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Parkinsonism & Related Disorders May 2019Although trimetazidine may induce parkinsonian symptoms in some patients, no systematic characterization has been reported on parkinsonism occurring during trimetazidine...
BACKGROUND
Although trimetazidine may induce parkinsonian symptoms in some patients, no systematic characterization has been reported on parkinsonism occurring during trimetazidine treatment since the first case reports.
OBJECTIVE
To systematically investigate parkinsonism occurring during trimetazidine use.
METHODS
Thirty-three consecutive patients on trimetazidine treatment with previously unrecognized parkinsonian symptoms were enrolled. Detailed neurological and neuropsychological examinations were performed at baseline and 1 and 12 months after trimetazidine withdrawal. In cases with persisting parkinsonian symptoms and suspected de novo Parkinson's disease, antiparkinsonian treatment was initiated. Twenty of the 33 patients underwent DaTSCAN imaging.
RESULTS
After trimetazidine withdrawal, parkinsonism was completely resolved in 11 cases. The comparison of baseline data of patients with reversible and persisting parkinsonism showed that trimetazidine-induced reversible parkinsonism was mainly characterized by akinesia, rigidity, postural instability and gait disturbances (PIGD; PIGD scores: 5.3 ± 3.8 vs. 2.0 ± 1.6 points, p = 0.006) rather than tremors (tremor scores: 1.5 ± 2.2 vs. 7.7 ± 4.6 points, p = 0.000). Trimetazidine-induced reversible parkinsonism was also more symmetrical (asymmetry index: 3.1 ± 3.6 vs. 40.1 ± 22.2, p = 0.000) and milder in severity (MDS-UPDRS Part III. scores: 10.5 ± 19. vs. 30.5 ± 11.3, p = 0.040) than nonreversible parkinsonism. DaTSCAN images were normal in all trimetazidine-induced reversible parkinsonism patients, while these images were abnormal in every patient with nonreversible parkinsonism. In cases of nonreversible parkinsonism, preexisting, incipient Parkinson's disease was suspected by clinical appearance and a good response to antiparkinsonian medication.
CONCLUSIONS
Mild and symmetrical appearance of parkinsonism with normal DaTSCAN results can indicate drug-induced parkinsonism. Trimetazidine discontinuation generally results in permanent remission in such cases.
Topics: Aged; Antiparkinson Agents; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Prospective Studies; Tremor; Trimetazidine
PubMed: 30638818
DOI: 10.1016/j.parkreldis.2019.01.005 -
Movement Disorders : Official Journal... Nov 2019Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar impairment, and... (Review)
Review
Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. The pathologic hallmark is the accumulation of aggregated α-synuclein in oligodendrocytes, forming glial cytoplasmic inclusions, which qualifies MSA as a synucleinopathy together with Parkinson's disease and dementia with Lewy bodies. The underlying pathogenesis is still not well understood. Some symptomatic treatments are available, whereas neuroprotection remains an urgent unmet treatment need. In this review, we critically appraise significant developments of the past decade with emphasis on pathogenesis, diagnosis, prognosis, and treatment development. We further discuss unsolved questions and highlight some perspectives. © 2019 International Parkinson and Movement Disorder Society.
Topics: Autonomic Nervous System Diseases; Humans; Lewy Bodies; Multiple System Atrophy; Oligodendroglia; Parkinson Disease; Parkinsonian Disorders
PubMed: 31692132
DOI: 10.1002/mds.27894 -
La Revue Du Praticien Oct 2021ATYPICAL PARKINSONIAN SYNDROMES Idiopathic Parkinson's disease is the most common cause of parkinsonism, but in almost 40 % of cases, parkinsonism is due to other...
ATYPICAL PARKINSONIAN SYNDROMES Idiopathic Parkinson's disease is the most common cause of parkinsonism, but in almost 40 % of cases, parkinsonism is due to other causes. The diagnosis of atypical parkinsonian syndromes remains difficult at the early stage. Parkinson's syndrome is associated with other symptoms called «red flags». These red flags need to be identified during the clinical examination. Unlike Parkinson's disease, dopaminergic treatment are slightly effective on motor symptoms. The prognosis is worst, with a faster progression. The life expectation is reduced compared to Parkinson's disease. Diagnosis certainty, given by anatomopathology, is not available during the patient's lifetime. Advances in functional imaging improve diagnosis accuracy. Clinical course answers diagnosis uncertainties in a few month or years. The follow up is multidisciplinary. No treatment is currently available.
Topics: Diagnosis, Differential; Humans; Parkinson Disease; Parkinsonian Disorders; Prognosis
PubMed: 35147346
DOI: No ID Found -
Parkinsonism & Related Disorders Jan 2016Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease.... (Review)
Review
Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are commonly summarized under this umbrella term. Significant developments in research have expanded knowledge and have broadened available symptomatic treatments, particularly for the treatment of neurogenic orthostatic hypotension. Nonetheless, symptomatic support still remains limited in all of these disorders. Currently, there exists no effective treatment to delay disease progression and disease-modifying trials have failed to provide coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin (in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results. Nevertheless, large cohorts of patients were recruited for interventional studies in the last few years which improved our understanding of trial methodology in APDs immensely. In addition, remarkable progress in basic research has been reported recently and will provide a solid foundation for future therapeutic trials. In this review, we will summarize published randomized, placebo-controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing and unpublished interventions will be presented.
Topics: Basal Ganglia Diseases; Calcium-Binding Proteins; Diagnosis, Differential; Early Medical Intervention; Humans; Membrane Proteins; Multiple System Atrophy; Muscle Proteins; Parkinson Disease; Parkinsonian Disorders; Randomized Controlled Trials as Topic; Supranuclear Palsy, Progressive
PubMed: 26421389
DOI: 10.1016/j.parkreldis.2015.09.038 -
Handbook of Clinical Neurology 2021This chapter provides a review of mood, emotional disorders, and emotion processing deficits associated with diseases that cause movement disorders, including... (Review)
Review
This chapter provides a review of mood, emotional disorders, and emotion processing deficits associated with diseases that cause movement disorders, including Parkinson's disease, Lewy body dementia, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with parkinsonism, Huntington's disease, essential tremor, dystonia, and tardive dyskinesia. For each disorder, a clinical description of the common signs and symptoms, disease progression, and epidemiology is provided. Then the mood and emotional disorders associated with each of these diseases are described and discussed in terms of clinical presentation, incidence, prevalence, and alterations in quality of life. Alterations of emotion communication, such as affective speech prosody and facial emotional expression, associated with these disorders are also discussed. In addition, if applicable, deficits in gestural and lexical/verbal emotion are reviewed. Throughout the chapter, the relationships among mood and emotional disorders, alterations of emotional experiences, social communication, and quality of life, as well as treatment, are emphasized.
Topics: Humans; Huntington Disease; Movement Disorders; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Quality of Life
PubMed: 34389117
DOI: 10.1016/B978-0-12-822290-4.00015-3 -
Movement Disorders : Official Journal... Dec 2023Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from...
BACKGROUND
Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from excitotoxicity through the glutamate-aspartate transporter (GLAST), whose alterations have been reported in PD. Noninvasive brain stimulation using intermittent theta-burst stimulation (iTBS) acts on striatal neurons and glia, inducing neuromodulatory effects and functional recovery in experimental parkinsonism.
OBJECTIVE
Because PD is associated with altered astrocyte function, we hypothesized that acute iTBS, known to rescue striatal glutamatergic transmission, exerts regional- and cell-specific effects through modulation of glial functions.
METHODS
6-Hydroxydopamine-lesioned rats were exposed to acute iTBS, and the areas predicted to be more responsive by a biophysical, hyper-realistic computational model that faithfully reconstructs the experimental setting were analyzed. The effects of iTBS on glial cells and motor behavior were evaluated by molecular and morphological analyses, and CatWalk and Stepping test, respectively.
RESULTS
As predicted by the model, the hippocampus, cerebellum, and striatum displayed a marked c-FOS activation after iTBS, with the striatum showing specific morphological and molecular changes in the astrocytes, decreased phospho-CREB levels, and recovery of GLAST. Striatal-dependent motor performances were also significantly improved.
CONCLUSION
These data uncover an unknown iTBS effect on astrocytes, advancing the understanding of the complex mechanisms involved in TMS-mediated functional recovery. Data on numerical dosimetry, obtained with a degree of anatomical details never before considered and validated by the biological findings, provide a framework to predict the electric-field induced in different specific brain areas and associate it with functional and molecular changes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Rats; Animals; Astrocytes; Transcranial Magnetic Stimulation; Parkinsonian Disorders; Parkinson Disease; Corpus Striatum; Magnetic Phenomena
PubMed: 37700489
DOI: 10.1002/mds.29599 -
Parkinsonism & Related Disorders May 2024Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical... (Review)
Review
Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical features and neuropathologic signatures can now be supplemented by in-vivo interrogation of genetic and biological substrates of disease, offering great opportunity for further refining the diagnosis of PD. In this mini-review, we discuss the historical perspectives which shaped our thinking surrounding the definition and diagnosis of PD. We highlight the clinical, genetic, pathologic and biologic diversity which underpins the condition, and proceed to discuss how recent developments in our ability to define biologic and pathologic substrates of disease might impact PD definition, diagnosis, individualised prognostication, and personalised clinical care. We argue that Parkinson's 'disease', as currently diagnosed in the clinic, is actually a syndrome. It is the outward manifestation of any array of potential dysfunctional biologic processes, neuropathological changes, and disease aetiologies, which culminate in common outward clinical features which we term PD; each person has their own unique disease, which we can now define with increasing precision. This is an exciting time in PD research and clinical care. Our ability to refine the clinical diagnosis of PD, incorporating in-vivo assessments of disease biology, neuropathology, and neurogenetics may well herald the era of biologically-based, precision medicine approaches PD management. With this however comes a number of challenges, including how to integrate these technologies into clinical practice in a way which is acceptable to patients, promotes meaningful changes to care, and minimises health economic impact.
Topics: Humans; Parkinson Disease
PubMed: 38360507
DOI: 10.1016/j.parkreldis.2024.106041 -
Canadian Family Physician Medecin de... Jan 2023To provide family physicians an updated approach to the diagnosis of Parkinson disease (PD).
OBJECTIVE
To provide family physicians an updated approach to the diagnosis of Parkinson disease (PD).
SOURCES OF INFORMATION
Published guidelines on the diagnosis and management of PD were reviewed. Database searches were conducted to retrieve relevant research articles published between 2011 and 2021. Evidence levels ranged from I to III.
MAIN MESSAGE
Diagnosis of PD is predominantly clinical. Family physicians should evaluate patients for specific features of parkinsonism, then determine whether symptoms are attributable to PD. Levodopa trials can be used to help confirm the diagnosis and alleviate motor symptoms of PD. "Red flag" features and absence of response to levodopa may point to other causes of parkinsonism and prompt more urgent referral.
CONCLUSION
Access to neurologists and specialized clinics varies, and Canadian family physicians can be important players in facilitating early and accurate diagnosis of PD. Applying an organized approach to diagnosis and considering motor and nonmotor symptoms can greatly benefit patients with PD. Part 2 in this series will review management of PD.
Topics: Humans; Parkinson Disease; Levodopa; Canada; Parkinsonian Disorders; Patients
PubMed: 36693741
DOI: 10.46747/cfp.690120 -
Reviews in the Neurosciences Feb 2021Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967-2019)... (Meta-Analysis)
Meta-Analysis Review
Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967-2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, was predominantly associated with gastrointestinal cancers with breast cancer, and with head-and-neck cancers. In asymptomatic carriers, was predominantly associated with gastrointestinal and prostate cancers, with prostate and genitourinary tract cancers, with sarcoma, and deletion with leukemia. In symptomatic genetic parkinsonism, was associated with nonmelanoma skin cancers and breast cancers, and with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.
Topics: Humans; Male; Neoplasms; Parkinson Disease; Parkinsonian Disorders
PubMed: 33151182
DOI: 10.1515/revneuro-2020-0083 -
Movement Disorders : Official Journal... Jul 2019
Topics: Brain; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neuroprotective Agents; Parkinson Disease; Parkinsonian Disorders
PubMed: 31322771
DOI: 10.1002/mds.27721