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Treatment of advanced Parkinson's disease.

ABSTRACT: Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease.We will discuss the latest pharmacological strategies (e.g., inhibitors of dopamine-metabolizing enzymes, dopamine agonists, and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of nonmotor symptoms in the advanced Parkinson's disease patient. We will conclude by detailing the potential nonpharmacological and multidisciplinary approaches for advanced stage Parkinson's disease.The optimization of levodopa is, in most cases, the most powerful therapeutic option available; however, medication optimization requires an advanced understanding of Parkinson's disease. Failure of conventional pharmacotherapy should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Nonmotor symptoms will affect quality of life more than the motor Parkinson's disease symptoms, and these nonmotor symptoms should be aggressively treated. Many advanced Parkinson's disease patients will likely benefit from multi and interdisciplinary Parkinson's disease teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient.

SUBMITTER: Giugni JC

PROVIDER: S-EPMC4140171 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Treatment of advanced Parkinson's disease.

Giugni Juan C JC Okun Michael S MS

Current opinion in neurology 20140801 4

<h4>Purpose of review</h4>Later stage Parkinson's disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinson's disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinson's disease.<h4>Recent findings</h4>We will discuss the latest pharmacological strategies ...[more]

PMID: 24978634

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Project description:Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.

Project description:BackgroundParkinson's disease is a progressive neurodegenerative disease, which significantly impacts patients' quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson's disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory.ObjectiveWe aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson's disease in England, using real-world data.MethodsA Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson's disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted.ResultsTotal costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG.ConclusionsThe base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England.

Project description:IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson's disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson's disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.

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Treatment of advanced Parkinson's disease.

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Treatment of advanced Parkinson's disease.

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