scholarly journals Treatment of Parkinson's Disease

2003 ◽  
Vol 30 (S1) ◽  
pp. S27-S33 ◽  
Author(s):  
W.R. Wayne Martin ◽  
Marguerite Wieler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Disability ◽  
Neurodegenerative Disorder ◽  
Holistic Approach ◽  
Symptomatic Treatment ◽  
Therapeutic Interventions ◽  
Dopaminergic Therapy ◽  
Comprehensive Management ◽  
The Individual

Parkinson's disease is a progressive neurodegenerative disorder that demands a holistic approach to treatment. Both pharmacologic and nonpharmacologic interventions play an important role in the comprehensive management of this disorder. While levodopa remains the single most effective medication for symptomatic treatment, dopamine agonists are playing an increasingly important role. Motor complications of dopaminergic therapy are a significant issue, particularly in patients with more advanced disease who have been on levodopa for several years. All therapeutic interventions must be tailored to the individual and modified as the disease progresses, with the goal of minimizing significant functional disability as much as possible.

scholarly journals Functional and Cognitive Improvement After an Intensive Inpatient Multidisciplinary Rehabilitation Program in Mild to Severe Parkinson's Disease: A Retrospective and Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Meloni ◽  
Francesca Lea Saibene ◽  
Sonia Di Tella ◽  
Monica Di Cesare ◽  
Francesca Borgnis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Observational Study ◽  
Functional Disability ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Rehabilitation Program ◽  
Semantic Fluency ◽  
Multidisciplinary Rehabilitation ◽  
Cognitive Improvement

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor (resting tremor, rigidity, bradykinesia, postural instability, and gait disturbances) and nonmotor symptoms (cognitive, neuropsychiatric, and autonomic problems). In recent years, several studies demonstrated that neurorehabilitation therapy is an effective treatment in addition to pharmacological personalized interventions in persons with PD (PwPD). The main aim of this study was to explore the short-term changes in functional, cognitive, and geriatric domains after a multidimensional rehabilitation program in PwPD (as primary condition) in mild–moderate (M-Ms) to severe (Ss) stages. Our second aim was to compare the effects of multidimensional rehabilitation in M-Ms versus Ss of PD. Twenty-four PwPD in M-Ms to Ss [age (mean ± SD) = 76.25 ± 9.42 years; male/female = 10/14; Hoehn and Yahr (median; IQR) = 4.00; 1.75] were included in a retrospective, observational study. Motor, cognitive, functional, and neuropsychiatric aspects were collected in admission (T0) and in discharge (T1). PwPD were involved in a person-tailored (to individual's needs), inpatient, intensive (5–7 days per week), multidisciplinary (combining cognitive, physical, occupational, and speech therapies), comprehensive, and rehabilitative program. According to Movement Disorders Society Unified Parkinson's Disease Rating Scale III cutoff, PwPD were classified in M-Ms or Ss (M-Ms ≤59; Ss >59); 87.50% of our sample reported significant reduction of functional disability at Barthel Index (p < 0.001). A significant improvement in Token test (p = 0.021), semantic fluency (p = 0.036), Rey's Figure-Copy (p < 0.001), and Raven's Colored Progressive Matrices (p = 0.004) was observed. The pain intensity perception (p < 0.001) and the risk of developing pressure ulcers (p < 0.001) as assessed, respectively, by the Numeric Rating Scale and by the Norton Scale were improved. With regard to the second aim, in M-Ms group, we found a positive correlation between the number of neuromotor sessions and the change in functional disability and language comprehension; in the Ss group, on the other hand, despite a higher number of hospitalization days, the total number of completed sessions was positively associated with the change in visuoconstructional abilities. Our findings suggest that an intensive, inpatient, and multidisciplinary rehabilitation program may improve functional abilities, some strategic cognitive functions, and geriatric aspects in PwPD with mild–moderate motor impairment.

scholarly journals A Multi-Scale Computational Model of Excitotoxic Loss of Dopaminergic Cells in Parkinson’s Disease

2020 ◽  
Author(s):  
Vignayanandam R. Muddapu ◽  
V. Srinivasa Chakravarthy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Computational Model ◽  
Neurodegenerative Disorder ◽  
Cell Loss ◽  
Therapeutic Interventions ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Multi Scale

ABSTRACTParkinson’s disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc). Although the exact cause of the cell death is not clear, the hypothesis that metabolic deficiency is a key facor has been gaining attention in the recent years. In the present study, we investigate this hypothesis using a multi-scale computational model of the subsystem of the basal ganglia comprising Subthalamic Nucleus (STN), Globus Pallidus externa (GPe) and SNc. The model is a multiscale model in that interactions among the three nuclei are simulated using more abstract Izhikevich neuron models, while the molecular pathways involved in cell death of SNc neurons are simulated in terms of detailed chemical kinetics. Simulation results obtained from the proposed model showed that energy deficiencies occurring at cellular and network levels could precipitate the excitotoxic loss of SNc neurons in PD. At the subcellular level, the models show how calcium elevation leads to apoptosis of SNc neurons. The therapeutic effects of several neuroprotective interventions are also simulated in the model. From neuroprotective studies, it was clear that glutamate inhibition and apoptotic signal blocker therapies were able to halt the progression of SNc cell loss when compared to other therapeutic interventions, which only slows down the progression of SNc cell loss.

scholarly journals Biology of Parkinson's disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder

2004 ◽  
Vol 6 (3) ◽  
pp. 259-280 ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Experimental Studies ◽  
Symptomatic Treatment ◽  
Motor Dysfunction ◽  
Motor Impairments ◽  
Neurodegenerative Process ◽  
Midbrain Dopamine ◽  
Proteolytic Stress

Parkinson's disease (PD) is the second most common movement disorder. The characteristic motor impairments - bradykinesia, rigidity, and resting tremor - result from degenerative loss of midbrain dopamine (DA) neurons in the substantia nigra, and are responsive to symptomatic treatment with dopaminergic medications and functional neurosurgery. PD is also the second most common neurodegenerative disorder. Viewed from this perspective, PD is a disorder of multiple functional systems, not simply the motor system, and of multiple neurotransmitter systems, not merely that of DA. The characteristic pathology - intraneuronal Lewy body inclusions and reduced numbers of surviving neurons - is similar in each of the targeted neuron groups, suggesting a common neurodegenerative process. Pathological and experimental studies indicate that oxidative stress, proteolytic stress, and inflammation figure prominently in the pathogenesis of PD. Yet, whether any of these mechanisms plays a causal role in human PD is unknown, because to date we have no proven neuroprotective therapies that slow or reverse disease progression in patients with PD. We are beginning to understand the pathophysiology of motor dysfunction in PD, but its etiopathogenesis as a neurodegenerative disorder remains poorly understood.

Parkinson's disease: treatment and non-motor features

2012 ◽  
Vol 22 (4) ◽  
pp. 243-260 ◽  
Author(s):  
Graeme JA Macphee ◽  
David A Stewart
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Disease Treatment ◽  
Dopaminergic Therapy ◽  
Co Morbidity ◽  
The Individual ◽  
Non Motor Symptoms ◽  
Inhibitor Treatment

SummaryThis review on Parkinson's disease (PD) considers pharmacological and surgical management and important non-motor symptoms (NMS) such as depression, dementia and sleep disorder. In the absence of a proven neuroprotective drug, therapy remains symptomatic and may be initiated with levodopa or a dopamine agonist or a monoamine oxidase inhibitor. Treatment should be tailored to the individual patient, with patient preference, extent of functional impairment and co-morbidity more important than ageper se. As disease progresses, therapy usually becomes more complex and apomorphine, duodopa and surgical intervention may be useful.NMS may be present at any stage of illness but become more common in severity and frequency with advanced disease, when neuropsychiatric features such as dementia and psychosis dominate the clinical picture. NMS are often unrecognized and undeclared by patients and carers in clinic. Novel agents for treating non-motor features, which are often poorly responsive to dopaminergic therapy, are urgently required.

scholarly journals Chaperone-Based Therapies for Disease Modification in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Erik L. Friesen ◽  
Mitch L. De Snoo ◽  
Luckshi Rajendran ◽  
Lorraine V. Kalia ◽  
Suneil K. Kalia
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Chaperones ◽  
Neurodegenerative Disorder ◽  
Therapeutic Interventions ◽  
Neuroprotective Activity ◽  
New Approach ◽  
Molecular Machinery ◽  
Intracellular Aggregates ◽  
Preclinical And Clinical Studies

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by the presence of pathological intracellular aggregates primarily composed of misfolded α-synuclein. This pathology implicates the molecular machinery responsible for maintaining protein homeostasis (proteostasis), including molecular chaperones, in the pathobiology of the disease. There is mounting evidence from preclinical and clinical studies that various molecular chaperones are downregulated, sequestered, depleted, or dysfunctional in PD. Current therapeutic interventions for PD are inadequate as they fail to modify disease progression by ameliorating the underlying pathology. Modulating the activity of molecular chaperones, cochaperones, and their associated pathways offers a new approach for disease modifying intervention. This review will summarize the potential of chaperone-based therapies that aim to enhance the neuroprotective activity of molecular chaperones or utilize small molecule chaperones to promote proteostasis.

scholarly journals The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 579
Author(s):  
Melissa Vos ◽  
Christine Klein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Neurodegenerative Disorder ◽  
Symptomatic Treatment ◽  
Good Alternative ◽  
Disease Genes ◽  
Disease Etiology ◽  
Underlying Mechanisms ◽  
Disease Pathways

Parkinson’s disease (PD) is a complex neurodegenerative disorder that is currently incurable. As a consequence of an incomplete understanding of the etiology of the disease, therapeutic strategies mainly focus on symptomatic treatment. Even though the majority of PD cases remain idiopathic (~90%), several genes have been identified to be causative for PD, facilitating the generation of animal models that are a good alternative to study disease pathways and to increase our understanding of the underlying mechanisms of PD. Drosophila melanogaster has proven to be an excellent model in these studies. In this review, we will discuss the different PD models in flies and key findings identified in flies in different affected pathways in PD. Several molecular changes have been identified, of which mitochondrial dysfunction and a defective endo-lysosomal pathway emerge to be the most relevant for PD pathogenesis. Studies in flies have significantly contributed to our knowledge of how disease genes affect and interact in these pathways enabling a better understanding of the disease etiology and providing possible therapeutic targets for the treatment of PD, some of which have already resulted in clinical trials.

scholarly journals Adjusting vascular permeability, leukocyte infiltration, and microglial cell activation to rescue dopaminergic neurons in rodent models of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hua-Ying Cai ◽  
Xiao-Xiao Fu ◽  
Hong Jiang ◽  
Shu Han
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Studies ◽  
Cell Activation ◽  
Inflammatory Cell ◽  
Functional Disability ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
The Central Nervous System ◽  
The Individual

AbstractAnimal studies have indicated that increased blood-brain barrier (BBB) permeability and inflammatory cell infiltration are involved during the progression of Parkinson’s disease (PD). This study used C16, a peptide that competitively binds to integrin αvβ3 and inhibits inflammatory cell infiltration, as well as angiopoietin-1 (Ang-1), an endothelial growth factor crucial for blood vessel protection, to reduce inflammation and improve the central nervous system (CNS) microenvironment in murine models of PD. The combination of C16 and Ang-1 yielded better results compared to the individual drugs alone in terms of reducing dopaminergic neuronal apoptosis, ameliorating cognitive impairment, and electrophysiological dysfunction, attenuating inflammation in the CNS microenvironment, and improving the functional disability in PD mice or rats. These results suggest neuroprotective and anti-inflammatory properties of the C16 peptide plus Ang-1 in PD.

scholarly journals Personalized Medicine Approach in Treating Parkinson’s Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice

2021 ◽  
Vol 11 (8) ◽  
pp. 720
Author(s):  
Helga María Grétarsdóttir ◽  
Erik Widman ◽  
Anders Johansson ◽  
Dag Nyholm
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Medical Records ◽  
Symptomatic Treatment ◽  
Fine Tuning ◽  
Symptom Improvement ◽  
User Friendliness ◽  
Patient Reported ◽  
The Individual

Background: The most effective symptomatic treatment in Parkinson’s disease (PD) is levodopa in standard doses. However, as the disease progresses, there may be a need for a more personalized approach and fine tuning, in accordance with the patients’ needs. This study aims to evaluate the individual experience of levodopa/carbidopa 5/1.25 mg microtablets (LC-5) in clinical practice with respect to efficacy, tolerability, and usability. The method used was as follows: patients answered a questionnaire concerning the effect and usability of LC-5, and their medical records were reviewed. Regarding results, thirty-five survey responses were obtained, and 29 patients’ medical records were reviewed. The LC-5 dose dispenser usability was generally rated positively and facilitated medication adherence. The majority (85%) of patients reported symptom improvement while using LC-5, compared with previous standard treatments. These results suggest that LC-5 therapy is generally well-tolerated, with favorable patient-reported efficacy and user friendliness, as well as the possibility for an individualized, fine-tuned PD treatment. Further studies with a prospective design and larger study population are needed to confirm the results.

Patient with Parkinson’s disease and neuropathic pain – case report

2021 ◽  
Vol 14 (3) ◽  
pp. 318-321
Author(s):  
Dariusz Koziorowski
Keyword(s):  
Parkinson’S Disease ◽  
Chronic Pain ◽  
Parkinson's Disease ◽  
Neuropathic Pain ◽  
Pain Therapy ◽  
Clinical Symptoms ◽  
Symptomatic Treatment ◽  
Acid Decarboxylase ◽  
Nigrostriatal Pathway ◽  
Dopaminergic Therapy

Parkinson’s disease is a complex neurodegenerative process involving various structures in the nervous system. Parkinson’s disease is diagnosed mainly on the basis of clinical symptoms resulting from damage to the nigrostriatal pathway, which gives the characteristic motor symptoms. Therefore, traditional symptomatic treatment consists of administering dopamine precursor levodopa with an aromatic amino acid decarboxylase inhibitor or directly stimulating the striatal dopamine receptors. The problem of dopaminergic therapy is the limited influence on the symptoms of the disease, including pain. Central pain is one type of pain that occurs in Parkinson’s disease patients and dopaminergic therapy may be of limited value in treating it. Proper diagnosis of the problem and the application of appropriate chronic pain therapy are essential for the quality of life of patients. The author presents the case of a 65-year-old man with Parkinson’s disease and chronic pain who required modification of dopaminergic treatment and implementation of central neuropathic pain therapy.

Monitoring mitochondrial dynamics and complex I dysfunction in neurons: implications for Parkinson's disease

2013 ◽  
Vol 41 (6) ◽  
pp. 1618-1624 ◽  
Author(s):  
Eve M. Simcox ◽  
Amy Reeve ◽  
Doug Turnbull
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Dynamics ◽  
Cell Loss ◽  
Transport Chain ◽  
The Individual ◽  
And Function ◽  
Energy Dependent

Mitochondrial dynamics are essential for maintaining organelle stability and function. Through fission, fusion and mitophagic events, optimal populations of mitochondria are retained. Subsequently, alterations in such processes can have profound effects on the individual mitochondrion and the cell within which they reside. Neurons are post-mitotic energy-dependent cells and, as such, are particularly vulnerable to alterations in cellular bioenergetics and increased stress that may occur as a direct or indirect result of mitochondrial dysfunction. The trafficking of mitochondria to areas of higher energy requirements, such as synapses, where mitochondrial densities fluctuate, further highlights the importance of efficient mitochondrial dynamics in neurons. PD (Parkinson's disease) is a common progressive neurodegenerative disorder which is characterized by the loss of dopaminergic neurons within the substantia nigra. Complex I, the largest of all of the components of the electron transport chain is heavily implicated in PD pathogenesis. The exact series of events that lead to cell loss, however, are not fully elucidated, but are likely to involve dysfunction of mitochondria, their trafficking and dynamics.

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