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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 -
Neurology India 2018Parkinson's disease is a common movement disorder seen in neurological practice, but the diagnosis and management is challenging. The diagnosis is clinical and sometimes... (Review)
Review
Parkinson's disease is a common movement disorder seen in neurological practice, but the diagnosis and management is challenging. The diagnosis is clinical and sometimes difficult, considering a large number of motor and non-motor symptoms in PD patients. The medical management of PD patients is difficult, as choices of drugs are limited and levodopa is the mainstay of treatment. However, levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after a long duration of treatment, but occasionally, this may be seen even after a few days or months of treatment. Different types of surgical approaches, including unilateral pallidotomy and deep brain stimulation, have given very good results in PD patients, who cannot be managed by medications alone.
Topics: Antiparkinson Agents; Deep Brain Stimulation; Humans; Levodopa; Parkinson Disease; Treatment Outcome
PubMed: 29503325
DOI: 10.4103/0028-3886.226451 -
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 -
International Journal of Molecular... Mar 2017Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging... (Review)
Review
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson's disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin-proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol--methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the "wearing-off phenomenon", with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.
Topics: Adult; Aged; Aged, 80 and over; Animals; Antiparkinson Agents; Disease Susceptibility; Dopaminergic Neurons; Humans; Middle Aged; Oxidative Stress; Parkinson Disease; Pharmacogenetics; Pharmacogenomic Variants; Risk Factors
PubMed: 28273839
DOI: 10.3390/ijms18030551 -
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 -
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 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 -
Internal Medicine (Tokyo, Japan) Jan 2023Parkinson's disease (PD) is a neurodegenerative disease manifesting with motor and non-motor symptoms. Current treatment mainly relies on medication as a symptomatic... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease manifesting with motor and non-motor symptoms. Current treatment mainly relies on medication as a symptomatic therapy modulating neurotransmitters. Dopamine replacement therapy has been established, and levodopa is the gold standard for treatment of PD. However, the emergence of motor complications, such as a wearing-off phenomenon, is a clinical problem. Both primary symptoms and motor complications have been targets for the development of treatments for PD. Recent progression in the management of motor complications is supported by newly developed agents and advances in device and formulation technology to deliver drugs continuously. Elucidation of the pathophysiology of PD and the development of disease-modifying therapy that affects the underlying fundamental pathophysiology of the disease are also progressing. In this review, we introduce current knowledge on developments concerning medications for patients with PD.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Neurodegenerative Diseases; Levodopa
PubMed: 35110492
DOI: 10.2169/internalmedicine.8940-21 -
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 -
Drugs & Aging Apr 2019Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss,... (Review)
Review
Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer's changes in their brains, explaining the wide variability in this disease's clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.
Topics: Age Factors; Aged; Anticonvulsants; Antiparkinson Agents; Cholinesterase Inhibitors; Clinical Trials, Phase II as Topic; Clonazepam; Humans; Levodopa; Lewy Body Disease; Melatonin; Randomized Controlled Trials as Topic; Zonisamide
PubMed: 30680679
DOI: 10.1007/s40266-018-00636-7