PLoS One. 2012;7(6):e38855. Differential patterns of planning impairments in Parkinson's disease and sub-clinical signs of dementia? A latent-class model-based approach. Köstering L(1), McKinlay A, Stahl C, Kaller CP. Author information: (1)Department of Neurology, University Medical Center, University of Freiburg, Freiburg, Germany.
Planning impairments mark a well-documented consequence of neurodegenerative diseases such as Parkinson's disease (PD). Recently, using the Tower of London task we demonstrated that, rather than being generally impaired, PD patients selectively fail when planning requires flexible in-breadth search strategies. For a better understanding of the interindividual patterns underlying specific planning impairments, here we performed an explorative re-analysis of the original data using a latent-class model-based approach. Data-driven classification according to subjects' performance was based on a multinomial processing tree (MPT) model accommodating the impact of increased breadth versus depth of looking ahead during planning. In order to assess interindividual variability in coping with these different task demands, an extension of MPT models was used in which sample-immanent heterogeneity is accounted for by identifying different latent classes of individuals. Two latent classes were identified that differed considerably in performance for problems placing high demands on the depth of anticipatory search processes. In addition, these impairments were independent of PD diagnosis. However, latent-class mediated search depth-related deficits in planning performance were associated with poorer outcomes in dementia screenings, albeit sub-clinical. PD patients exhibited additional deficits related to the breadth of searching ahead. Taken together, results revealed dissociable impairments in specific planning processes within a single task of visuospatial problem solving. Present analyses put forward the hypothesis that cognitive sequelae of PD and sub-clinical signs of dementia may be related to differential patterns of planning impairments.
Z Evid Fortbild Qual Gesundhwes. 2014;108 Suppl 1:S29-35. [Potential analysis for research on physiotherapy-led treadmill training in Parkinson's disease]. [Article in German] Lohkamp M(1), Braun C(2), Wasner M(3), Voigt-Radloff S(4). Author information: (1)Fakultät für Therapiewissenschaften, SRH Hochschule Heidelberg, Heidelberg, Deutschland. Electronic address: monika.lohkamp@hochschule-heidelberg.de. (2)hochschule 21, Buxtehude, Deutschland. (3)Fakultät für Therapiewissenschaften, SRH Hochschule Heidelberg, Heidelberg, Deutschland. (4)Deutsches Cochrane Zentrum, Universitätsklinikum Freiburg, Freiburg, Deutschland.
HEALTH PROBLEM: Parkinson's disease is one of the major neurodegenerative disorders with prevalence rates between 0.1 and 0.2 % in the global population and 1.8 % in people aged 64 years and over. Future incidence rates are estimated to increase within aging societies. The progressive course of Parkinson's disease is clinically characterised by bradykinesia, rigidity and tremor. These limitations in motor functioning reduce the capacity to work, social participation and the clients' quality of life. Parkinson's disease causes incapacity to work and a large number of days off from work. The benefits clients expect from physiotherapy-led treatment include an improvement of gait, a better speed of motion and the decrease of fatigue and rigidity.
CORPUS OF EVIDENCE: A recent Cochrane review (Mehrholz et al., 2010) analysed seven randomised comparisons with 153 participants and found that treadmill training compared with no treatment improved gait speed (SMD 0.50; 95 % confidence interval [0.17 to 0.84]). A lack of evidence exists on how to reduce fatigue and rigidity. There is also need to evaluate long-term effects and cost-effectiveness. Furthermore, an updated meta-analysis should include eleven new randomised trials on treadmill training after 2009. Physiotherapy-led treadmill training can easily be transferred into the German healthcare context since the environmental and educational preconditions are met by German physiotherapeutic care.
IMPLICATION FOR RESEARCH: Within the German context, there is need to prepare a randomised clinical trial evaluating the impact of physiotherapy-led treadmill training on motor functioning, quality of life, costs, adverse events und long-term effects. Prior to this, a feasibility study should explore the acceptance and intensity of treadmill training as well as the access of private physiotherapy practices to people suffering from early- to mid-stage Parkinson's disease.
Dear Editor, We read the publication “Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson’s disease“1 with considerable interest. At the end of the text the authors conclude that “both selegiline and rasagiline might be considered equally effective in early stages of Parkinson’s disease“. They also remark that their results contradict ours2. We will try to resolve this contradiction. 1. The authors performed a more selective literature search compared to ours2. They did their search solely in data banks and failed to give any details as to the time frame of the search or the key words they referenced. Our metaanalysis made use of data banks, registers of ongoing studies and review articles as well, with the goal of doing as extensive a search as possible and most of all in the hopes of finding the most complete evidence available to date for a metaanalysis. One should get the impression that we succeeded here merly by looking at the number of publications we included. 2. The metaanalysis in Marconi et al1 is insufficiently described: There is no information as to any degree of heterogeneity, or the model applied (which smd was applied: Cohen’s d or Hedge’s g, or whether the effect model was fixed or random, etc.). The Forest plot (Figure 4) indicates that there are studies on rasagiline and selegiline which contribute to heterogeneity. An example is ADAGIORCT in rasagilin and Olanow-RCT in selegiline. On this point a Funnel plot should be calculated (as in our publication2 which, as a sensitivity analysis, serves the purpose of obtaining greater reliability when interpreting the results). 3. Marconi and Zwingers did not consider the different therapy concepts for Parkinson’s disease, they went into monotherapy and combination therapy in a meta-analysis, while we2 treated the therapies separately. Summarizing, we conclude that the text by Marconi fails to address essential parameters of metaanalysis with the result that the conclusion of such a meta-analysis (SEL = RAS) cannot be evaluated or validated. Our metaanalysis fully conforms to the recommendationds of the Cochrane Collaboration, as we mention several times in our text. According to our metaanalysis, then, there is a distinct superiority to be found in rasagline. ––––––––––––––––––––– Conflict of Interest The Authors declare that they have no conflict of interests. References 1) MARCONI S, ZWINGERS T. Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson’s disease. Eur Rev Med Pharmacol Sci 2014; 18: 1879-1882. 2) JOST WH, FRIEDE M, SCHNITKER J. Indirect metaanalysis of randomized placebo-controlled clinical trials on rasagiline and selegiline in the symptomatic treatment of Parkinson’s disease. Basal Ganglia 2012; 2: S17-S26. W.H. Jost1, M. Friede2, J. Schnitker3 1Parkinson-Klinik Wolfach, University of Freiburg, Wolfach, Germany 2Lundbeck, Hamburg, Germany 3Institut für angewandte Statistik, Bielefeld, Germany European Review for Medical and Pharmacological Sciences 2014; 18: 3349-3349 Corresponding Author: Wolfgang H. Jost, MD; e-mail: w.jost@parkinson-klinik.de 3349 Comment to Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson’s disease
Arq Neuropsiquiatr. 2014 Dec;72(12):978-9. Embryonic stem cells in neurology - current clinical transplantation trials in Parkinson's (PD) and Huntington's (HD) disease. Lopez WO(1), Nikkhah G(2), Maciaczyk J(3). Author information: (1)Department of Neurosurgery, University of Freiburg, Baden-Württemberg, Germany. (2)Department of Neurosurgery, University of Erlangen, Erlangen, Schwabachanlage, Germany. (3)Neurosurgery Department, Heinrich-Heine University, Düsseldorf, Germany.
Mov Disord. 2015 May 23. Brain alterations with deep brain stimulation: New insight from a neuropathological case series. Kronenbuerger M(1), Nolte KW(2), Coenen VA(3), Burgunder JM(4), Krauss JK(5), Weis J(2). Author information: (1)Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA. (2)Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany. (3)Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany. (4)Department of Neurology, University of Berne, Inselspital, Berne, Switzerland. (5)Department of Neurosurgery, Medical School Hannover (MHH), Hannover, Germany.
BACKGROUND: Previous studies on human brain tissue alterations caused by deep brain stimulation described glial and reactive inflammatory changes. In the current pathoanatomical study, we extended the analysis to signs of axonal changes and the influence of concomitant disease.
METHODS: Brains of 10 patients with Parkinson's disease or essential tremor and a total of 18 electrodes were systematically examined up to 7.5 y after surgery.
RESULTS: In general, tissue that had long-term contact with the electrode material exhibited astrogliosis in all, T-lymphocytes in 93%, and multinucleated giant cells in 68% of patients. Immunohistochemistry showed an increase in amyloid precursor protein immunoreactive axonal swellings in the brain at the electrically active parts of the electrodes. Patients who died of septicemia showed a more severe astrogliosis and giant cell reaction than patients who died of cardiovascular events. Parkinson's disease or essential tremor did not differentially produce histopathological changes around the electrodes.
CONCLUSION: Long-term electrical stimulation by deep brain stimulation causes minor axonal changes. The cause of death, but not the underlying neurological disease, affects the histopathological changes around the electrode. The findings need to be reproduced by examining larger patient subgroups.
Eur J Hum Genet. 2015 Jan 21. Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease. Schulte EC(1), Fukumori A(2), Mollenhauer B(3), Hor H(4), Arzberger T(5), Perneczky R(6), Kurz A(7), Diehl-Schmid J(7), Hüll M(8), Lichtner P(9), Eckstein G(10), Zimprich A(11), Haubenberger D(11), Pirker W(11), Brücke T(12), Bereznai B(13), Molnar MJ(13), Lorenzo-Betancor O(14), Pastor P(14), Peters A(15), Gieger C(16), Estivill X(4), Meitinger T(17), Kretzschmar HA(5), Trenkwalder C(3), Haass C(18), Winkelmann J(19). Author information: (1)1] Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany [2] Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany. (2)1] Department of Biochemistry, Adolf-Butenandt-Institut, Ludwig-Maximilians Universität München, Munich, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. (3)1] Paracelsus Elena Klinik, Kassel, Germany [2] Neurochirurgische Klinik, Georg August Universität Göttingen, Göttingen, Germany. (4)Genomics and Disease Group, Centre for Genomic Regulation (CRG), Pompeu Fabra University (UPF) and Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Barcelona, Spain. (5)Institut für Neuropathologie, Ludwig-Maximillians Universität München, Munich, Germany. (6)1] Psychiatrische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany [2] Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK. (7)Psychiatrische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. (8)Psychiatrische Universitätsklinik, Albert Ludwigs Universität, Freiburg, Germany. (9)1] Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany [2] Institut für Humangenetik, Technische Universität München, Munich, Germany. (10)Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany. (11)Department of Neurology, Medical University of Vienna, Vienna, Austria. (12)Neurologische Klinik, Wilhelminenspital, Vienna, Austria. (13)Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary. (14)1] Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain [2] Department of Neurology, Clinica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain [3] CIBERNED, Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain. (15)Institut für Epidemiologie II, Helmholtz Zentrum München, Munich, Germany. (16)Institut für Genetische Epidemiologie, Helmholtz Zentrum München, Munich, Germany. (17)1] Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany [2] Institut für Humangenetik, Technische Universität München, Munich, Germany [3] Munich Cluster for Systems Neurology, SyNergy, Munich, Germany. (18)1] Department of Biochemistry, Adolf-Butenandt-Institut, Ludwig-Maximilians Universität München, Munich, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Munich, Germany [3] Munich Cluster for Systems Neurology, SyNergy, Munich, Germany. (19)1] Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany [2] Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany [3] Institut für Humangenetik, Technische Universität München, Munich, Germany [4] Munich Cluster for Systems Neurology, SyNergy, Munich, Germany. Many individuals with Parkinson's disease (PD) develop cognitive deficits, and a phenotypic and molecular overlap between neurodegenerative diseases exists. We investigated the contribution of rare variants in seven genes of known relevance to dementias (β-amyloid precursor protein (APP), PSEN1/2, MAPT (microtubule-associated protein tau), fused in sarcoma (FUS), granulin (GRN) and TAR DNA-binding protein 43 (TDP-43)) to PD and PD plus dementia (PD+D) in a discovery sample of 376 individuals with PD and followed by the genotyping of 25 out of the 27 identified variants with a minor allele frequency <5% in 975 individuals with PD, 93 cases with Lewy body disease on neuropathological examination, 613 individuals with Alzheimer's disease (AD), 182 cases with frontotemporal dementia and 1014 general population controls. Variants identified in APP were functionally followed up by Aβ mass spectrometry in transiently transfected HEK293 cells. PD+D cases harbored more rare variants across all the seven genes than PD individuals without dementia, and rare variants in APP were more common in PD cases overall than in either the AD cases or controls. When additional controls from publically available databases were added, one rare variant in APP (c.1795G>A(p.(E599K))) was significantly associated with the PD phenotype but was not found in either the PD cases or controls of an independent replication sample. One of the identified rare variants (c.2125G>A (p.(G709S))) shifted the Aβ spectrum from Aβ40 to Aβ39 and Aβ37. Although the precise mechanism remains to be elucidated, our data suggest a possible role for APP in modifying the PD phenotype as well as a general contribution of genetic factors to the development of dementia in individuals with PD.
Clin Neurophysiol. 2014 Dec 4. pii: S1388-2457(14)00837-2. TMS and drugs revisited 2014. Ziemann U(1), Reis J(2), Schwenkreis P(3), Rosanova M(4), Strafella A(5), Badawy R(6), Müller-Dahlhaus F(7). Author information: (1)Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Tübingen, Germany. Electronic address: ulf.ziemann@uni-tuebingen.de. (2)Department of Neurology, Albert-Ludwigs-University Freiburg, Freiburg, Germany. (3)Department of Neurology, BG-University Hospital Bergmannsheil Bochum, Bochum, Germany. (4)Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy; Fondazione Europea di Ricerca Biomedica, FERB Onlus, Milan, Italy. (5)Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada. (6)Department of Neurology, Saint Vincent's Hospital, Fitzroy, The University of Melbourne, Parkville, Victoria, Australia; Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia. (7)Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Tübingen, Germany. The combination of pharmacology and transcranial magnetic stimulation to study the effects of drugs on TMS-evoked EMG responses (pharmaco-TMS-EMG) has considerably improved our understanding of the effects of TMS on the human brain. Ten years have elapsed since an influential review on this topic has been published in this journal (Ziemann, 2004). Since then, several major developments have taken place: TMS has been combined with EEG to measure TMS evoked responses directly from brain activity rather than by motor evoked potentials in a muscle, and pharmacological characterization of the TMS-evoked EEG potentials, although still in its infancy, has started (pharmaco-TMS-EEG). Furthermore, the knowledge from pharmaco-TMS-EMG that has been primarily obtained in healthy subjects is now applied to clinical settings, for instance, to monitor or even predict clinical drug responses in neurological or psychiatric patients. Finally, pharmaco-TMS-EMG has been applied to understand the effects of CNS active drugs on non-invasive brain stimulation induced long-term potentiation-like and long-term depression-like plasticity. This is a new field that may help to develop rationales of pharmacological treatment for enhancement of recovery and re-learning after CNS lesions. This up-dated review will highlight important knowledge and recent advances in the contribution of pharmaco-TMS-EMG and pharmaco-TMS-EEG to our understanding of normal and dysfunctional excitability, connectivity and plasticity of the human brain.
MJoTA has been published since 2006 by Emerald Pademelon Press LLC. PO Box 381 Haddonfield, NJ 08033, USA. MJoTA.org and drsusanna.org hosts MJoTA, and the Medical Writing Institute, which is a New Jersey nonprofit corporation. All inquiries for the Medical Writing Institute or Emerald Pademelon Press LLC: 01-609-792-1571; publisher@mjota.org. Contact the publisher directly through Facebook click here