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Brain : a Journal of Neurology Mar 2020Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the... (Review)
Review
Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes.
Topics: Animals; Humans; Hypokinesia; Levodopa; Neural Pathways; Parkinsonian Disorders
PubMed: 31834375
DOI: 10.1093/brain/awz344 -
Journal of Parkinson's Disease 2023The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological... (Review)
Review
The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological treatment. Levodopa is the most efficacious drug for most patients and should be used as primary approach to control troublesome tremor. While the efficacy of oral dopamine agonists on PD tremor has been demonstrated in controlled trials, there is no evidence of greater antitremor efficacy compared to levodopa. The magnitude of the antitremor effect of anticholinergics is generally lower than that of levodopa. Due to their adverse effects, anticholinergics have a limited role in selected young and cognitively intact patients. Propranolol may improve resting and action tremor and may be considered as an adjunct in patients with insufficient tremor response to levodopa and this also applies to clozapine, despite its unfavorable adverse effect profile. Treating motor fluctuations with MAO-B and COMT inhibitors, dopamine agonists, amantadine, or on-demand treatments such as subcutaneous or sublingual apomorphine and inhaled levodopa as well as with continuous infusions of levodopa or apomorphine will improve off period tremor episodes. For patients with drug-refractory PD tremor despite levodopa optimization deep brain stimulation and focused ultrasound are first-line considerations. Surgery can also be highly effective for the treatment medication-refractory tremor in selected patients without motor fluctuations. The present review highlights the clinical essentials of parkinsonian tremor, critically examines available trial data on the effects of medication and surgical approaches and provides guidance for the choice of treatments to control PD tremor in clinical practice.
Topics: Humans; Parkinson Disease; Levodopa; Tremor; Dopamine Agonists; Antiparkinson Agents; Apomorphine; Cholinergic Antagonists
PubMed: 36847017
DOI: 10.3233/JPD-225060 -
Neurobiology of Disease Feb 2020Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.
Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Mice; Parkinson Disease
PubMed: 31809788
DOI: 10.1016/j.nbd.2019.104700 -
Journal of Parkinson's Disease 2021Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from... (Review)
Review
Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD.
Topics: Animals; Humans; Mitochondrial Diseases; Parkinson Disease
PubMed: 33074190
DOI: 10.3233/JPD-201981 -
Journal of Parkinson's Disease 2020Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson's disease (PD). Despite the acknowledgement of the... (Review)
Review
Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson's disease (PD). Despite the acknowledgement of the benefits of exercise for people with PD (PwPD), frequently, exercise recommendations lack specificity in terms of frequency, intensity and duration. Additionally, conflating physical activity with exercise has contributed to providing vague exercise recommendations to PwPD. Therefore, the beneficial effects of exercise may not be fully realized in PwPD. Data provided by animal studies and select human trials indicate aerobic exercise may facilitate structural and functional changes in the brain. Recently, several large human clinical trials have been completed and collectively support the use of aerobic exercise, specifically high-intensity aerobic exercise, in improving PD motor symptoms. Data from these and other studies provide the basis to include aerobic exercise as an integral component in treating PD. Based on positive clinical findings and trials, it is advised that PwPD perform aerobic exercise in the following dose: 3x/week, 30-40-minute main exercise set, 60-80% of heart rate reserve or 70-85% of heart rate max. In lieu of heart rate, individuals can achieve an intensity of 14-17 on a 20-point RPE scale. Ongoing clinical trials, SPARX3 and CYCLE-II, have potential to further develop patient-specific exercise recommendations through prognostic modeling.
Topics: Animals; Exercise; Exercise Therapy; Humans; Parkinson Disease; Prescriptions
PubMed: 32925109
DOI: 10.3233/JPD-202100 -
Journal of Neurology Nov 2020Disturbances of balance, gait and posture are a hallmark of parkinsonian syndromes. Recognition of these axial features can provide important and often early clues to... (Review)
Review
Disturbances of balance, gait and posture are a hallmark of parkinsonian syndromes. Recognition of these axial features can provide important and often early clues to the nature of the underlying disorder, and, therefore, help to disentangle Parkinson's disease from vascular parkinsonism and various forms of atypical parkinsonism, including multiple system atrophy, progressive supranuclear palsy, and corticobasal syndrome. Careful assessment of axial features is also essential for initiating appropriate treatment strategies and for documenting the outcome of such interventions. In this article, we provide an overview of balance, gait and postural impairment in parkinsonian disorders, focusing on differential diagnostic aspects.
Topics: Gait; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 31119450
DOI: 10.1007/s00415-019-09382-1 -
International Journal of Molecular... Jan 2020In recent years, therapeutic strategies [...].
In recent years, therapeutic strategies [...].
Topics: Animals; Disease Susceptibility; Humans; Parkinson Disease; Research
PubMed: 31991804
DOI: 10.3390/ijms21030793 -
Genes Jun 2021The genetic landscape of Parkinson's disease (PD) is characterised by rare high penetrance pathogenic variants causing familial disease, genetic risk factor variants... (Review)
Review
The genetic landscape of Parkinson's disease (PD) is characterised by rare high penetrance pathogenic variants causing familial disease, genetic risk factor variants driving PD risk in a significant minority in PD cases and high frequency, low penetrance variants, which contribute a small increase of the risk of developing sporadic PD. This knowledge has the potential to have a major impact in the clinical care of people with PD. We summarise these genetic influences and discuss the implications for therapeutics and clinical trial design.
Topics: Genetic Predisposition to Disease; Humans; Mutation; Parkinson Disease; Penetrance; Polymorphism, Single Nucleotide
PubMed: 34208795
DOI: 10.3390/genes12071006 -
Journal of Neural Transmission (Vienna,... Sep 2022The question whether life style may impair the advent or course of the disease in patients with Parkinsonism is of great importance for patients and physicians alike. We... (Review)
Review
The question whether life style may impair the advent or course of the disease in patients with Parkinsonism is of great importance for patients and physicians alike. We present here comprehensive information on the influence of the environment, diet (especially caffeine, nicotine, alcohol, chocolate and dairy products), physical activity and sleep on risk and course of Parkinson's disease.
Topics: Caffeine; Exercise; Humans; Life Style; Parkinson Disease; Parkinsonian Disorders
PubMed: 35606622
DOI: 10.1007/s00702-022-02509-1 -
BMJ Open Sep 2020To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and managed.
METHODS
MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Control Trials and Cochrane Database of Systematic Reviews were searched to 17 May 2017. An updated review was run from 17 May 2017 to 28 January 2019. The grey literature was searched using the CADTH Grey Matters tool. Original peer-reviewed research was included if it included individuals with PD and apathy. Non-original data was only included if it was in the form of meta-analysis. All information regarding diagnosis, treatment and management of PD was extracted. Citation screening and extraction were performed in duplicate.
RESULTS
From 11 375 citations, 362 articles were included in the final review. The majority of included studies focussed on prevalence, with few studies examining treatment. Twenty screening tools for apathy were identified. Fifty per cent of treatment studies were randomised control trials (RCTs). RCTs applied treatment methods including: exercise, mindfulness, rotigotine (Neupro) transdermal patch and rivastigmine (Exelon).
CONCLUSIONS
This review identified a large body of literature describing current knowledge on diagnosing, treating and managing apathy in PD. Future research should aim to detect an ideal screening tool for apathy in PD, to identify the best treatment options for apathy and the variety of comorbidities it may present with and finally aim to better understand postoperative apathy in those with deep brain stimulation.
Topics: Apathy; Humans; Parkinson Disease; Systematic Reviews as Topic; Transdermal Patch
PubMed: 32907903
DOI: 10.1136/bmjopen-2020-037632