepiness to screen and to measure severity; the inappropriate sleep composite score (ISCS) is suggested for rating severe daytime sleepiness or sleep attacks to screen and to measure severity; and the Stanford sleepiness scale (SSS) is suggested for rating sleepiness and to measure severity at a specific moment. The task force does not recommend the development of new scales, but emphasizes the need for educational efforts to train physicians in sleep interview techniques and polysomnography.

10 Clinical Trial Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. 2018

Katzenschlager, Regina / Poewe, Werner / Rascol, Olivier / Trenkwalder, Claudia / Deuschl, Günther / Chaudhuri, K Ray / Henriksen, Tove / van Laar, Teus / Spivey, Kevin / Vel, Senthil / Staines, Harry / Lees, Andrew. ·Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital, Vienna, Austria. Electronic address: regina.katzenschlager@wienkav.at. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Université de Toulouse 3, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Centre d'Investigation Clinique CIC1436, Réseau Ns-Park, French Clinical Research Infrastructure Network, Centre Expert Parkinson de Toulouse, Centre d'Excellence en Maladies Neuro-dégénératives NeuroToul, Department of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, Toulouse, France. · Department of Neurosurgery, University Medical Center Goettingen, and Centre of Parkinsonism and Movement Disorders, Elena Hospital, Kassel, Germany. · Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany; Christian-Albrechts University, Kiel, Germany. · National Parkinson Foundation Centre of Excellence, Kings College Hospital, London, UK. · Movement Disorder Clinic, Bispebjerg Hospital, Copenhagen, Denmark. · Department of Neurology, University Medical Centre, Groningen, Netherlands. · Britannia Pharmaceuticals, Reading, UK. · Sigma Statistical Services, Balmullo, UK. · University College London Institute of Neurology, London, UK. ·Lancet Neurol · Pubmed #30055903.

ABSTRACT: BACKGROUND: Subcutaneous apomorphine infusion is a clinically established therapy for patients with Parkinson's disease with motor fluctuations not optimally controlled by oral medication. Open-label studies have shown that apomorphine infusion is effective in reducing off time (periods when antiparkinsonian drugs have no effect), dyskinesias, and levodopa dose, but confirmatory evidence from double-blind, controlled studies is lacking. We aimed to investigate the efficacy and safety of apomorphine infusion compared with placebo in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal treatment. METHODS: In this randomised, placebo-controlled, double-blind, multicentre trial, we enrolled patients at 23 European hospitals who had been diagnosed with Parkinson's disease more than 3 years previously and had motor fluctuations not adequately controlled by medical treatment. Patients were randomly assigned (1:1) with a computer-generated randomisation code, stratified by site, to receive 3-8 mg/h apomorphine or placebo saline infusion during waking hours (16 h a day [range 14-18 was acceptable]) for 12 weeks. The flow rate of the study drug and other oral medications could be adjusted during the first 4 weeks on the basis of individual efficacy and tolerability, after which patients entered an 8-week maintenance period. The primary endpoint was the absolute change in daily off time based on patient's diaries, and was assessed in the full analysis set, which was defined as all patients who received at least one dose of allocated study drug and had efficacy data available at any timepoint post-baseline. Safety was assessed in all patients who received at least one dose of apomorphine or placebo. All study participants and investigators were masked to treatment assignment. Both the 12-week double-blind phase and the 52-week open-label phase of this study are now complete; this paper reports results for the double-blind phase only. This study is registered with ClinicalTrials.gov (NCT02006121). FINDINGS: Between March 3, 2014, and March 1, 2016, 128 patients were screened for eligibility and 107 were randomly assigned, of whom 106 were included in the full analysis set (n=53 in both groups). Apomorphine infusion (mean final dose 4·68 mg/h [SD 1·50]) significantly reduced off time compared with placebo (-2·47 h per day [SD 3·70] in the apomorphine group vs -0·58 h per day [2·80] in the placebo group; difference -1·89 h per day, 95% CI -3·16 to -0·62; p=0·0025). Apomorphine was well tolerated without any unexpected safety signals. Six patients in the apomorphine group withdrew from the study because of treatment-related adverse events. INTERPRETATION: Apomorphine infusion results in a clinically meaningful reduction in off time in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal therapy. FUNDING: Britannia Pharmaceuticals.

11 Clinical Trial Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson's disease (EASE LID 3). 2017

Oertel, Wolfgang / Eggert, Karla / Pahwa, Rajesh / Tanner, Caroline M / Hauser, Robert A / Trenkwalder, Claudia / Ehret, Reinhard / Azulay, Jean Philippe / Isaacson, Stuart / Felt, Larissa / Stempien, Mary Jean. ·Philipps University, Marburg, Germany. · University of Kansas Medical Center, Kansas City, Kansas, USA. · University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · University of South Florida, Tampa, Florida, USA. · Paracelsus-Elena-Klinik, Kassel and Clinic Neurosurgery, University Medical Center, Goettingen, Germany. · Praxis Neurologie, Berlin, Germany. · Hôpital de la Timone, Marseille, France. · Parkinson's Disease and Movement Disorders Center, Boca Raton, Florida, USA. · Adamas Pharmaceuticals, Inc., Emeryville, California, USA. ·Mov Disord · Pubmed #28833562.

ABSTRACT: BACKGROUND: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy. OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of 274 mg ADS-5102 (amantadine) extended-release capsules (equivalent to 340-mg amantadine HCl) for levodopa-induced dyskinesia in a randomized controlled trial. METHODS: PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS-5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent-to-treat population. OFF time was a key secondary measure. RESULTS: At week 12, least-squares mean change in the Unified Dyskinesia Rating Scale was -20.7 (standard error 2.2) for ADS-5102 (n = 37) and -6.3 (standard error 2.1) for placebo (n = 38; treatment difference -14.4, 95% confidence interval -20.4 to -8.3, P < .0001), indicating improvement in levodopa-induced dyskinesia. OFF time decreased 0.5 hours (standard error 0.3) for ADS-5102 from a baseline mean of 2.6 hours and increased 0.6 hours (standard error 0.3) for placebo from a baseline mean of 2.0 hours (treatment difference -1.1 hours, 95% confidence interval -2.0 to -0.2, P = .0199). The most common adverse events (ADS-5102 versus placebo) included dry mouth (13.5% versus 2.6%), nausea (13.5% versus 2.6%), decreased appetite (10.8% versus 0%), insomnia (10.8% versus 0%), orthostatic hypotension (10.8% versus 0%), constipation (8.1% versus 0%), falls (8.1% versus 5.3%), and visual hallucinations (8.1% versus 5.3%). Adverse events led to treatment discontinuation in 19% versus 8%, respectively. CONCLUSION: ADS-5102 274 mg is an oral pharmacotherapy demonstrating a significant decrease in levodopa-induced dyskinesia and improving OFF time. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

12 Clinical Trial A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease. 2016

Tison, François / Keywood, Charlotte / Wakefield, Mark / Durif, Franck / Corvol, Jean-Christophe / Eggert, Karla / Lew, Mark / Isaacson, Stuart / Bezard, Erwan / Poli, Sonia-Maria / Goetz, Christopher G / Trenkwalder, Claudia / Rascol, Olivier. ·Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. francois.tison@chu-bordeaux.fr. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. francois.tison@chu-bordeaux.fr. · Service de Neurologie, CHU de Bordeaux, Bordeaux, France. francois.tison@chu-bordeaux.fr. · NS-Park/FCRIN Network, UMS 015, Toulouse, France. francois.tison@chu-bordeaux.fr. · Addex Pharma SA, Plan Les Ouates, Switzerland. · NS-Park/FCRIN Network, UMS 015, Toulouse, France. · Neurology Service, A, Hôpital Gabriel Montpied, Clermont Ferrand, France. · Sorbonne Universités and UPMC Univ Paris 06, INSERM UMRS-1127 and CIC-1422; CNRS UMR-7225; AP-HP; and ICM, Hôpital Pitié-Salpêtrière, Paris, France. · Universitätsklinikum Giessen und Marburg, Klinik für Neurologie, Marburg, Germany. · Department of Neurology USC/Keck School of Medicine, Los Angeles, California, USA. · Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, USA. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. · CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. · Rush University Medical Center, Dept. of Neurological Sciences, Movement Disorder Section, Chicago, Illinois, USA. · Paracelsus Elena Klinik, centre for Parkinson's Disease & Movement Disorders, Kassel, Germany. · CIC9302, Departments of Clinical Pharmacology and Neurosciences and NeuroToul COEN Center; INSERM, University Hospital of Toulouse and University of Toulouse 3, Toulouse, France. ·Mov Disord · Pubmed #27214664.

ABSTRACT: BACKGROUND: The metabotropic glutamate receptor 5-negative allosteric modulator dipraglurant reduces levodopa-induced dyskinesia in the MPTP-macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa-induced dyskinesia in Parkinson's disease (PD). METHODS: The study was a phase 2A double-blind, placebo-controlled, randomized (2:1), 4-week, parallel-group, multicenter dose-escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa-induced dyskinesia. Safety and tolerability were assessed based on clinical and biological examination and adverse events recording. Secondary efficacy outcome measures included the modified Abnormal Involuntary Movement Scale, UPDRS, and diaries. Pharmacokinetics were measured at 3 visits following a single dose. RESULTS: Fifty-two patients were exposed to dipraglurant and 24 to placebo. There were no major safety concerns. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%; P = 0.04) and on day 14 (100 mg, 32%; P =0 .04) and across a 3-hour postdose period on day 14 (P = 0.04). There was no evidence of worsening of parkinsonism. Dipraglurant was rapidly absorbed (tmax = 1 hour). The 100-mg dose led to a mean Cmax of 1844 ng/mL on day 28. CONCLUSIONS: Dipraglurant proved to be safe and well tolerated in its first administration to PD patients. Its efficacy in reversing levodopa-induced dyskinesia warrants further investigations in a larger number of patients. © 2016 International Parkinson and Movement Disorder Society.

13 Clinical Trial Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies. 2016

Trenkwalder, Claudia / Stocchi, Fabrizio / Poewe, Werner / Dronamraju, Nalina / Kenney, Chris / Shah, Amy / von Raison, Florian / Graf, Ana. ·Paracelsus-Elena Klinik, Kassel 34128, Germany; Department of Neurosurgery, University Medical Center, Goettingen, Germany. · IRCCS San Raffaele Pisana, Rome, Italy. · Department of Neurology, Medical University, Innsbruck, Austria. · Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. · Novartis Pharma AG, Basel, Switzerland. ·Mov Disord · Pubmed #27214258.

ABSTRACT: BACKGROUND: Two phase 2 randomized, double-blind studies were designed to evaluate efficacy and safety of immediate-release (study 1) and modified-release (study 2) mavoglurant formulations in PD l-dopa-induced dyskinesia. METHODS: Patients were randomized to mavoglurant 100-mg or placebo (4:3) groups (study 1) and mavoglurant 200-mg, mavoglurant 150-mg, or placebo (2:1:1) groups (study 2). Primary outcome was antidyskinetic efficacy, as measured by change from baseline to week 12 in modified Abnormal Involuntary Movement Scale total score. RESULTS: Differences in least-squares mean (standard error) change in modified Abnormal Involuntary Movement Scale total score in week 12 did not reach statistical significance in either study (study 1: mavoglurant 100 mg twice a day versus placebo, 1.7 [1.31]; study 2: mavoglurant 150 mg twice a day (-1.3 [1.16]) and 200 mg twice a day (-0.2 [1.03]) versus placebo). Adverse events incidence was higher with mavoglurant than with placebo. CONCLUSIONS: Both studies failed to meet the primary objective of demonstrating improvement of dyskinesia with mavoglurant treatment. © 2016 International Parkinson and Movement Disorder Society.

14 Clinical Trial A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia. 2016

Trenkwalder, Claudia / Berg, Daniela / Rascol, Olivier / Eggert, Karla / Ceballos-Baumann, Andres / Corvol, Jean-Christophe / Storch, Alexander / Zhang, Lin / Azulay, Jean-Philippe / Broussolle, Emmanuel / Defebvre, Luc / Geny, Christian / Gostkowski, Michal / Stocchi, Fabrizio / Tranchant, Christine / Derkinderen, Pascal / Durif, Franck / Espay, Alberto J / Feigin, Andrew / Houeto, Jean-Luc / Schwarz, Johannes / Di Paolo, Thérèse / Feuerbach, Dominik / Hockey, Hans-Ulrich / Jaeger, Judith / Jakab, Annamaria / Johns, Donald / Linazasoro, Gurutz / Maruff, Paul / Rozenberg, Izabela / Sovago, Judit / Weiss, Markus / Gomez-Mancilla, Baltazar. ·Paracelsus-Elena Hospital, Kassel, Germany. · Department of Neurosurgery, University Medical Center, Goettingen, Germany. · German Parkinson Study Group, Marburg, Germany. · Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany. · Department of Clinical Pharmacology and Neurosciences, NeuroToul Excellence Center for Neurodegenerative Disorders, University UPS of Toulouse III, CIC-9302/INSERM UMR825, Hôpital Purpan - Pavillon Riser, Toulouse, France. · NS PARK/FCRIN Network, France. · Department of Neurology, Philipps-University of Marburg, Marburg, Germany. · Schön Klinik München-Schwabing, München, Germany. · Sorbonne Universités, UPMC Univ Paris 06, and INSERM UMRS 1127 /CIC-1422, and CNRS UMR 7225, and AP-HP, and ICM, Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, Paris, France. · Division of Neurodegenerative Diseases, Department of Neurology, Dresden University of Technology, Dresden, Germany. · Department of Neurology, UC Davis MIND Institute, Sacramento, California, USA. · Service de Neurologie et pathologie du Mouvement, Hôpital de la Timone, Marseille Cedex, France. · Univisité Lyon 1, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France. · CNRS UMR 5229, Centre de Neurosciences Cognitives, Team Basal Ganglia, Bron, France. · Service de Neurologie et Pathologie du movement, EA 1046, CHU de Lille, Hôpital Roger Salengro, Lille, France. · Movement to Health (M2H) laboratory, Euromov, University Montpellier 1, Hôpital gui de Chauliac, Montpellier, France. · Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Institute for Research and Medical Care, IROCS, Rome, Italy. · Service de Neurologie, Hôpital de Hautepierre, Strasbourg, France. · Centre Investigation Clinique Neurologie, CHU Nantes, Hôpital G&R Laennec, Nantes, France. · Service de Neurologie, Hôpital Gabriel Montpied, Clermont-Ferrand, France. · Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA. · Feinstein Institute for Medical Research, North Shore - LIJ Health System, Manhasset, New York, USA. · Service de Neurologie, CIC-INSERM 1402, CHU de Poitiers, Université de Poitiers, Poitiers, France. · Klinik Haag, Haag, Germany. · Neuroscience Research Unit, Centre de recherche du CHU de Québec, Québec, Canada. · Faculty of Pharmacy, Laval University, Québec, Canada. · Novartis Institutes for BioMedical Research, Basel, Switzerland. · Biometrics Matters Ltd, Hamilton, New Zealand. · Albert Einstein College of Medicine, New York, NY, USA, and CognitionMetrics, LLC, Wilmington, Delaware, USA. · Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. · Inbiomed, San Sebastian, Spain. · CogState, Inc, New Haven, Connecticut, USA. · Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada. ·Mov Disord · Pubmed #26990766.

ABSTRACT: BACKGROUND: This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia. METHODS: Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics. RESULTS: In total, 67 patients completed the study. AQW051-treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls. CONCLUSIONS: AQW051 did not significantly reduce dyskinesia or parkinsonian severity. © 2016 International Parkinson and Movement Disorder Society.

15 Clinical Trial Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial. 2015

Trenkwalder, Claudia / Chaudhuri, K Ray / Martinez-Martin, Pablo / Rascol, Olivier / Ehret, Reinhard / Vališ, Martin / Sátori, Maria / Krygowska-Wajs, Anna / Marti, Maria J / Reimer, Karen / Oksche, Alexander / Lomax, Mark / DeCesare, Julia / Hopp, Michael / Anonymous5360846. ·Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurosurgery, University Medical Centre, Goettingen, Germany. Electronic address: ctrenkwalder@gmx.de. · National Parkinson's Foundation, Parkinson's Centre of Excellence, King's College Hospital, London, UK; Biomedical Research Unit for Dementia, King's College, London, UK. · National Centre of Epidemiology, Carlos III Institute of Health, Madrid, Spain. · Clinical Investigation Centre 1436, INSERM, Toulouse, France; University Hospital, Toulouse, France. · Neurologie Berlin, Gemeinschaftspraxis, Berlin, Germany. · Poliklinika Chocen Neuro, Chocen, Czech Republic; Department of Neurology, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic. · Department of Neurology, Vaszary Kolos Hospital, Esztergom, Hungary. · Department of Neurology, Jagiellonian University, Krakow, Poland. · Parkinson's Disease and Movement Disorders Unit, Department of Neurology, Hospital Clinic, CIBERNED, Barcelona, Spain. · Mundipharma Research, Limburg an der Lahn, Germany; Private University Witten/Herdecke, Faculty of Health, Witten, Germany. · Mundipharma Research, Limburg an der Lahn, Germany; Rudolf-Buchheim Institute of Pharmacology, Justus-Liebig-Universität Giessen, Germany. · Mundipharma Research, Cambridge, UK. · Mundipharma Research, Limburg an der Lahn, Germany. ·Lancet Neurol · Pubmed #26494524.

ABSTRACT: BACKGROUND: Pain is a common non-motor symptom of Parkinson's disease. We investigated the analgesic efficacy of prolonged-release oxycodone-naloxone (OXN PR) in patients with Parkinson's disease and chronic, severe pain. METHODS: We did this phase 2 study in 47 secondary care centres in the Czech Republic, Germany, Hungary, Poland, Romania, Spain, and the UK. We enrolled patients with Hoehn and Yahr Stage II-IV Parkinson's disease, at least one type of severe pain, and an average 24-h pain score of at least 6 (assessed on an 11-point rating scale from 0=no pain to 10=pain as bad as you can imagine). Participants were randomly assigned (1:1) with a validated automated system (block size four) to either oral OXN PR or placebo for 16 weeks (starting dose oxycodone 5 mg, naloxone 2·5 mg, twice daily). Patients and investigators were masked to treatment assignment. The primary endpoint was average 24-h pain score at 16 weeks in the full analysis population. This study is registered with EudraCT (2011-002901-31) and ClinicalTrials.gov (NCT01439100). FINDINGS: We enrolled 202 patients; 93 were assigned to OXN PR and 109 to placebo; the full analysis population consisted of 88 patients versus 106 patients. Least squares mean average 24-h pain score at 16 weeks in the full analysis population was 5·0 (95% CI 4·5 to 5·5) in the OXN PR group versus 5·6 (5·1 to 6·0) in the placebo group (difference -0·6, 95% CI -1·3 to 0·0; p=0·058). Similar proportions of patients in each group had adverse events (60/92 [65%] vs 76/109 [70%]), treatment-related adverse events (52/92 [57%] vs 62/109 [57%]), and serious adverse events (5/92 [5%] vs 7/109 [6%]). Treatment-related nausea was more common in the OXN PR group than in the placebo group (16/92 [17%] vs 10/109 [9%]), as was treatment-related constipation (16/92 [17%] vs 6/109 [6%]). INTERPRETATION: The primary endpoint, based on the full analysis population at week 16, was not significant. Nonetheless, the results of this study highlight the potential efficacy of OXN PR for patients with Parkinson's disease-related pain and might warrant further research on OXN PR in this setting. FUNDING: Mundipharma Research.

16 Clinical Trial Rare variants in PLXNA4 and Parkinson's disease. 2013

Schulte, Eva C / Stahl, Immanuel / Czamara, Darina / Ellwanger, Daniel C / Eck, Sebastian / Graf, Elisabeth / Mollenhauer, Brit / Zimprich, Alexander / Lichtner, Peter / Haubenberger, Dietrich / Pirker, Walter / Brücke, Thomas / Bereznai, Benjamin / Molnar, Maria J / Peters, Annette / Gieger, Christian / Müller-Myhsok, Bertram / Trenkwalder, Claudia / Winkelmann, Juliane. ·Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität, München, Munich, Germany ; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany. ·PLoS One · Pubmed #24244438.

ABSTRACT: Approximately 20% of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.

17 Clinical Trial To the influence of general slowing and medication on identity- and location-based priming effects in patients with Parkinson's disease. 2009

Troche, S J / Trenkwalder, C / Morelli-Canelo, M / Gibbons, H / Rammsayer, T H. ·Institute for Psychology, University of Bern, Bern, Switzerland. stefan.troche@psy.unibe.ch ·J Neuropsychol · Pubmed #19338711.

ABSTRACT: Previous studies on inhibitory mechanisms assessed by negative priming (NP) paradigms in patients suffering from Parkinson's disease (PD) have yielded highly ambiguous results. The present study examined two possible reasons for this heterogeneity: general slowing and anti-Parkinsonian medication. Their effects on identity and location NP and positive priming (PP) were investigated. Twenty medicated PD patients and 20 PD patients after drug withdrawal were compared to 20 sex- and age-matched healthy controls. The influence of PD patients' general slowing on priming effects was statistically controlled. Location NP was found not to be affected by PD, whereas identity NP was reduced in medicated PD patients compared to non-medicated PD patients and healthy controls. At first, identity and location PP appeared to be enhanced in both PD groups. After controlling for general slowing, however, differences between PD patients and healthy controls disappeared. These findings endorse the notion that uncontrolled effects of both, PD-related general slowing and anti-Parkinsonian medication may have contributed to previously conflicting results on priming effects in PD patients.

18 Clinical Trial Training effects outweigh effects of single-session conventional rTMS and theta burst stimulation in PD patients. 2009

Rothkegel, Holger / Sommer, Martin / Rammsayer, Thomas / Trenkwalder, Claudia / Paulus, Walter. ·Department of Clinical Neurophysiology, University of Göttingen, Göttingen, Germany. ·Neurorehabil Neural Repair · Pubmed #18978029.

ABSTRACT: BACKGROUND: Focal single-session repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been claimed to be capable of improving motor function in Parkinson's disease. OBJECTIVE: The authors sought to determine which type of rTMS protocol holds the highest potential for future therapeutic application. METHODS: Twenty-two patients with Parkinson's disease received 5 different rTMS protocols on 5 consecutive days in a pseudorandomized and counterbalanced order either in the defined OFF condition or with their usual medication. The protocols tested in the present study included 2 conventional rTMS protocols (0.5 and 10 Hz) as well as the recently introduced theta burst stimulation (cTBS, iTBS) and a sham condition. Cortical excitability, motor performance (pointing movement, pronation-supination, Purdue Pegboard Test, walking), and mood were assessed before and after each session. RESULTS: The authors observed motor training from days 1 to 4, particularly in the group on dopaminergic medication. None of the rTMS paradigms excelled placebo stimulation. The only exception was the Purdue Pegboard Test, in which all active stimulation paradigms yielded slightly stronger effects than sham stimulation. CONCLUSIONS: Within a single session, no clinically relevant difference in the rTMS protocols could be detected. Training effects outweigh and may have masked rTMS effects, particularly in the group on dopaminergic mediation.

19 Article First comprehensive tool for screening pain in Parkinson's disease: the King's Parkinson's Disease Pain Questionnaire. 2018

Martinez-Martin, P / Rizos, A M / Wetmore, J / Antonini, A / Odin, P / Pal, S / Sophia, R / Carroll, C / Martino, D / Falup-Pecurariu, C / Kessel, B / Andrews, T / Paviour, D / Trenkwalder, C / Chaudhuri, K R / Anonymous771112. ·National Center of Epidemiology, Carlos III Institute of Health, Madrid, Spain. · Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain. · Institute of Psychiatry, Psychology & Neuroscience at King's College, King's College Hospital NHS Foundation Trust, London, UK. · Neurology, University of Padua, Venice, Italy. · Neurology, University of Lund, Lund, Sweden. · Neurology, Forth Valley Royal Hospital, Larbert, Scotland, UK. · Geriatric Medicine, Yeovil Hospital, Somerset, UK. · Neurology, Derriford Hospital, Plymouth, UK. · Department of Clinical Neurosciences, University of Calgary, Calgary, Canada. · Neurology, Transylvania University, Brasov, Romania. · Medicine for the Elderly, Princess Royal University Hospital site, King's College Hospital, Kent, UK. · Neurology, Guy's Hospital, London, UK. · Neurology, St Georges's Hospital, London, UK. · Department of Neurosurgery, University Medical Center, Goettingen, Germany. ·Eur J Neurol · Pubmed #29806962.

ABSTRACT: BACKGROUND AND PURPOSE: Pain is highly prevalent in Parkinson's disease (PD), impacting patients' ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. METHODS: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test-retest) and diagnostic performance of the questionnaire were analysed. RESULTS: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (r CONCLUSIONS: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes.

20 Article The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. 2018

Heintz-Buschart, Anna / Pandey, Urvashi / Wicke, Tamara / Sixel-Döring, Friederike / Janzen, Annette / Sittig-Wiegand, Elisabeth / Trenkwalder, Claudia / Oertel, Wolfgang H / Mollenhauer, Brit / Wilmes, Paul. ·Eco-Systems Biology Research Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg. · Paracelsus-Elena-Klinik, Kassel, Germany. · Department of Neurology, Philipps University Marburg, Germany. · University Medical Center Goettingen, Department of Neurosurgery, Goettingen, Germany. · University Medical Center Goettingen, Department of Neurology, Goettingen, Germany. ·Mov Disord · Pubmed #28843021.

ABSTRACT: BACKGROUND: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. OBJECTIVES: To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. METHODS: Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. RESULTS: Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. CONCLUSION: Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

21 Article Drug Safety Analysis in a Real-Life Cohort of Parkinson's Disease Patients with Polypharmacy. 2017

Müller-Rebstein, Saskia / Trenkwalder, Claudia / Ebentheuer, Jens / Oertel, Wolfgang H / Culmsee, Carsten / Höglinger, Günter U. ·Department of Neurosurgery, Paracelsus-Elena Klinik Kassel, University Medical Center, Goettingen, Germany. · Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81677, Munich, Germany. · Department of Neurology, Philipps Universität, Marburg, Germany. · Department of Pharmacy, Philipps Universität, Marburg, Germany. · Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81677, Munich, Germany. guenter.hoeglinger@dzne.de. · Department of Neurology, Technische Universität München, Munich, Germany. guenter.hoeglinger@dzne.de. ·CNS Drugs · Pubmed #29139041.

ABSTRACT: BACKGROUND: Polypharmacy is common in geriatric Parkinson's disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory. OBJECTIVE: The aim of this study was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life. METHODS: We conducted a prospective observational study in a multimorbid cohort of PD patients with polypharmacy admitted to a specialized hospital. Inclusion criteria were the presence of at least one comorbidity requiring pharmacotherapy and at least five different drugs in the discharge prescription. Hoehn and Yahr stage during the 'on' state, therapeutic problems related to motor and non-motor PD symptoms, comorbidities, and drug regimens on admission and discharge were analyzed for contraindications and interactions. RESULTS: Overall, 127 patients were included (medium Hoehn and Yahr stage = IV, range II-V). Interactions with the anti-PD medication were mainly caused by other central nervous system (CNS)-active substances, cytochrome P450-metabolized substances, and QT-time prolonging substances. Contraindications against the anti-PD medication mainly occurred from internal, haematopoietic, neurologic and psychiatric diseases, and QT-time prolonging drugs. The highest frequency of interactions and contraindications were identified with levodopa (n = 119 at admission/n = 126 at discharge), entacapone (n = 46/42), pramipexole (n = 44/24), and amantadine (n = 32/30). CONCLUSIONS: Several medically relevant risk factors (interactions and contraindications) frequently occurred in advanced PD patients. These findings provide a basis for developing programmes for awareness, education, monitoring, and preventive interventions to avoid adverse incidents. Future studies will need to evaluate preventive efficacy of structured drug safety programmes.

22 Article Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid. 2017

Shahnawaz, Mohammad / Tokuda, Takahiko / Waragai, Masaaki / Mendez, Nicolas / Ishii, Ryotaro / Trenkwalder, Claudia / Mollenhauer, Brit / Soto, Claudio. ·Mitchell Center for Alzheimer's Disease and Related Brain Disorders, The University of Texas School of Medicine at Houston. · Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan3Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan4Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology, Tokyo, Japan. · Department of Neurology, Higashi Matsudo Municipal Hospital, Matsudo, Japan. · Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan3Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan. · Paracelsus-Elena-Klinik Kassel, Kassel, Germany7Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany8Clinic for Neurosurgery, University Medical Center, Goettingen, Germany. · Paracelsus-Elena-Klinik Kassel, Kassel, Germany7Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany9Department of Neurosurgery, University Medical Center Goettingen, Goettingen, Germany. ·JAMA Neurol · Pubmed #27918765.

ABSTRACT: Importance: Parkinson disease (PD) is a highly prevalent and incurable neurodegenerative disease associated with the accumulation of misfolded α-synuclein (αSyn) aggregates. An important problem in this disease is the lack of a sensitive, specific, and noninvasive biochemical diagnosis to help in clinical evaluation, monitoring of disease progression, and early differential diagnosis from related neurodegenerative diseases. Objective: To develop a novel assay with high sensitivity and specificity to detect small quantities of αSyn aggregates circulating in cerebrospinal fluid (CSF) of patients affected by PD and related synucleinopathies. Design, Setting, and Participants: The strategy evaluated in this proof-of-concept study uses the protein misfolding cyclic amplification (PMCA) technology that detects minute amounts of misfolded oligomers by taking advantage of their ability to nucleate further aggregation, enabling a very high amplification of the signal. The technology was first adapted with synthetic αSyn oligomers prepared in vitro and used to screen in 2 blinded cohorts of CSF samples from German and Japanese patients with PD (n = 76) and individuals serving as controls affected by other neurologic disorders (n = 65), neurodegenerative diseases (n = 18), and Alzheimer disease (n = 14). The kinetics of αSyn aggregation were measured by αSyn-PMCA in the presence of CSF samples from the participants to detect αSyn oligomeric seeds present in this biological fluid. The assays were conducted from November 15, 2013, to August 28, 2015. Main Outcomes and Measures: Kinetic parameters correlated with disease severity at the time of sample collection, measured by the Hoehn and Yahr scale, with the lowest grade indicating unilateral involvement with minimal or no functional impairment, and the highest grade defining patients with complete confinement to wheelchair or bed. Results: Studies with synthetic αSyn aggregates showed that αSyn-PMCA enabled to detect as little as 0.1 pg/mL of αSyn oligomers. The αSyn-PMCA signal was directly proportional to the amount of αSyn oligomers added to the reaction. A blinded study of CSF samples correctly identified patients affected by PD with an overall sensitivity of 88.5% (95% CI, 79.2%-94.6%) and specificity of 96.9% (95% CI, 89.3%-99.6%). The αSyn-PMCA results for different patients correlated with the severity of the clinical symptoms of PD (Japanese cohort: rs = -0.54, P = .006; German cohort: rs = -0.36, P = .02). Conclusions and Relevance: The findings suggest that detection of αSyn oligomers by αSyn-PMCA in the CSF of patients affected by PD may offer a good opportunity for a sensitive and specific biochemical diagnosis of the disease. Further studies are needed to investigate the usefulness of αSyn-PMCA to monitor disease progression and for preclinical identification of patients who may develop PD.

23 Article Asphyxia due to laryngeal spasm as a severe complication of awake deep brain stimulation for Parkinson's disease: a case report. 2016

von Eckardstein, Kajetan L / Sixel-Döring, Friederike / Kazmaier, Stephan / Trenkwalder, Claudia / Hoover, Jason M / Rohde, Veit. ·Department of Neurosurgery, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany. kajetan.voneckardstein@med.uni-goettingen.de. · Paracelsus Elena-Klinik, Kassel, Germany. · Department of Anasthesiology, Universitätsmedizin Göttingen, Göttingen, Germany. · Department of Neurosurgery, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany. · The Texas Brain and Spine Institute, Bryan, TX, USA. ·BMC Neurol · Pubmed #27821134.

ABSTRACT: BACKGROUND: In accordance with German neurosurgical and neurological consensus recommendations, lead placements for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) are usually performed with the patient awake and in "medication off" state. This allows for optimal lead position adjustment according to the clinical response to intraoperative test stimulation. However, exacerbation of Parkinsonian symptoms after withdrawal of dopaminergic medication may endanger the patient by inducing severe "off" state motor phenomena. In particular, this can be a problem in awake craniotomies utilizing intraoperative airway management and resuscitation. CASE PRESENTATION: We report the case of a PD patient with progressive orofacial and neck muscle dystonia resulting in laryngeal spasm during DBS lead placement. This led to upper airway compromise and asphyxia, requiring resuscitation. CONCLUSIONS: Laryngeal spasms may occur as a rare "off" state motor complication in patients with PD. Other potential causes of intraoperative difficulties breathing include bilateral vocal cord palsy, positional asphyxia, and silent aspiration. In our practice, we have adjusted our medication regimen and now allow patients to receive their standard dopaminergic medication until the morning of surgery. Neurologists and neurosurgeons performing lead placement procedures for PD should be aware of this rare but unsafe condition to most optimized treatment.

24 Article Clinically relevant cut-off values for the Parkinson's Disease Sleep Scale-2 (PDSS-2): a validation study. 2016

Muntean, Maria-Lucia / Benes, Heike / Sixel-Döring, Friederike / Chaudhuri, Kallol Ray / Suzuki, Keisuke / Hirata, Koichi / Zimmermann, Johannes / Trenkwalder, Claudia. ·Paracelsus Elena Hospital, Kassel, Germany; Department of Clinical Neurophysiology, University of Göttingen, Göttingen, Germany. Electronic address: luciamuntean@yahoo.com. · Somni Bene Institute for Clinical Research and Sleep Medicine Schwerin and Medical Center University of Rostock, Rostock, Germany. · Paracelsus Elena Hospital, Kassel, Germany; Department of Neurology, Philipps-University, Marburg, Germany. · National Parkinson Foundation Centre of Excellence, Kings College Hospital, London, United Kingdom. · Department of Neurology, Dokkyo Medical University, Tochigi, Japan. · Psychologische Hochschule, Berlin, Germany. · Paracelsus Elena Hospital, Kassel, Germany; Department Neurosurgery, University of Göttingen, Göttingen, Germany. ·Sleep Med · Pubmed #27810191.

ABSTRACT: BACKGROUND: Sleep disturbances are a major problem encountered by neurologists attending Parkinson's disease (PD) patients. The Parkinson's Disease Sleep Scale-2 (PDSS-2) assesses a wide spectrum of disease-specific sleep problems and is easy to administer as a patient self-rating scale. The validation study showed that the scale is reliable, valid, and precise. Until now, however, only one Japanese study has assessed cut-off scores to define poor sleepers. OBJECTIVES: In this context we aimed to determine the PDSS-2 cut-off values that define a sleep disturbance severe enough to require referral of the patient to a sleep center or the need for specific treatment. METHODS: Inpatients with idiopathic PD consecutively admitted to our hospital were enrolled. Patients completed the PDSS-2. The attending physician, who was blinded to the PDSS-2 results, but familiar with the patients' history and current disease status, completed a questionnaire consisting of two general questions on the presence of PD-specific and non-PD related sleep problems. Statistical analysis was performed to determine cut-off values for the PDSS-2 and correlation with the physician's evaluation of sleep disturbance severity. A natural cohort of non-PD patients with sleep disorders represented the control group. RESULTS: The sample consisted of 52 (56%) men and 41 (44%) women with an average age of 69.22 ± 8.74 years. PDSS-2 showed a sensitivity of 77.6% and a specificity of 74.3% in relation to physician's evaluation of PD-specific sleep problems. According to the physician's evaluation, PD-specific sleep disturbances occurred in 62% of the patients. 83% of patients with PDSS-2 scores ≥18 had clinically relevant sleep disturbances compared to only 33% of PD patients with scores <18. The severity of PD-specific sleep problems was well correlated with the PDSS-2 total score (r = 0.49). CONCLUSIONS: To our knowledge, this is the first study to define PDSS-2 cut-off values for the severity of sleep disturbances in a European PD sample. Our study shows that scores ≥18 define clinically relevant PD-specific sleep disturbances.

25 Article Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study. 2016

Kalbe, Elke / Rehberg, Sarah Petra / Heber, Ines / Kronenbuerger, Martin / Schulz, Jörg B / Storch, Alexander / Linse, Katharina / Schneider, Christine / Gräber, Susanne / Liepelt-Scarfone, Inga / Berg, Daniela / Dams, Judith / Balzer-Geldsetzer, Monika / Hilker, Rüdiger / Oberschmidt, Carola / Witt, Karsten / Schmidt, Nele / Mollenhauer, Brit / Trenkwalder, Claudia / Spottke, Annika / Roeske, Sandra / Wittchen, Hans-Ulrich / Riedel, Oliver / Dodel, Richard. ·Medical Psychology, Neuropsychology and Gender Studies, Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Cologne, Cologne, Germany. · Department of Neurology, University Hospital, RWTH University Aachen, Aachen, Germany. · Department of Neurology, University Hospital, RWTH University Aachen, Aachen, Germany JARA Brain Institute 2, RWTH University and Forschungszentrum Jülich, Germany. · Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany Department of Neurology, University of Rostock, Rostock, Germany. · Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany. · German Center of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, Tübingen, Germany. · German Center of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, Tübingen, Germany Department of Neurology, Christian Albrecht University, Kiel, Germany. · Department of Neurology, Philipps University Marburg, Marburg, Germany. · Department of Neurology, J.W. Goethe University, Frankfurt/Main, Germany. · Department of Neurology, Christian Albrecht University, Kiel, Germany. · Paracelsus-Elena Clinic, Centre of Parkinsonism and Movement Disorders, Kassel, Germany. · Department of Neurology, University Hospital Bonn, and German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. · Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany. · Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany. ·J Neurol Neurosurg Psychiatry · Pubmed #27401782.

ABSTRACT: OBJECTIVE: Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. METHODS: Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. RESULTS: 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. CONCLUSIONS: This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

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