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Acta Medica Portuguesa Oct 2019Parkinson's disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented.... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented. Environmental and genetic factors contribute to the pathophysiology of this disease, and 5% - 10% of cases have a monogenic cause. The diagnosis relies on clinical findings, supported by adequate testing. There is no absolute method to diagnose Parkinson's disease in vivo, except for genetic testing in specific circumstances, whose usefulness is limited to a minority of cases. New diagnostic criteria have been recently proposed with the aim of improving diagnostic accuracy, emphasizing findings that might point to other causes of parkinsonism. The available therapeutic options are clinically useful, as they improve the symptoms as well as the quality of life of patients. After the introduction of levodopa, deep brain stimulation emerged as the second therapy with an important symptomatic impact in the treatment of Parkinson's disease. Non-motor symptoms and motor complications are responsible for a large proportion of disability, so these should be identified and treated. Current scientific research is focused on the identification of disease biomarkers allowing correct and timely diagnosis, and on creating more effective therapies, thus fulfilling current clinical unmet needs. This paper presents an updated review on Parkinson's disease, guiding the readership through current concepts, and allowing their application to daily clinical practice.
Topics: Antiparkinson Agents; Biomarkers; Deep Brain Stimulation; Diagnosis, Differential; Humans; Levodopa; Parkinson Disease; Symptom Assessment
PubMed: 31625879
DOI: 10.20344/amp.11978 -
Biomolecules Apr 2021Parkinson's disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder... (Review)
Review
Parkinson's disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson's (PwP): rehabilitate, therapy, restorative, maintenance, and surgery. Rehabilitating begins following the diagnosis and throughout any additional treatment processes, especially vis-à-vis consulting with physical, occupational, and/or speech pathology therapist(s). Therapy uses daily administration of either the dopamine precursor levodopa (with carbidopa) or a dopamine agonist, compounds that preserve residual dopamine, and other specific motor/non-motor-related compounds. Restorative uses strenuous aerobic exercise programs that can be neuroprotective. Maintenance uses complementary and alternative medicine substances that potentially support and protect the brain microenvironment. Finally, surgery, including deep brain stimulation, is pursued when PwP fail to respond positively to other treatment options. There is currently no cure for PD. In conclusion, the best strategy for treating PD is to hope to slow disorder progression and strive to achieve stability with neuroprotection. The ultimate goal of any management program is to improve the quality-of-life for a person with Parkinson's disease.
Topics: Animals; Antiparkinson Agents; Clinical Trials as Topic; Deep Brain Stimulation; Exercise Therapy; Humans; Movement; Parkinson Disease; Psychotropic Drugs
PubMed: 33924103
DOI: 10.3390/biom11040612 -
Translational Neurodegeneration 2020Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and... (Review)
Review
BACKGROUND
Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed.
MAIN BODY
In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising.
CONCLUSION
FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.
Topics: Antiparkinson Agents; Deep Brain Stimulation; Electric Stimulation Therapy; Gait Disorders, Neurologic; Humans; Parkinson Disease; Risk Factors; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 32322387
DOI: 10.1186/s40035-020-00191-5 -
Bosnian Journal of Basic Medical... Aug 2021Among the popular animal models of Parkinson's disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3,... (Review)
Review
Among the popular animal models of Parkinson's disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antiparkinson Agents; Apoptosis; Disease Models, Animal; Dopaminergic Neurons; Mice; Neuroprotective Agents; Oxidative Stress; Parkinson Disease
PubMed: 33357211
DOI: 10.17305/bjbms.2020.5181 -
American Family Physician Dec 2020Parkinson disease is a progressive neurodegenerative disorder with significant morbidity and mortality. Most patients consult with their primary care physician about...
Parkinson disease is a progressive neurodegenerative disorder with significant morbidity and mortality. Most patients consult with their primary care physician about Parkinson disease symptoms before seeking care from a specialist. The diagnosis of Parkinson disease is clinical, and key disease features are bradykinesia, rigidity, and tremor. The main diagnostic signs of Parkinson disease are motor symptoms; however, Parkinson disease is also associated with nonmotor symptoms, including autonomic dysfunction, depression, and hallucinations, which can make the initial diagnosis of Parkinson disease difficult. Disease progression is variable and clinical signs cannot be used to predict progression accurately. Therapies, including levodopa, have not demonstrated the ability to slow disease progression. Motor symptoms are managed with carbidopa/levodopa, monoamine oxidase-B inhibitors, and nonergot dopamine agonists. Prolonged use and higher doses of levodopa result in dyskinesias and motor symptom fluctuations over time. Deep brain stimulation surgery is performed for patients who do not achieve adequate control with levodopa therapy. Deep brain stimulation is most effective for significant motor fluctuations, dyskinesias, and tremors. Nonmotor symptom therapies target patient-specific conditions during the disease course. Interdisciplinary team care can alleviate multiple symptoms of Parkinson disease.
Topics: Antiparkinson Agents; Carbidopa; Combined Modality Therapy; Deep Brain Stimulation; Disease Progression; Drug Combinations; Family Practice; Humans; Levodopa; Parkinson Disease; Physical Therapy Modalities
PubMed: 33252908
DOI: No ID Found -
Journal of Neurochemistry May 2021Parkinson disease (PD) is a prevalent neurodegenerative disease, in which the formation of misfolded and aggregated α-synuclein is a key neuropathological hallmark.... (Review)
Review
Parkinson disease (PD) is a prevalent neurodegenerative disease, in which the formation of misfolded and aggregated α-synuclein is a key neuropathological hallmark. Recent studies reveal that extracellular vesicles such as exosomes present a potential mechanism for propagation of pathological α-synuclein throughout the brain. The ability of exosomes to transport proteins and genetic material between cells, including mRNA and microRNAs which have been implicated in PD pathology, provides critical insights as to how exosomes may contribute to pathological progression in PD. Advances have also been made in the investigation of exosomes as potential tools for the modulation of Parkinson's pathology; their detection extracellularly may facilitate their use as biomarkers, while their small size could be utilised as vectors for the delivery of therapeutics. The aim of this review was to highlight our current knowledge of the role of exosomes in PD and potential clinical application.
Topics: Animals; Antiparkinson Agents; Biomarkers; Exosomes; Extracellular Space; Humans; Parkinson Disease
PubMed: 33372290
DOI: 10.1111/jnc.15288 -
Journal of Parkinson's Disease 2020Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only... (Review)
Review
Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only unsystematically. Pain etiology and pain character are often complex and multi-causal, and data regarding treatment recommendations are limited. Pain can be primarily related to PD but frequently it is associated with secondary diseases, such as arthrosis of the spine or joints. However, even basically PD-unrelated pain often is amplified by motor- or non-motor PD symptoms, such as akinesia or depression. Beyond an optimization of anti-parkinsonian treatment, additional pain treatment strategies are usually needed to properly address pain in PD. A careful pain history and diagnostic work-up is essential to rate the underlying pain pathophysiology and to develop a targeted therapeutic concept. This review gives an overview on how pain is treated in PD patients and how patients assess the effectiveness of these therapies; here, the manuscript focuses on pathophysiology-driven suggestions for a multimodal pain management in clinical practice.
Topics: Analgesics; Antiparkinson Agents; Humans; Pain; Pain Management; Pain Measurement; Parkinson Disease; Quality of Life
PubMed: 32568113
DOI: 10.3233/JPD-202069 -
Cells Nov 2022The most commonly used treatment for Parkinson's disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients with PD undergo dopamine... (Review)
Review
The most commonly used treatment for Parkinson's disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients with PD undergo dopamine replacement therapy using levodopa during the course of the disease's progression. However, despite the fact that levodopa is the "gold standard" in PD treatments and has the ability to significantly alleviate PD symptoms, it comes with side effects in advanced PD. Levodopa replacement therapy remains the current clinical treatment of choice for Parkinson's patients, but approximately 80% of the treated PD patients develop levodopa-induced dyskinesia (LID) in the advanced stages of the disease. A better understanding of the pathological mechanisms of LID and possible means of improvement would significantly improve the outcome of PD patients, reduce the complexity of medication use, and lower adverse effects, thus, improving the quality of life of patients and prolonging their life cycle. This review assesses the recent advancements in understanding the underlying mechanisms of LID and the therapeutic management options available after the emergence of LID in patients. We summarized the pathogenesis and the new treatments for LID-related PD and concluded that targeting pathways other than the dopaminergic pathway to treat LID has become a new possibility, and, currently, amantadine, drugs targeting 5-hydroxytryptamine receptors, and surgery for PD can target the Parkinson's symptoms caused by LID.
Topics: Humans; Levodopa; Parkinson Disease; Dyskinesia, Drug-Induced; Antiparkinson Agents; Quality of Life; Dopamine
PubMed: 36496996
DOI: 10.3390/cells11233736 -
Revista de Neurologia Oct 2022Parkinson's disease (PD) is a neurodegenerative multisystemic disorder that affects approximately 1% of the population over 55 years old, with the mean age of onset at... (Review)
Review
INTRODUCTION
Parkinson's disease (PD) is a neurodegenerative multisystemic disorder that affects approximately 1% of the population over 55 years old, with the mean age of onset at 60 years old, and the prevalence of the disease constantly growing.
DEVELOPMENT
PD is a progressive disease characterized by motor and non-motor symptoms that compromise patients' daily activities. It has a variable profile of onset and clinical evolution. Although currently available treatments have failed to clinically demonstrate neuroprotective properties, most motor symptoms are acceptably managed with dopaminergic medication. More than 50 years after launching levodopa, it remains the most effective treatment of motor symptoms in PD, able to provide sustained benefit throughout the entire course of the disease. Nevertheless, after two to three years of treatment, certain fluctuations start to appear in motor and non-motor responses to different doses of levodopa. Early identification and treatment of these fluctuations have a strong positive impact on the quality of life of the patient. Frequently accompanied by involuntary movements, proper control of fluctuations requires periodical adjustments of the medication and expert supplementation with dopaminergic and non-dopaminergic adjuvants.
CONCLUSIONS
The main purpose of this work is to offer a practical, updated guideline for neurologists regarding the use of dopaminergic agents from the initial stages of PD. Special emphasis is placed on the critical period after the end of the 'honeymoon' phase when variations in the symptomatology presented by each patient appear, forcing re-adjustment of the medication to fit their individual needs.
Topics: Humans; Middle Aged; Levodopa; Parkinson Disease; Antiparkinson Agents; Quality of Life; Dyskinesias
PubMed: 36342310
DOI: 10.33588/rn.75s04.2022217 -
Journal of Neural Transmission (Vienna,... Jun 2023Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong... (Review)
Review
Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson's disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson's disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Monoamine Oxidase; Catechol O-Methyltransferase; Levodopa; Catechol O-Methyltransferase Inhibitors; Monoamine Oxidase Inhibitors
PubMed: 36964457
DOI: 10.1007/s00702-023-02623-8