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Movement Disorders Clinical Practice Feb 2022The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor... (Review)
Review
BACKGROUND
The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson's disease (PD) is lacking.
OBJECTIVE
To address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS.
METHODS
We used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted.
RESULTS
The STN-DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS-III at both 6- and 12-month follow-ups ( < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow-up times. For the sub-scores of UPDRS-III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor ( = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS-III total score at a median follow-up of 12 months ( = 0.030).
CONCLUSION
The current study confirmed the value of preoperative levodopa responsiveness for prediction of the short-term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short-term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long-term motor outcomes were highlighted by this study.
PubMed: 35146054
DOI: 10.1002/mdc3.13379 -
Journal of Parkinson's Disease 2021Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities,...
BACKGROUND
Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation.
OBJECTIVES
To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD.
METHODS
References were identified by performing a systematic search in the PubMed and Web of Science databases in accordance with the PRISMA statement. In the absence of universal cost-effectiveness definitions, the gross domestic product per capita (GDP) in the country where a study was performed was used as a cut-off for cost-effectiveness based on cost per quality adjusted life year (QALY) gained.
RESULTS
In total 30 studies were retrieved. All device-aided therapies improved quality of life compared to best medical treatment, with improvements in QALYs between 0.88 and 1.26 in the studies with long temporal horizons. For DBS, nearly all studies showed that cost per QALY was below the GDP threshold. For infusion therapies only three studies showed a cost per QALY below this threshold, with several studies with long temporal horizons showing costs below or near the GDP threshold.
CONCLUSION
Of the device-aided therapies, DBS can be considered cost-effective, but the majority of infusion therapy studies showed that these were less cost-effective. However, long-term use of the infusion therapies appears to improve their cost-effectiveness and in addition, several strategies are underway to reduce these high costs.
Topics: Antiparkinson Agents; Apomorphine; Cost-Benefit Analysis; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33386813
DOI: 10.3233/JPD-202348 -
Heliyon Mar 2024Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In... (Review)
Review
Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In this study, the risk for dyskinesia in patients with Parkinson's disease receiving levodopa was evaluated via meta-analysis and meta-regression approaches to examine dyskinesia risk factors more reliably and improve treatment strategies and patient care. The PubMed and Embase databases were searched to identify randomized controlled trials comparing levodopa with other anti-Parkinson's drugs published in English before June 31, 2023. The primary outcome was dyskinesia, and a risk of bias assessment was performed. In total, 24 studies met the inclusion criteria; 21 had a low risk of bias, and 3 had a high risk of bias. These studies included 4698 patients with Hoehn and Yahr Grade I-III Parkinson's disease. Our meta-analysis showed that the risk of dyskinesia was higher for levodopa than for other anti-Parkinson's drugs (odds ratio: 2.52 [95% confidence interval: 1.84-3.46]). Dyskinesia was not related to age (slope coefficient: 0.185 [0.095]; = 0.061), disease duration (slope coefficient: 0.011 [0.018]; = 0.566), or treatment duration (slope coefficient: 0.008 [0.007]; = 0.216). The mean levodopa equivalent dose (slope coefficient: 0.004 [0.001]; = 0.001) in the experimental group and the differences in drug doses between the experimental and control groups were correlated with the risk of dyskinesia. Results of randomized controlled trials supported an association between the levodopa dose and dyskinesia in patients with Parkinson's disease. Compared with levodopa users, users of other anti-Parkinson's drugs had a lower incidence of dyskinesia. Age, disease duration, and treatment duration were not correlated with dyskinesia. These findings suggest that anti-Parkinson's drugs other than levodopa, particularly in cases of early-stage Parkinson's disease, should be considered to reduce the risk of dyskinesia.
PubMed: 38515703
DOI: 10.1016/j.heliyon.2024.e27956 -
Frontiers in Aging Neuroscience 2022Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD...
The Comparative Efficacy of Non-ergot Dopamine Agonist and Potential Risk Factors for Motor Complications and Side Effects From NEDA Use in Early Parkinson's Disease: Evidence From Clinical Trials.
BACKGROUND/OBJECTIVES
Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD motor symptoms. However, systematic evaluations of the risk of motor complications induced by NEDA and risk factors potentially associated with motor complications are still lacking.
METHODS
Medline, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for potentially eligible randomized controlled trials. The incidence of motor complications (dyskinesia, motor fluctuations), impulsive-compulsive behaviors and adverse events and clinical disability rating scale (UPDRS) scores were evaluated using standard meta-analytic methods. Metaregression was conducted on the incidence of motor complications (dyskinesia) with treatment duration and NEDA dose as covariates.
RESULTS
Patients treated with NEDA had significantly lower UPDRS total scores, motor scores and activity of daily living (ADL) scores than those receiving a placebo (weighted mean difference (WMD) -4.81, 95% CI -6.57 to -3.05; WMD -4.901, 95% CI -7.03 to -2.77; WMD -1.52, 95% CI -2.19 to -0.84, respectively). Patients in the NEDA and NEDA+open Levodopa (LD) groups had lower odds for dyskinesia than patients in the LD group (OR = 0.21, 95% CI: 0.15-0.29; OR = 0.31, 95% CI 0.24-0.42, respectively). Metaregressions indicated that the mean LD dose of the NEDA group increased, and the odds of developing dyskinesia increased ( = 0.012). However, the odds of developing dyskinesia in the NEDA group were not related to treatment duration ( = 0.308). PD patients treated with NEDA or NEDA+open LD had a lower risk of wearing-off implications than those treated with LD (all < 0.05). No significant difference was found between the NEDA and placebo groups in impulsive-compulsive behavior development ( > 0.05). Patients in the NEDA group were more likely to suffer somnolence, edema, constipation, dizziness, hallucinations, nausea and vomiting than those in the placebo or LD group.
CONCLUSION
NEDA therapy reduces motor symptoms and improves ADLs in early PD. The odds of developing motor complications were lower with NEDA than with LD, and dyskinesia increased with increasing LD equivalent dose and was not influenced by NEDA treatment duration. Therefore, long-term treatment with an appropriate dosage of NEDA might be more suitable than LD for early PD patients.
REGISTRATION
PROSPERO CRD42021287172.
PubMed: 35527736
DOI: 10.3389/fnagi.2022.831884 -
Frontiers in Neurology 2019Currently, some advanced treatments such as Levodopa-Carbidopa intestinal gel infusion (LCIG), deep-brain stimulation (DBS), and subcutaneous apomorphine infusion have...
Comparison Between Levodopa-Carbidopa Intestinal Gel Infusion and Subthalamic Nucleus Deep-Brain Stimulation for Advanced Parkinson's Disease: A Systematic Review and Meta-Analysis.
Currently, some advanced treatments such as Levodopa-Carbidopa intestinal gel infusion (LCIG), deep-brain stimulation (DBS), and subcutaneous apomorphine infusion have become alternative strategies for advanced Parkinson's disease (PD). However, which treatment is better for individual patients remains unclear. This review aims to compare therapeutic effects of motor and/or non-motor symptoms of advanced PD patients between LCIG and DBS. We manually searched electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included articles published until April 04, 2019 using related terms, without language restriction. We included case-controlled cohort studies and randomized-controlled trials, which directly compared differences between LCIG and DBS. The Newcastle-Ottawa scale (NOS), proposed by the Cochrane Collaboration, was utilized to assess the quality of the included studies. Two investigators independently extracted data from each trial. Pooled standard-mean differences (SMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated by meta-analysis. Outcomes were grouped according to the part III and part IV of the Unified Parkinson Disease Rating Scale (UPDRS) and adverse events. We also descriptively reviewed some data, which were unavailable for statistical analysis. This review included five cohort trials of 257 patients for meta-analysis. There were no significant differences between LCIG and subthalamic nucleus deep-brain stimulation (STN-DBS) on UPDRS-III and adverse events comparisons: UPDRS-III (pooled SMDs = 0.200, 95% CI: -0.126-0.527, = 0.230), total adverse events (pooled RRs = 1.279, 95% CI: 0.983-1.664, = 0.067), serious adverse events (pooled RRs = 1.539, 95% CI: 0.664-3.566, = 0.315). Notably, the improvement of UPDRS-IV was more significant in STN-DBS groups: pooled SMDs = 0.857, 95% CI: 0.130-1.584, = 0.021. However, the heterogeneity was moderate for UPDRS-IV ( = 73.8%). LCIG has comparable effects to STN-DBS on motor function for advanced PD, with acceptable tolerability. More large, well-designed trials are needed to assess the comparability of LCIG and STN-DBS in the future.
PubMed: 31507529
DOI: 10.3389/fneur.2019.00934 -
Frontiers in Aging Neuroscience 2024Nutrition plays a pivotal role in the multidisciplinary approach to rehabilitating middle to old-aged patients with neurological diseases including movement disorders...
INTRODUCTION
Nutrition plays a pivotal role in the multidisciplinary approach to rehabilitating middle to old-aged patients with neurological diseases including movement disorders (MDs). Despite the prevalence of vitamin D deficiency in many patients with MDs, data supporting supplementation's effectiveness and safety is sparse and conflicting, therefore, our explicit objective was to provide an all-encompassing review of the subject.
METHODS
A comprehensive search of PubMed, Embase, and other scientific databases was conducted up to November 1 2023. The searches included RCTs in all languages with human participants aged 35 and above and not meeting these requirements led to exclusion.
RESULTS
Four studies on Parkinson's disease (PD) and one on restless legs syndrome (RLS) including 369 MD patients, however, none in a rehabilitation context, were found. Although three of the four PD studies showed better outcomes, such as decreasing levodopa-induced dyskinesia or enhancing physical performance in some or all domains, the RLS study did not identify symptom improvement. The one serious adverse effect observed, cerebral infarction, aroused safety concerns, however its relationship to vitamin D consumption is questionable. Structurally the studies can be characterized by large variations in patient populations, in primary outcomes, and disease severity, but typically a relatively short duration of therapy in most cases. With other limitations such as the small number of studies, major trial design heterogeneity, limited sample sizes, and a greatly variable Cochrane risk of bias (RoB) evaluation, only a qualitative synthesis was feasible.
DISCUSSION
Two main implications can be inferred from these results, which we interpret as cautiously promising but overall insufficient for firm recommendations. First, there is an urgent need for more research on the role of vitamin D in MDs in the middle- to older-aged population, particularly during rehabilitation. Second, given the benefits of vitamin D supplementation for those who are deficient, we recommend routine screening and supplementation for MD patients.
PubMed: 38343878
DOI: 10.3389/fnagi.2024.1333217 -
Tremor and Other Hyperkinetic Movements... Jul 2020Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being...
BACKGROUND
Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being "primary" when it is attributed to Huntington's disease (HD) or other genetic etiologies, or "secondary" when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction.
METHODS
A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea.
RESULTS
There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion.
DISCUSSION
Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea.
HIGHLIGHTS
There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.
Topics: Chorea; Humans; Tardive Dyskinesia
PubMed: 32775036
DOI: 10.5334/tohm.351 -
Parkinson's Disease 2022Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in...
BACKGROUND
Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in Parkinson's disease with motor fluctuations.
OBJECTIVES
This meta-analysis aimed to provide updated evidence on the efficacy for motor and nonmotor symptoms and the safety of rasagiline/levodopa versus levodopa in patients with Parkinson's disease experiencing motor fluctuations.
METHODS
A systematic literature search was conducted (January 18-19, 2021) using PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar to identify randomized controlled trials comparing rasagiline/levodopa versus placebo/levodopa in patients with Parkinson's disease experiencing motor fluctuations. Outcomes included change in wearing-off time, Unified Parkinson's Disease Rating Scale (UPDRS)/Movement Disorder Society-UPDRS (MDS-UPDRS) II and III scores, treatment-emergent adverse events (TEAEs), and Parkinson's Disease Questionnaire (PDQ-39) summary index score. A random effect model was used to estimate the treatment effects.
RESULTS
Six studies were included (1912 patients). Significant improvements in wearing-off time (standardized mean difference [SMD]: -0.50, 95% confidence interval [CI]: -0.92 to -0.09, = 0.002), levodopa dosage (SMD: -0.18, 95% CI: -0.35 to -0.01, = 0.041), UPDRS/MDS-UPDRS II (SMD: -0.39, 95% CI: -0.52 to -0.25, < 0.0001), UPDRS/MDS-UPDRS III (SMD: -0.30, 95% CI: -0.44 to -0.16, < 0.0001), and PDQ-39 summary index score (SMD: -0.21, 95% CI: -0.37 to -0.04, = 0.013) were observed with rasagiline/levodopa versus placebo/levodopa. The incidence of TEAEs did not differ between treatments (risk ratio: 1.13, 95% CI: 0.98-1.30, = 0.093).
CONCLUSIONS
This meta-analysis further indicated the superiority of rasagiline/levodopa in improving motor and nonmotor symptoms of Parkinson's disease, with a similar safety profile to that of levodopa in Parkinson's disease with motor fluctuations.
PubMed: 36081594
DOI: 10.1155/2022/4216452 -
Journal of Integrative Neuroscience Jan 2023Camptocormia is one of the most common postural disorders of Parkinson's disease (PD) which has limited treatment options. In this review, we summarize the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Camptocormia is one of the most common postural disorders of Parkinson's disease (PD) which has limited treatment options. In this review, we summarize the efficacy of deep brain stimulation (DBS) for camptocormia in PD.
METHODS
The PubMed (https://pubmed.ncbi.nlm.nih.gov/) and EMBASE databases (https://www.embase.com/) were searched for the terms "Parkinson Disease" and "camptocormia" in combination with "deep brain stimulation". We then explored the efficacy of DBS for camptocormia by statistical analysis of the bending angle, the Unified Parkinson's Disease Rating Scale III (UPDRS-III) and L-dopa equivalent daily dose (LEDD), and by evaluating the prognosis after DBS.
RESULTS
Twenty articles that reported results for 152 patients were included in this review. These comprised 136 patients from 16 studies who underwent subthalamic nucleus deep brain stimulation (STN-DBS), and 13 patients from 3 studies who underwent globus pallidus internus deep brain stimulation (GPi-DBS). One study used both STN-DBS (2 patients) and GPi-DBS (one patient). After 3-21 months of follow-up, the mean bending angle during the Off-period was significantly reduced compared to pre-DBS (31.5 ± 21.4 vs. 53.6 ± 22.7, respectively; < 0.0001). For the STN-DBS trials, the mean post-operative bending angles during both Off- and On-periods were significantly reduced compared to pre-operative (32.1 ± 22.7 vs. 55.4 ± 24.1, = 0.0003; and 33.1 ± 21.5 vs. 43.7 ± 20.6, = 0.0003, respectively). For GPi-DBS, the mean bending angle post-DBS during the Off-period was considerably lower than pre-DBS (28.5 ± 10.7 vs. 42.9 ± 9.9, < 0.001). The decrease in bending angle after DBS was negatively correlated with the duration of camptocormia (R = - 0.433, = 0.013), whereas positively associated with the pre-bending angle (R = 0.352, = 0.03).
CONCLUSIONS
DBS is an effective treatment for camptocormia in PD. Patients in the early stage of camptocormia with more significant bending angle may benefit more from DBS.
Topics: Humans; Parkinson Disease; Levodopa; Databases, Factual; Mental Status and Dementia Tests; Subthalamic Nucleus
PubMed: 36722246
DOI: 10.31083/j.jin2201011 -
Frontiers in Neurology 2021Parkinson's disease (PD) is a common, chronic, progressive, debilitating neurodegenerative disease. The current levodopa treatment requires the addition of other drugs,...
Parkinson's disease (PD) is a common, chronic, progressive, debilitating neurodegenerative disease. The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Therefore, a theoretical reference for treatment is urgently needed. In this study, an appropriate search strategy was used to screen eligible studies on different drugs to treat patients with PD from the Embase, PubMed, and Cochrane Library. The publication dates were from January 1990 to June 2021. We integrated eligible randomized controlled trials, and statistical analysis was performed on three kinds of effectiveness outcomes and two types of safety outcomes. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. In terms of efficacy, entacapone (mean difference [MD], 0.64 h; 95% CI, 0.29-1.0), opicapone (MD, 0.92 h; 95% CI, 0.35-1.5), and tolcapone (MD, 3.2 h; 95% CI, 2.1-4.2) increased patients' total ON-time compared to placebo. Tolcapone (MD, -100 mg; 95% CI -160 to -45) reduced the total daily dose of levodopa therapy. None of these three drugs was found to have statistical significance in mean change from baseline in UPDRS part III scores when compared with others. In terms of safety, tolcapone (MD, 3.8; 95% CI, 2.1-6.8), opicapone (MD, 3.7; 95% CI, 2-7.2), and entacapone (MD, 2.2; 95% CI, 1.5-3.3) increased the number of cases of dyskinesia compared to placebo. Entacapone (MD, 1.7; 95% CI, 1.3-2.2) and tolcapone (MD, 4.3; 95% CI, 1.3-15) were more likely to cause adverse events than placebo. In conclusion, opicapone showed higher efficiency and fewer safety problems in five indicators we selected when compared with the other two drugs.
PubMed: 34630283
DOI: 10.3389/fneur.2021.707723