scholarly journals Fatal outcome after postexposure rabies vaccination in a patient with Parkinson’s disease

2004 ◽  
Vol 57 (9-10) ◽  
pp. 487-492 ◽  
Author(s):  
Dusan Lalosevic ◽  
Vesna Lalosevic ◽  
Milorad Saric ◽  
Jasenka Mazibrada ◽  
Sinisa Babovic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cause Of Death ◽  
Fatal Outcome ◽  
Lewy Bodies ◽  
Rabies Vaccine ◽  
Human Rabies ◽  
Direct Immunofluorescence ◽  
Immunofluorescence Test ◽  
Rabies Vaccination

Introduction In Serbia and Montenegro postexposure rabies vaccination is performed using five doses of rabies vaccine with a potency of 2.5 I.U. It is given on 0, 3rd, 7th, 14th and 28th day, combined with human rabies immunoglobulin with the first dose. Modern rabies vaccines produced in cell cultures rarely cause neurological complications, among which Guillain-Barre syndrome and parkinsonism. Case report The authors report a case of a 78-year-old woman with a documented five-year history of Parkinson's disease, who was bitten by a rabid cat. Twelve hours later, when the rabies infection of the cat was confirmed by an immunofluorescence test, the patient received the first dose of rabies vaccine Verorab (Aventis), a cell culture vaccine, together with the human rabies immunoglobulin produced in Belgrade. After the third dose of rabies vaccine, the symptoms of Parkinson's disease progressed and vaccination was interrupted. However, one month later, the patient died with predominantly neurological symptoms. As the patient died at the time when incubation of rabies might have been expected, autopsy and rabies diagnostics were performed. Autopsy and pathohistologic findings The autopsy and pathohistologic findings from the specimens treated with routine hematoxylin and eosin staining, together with immunofluorescence test, excluded rabies as a cause of death and revealed neurodegenerative changes typical for Parkinson's disease. Using two different fluorescent rabies antibodies, we performed a direct immunofluorescence antibody tests, but no rabies antigens were detected. However, in histologic slides of the brain stem, large intracytoplasmic inclusions were found in some neurons, identified as Lewy bodies characteristic for Parkinson's disease Conclusion Parkinson's disease, with its complications, was the cause of death of the patient bitten by a rabid cat. Furthermore, the coincidence of the progression of Parkinson's disease symptoms, at the time of post exposure rabies vaccination, points to the vaccine as a possible contributing factor to aggravation of the disease and lethal outcome.

Differences in glucose metabolism between dementia with Lewy bodies and dementia associated with Parkinson's disease

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
P Häussermann ◽  
A.O Ceballos-Baumann ◽  
H Förstl ◽  
R Feurer ◽  
B Conrad ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Glucose Metabolism ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies

scholarly journals Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders

2021 ◽  
Author(s):  
Daniel Erskine ◽  
David Koss ◽  
Viktor I. Korolchuk ◽  
Tiago F. Outeiro ◽  
Johannes Attems ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Mitochondrial Diseases ◽  
Model Systems ◽  
Lipid Homeostasis ◽  
Lysosomal Storage ◽  
Iron Storage ◽  
Monogenic Disorders ◽  
Storage Disorders

AbstractAccumulation of the protein α-synuclein into insoluble intracellular deposits termed Lewy bodies (LBs) is the characteristic neuropathological feature of LB diseases, such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with LB (DLB). α-Synuclein aggregation is thought to be a critical pathogenic event in the aetiology of LB disease, based on genetic analyses, fundamental studies using model systems, and the observation of LB pathology in post-mortem tissue. However, some monogenic disorders not traditionally characterised as synucleinopathies, such as lysosomal storage disorders, iron storage disorders and mitochondrial diseases, appear disproportionately vulnerable to the deposition of LBs, perhaps suggesting the process of LB formation may be a result of processes perturbed as a result of these conditions. The present review discusses biological pathways common to monogenic disorders associated with LB formation, identifying catabolic processes, particularly related to lipid homeostasis, autophagy and mitochondrial function, as processes that could contribute to LB formation. These findings are discussed in the context of known mediators of α-synuclein aggregation, highlighting the potential influence of impairments to these processes in the aetiology of LB formation.

scholarly journals Fibroblast Growth Factor 20 Gene Polymorphism in Parkinson’s Disease in Asian Population: A Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 674
Author(s):  
Han-Lin Chiang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Meta Analysis ◽  
Lewy Bodies ◽  
Asian Population ◽  
Protective Role ◽  
Lewy Neurites ◽  
Chinese Populations ◽  
Study Results

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3′ untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = −3.96; p < 0.0001) and the dominant models (Z = −4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.

Generalized Rhythmic Delta Activity Frontally Predominant Differentiates Dementia With Lewy Bodies From Alzheimer's Disease and Parkinson's Disease Dementia: A Conventional Electroencephalography Visual Analysis

2021 ◽  
pp. 155005942199714
Author(s):  
Lucia Zinno ◽  
Anna Negrotti ◽  
Chiara Falzoi ◽  
Giovanni Messa ◽  
Matteo Goldoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Dementia With Lewy Bodies ◽  
Visual Analysis ◽  
Lewy Bodies ◽  
Delta Activity ◽  
Rhythmic Delta Activity

Introduction. An easily accessible and inexpensive neurophysiological technique such as conventional electroencephalography may provide an accurate and generally applicable biomarker capable of differentiating dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and Parkinson’s disease-associated dementia (PDD). Method. We carried out a retrospective visual analysis of resting-state electroencephalography (EEG) recording of 22 patients with a clinical diagnosis of 19 probable and 3 possible DLB, 22 patients with probable AD and 21 with PDD, matched for age, duration, and severity of cognitive impairment. Results. By using the grand total EEG scoring method, the total score and generalized rhythmic delta activity frontally predominant (GRDAfp) alone or, even better, coupled with a slowing of frequency of background activity (FBA) and its reduced reactivity differentiated DLB from AD at an individual level with an high accuracy similar to that obtained with quantitative EEG (qEEG). GRDAfp alone could also differentiate DLB from PDD with a similar level of diagnostic accuracy. AD differed from PDD only for a slowing of FBA. The duration and severity of cognitive impairment did not differ between DLB patients with and without GRDAfp, indicating that this abnormal EEG pattern should not be regarded as a disease progression marker. Conclusions. The findings of this investigation revalorize the role of conventional EEG in the diagnostic workup of degenerative dementias suggesting the potential inclusion of GRDAfp alone or better coupled with the slowing of FBA and its reduced reactivity, in the list of supportive diagnostic biomarkers of DLB.

scholarly journals Parkinson’s Disease Causative Mutation in Vps35 Disturbs Tetherin Trafficking to Cell Surfaces and Facilitates Virus Spread

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 746
Author(s):  
Yingzhuo Ding ◽  
Yan Li ◽  
Gaurav Chhetri ◽  
Xiaoxin Peng ◽  
Jing Wu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ectopic Expression ◽  
Lewy Bodies ◽  
Cell Protein ◽  
Causative Mutation ◽  
Virus Spread ◽  
Cell Surfaces ◽  
Vacuolar Protein ◽  
Hsv 1

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons in the substantia nigra, intraneuronal deposition of misfolded proteins known as Lewy bodies, and chronic neuroinflammation. PD can arise from monogenic mutations, but in most cases, the etiology is unclear. Viral infection is gaining increasing attentions as a trigger of PD. In this study, we investigated whether the PD-causative 620 aspartate (D) to asparagine (N) mutation in the vacuolar protein sorting 35 ortholog (Vps35) precipitated herpes simplex virus (HSV) infection. We observed that ectopic expression of Vps35 significantly reduced the proliferation and release of HSV-1 virions; the D620N mutation rendered Vps35 a partial loss of such inhibitory effects. Tetherin is a host cell protein capable of restricting the spread of encapsulated viruses including HSV-1 and SARS-Cov-2, both of which are implicated in the development of parkinsonism. Compared with cells overexpressing wildtype Vps35, cells expressing mutant Vps35 with D620N had less Tetherin on cell surfaces. Real-time and static cell imaging revealed that Tetherin recycled through Vps35-positive endosomes. Expression of Vps35 with D620N reduced endosomal dynamics and frequency of motile Tetherin-containing vesicles, a sign of defective production of recycling carriers. Our study suggests that the D620N mutation in Vps35 hinders Tetherin trafficking to cell surfaces and facilitates virus spread.

scholarly journals The Nigral Coup in Parkinson’s Disease by α-Synuclein and Its Associated Rebels

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 598
Author(s):  
Jeswinder Sian-Hulsmann ◽  
Peter Riederer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Viral Infections ◽  
Genetic Defect ◽  
Lewy Bodies ◽  
Common Denominator ◽  
Metabolic Disturbances ◽  
Trigger Factors ◽  
Protein Clearance ◽  
Sporadic Parkinson’S Disease

The risk of Parkinson’s disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson’s disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder.

scholarly journals Prognostic predictors relevant to end-of-life palliative care in Parkinson’s disease and related disorders: a systematic review

2021 ◽  
pp. jnnp-2020-323939
Author(s):  
Umer Akbar ◽  
Robert Brett McQueen ◽  
Julienne Bemski ◽  
Julie Carter ◽  
Elizabeth R Goy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Palliative Care ◽  
Parkinson's Disease ◽  
End Of Life ◽  
Cause Of Death ◽  
Quantitative Research ◽  
Motor Dysfunction ◽  
Clinical Markers ◽  
Hospice Referral ◽  
Survey Responses

Parkinson’s disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970–2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson’s Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.

scholarly journals Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases

2021 ◽  
Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy M. Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Lewy Body ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Subsequent Development ◽  
Lewy Body Dementia ◽  
Anterior Cingulate ◽  
Lewy Body Diseases

AbstractParkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

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