18 research outputs found

    Pros and cons of a prion-like pathogenesis in Parkinson's disease

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    Background: Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and alpha-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system. Discussion: It has recently been found that alpha-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of alpha-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities. Summary: At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities

    Detecting trends in landuse and landcover change of Nech Sar National Park, Ethiopia

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    Nech Sar National Park (NSNP) is one of the most important biodiversity centers in Ethiopia. In recent years, a widespread decline of the terrestrial ecosystems has been reported, yet to date there is no comprehensive assessment on degradation across the park. In this study, changes in landcover were analyzed using 30 m spatial resolution Landsat imagery. Interannual variations of normalized difference vegetation index (NDVI) were examined and compared with climatic variables. The result presented seven landcover classes and five of the seven landcover classes (forest, bush/shrubland, wooded grassland, woodland and grassland) were related to natural vegetation and two landcover types (cultivated land and area under encroaching plants) were direct results of anthropogenic alterations of the landscape. The forest, grassland, and wooded grassland are the most threatened habitat types. A considerable area of the grassland has been replaced by encroaching plants, prominently by Dichrostachys cinerea, Acacia mellifera, A. nilotica, A. oerfota, and A. seyal and is greatly affected by expansion of herbaceous plants, most commonly the species of the family Malvaceae which include Abutilon anglosomaliae, A.bidentatum and A.figarianu. Thus, changes in vegetation of NSNP may be attributed to (i) degradation of existing vegetation through deforestation and (ii) replacement of existing vegetation by encroaching plants. While limited in local meteorological station, NDVI analysis indicated that climate related changes did not have major effects on park vegetation degradation, which suggests anthropogenic impacts as a major driver of observed disturbance

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

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    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

    Structural brain signature of cognitive decline in Parkinson's disease: DTI-based evidence from the LANDSCAPE study

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    Background: The nonmotor symptom spectrum of Parkinson's disease (PD) includes progressive cognitive decline mainly in late stages of the disease. The aim of this study was to map the patterns of altered structural connectivity of patients with PD with different cognitive profiles ranging from cognitively unimpaired to PD-associated dementia. Methods: Diffusion tensor imaging and neuropsychological data from the observational multicentre LANDSCAPE study were analyzed. A total of 134 patients with PD with normal cognitive function (56 PD-N), mild cognitive impairment (67 PD-MCI), and dementia (11 PD-D) as well as 72 healthy controls were subjected to whole-brain-based fractional anisotropy mapping and covariance analysis with cognitive performance measures. Results: Structural data indicated subtle changes in the corpus callosum and thalamic radiation in PD-N, whereas severe white matter impairment was observed in both PD-MCI and PD-D patients including anterior and inferior fronto-occipital, uncinate, insular cortices, superior longitudinal fasciculi, corona radiata, and the body of the corpus callosum. These regional alterations were demonstrated for PD-MCI and were more pronounced in PD-D. The pattern of involved regions was significantly correlated with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score. Conclusions: The findings in PD-N suggest impaired cross-hemispherical white matter connectivity that can apparently be compensated for. More pronounced involvement of the corpus callosum as demonstrated for PD-MCI together with affection of fronto-parieto-temporal structural connectivity seems to lead to gradual disruption of cognition-related cortico-cortical networks and to be associated with the onset of overt cognitive deficits. The increase of regional white matter damage appears to be associated with the development of PD-associated dementia

    Negative impact of borderline global cognitive scores on quality of life after subthalamic nucleus stimulation in Parkinson's disease

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    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves quality of life (QoL) in Parkinson's disease (PD). Dementia is considered as a contraindication for STN-DBS. However, no controlled study assessed the impact of STN-DBS on the QoL and motor outcome in PD patients with a borderline global cognitive impairment. We studied clinical baseline and progression parameters in a cohort of STN-DBS patients with a global cognitive score still in the non-demented range but scoring in the lowest quartile of the Mattis Dementia Rating Scale (MDRS), a measure of global cognitive functioning. Data from a German randomised controlled study comparing DBS (60 patients) with best medical treatment (BMT, 59 patients) were analysed. Changes in patients' QoL scores were assessed using the Parkinson's disease questionnaire (PDQ-39) at baseline and at the 6 months follow up. Patients were split into four groups according to their MDRS performance at baseline and these groups were compared in the context of motor outcome and QoL Twelve out of sixty patients of the STN-DBS group scored in the lowest quartile of the MDRS (range between one hundred thirty and one hundred thirty seven points). An individual analysis revealed that 3 of 12 patients showed a clinical relevant improvement in QoL whereas the group statistics did not reveal any significant improvement in QoL measures after STN-DBS compared to the BMT group. Since this failure to improve in QoL cannot be explained by a failure to improve in motor functions, stimulation settings and psychiatric scales after STN-DBS, the failure to improve in QoL in patients with a borderline global cognitive score might be specifically related to lower cognitive functioning. (C) 2011 Elsevier B.V. All rights reserved

    Is improvement in the quality of life after subthalamic nucleus stimulation in Parkinson's disease predictable?

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    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves quality of life (QoL) in PD. However, QoL fails to improve in a relevant proportion of patients. We studied clinical baseline and progression parameters associated with improvement in QoL after DBS. Data from a German randomized, controlled study comparing DBS (60 patients) with best medical treatment (59 patients) were analyzed. Changes in patients' QoL were assessed using the Parkinson's Disease Questionnaire (PDQ-39) at baseline and at the 6-month follow-up. For the STN-DBS patients, the changes in PDQ-39 were correlated with predefined clinical preoperative and progression parameters. Scores for QoL improved after STN-DBS for 57% of the patients, and for 43% patients, they did not improve. Patients with improvement in QoL showed significantly higher cumulative daily off time. Changes in the PDQ-39 showed a significant positive correlation with the cumulative daily off time at baseline. Logistic regression analysis revealed that 1 additional hour off time at baseline increases the odds for improvement on PDQ-39 by a factor of 1.33 (odds ratio). In the postoperative course, changes in the PDQ-39 significantly correlated with the reduction of cumulative daily off time, an improvement on the UPDRS (UPDRS III off), and positive mood changes. Among the baseline parameters, the cumulative daily off time is the strongest predictor for improvement in disease-related QoL after DBS. Improvement in QoL after STN-DBS is also correlated with changes in motor functions and changes in depression and anxiety. (c) 2011 Movement Disorder Societ
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