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Biomolecules Jul 2023Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend... (Review)
Review
Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend beyond the globus pallidus (as seen with manganism) to the entire basal ganglia, including the substantia nigra pars compacta. This change of exposure paradigm has prompted numerous epidemiological investigations of the occurrence of Parkinson's disease (PD), or parkinsonism, due to the long-term impact of Mn. In parallel, experimental research has focused on the underlying pathogenic mechanisms of Mn and its interactions with genetic susceptibility. In this review, we provide evidence from both types of studies, with the aim to link the epidemiological data with the potential mechanistic interpretation.
Topics: Humans; Manganese; Parkinsonian Disorders; Parkinson Disease; Genetic Predisposition to Disease
PubMed: 37627255
DOI: 10.3390/biom13081190 -
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 -
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 -
Journal of Neurology, Neurosurgery, and... Apr 2008Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable... (Review)
Review
OBJECTIVE
Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders.
METHODS
A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms".
RESULTS
Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD.
CONCLUSIONS
A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
Topics: Diagnosis, Differential; Humans; Neurologic Examination; Parkinson Disease; Parkinsonian Disorders
PubMed: 18344392
DOI: 10.1136/jnnp.2007.131045 -
Journal of Parkinson's Disease 2018Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to... (Review)
Review
Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.
Topics: Aging; Global Health; Humans; Pandemics; Parkinson Disease; Parkinsonian Disorders; Survival Rate
PubMed: 30584159
DOI: 10.3233/JPD-181474 -
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 -
Journal of Neural Transmission (Vienna,... Sep 2022To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is... (Review)
Review
To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.
Topics: Biomarkers; Brain; Humans; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 35695938
DOI: 10.1007/s00702-022-02520-6 -
Tidsskrift For Den Norske Laegeforening... Sep 2008The dopamine deficiency syndrome Parkinson's disease (PD) is characterized by tremor, rigidity, bradykinesia and reduced postural reflexes. Conditions with similar... (Review)
Review
BACKGROUND
The dopamine deficiency syndrome Parkinson's disease (PD) is characterized by tremor, rigidity, bradykinesia and reduced postural reflexes. Conditions with similar symptoms but other causes than PD (about 1/3 of cases) are called atypical parkinsonism. From a neuropathological perspective, PD is associated with loss of nigro-striatal dopaminergic neurons (related to motor symptoms) and accumulation of alpha-synuclein-containing Lewy bodies in the mid-brain. Nigro-striatal pathways may also be involved in atypical parkinsonism, but lesions in other parts of the brain/basal ganglions dominate. Parkinsonism may also be related to chronic cerebrovascular disease or use of drugs with extrapyramidal side effects.
MATERIAL AND METHODS
Articles retrieved from PubMed were reviewed to examine current knowledge on diseases other than PD that can induce parkinsonism.
RESULTS AND INTERPRETATION
Diseases with atypical parkinsonism usually start more symmetric than PD and tremor is either not present or differs from the typical rest tremor seen in PD. An exception is corticobasal degeneration with very asymmetric symptoms. Other (plus-) symptoms in atypical parkinsonism are (early) falling tendency, dizziness upon change of position, coordination difficulties or early cognitive decline. The article describes the clinical characteristics of atypical parkinsonism, possibilities of improved diagnostics with supplementary examinations and alternative treatment strategies.
Topics: Brain; Diagnosis, Differential; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Prognosis; Supranuclear Palsy, Progressive
PubMed: 18846125
DOI: No ID Found -
The Lancet. Neurology Jan 2006The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic... (Review)
Review
The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.
Topics: Diagnosis, Differential; Humans; Parkinson Disease; Parkinson Disease, Secondary
PubMed: 16361025
DOI: 10.1016/S1474-4422(05)70285-4 -
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