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Clinics in Geriatric Medicine Feb 2020Parkinsonism is one of the most common neurologic disorders in the aging population. Although Parkinson disease (PD) is the most common cause, there is a lengthy... (Review)
Review
Parkinsonism is one of the most common neurologic disorders in the aging population. Although Parkinson disease (PD) is the most common cause, there is a lengthy differential diagnosis. The diagnosis of PD hinges on recognizing its typical features, including bradykinesia, rest tremor, unilateral onset, cogwheel rigidity, and beneficial and sustained response to levodopa. Equally important is to be familiar with the "red flags," which are features not expected with PD and suggest an alternative diagnosis, usually a parkinsonian syndrome. In general, it is best to have the diagnosis confirmed by a neurologist, especially one with expertise in movement disorders.
Topics: Aged; Diagnosis, Differential; Humans; Neurologic Examination; Parkinson Disease
PubMed: 31733693
DOI: 10.1016/j.cger.2019.09.014 -
Seminars in Neurology Aug 2023Gastrointestinal (GI) dysfunction is a common nonmotor symptom in Parkinson's disease (PD) as well as other parkinsonian syndromes and may precede the onset of motor... (Review)
Review
Gastrointestinal (GI) dysfunction is a common nonmotor symptom in Parkinson's disease (PD) as well as other parkinsonian syndromes and may precede the onset of motor symptoms by decades. Involvement of all segments of the GI tract can lead to altered responses to medications and worsened quality of life for patients. While some GI symptoms occur in isolation, others overlap. Therefore, understanding the changes in different segments of the GI tract and how they relate to altered responses to PD treatment can guide both diagnostic and pharmacological interventions. Gut microbiota plays a critical role in immune activity and modulation of the enteric and central nervous systems. Understanding this bidirectional relationship helps to elucidate the pathogenesis of neurodegeneration. This review will describe the current understanding of how GI dysfunction develops in parkinsonian syndromes, common symptoms in PD and related disorders, and available treatments.
Topics: Humans; Quality of Life; Parkinsonian Disorders; Gastrointestinal Diseases; Parkinson Disease; Central Nervous System
PubMed: 37703887
DOI: 10.1055/s-0043-1771461 -
Biochemical Society Transactions Feb 2023The prevalence of neurological diseases is currently growing due to the combination of several factor, including poor lifestyle and environmental imbalance which enhance... (Review)
Review
The prevalence of neurological diseases is currently growing due to the combination of several factor, including poor lifestyle and environmental imbalance which enhance the contribution of genetic factors. Parkinson's disease (PD), a chronic and progressive neurological condition, is one of the most prevalent neurodegenerative human diseases. Development of models may help to understand its pathophysiology. This review focuses on studies using invertebrate models to investigate certain chemicals that generate parkinsonian-like symptoms models. Additionally, we report some preliminary results of our own research on a crustacean (the crab Ucides cordatus) and a solitary ascidian (Styela plicata), used after induction of parkinsonism with 6-hydroxydopamine and the pesticide rotenone, respectively. We also discuss the advantages, limits, and drawbacks of using invertebrate models to study PD. We suggest prospects and directions for future investigations of PD, based on invertebrate models.
Topics: Humans; Animals; Parkinsonian Disorders; Parkinson Disease; Rotenone; Invertebrates; Disease Models, Animal
PubMed: 36645005
DOI: 10.1042/BST20221172 -
Cells Feb 2023Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia,... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia, resulting in movement impairment referred to as parkinsonism. However, the etiology of PD is not well known, with genetic factors accounting only for 10-15% of all PD cases. The pathogenetic mechanism of PD is not completely understood, although several mechanisms, such as oxidative stress and inflammation, have been suggested. Understanding the mechanisms of PD pathogenesis is critical for developing highly efficacious therapeutics. In the PD brain, dopaminergic neurons degenerate mainly in the basal ganglia, but recently emerging evidence has shown that astrocytes also significantly contribute to dopaminergic neuronal death. In this review, we discuss the role of astrocytes in PD pathogenesis due to mutations in α-synuclein (PARK1), DJ-1 (PARK7), parkin (PARK2), leucine-rich repeat kinase 2 (LRRK2, PARK8), and PTEN-induced kinase 1 (PINK1, PARK6). We also discuss PD experimental models using neurotoxins, such as paraquat, rotenone, 6-hydroxydopamine, and MPTP/MPP+. A more precise and comprehensive understanding of astrocytes' modulatory roles in dopaminergic neurodegeneration in PD will help develop novel strategies for effective PD therapeutics.
Topics: Humans; Parkinson Disease; Astrocytes; Parkinsonian Disorders; Lewy Bodies; Dopamine; Mutation
PubMed: 36831289
DOI: 10.3390/cells12040622 -
Neuroscience and Biobehavioral Reviews Jan 2022Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation... (Review)
Review
Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation (DBS) in this region has been proven as an effective treatment for this disease. The STN possesses a special ability to switch from the spike to the burst firing mode in response to dopamine deficiency in parkinsonism, and this STN burst is considered an electrophysiological signature of the cortico-basal ganglia circuit in the brains of PD patients. This review focuses on the role of STN burst firing in the pathophysiology of PD and during DBS. Here, we review existing literature on how STN bursts originate and the specific factors affecting their formation; how STN burst firing causes motor symptoms in PD and how interventions can rescue these symptoms. Finally, the similarities and differences between the two electrophysiological hallmarks of PD, STN burst firing and beta-oscillation, are discussed. STN burst firing should be considered as a pathophysiological target in PD during treatment with DBS.
Topics: Basal Ganglia; Deep Brain Stimulation; Humans; Parkinson Disease; Parkinsonian Disorders; Subthalamic Nucleus
PubMed: 34856222
DOI: 10.1016/j.neubiorev.2021.11.044 -
International Journal of Molecular... Aug 2022Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra... (Review)
Review
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.
Topics: COVID-19; Cell Communication; Humans; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; RNA, Viral; SARS-CoV-2; alpha-Synuclein
PubMed: 36077138
DOI: 10.3390/ijms23179739 -
Multiple Sclerosis and Related Disorders Jun 2022Rare cases of coexisting multiple sclerosis and parkinsonism have been reported in the literature. However, the true prevalence, clinical characteristics, and causal... (Observational Study)
Observational Study
BACKGROUND
Rare cases of coexisting multiple sclerosis and parkinsonism have been reported in the literature. However, the true prevalence, clinical characteristics, and causal relation between the two entities have not been systematically evaluated.
OBJECTIVE
To evaluate the prevalence of parkinsonism in patients with multiple sclerosis and examine the causal relationship, if any.
METHODS
Consecutive patients referred to the multiple sclerosis clinic were evaluated by a neurologist with double training in both neuroimmunology and movement disorders. All patients were specifically screened for movement disorders via a movement disorder survey and a focused exam. Video samples were independently rated by two blinded movement disorder raters. Pre-specified criteria were developed for five potential clinical scenarios: incidental idiopathic Parkinson's disease, incidental Parkinson-plus syndrome, drug-induced parkinsonism, acute symptomatic parkinsonism, and chronic symptomatic parkinsonism.
RESULTS
From 2016 to 2021, 336 patients were evaluated. Of those, 12 patients (3.6%) had clinical parkinsonism (average age 68 years, 66% females). Nine patients (75%) were deemed to have incidental Parkinson's disease, 2 (17%) had drug-induced parkinsonism, and 1 (8.3%) was deemed to have demyelination-related chronic symptomatic parkinsonism. The latter presented with gradual and progressive parkinsonism without prodromal symptoms. Both blinded raters agreed with the parkinsonism phenomenology. In addition to typical enhancing and non-enhancing demyelinating lesions, the patient had lesions bilaterally in the basal ganglia. She had positive oligoclonal bands in the cerebrospinal fluid. DAT scan was normal. She was diagnosed with PPMS with activity and progression manifesting solely with secondary parkinsonism. Her disease stabilized with ocrelizumab. There were no cases of acute symptomatic parkinsonism or co-existing Parkinson-plus syndrome over the five-year duration of the study. Three of the incidental idiopathic Parkinson's disease cases had radiologically isolated syndrome.
CONCLUSION
Parkinsonism in MS is rare and most cases are incidental. However, clinicians need to recognize the entity of demyelination-related chronic symptomatic parkinsonism in patients with progressive MS phenotypes and demyelinating lesions in the basal ganglia and/or upper midbrain. Parkinsonism may be the sole clinical presentation of progressive MS and the only indication for DMT initiation or escalation. There is an over-representation of radiologically isolated syndrome in patients with presumptive incidental demyelination and idiopathic Parkinson's disease. Prospective studies utilizing high-field MRI and longitudinal DAT scans are needed to better characterize the complex relationship between demyelination and parkinsonism.
Topics: Demyelinating Diseases; Female; Humans; Male; Multiple Sclerosis; Parkinson Disease; Parkinson Disease, Secondary; Parkinsonian Disorders; Prospective Studies; Syndrome
PubMed: 35428029
DOI: 10.1016/j.msard.2022.103796 -
Seminars in Neurology Feb 2023Neuroimaging is an important adjunct to the clinical assessment of Parkinson disease (PD). Parkinsonism can be challenging to differentiate, especially in early disease...
Neuroimaging is an important adjunct to the clinical assessment of Parkinson disease (PD). Parkinsonism can be challenging to differentiate, especially in early disease stages, when it mimics other movement disorders or when there is a poor response to dopaminergic therapies. There is also a discrepancy between the phenotypic presentation of degenerative parkinsonism and the pathological outcome. The emergence of more sophisticated and accessible neuroimaging can identify molecular mechanisms of PD, the variation between clinical phenotypes, and the compensatory mechanisms that occur with disease progression. Ultra-high-field imaging techniques have improved spatial resolution and contrast that can detect microstructural changes, disruptions in neural pathways, and metabolic and blood flow alterations. We highlight the imaging modalities that can be accessed in clinical practice and recommend an approach to the diagnosis of clinically uncertain parkinsonism.
Topics: Humans; Parkinsonian Disorders; Parkinson Disease; Neuroimaging; Disease Progression; Molecular Imaging
PubMed: 36878467
DOI: 10.1055/s-0043-1764228 -
Movement Disorders : Official Journal... Feb 2020Objective assessments of movement impairment are needed to support clinical trials and facilitate diagnosis. The objective of the current study was to determine if a...
BACKGROUND
Objective assessments of movement impairment are needed to support clinical trials and facilitate diagnosis. The objective of the current study was to determine if a rapid web-based computer mouse test (Hevelius) could detect and accurately measure ataxia and parkinsonism.
METHODS
Ninety-five ataxia, 46 parkinsonism, and 29 control participants and 229,017 online participants completed Hevelius. We trained machine-learning models on age-normalized Hevelius features to (1) measure severity and disease progression and (2) distinguish phenotypes from controls and from each other.
RESULTS
Regression model estimates correlated strongly with clinical scores (from r = 0.66 for UPDRS dominant arm total to r = 0.83 for the Brief Ataxia Rating Scale). A disease change model identified ataxia progression with high sensitivity. Classification models distinguished ataxia or parkinsonism from healthy controls with high sensitivity (≥0.91) and specificity (≥0.90).
CONCLUSIONS
Hevelius produces a granular and accurate motor assessment in a few minutes of mouse use and may be useful as an outcome measure and screening tool. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ataxia; Child; Child, Preschool; Computers; Disease Progression; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Young Adult
PubMed: 31769069
DOI: 10.1002/mds.27915 -
Movement Disorders : Official Journal... May 2021Parkinson's disease (PD) is a genetically complex neurodegenerative disease with ~20 genes known to contain mutations that cause PD or atypical parkinsonism. Large-scale...
BACKGROUND
Parkinson's disease (PD) is a genetically complex neurodegenerative disease with ~20 genes known to contain mutations that cause PD or atypical parkinsonism. Large-scale next-generation sequencing projects have revolutionized genomics research. Applying these data to PD, many genes have been reported to contain putative disease-causing mutations. In most instances, however, the results remain quite limited and rather preliminary. Our aim was to assist researchers on their search for PD-risk genes and variant candidates with an easily accessible and open summary-level genomic data browser for the PD research community.
METHODS
Sequencing and imputed genotype data were obtained from multiple sources and harmonized and aggregated.
RESULTS
In total we included a total of 102,127 participants, including 28,453 PD cases, 1650 proxy cases, and 72,024 controls.
CONCLUSIONS
We present here the Parkinson's Disease Sequencing Browser: a Shiny-based web application that presents comprehensive summary-level frequency data from multiple large-scale genotyping and sequencing projects https://pdgenetics.shinyapps.io/VariantBrowser/. Published © 2021 This article is a U.S. Government work and is in the public domain in the USA. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: DNA; Humans; Mutation; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders
PubMed: 33497488
DOI: 10.1002/mds.28488