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Günter U. Höglinger: Parkinson-Syndrome kompakt
2020
Swiss Archives of Neurology, Psychiatry and Psychotherapy
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Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents?
2007
Neuromolecular medicine
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A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer's (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these
doi:10.1007/s12017-007-8016-8
pmid:17985252
pmcid:PMC2814816
fatcat:nk4rcyk3gvgbxokcqdbc2d33fe
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... mbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death pathways as those activated by environmental factors that trigger most sporadic disease cases. In this article we present a countervailing view that environmental neurotoxins may be the sole sufficient factor in at least three neurological disease clusters. For each, neurotoxins have been isolated and characterized that, at least in animal models, faithfully reproduce each disorder without the need for genetic co-factors. Based on these data, we will propose a set of principles that would enable any potential toxin to be evaluated as an etiological factor in a given neurodegenerative disease. Finally, we will attempt to put environmental toxins into the context of possible genetically-determined susceptibility.
The Differential Diagnosis and Treatment of Atypical Parkinsonism
2016
Deutsches Ärzteblatt International
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Reply to: "Brief Clinical Rating Scales Should Not Be Overlooked"
2020
Movement Disorders
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We thank Professor Lim and colleagues for commending the Progressive Supranuclear Palsy-Clinical Deficits Scale (PSP-CDS) 1 in their letter, "Brief clinical rating scales should not be overlooked." 2 The PSP-CDS is a physician-rated scale that was recently developed by members of the Movement Disorder Society (MDS)-endorsed PSP study group to reliably assess disease severity and progression in patients with PSP, regardless of the clinical phenotype. 1 The full version of the scale (PSP-CDS 7x3
doi:10.1002/mds.28273
pmid:33068467
fatcat:zpy4lsoqkfeklk2cmqucwqt5ha
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... comprises seven items with three response categories each (0 = no deficit; 1 = mild deficits not affecting activities of daily living (ADL); 2 = moderate deficits requiring partial external support; 3 = severe deficits necessitating permanent external support). The abbreviated PSP-CDS 7x2 scale omits the response category for mild clinical deficits, to be used in research settings, where such items without ADL-impact are of minor importance (eg, pivotal clinical trials). Finally, the short PSP-CDS 6x2 scale omits the item "Eye movements" from PSP-CDS 7x2 because their importance for ADL is controversial. As a measure of clinical meaningful deficits that generates scores with appropriate annual sensitivity to change and a completion time of~4 minutes, 1 we suggest the PSP-CDS be applied in the context of clinical trials and in clinical routine care to monitor disease progression and to identify clinical deficits requiring medical attention. We would like to point out, however, that we do not consider the PSP-CDS as a substitute for the Progressive Supranuclear Palsy Rating Scale (PSPRS) 3 in every instance, but rather a complementary instrument. The PSPRS is a 28-item scale to assess disease severity and progression in PSP. The PSPRS proved to be a reliable measure in many PSP randomized controlled trials and observation studies, as well as in routine clinical settings. 4-6 Compared to the PSP-CDS, the PSPRS assesses a larger number of items and has slightly better sensitivity to change but is less established for PSP with variant phenotypes (other than Richardson's syndrome) and takes more than three times as long to be completed. 3 This tradeoff needs to be considered based on the situation.
Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson's Disease?
2021
Brain Sciences
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The SARS-CoV-2 pandemic has affected the daily life of the worldwide population since 2020. Links between the newly discovered viral infection and the pathogenesis of neurodegenerative diseases have been investigated in different studies. This review aims to summarize the literature concerning COVID-19 and Parkinson's disease (PD) to give an overview on the interface between viral infection and neurodegeneration with regard to this current topic. We will highlight SARS-CoV-2 neurotropism,
doi:10.3390/brainsci11121654
pmid:34942956
pmcid:PMC8699589
fatcat:cckvnaqjhrdg7obrl6mw46euhe
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... athology and the suspected pathophysiological links between the infection and neurodegeneration as well as the psychosocial impact of the pandemic on patients with PD. Some evidence discussed in this review suggests that the SARS-CoV-2 pandemic might be followed by a higher incidence of neurodegenerative diseases in the future. However, the data generated so far are not sufficient to confirm that COVID-19 can trigger or accelerate neurodegenerative diseases.
FGF2 Affects Parkinson's Disease-Associated Molecular Networks Through Exosomal Rab8b/Rab31
2020
Frontiers in Genetics
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Copyright © 2020 Kumar, Donakonda, Müller, Bötzel, Höglinger and Koeglsperger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). ...
doi:10.3389/fgene.2020.572058
pmid:33101391
pmcid:PMC7545478
fatcat:bnofgwiswbctvdmdgpcguojsfq
Dopamine depletion impairs precursor cell proliferation in Parkinson disease
2004
Nature Neuroscience
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Rougon, Marseille, France); rabbit anti-human nestin, 1/1,000 (a gift of U. Lendahl, Stockholm, Sweden); rabbit anti-D1L receptor, 1/1,000 (a gift of B. ...
100 U/ml of DNase I on a rocking platform (30 min, 37 °C) and dissociated mechanically in DMEM/F-12 medium (Invitrogen) containing 0.7 mg/ml of ovomucoid (Sigma). ...
doi:10.1038/nn1265
pmid:15195095
fatcat:f7nqmxnqvnekvaf5zrouot6szy
Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches
2017
Lancet Neurology
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Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms
doi:10.1016/s1474-4422(17)30157-6
pmid:28653647
pmcid:PMC5802400
fatcat:gyto7vjo5raevl5rmqddqbmm2e
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... are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases. Death Richardson's syndrome Variant PSP syndromes Suggestive of PSP Asymptomatic Disease severity Time Presymptomatic PSP No clinical progression Clinical syndrome Richardson's syndrome Parkinsonism Gait freezing Corticobasal syndrome nfvPPA bvFTD Cerebellar ataxia PSP pathology Other pathology PSP with mixed pathology RS not due to PSP
Clinical Features Observed in General Practice Associated With the Subsequent Diagnosis of Progressive Supranuclear Palsy
2021
Frontiers in Neurology
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Copyright © 2021 Kwasny, Oleske, Zamudio, Diegidio and Höglinger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). ...
doi:10.3389/fneur.2021.637176
pmid:33967937
pmcid:PMC8100604
fatcat:xxyiczud2nfsjomu6ogb5d7ekq
Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations
2018
Parkinsonism & Related Disorders
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Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP.
doi:10.1016/j.parkreldis.2018.08.025
pmid:30201421
pmcid:PMC6399076
fatcat:7tmyj4okyzbtlpu4ddasjhy4ma
Evidence for pathogenicity of variant ATM Val1729Leu in a family with ataxia telangiectasia
2021
Neurogenetics
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AbstractAtaxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two ATM gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as
doi:10.1007/s10048-021-00639-4
pmid:33779842
pmcid:PMC8119284
fatcat:3o6fy2gx7fhw7bij6qqrrt5zya
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... ic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.
Prothrombotic immune thrombocytopenia after COVID-19 vaccine
2021
Blood
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ELISA reactivity was inhibited to OD <0.3 by heparin in all samples (2 U/ml, not shown). ...
Fluorescent intensity ratio of AZD1222 (or AZD1222+heparin 100 U/ml) to buffer is shown. (C) Schistocytes in blood smear high power field in patient 1, indicative of TMA, on day 4. ...
doi:10.1182/blood.2021011958
pmid:33909050
pmcid:PMC8084604
fatcat:3ph7u7wfdrcl5pjc2dpvoc4c7i
One Year Trajectory of Caregiver Burden in Parkinson's Disease and Analysis of Gender-Specific Aspects
2021
Brain Sciences
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Parkinson's disease (PD) is a slowly progressive neurodegenerative movement disorder that leads to impairments in activities of daily living. In addition to reducing patients' quality of life, this disease also affects caregivers' well-being. Until recently, caregiver burden was mainly assessed by generic questionnaires, which do not take the characteristics of the chronic disease into consideration. In the case of PD, this issue has been addressed by the introduction of the "Parkinson's
doi:10.3390/brainsci11030295
pmid:33652825
fatcat:cs4tujj5wbgnfftfuajvccqiwu
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... caregiver burden" questionnaire (PDCB). Data on longitudinal trajectories of caregiver burden are still missing in the literature. In this study, we assessed the one-year trajectory of caregiver burden by the PDCB as a disease-specific questionnaire. Further, gender-specific aspects of caregiver burden were analyzed by applying a caregiver task questionnaire. PDCB total score (n = 84 patients and caregivers) did not significantly change from baseline (30.4) to one year at follow-up (31.5). No significant difference was detected between female and male caregivers in global burden and-specific caregiver tasks. Our data showed only a mild increase of caregiver burden in the timeframe of one year. Gender-specific differences do not seem to impact-specific caregiver tasks in the presented study population.
One-year outcome of brain injured patients undergoing early neurological rehabilitation: a prospective observational study
2022
BMC Neurology
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Chi 2 tests and Mann-Whitney U tests were conducted to compare group differences. Linear relationships were examined with the Spearman correlation coefficient. ...
doi:10.1186/s12883-022-02549-w
pmid:35039012
pmcid:PMC8762846
fatcat:rn6fn56hwvfwbgzhjrgp7w2bby
Basic Fibroblast Growth Factor 2-induced Proteome Changes Endorse Lewy Body Pathology in Hippocampal Neurons
2020
iScience
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U S A 98, 5874. Zapiec, B., Dieriks, B.V., Tan, S., Faull, R.L.M., Mombaerts, P., and Curtis, M.A. (2017). ...
doi:10.1016/j.isci.2020.101349
pmid:32707433
pmcid:PMC7381695
fatcat:ukgrozsioreudhtfhkjih65qyy
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