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Ageing Research Reviews Sep 2016The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of... (Review)
Review
The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting the striatal dopamine terminal dysfunction present in idiopathic Parkinson's disease (PD) and atypical neurodegenerative parkinsonian disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DAT imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be used to support or refute a diagnosis of dopamine deficient parkinsonism in cases where this is unclear and rationalise a trial of dopamine replacement agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk for PD such as relatives of patients, susceptibility gene mutation carriers, and subjects with late onset hyposmia or sleep disorders. The presence of normal DAT availability on imaging can help categorise "subjects without evidence of dopamine deficiency" (SWEDDs) who on occasion mimic PD and include dystonic tremors, drug-induced and psychogenic parkinsonism in their ranks. Reduced levels of baseline striatal DAT availability on PET or SPECT scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism.
Topics: Animals; Dementia; Dopamine Plasma Membrane Transport Proteins; Humans; Molecular Imaging; Parkinson Disease; Parkinson Disease, Secondary
PubMed: 26802555
DOI: 10.1016/j.arr.2015.12.009 -
Presse Medicale (Paris, France : 1983) Mar 2017Parkinsonian syndrome is the clinical expression of a lesion within the nigro-striatal dopaminergic pathway. Akinesia is the main manifestation of parkinsonism. The... (Review)
Review
Parkinsonian syndrome is the clinical expression of a lesion within the nigro-striatal dopaminergic pathway. Akinesia is the main manifestation of parkinsonism. The clinical analysis of motor symptoms may guide clinical diagnosis. Parkinson's disease is characterized by a pure asymmetric parkinsonian syndrome, responsive to dopaminergic treatment. The evolution of Parkinson's disease is characterized by the occurrence of motor complications (dyskinesia and fluctuations). Gait disturbances (postural instability and freezing) are late in Parkinson's disease. When early (within the first three years), they point to atypical parkinsonian syndrome.
Topics: Antiparkinson Agents; Articulation Disorders; Corpus Striatum; Deglutition Disorders; Disease Progression; Dopamine Agonists; Dopaminergic Neurons; Gait Disorders, Neurologic; Humans; Hypokinesia; Levodopa; Movement; Muscle Hypertonia; Parkinson Disease; Parkinsonian Disorders; Postural Balance; Sensation Disorders; Substantia Nigra; Tremor
PubMed: 28233705
DOI: 10.1016/j.lpm.2017.01.003 -
International Journal of Environmental... Jul 2015Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure... (Review)
Review
Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD).
Topics: Brain; Dopamine; Glutamic Acid; Humans; Magnesium; Manganese Poisoning; Parkinson Disease; Parkinsonian Disorders; gamma-Aminobutyric Acid
PubMed: 26154659
DOI: 10.3390/ijerph120707519 -
International Review of Neurobiology 2017Atypical parkinsonism (AP) comprises mainly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which are distinct... (Review)
Review
Atypical parkinsonism (AP) comprises mainly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which are distinct pathological entities, presenting with a wide phenotypic spectrum. The classic syndromes are now called MSA-parkinsonism (MSA-P), MSA-cerebellar type (MSA-C), Richardson's syndrome, and corticobasal syndrome. Nonmotor features in AP have been recognized almost since the initial description of these disorders; however, research has been limited. Autonomic dysfunction is the most prominent nonmotor feature of MSA, but also gastrointestinal symptoms, sleep dysfunction, and pain, can be a feature. In PSP and CBD, the most prominent nonmotor symptoms comprise those deriving from the cognitive/neuropsychiatric domain. Apart from assisting the clinician in the differential diagnosis with Parkinson's disease, nonmotor features in AP have a big impact on quality of life and prognosis of AP and their treatment poses a major challenge for clinicians.
Topics: Autonomic Nervous System Diseases; Diagnosis, Differential; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 28805573
DOI: 10.1016/bs.irn.2017.06.001 -
Neurotherapeutics : the Journal of the... Jul 2023Ferroptosis is a programmed cell death pathway that is recently linked to Parkinson's disease (PD), where the key genes and molecules involved are still yet to be...
Ferroptosis is a programmed cell death pathway that is recently linked to Parkinson's disease (PD), where the key genes and molecules involved are still yet to be defined. Acyl-CoA synthetase long-chain family member 4 (ACSL4) esterifies polyunsaturated fatty acids (PUFAs) which is essential to trigger ferroptosis, and is suggested as a key gene in the pathogenesis of several neurological diseases including ischemic stroke and multiple sclerosis. Here, we report that ACSL4 expression in the substantia nigra (SN) was increased in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated model of PD and in dopaminergic neurons in PD patients. Knockdown of ACSL4 in the SN protected against dopaminergic neuronal death and motor deficits in the MPTP mice, while inhibition of ACSL4 activity with Triacsin C similarly ameliorated the parkinsonism phenotypes. Similar effects of ACSL4 reduction were observed in cells treated with 1-methyl-4-phenylpyridinium (MPP) and it specifically prevented the lipid ROS elevation without affecting the mitochondrial ROS changes. These data support ACSL4 as a therapeutic target associated with lipid peroxidation in PD.
Topics: Animals; Mice; Apoptosis; Dopaminergic Neurons; Lipids; Mice, Inbred C57BL; Parkinson Disease; Parkinsonian Disorders; Phenotype; Reactive Oxygen Species; Humans
PubMed: 37133631
DOI: 10.1007/s13311-023-01382-4 -
Journal of Neural Transmission (Vienna,... Jan 2023Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder of uncertain etiology that is characterized by various combinations of Parkinsonism,... (Review)
Review
Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder of uncertain etiology that is characterized by various combinations of Parkinsonism, autonomic, cerebellar and motor dysfunctions, with poor prognosis. Little is known about modifiable factors, such as depression, that has negative effects on quality of life in MSA. Depression, with an estimated prevalence of about 43%, is among the most common neuropsychiatric disorders in MSA similar to other atypical Parkinsonian disorders, the frequency of which is associated with increased disease progression, disease severity and autonomic dysfunctions. Depression in MSA, like in Parkinson disease, has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, such as involvement of serotonergic neuron groups in the brainstem, prefrontal cortical dysfunctions, and altered functional fronto-temporal-thalamic connectivities with disturbances of mood related and other essential resting-state brain networks. The pathophysiology and pathogenesis of depression in MSA, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for adequate treatment to improve the quality of life in this fatal disease.
Topics: Humans; Multiple System Atrophy; Depression; Quality of Life; Parkinsonian Disorders; Parkinson Disease
PubMed: 36348076
DOI: 10.1007/s00702-022-02560-y -
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 -
European Journal of Neurology Jul 2021Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease. However, clinical and experimental studies indicate that bradykinesia may also be observed in... (Review)
Review
BACKGROUND AND PURPOSE
Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease. However, clinical and experimental studies indicate that bradykinesia may also be observed in various neurological diseases not primarily characterized by parkinsonism. These conditions include hyperkinetic movement disorders, such as dystonia, chorea, and essential tremor. Bradykinesia may also be observed in patients with neurological conditions that are not seen as "movement disorders," including those characterized by the involvement of the cerebellum and corticospinal system, dementia, multiple sclerosis, and psychiatric disorders.
METHODS
We reviewed clinical reports and experimental studies on bradykinesia in non-parkinsonian conditions and discussed the major findings.
RESULTS
Bradykinesia is a common motor abnormality in non-parkinsonian conditions. From a pathophysiological standpoint, bradykinesia in neurological conditions not primarily characterized by parkinsonism may be explained by brain network dysfunction.
CONCLUSION
In addition to the pathophysiological implications, the present paper highlights important terminological issues and the need for a new, more accurate, and more widely used definition of bradykinesia in the context of movement disorders and other neurological conditions.
Topics: Dystonia; Essential Tremor; Humans; Hypokinesia; Parkinson Disease; Parkinsonian Disorders
PubMed: 33793037
DOI: 10.1111/ene.14851 -
Toxicon : Official Journal of the... Aug 2023Many studies have shown that botulinum toxin (BoNT) can be an option to treat motor and non-motor symptoms in Parkinson's disease (PD) and parkinsonian syndromes. The... (Review)
Review
Many studies have shown that botulinum toxin (BoNT) can be an option to treat motor and non-motor symptoms in Parkinson's disease (PD) and parkinsonian syndromes. The advantages of BoNT compared to oral medications include localized action and low incidence of systemic side effects, which is important in treating neurodegenerative disease. Motor symptoms that can be treated with BoNT include blepharospasm, apraxia of eyelid opening, tremor, cervical dystonia and limb dystonia. Other indications with less evidence include camptocormia, freezing of gait and dyskinesia. Non-motor symptoms that may improve with BoNT include sialorrhea, pain, overreactive bladder, dysphagia and constipation. However, the current evidence for use of BoNT in parkinsonism is mostly based on open-label studies and there are few randomized, controlled trials. BoNT can be a valuable tool to treat certain symptoms of PD and parkinsonian syndromes to improve the patient's quality of life. However, many of the uses are not supported by high quality studies and further studies are needed to provide further evidence of efficacy, define the optimal injection protocols such as doses and muscle selection.
Topics: Humans; Botulinum Toxins; Botulinum Toxins, Type A; Gait Disorders, Neurologic; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Quality of Life; Torticollis
PubMed: 37429465
DOI: 10.1016/j.toxicon.2023.107209 -
Movement Disorders : Official Journal... Sep 2021The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic... (Review)
Review
The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic etiology. However, the link between parkinsonism or tremor and chromosome disorders, both numerical and structural, has been neglected. We reviewed the occurrence and characteristics of parkinsonism and tremor syndromes in patients with chromosomic disorders. We searched PubMed for articles published until December 2018, using the non-MESH terms "Chromosomopathy," "karyotype," "chromosome," "aneuploidy," "deletion," "inversion," "insertion," "duplication," and "Parkinson," "Parkinsonism," "Tremor," and "Parkinsonian disorder." We restricted the search to human studies and selected articles for further analysis after abstract review. Tremor syndromes in which patients had another possible clinical reason for syndromes were excluded, as well as tremor syndromes associated with point mutations, imprinting syndromes, and patients presenting with other hyperkinetic disorders. Fifty-four articles were reviewed. Aneuploidies of sex chromosomes were the most common chromosomopathy. These patients more commonly exhibited postural and kinetic tremor, often meeting the description of essential tremor. In structural chromosomopathies, the most frequent association was PD and 22q11.2 deletion syndrome, but we found case reports and case series of several additional deletion and duplication syndromes. © 2021 International Parkinson and Movement Disorder Society.
Topics: DiGeorge Syndrome; Essential Tremor; Humans; Parkinson Disease; Parkinsonian Disorders; Tremor
PubMed: 34056754
DOI: 10.1002/mds.28663