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Handbook of Clinical Neurology 2022Positron emission tomography greatly advanced our understanding on the underlying neural mechanisms of movement disorders. PET with flurodeoxyglucose (FDG) is especially... (Review)
Review
Positron emission tomography greatly advanced our understanding on the underlying neural mechanisms of movement disorders. PET with flurodeoxyglucose (FDG) is especially useful as it depicts regional metabolic activity level that can predict patients' symptoms. Multivariate pattern analysis has been used to determine and quantify the co-varying brain networks associated with specific clinical traits of neurodegenerative disease. The result is a biomarker, useful for diagnosis, treatments, and follow up studies. Parkinsonian traits and parkinsonisms are associated with specific spatial pattern of metabolic abnormality useful for differential diagnosis. This approach has also been used for monitoring disease progression and novel treatment responses mostly in Parkinson's disease. In this book chapter, we, illustrate and discuss the significance of the brain networks associated with disease and their modification with neuroplastic changes.
Topics: Brain; Fluorodeoxyglucose F18; Humans; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography
PubMed: 35034729
DOI: 10.1016/B978-0-12-819410-2.00006-0 -
Biomolecules Jul 2022A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this... (Review)
Review
A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI's PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31-73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson's Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.
Topics: COVID-19; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; SARS-CoV-2
PubMed: 35883526
DOI: 10.3390/biom12070970 -
Journal of the Neurological Sciences Feb 2022Parkinsonism is a syndrome characterized by bradykinesia, rigidity, and tremor. Parkinsonism is a common manifestation of Parkinson's disease and other neurodegenerative... (Review)
Review
Parkinsonism is a syndrome characterized by bradykinesia, rigidity, and tremor. Parkinsonism is a common manifestation of Parkinson's disease and other neurodegenerative diseases referred to as atypical parkinsonism. However, a growing body of clinical and scientific evidence indicates that parkinsonism may be part of the phenomenological spectrum of various neurological conditions to a greater degree than expected by chance. These include neurodegenerative conditions not traditionally classified as movement disorders, e.g., dementia and motor neuron diseases. In addition, parkinsonism may characterize a wide range of central nervous system diseases, e.g., autoimmune diseases, infectious diseases, cerebrospinal fluid disorders (e.g., normal pressure hydrocephalus), cerebrovascular diseases, and other conditions. Several pathophysiological mechanisms have been identified in Parkinson's disease and atypical parkinsonism. Conversely, it is not entirely clear to what extent the same mechanisms and key brain areas are also involved in parkinsonism due to a broader etiopathogenetic spectrum. We aimed to provide a comprehensive and up-to-date overview of the various etiopathogenetic and pathophysiological mechanisms of parkinsonism in a wide spectrum of neurological conditions, with a particular focus on the role of the basal ganglia involvement. The paper also highlights potential implications in the diagnostic approach and therapeutic management of patients. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
Topics: Basal Ganglia; Humans; Hypokinesia; Parkinson Disease; Parkinsonian Disorders; Tremor
PubMed: 34642022
DOI: 10.1016/j.jns.2021.120012 -
Parkinsonism & Related Disorders Dec 2023Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example,...
INTRODUCTION
Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders.
METHODS
The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24).
RESULTS
The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases.
CONCLUSION
These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.
Topics: Humans; alpha-Synuclein; Synucleinopathies; Parkinsonian Disorders; Parkinson Disease; Multiple System Atrophy; Tauopathies
PubMed: 37591709
DOI: 10.1016/j.parkreldis.2023.105807 -
Annals of Clinical and Translational... Apr 2023Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. (Review)
Review
BACKGROUND
Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism.
METHODS
We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant articles. Studies were screened and reviewed comprehensively by two independent authors.
RESULTS
Of 863 references from our search, we included eight clinical studies, nine genetic studies, and five case reports. Regardless of age group, Parkinson's disease (PD) and parkinsonian syndromes were more frequently observed in patients with ASD, though the evidence for increased rates of parkinsonism is less clear for children and adolescents. Parkinsonian features and hypokinetic behavior were common in Rett syndrome, with prevalence estimates ranging from 40% to 80%. Frequently observed parkinsonian features include bradykinesia, rigidity, hypomimia, and gait freezing. PD gene PARK2 copy number variations appear more frequently in ASD cases than controls. Evidence suggests that RIT2 and CD157/BST1 are implicated in ASD and PD, while the evidence for other PD-related genes (DRD2, GPCR37, the SLC gene family, and SMPD1) is less clear. Rare mutations, such as ATP13A2, CLN3, and WDR45, could result in autistic behavior and concomitant parkinsonism.
CONCLUSION
The prevalence of parkinsonism in ASD is substantially greater than in the general population or matched controls. Various PD-associated gene loci, especially PARK2, could confer susceptibility to ASD as well. Important future directions include conducting prospective cohort studies to understand how parkinsonian symptoms may progress, genetic studies to reveal relevant gene loci, and pathophysiologic studies to identify potential therapeutic targets.
Topics: Child; Adolescent; Humans; Autism Spectrum Disorder; Prospective Studies; DNA Copy Number Variations; Parkinsonian Disorders; Parkinson Disease; Membrane Glycoproteins; Molecular Chaperones; Carrier Proteins
PubMed: 36738194
DOI: 10.1002/acn3.51736 -
Parkinsonism & Related Disorders Jun 2024The clinical features and outcomes of post-COVID parkinsonism have not been organized systematically, and the possible correlations between COVID-19 and parkinsonism... (Review)
Review
BACKGROUND
The clinical features and outcomes of post-COVID parkinsonism have not been organized systematically, and the possible correlations between COVID-19 and parkinsonism have not been elucidated. This scoping review addresses these two unmet needs.
METHODS
We searched two databases (Pubmed, Embase) for all published cases of post-COVID parkinsonism. Data were extracted from eligible studies using standardized forms and predefined inclusion and exclusion criteria. The patients' clinical features, their diagnosis and outcomes were assessed objectively.
RESULTS
Twenty-six cases of post-COVID parkinsonism were reported in 17 publications. Their presenting features were grouped into three clinical syndromes: typical parkinsonian motor syndrome (12 patients), parkinsonism with postural instability and gait disorder (three), or encephalopathy with parkinsonism (10). Patients had the following diagnoses: clinically established Parkinson's disease (PD, three cases), clinically probable PD (eight), clinically probable multiple system atrophy (one), acquired parkinsonism (six), unclassified parkinsonism (eight). Isolated parkinsonian motor syndromes typically followed uncomplicated COVID-19 illness or pneumonia; instead, encephalopathy with parkinsonism was observed following a wide spectrum of COVID-19-related presentations, including severe forms. PD cases mainly occurred following uncomplicated COVID-19, whereas acquired or unclassified parkinsonism were reported following different COVID-19 presentations.
CONCLUSIONS
Patients with uncomplicated COVID-19 are more likely to present PD and no signs of encephalopathy. There is no demonstration of a causative role of COVID-19, which can be coincidental in several cases. Patients with encephalopathy and parkinsonism constitute a distinct subset, suggesting a potentially different pathogenic role of SARS-CoV-2 infection. These findings provide a basis for further studies in the post-pandemic phase.
Topics: Humans; COVID-19; Parkinsonian Disorders; Aged; Middle Aged; Parkinson Disease; Female; Male
PubMed: 38480080
DOI: 10.1016/j.parkreldis.2024.106066 -
Movement Disorders : Official Journal... Jul 2021This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6,...
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society.
Topics: Genotype; Humans; Levodopa; Parkinson Disease; Parkinsonian Disorders; Phenotype
PubMed: 34396589
DOI: 10.1002/mds.28517 -
Journal of Parkinson's Disease 2021Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson's disease... (Review)
Review
Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson's disease (PD) have provided conflicting results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: 'Parkinson's disease' and 'parkinsonism' combined with: 'COVID-19'; 'SARS-CoV-2' and 'coronavirus'. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.
Topics: Antiparkinson Agents; COVID-19; Humans; Mortality; Pandemics; Parkinson Disease; Risk Factors; COVID-19 Drug Treatment
PubMed: 33492244
DOI: 10.3233/JPD-202320 -
Journal of Parkinson's Disease 2020
Topics: Antiparkinson Agents; Biomedical Research; Humans; Parkinson Disease; Patient Care; Quality of Life
PubMed: 32741843
DOI: 10.3233/JPD-209003 -
Movement Disorders : Official Journal... Jul 2022Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting... (Review)
Review
BACKGROUND
Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting carriers of GBA mutations/variants (GBA-NMC) constitute a potential PD preclinical population, whereas PD patients carrying some GBA mutations/variants (GBA-PD) have a higher risk of a more aggressive disease course. Different neuroimaging techniques are emerging as potential biomarkers in PD and have been used to study GBA-associated parkinsonism.
OBJECTIVE
The aim is to critically review studies applying neuroimaging to GBA-associated parkinsonism.
METHODS
Literature search was performed using PubMed and EMBASE databases (last search February 7, 2022). Studies reporting neuroimaging findings in GBA-PD, GD with and without parkinsonism, and GBA-NMC were included.
RESULTS
Thirty-five studies were included. In longitudinal studies, GBA-PD patients show a more aggressive disease than iPD at both structural magnetic resonance imaging and 123-fluoropropylcarbomethoxyiodophenylnortropane single-photon emission computed tomography. Fluorodeoxyglucose-positron emission tomography and brain perfusion studies reported a greater cortical involvement in GBA-PD compared to iPD. Overall, contrasting evidence is available regarding GBA-NMC for imaging and clinical findings, although subtle differences have been reported compared with healthy controls with no mutations.
CONCLUSIONS
Although results must be interpreted with caution due to limitations of the studies, in line with previous clinical observations, GBA-PD showed a more aggressive disease progression in neuroimaging longitudinal studies compared to iPD. Cognitive impairment, a "clinical signature" of GBA-PD, seems to find its neuroimaging correlate in the greater cortical burden displayed by these patients as compared to iPD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Gaucher Disease; Glucosylceramidase; Humans; Neuroimaging; Parkinson Disease; Parkinsonian Disorders
PubMed: 35521899
DOI: 10.1002/mds.29047