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Journal of Parkinson's Disease 2022STN-DBS is a cornerstone in the treatment of advanced Parkinson's disease (PD). The traditional approach is to use an awake operative technique with microelectrode... (Meta-Analysis)
Meta-Analysis
BACKGROUND
STN-DBS is a cornerstone in the treatment of advanced Parkinson's disease (PD). The traditional approach is to use an awake operative technique with microelectrode recording (MER). However, more centers start using an asleep MRI-guided technique without MER.
OBJECTIVE
We systematically reviewed the literature to compare STN-DBS surgery with and without MER for differences in clinical outcome.
METHODS
We systematically searched PubMed, Embase, MEDLINE, and Web of Science databases for randomized clinical trials and consecutive cohort studies published between 01-01-2000 and 26-08-2021, that included at least 10 PD patients who had received bilateral STN-DBS.
RESULTS
2,129 articles were identified. After abstract screening and full-text review, 26 studies were included in the final analysis, comprising a total of 34 study groups (29 MER and 5 non-MER). The standardized mean difference (SMD) in change in motor symptoms between baseline (OFF medication) and 6-24 months follow-up (OFF medication and ON stimulation) was 1.64 for the MER group and 1.87 for non-MER group (p = 0.59). SMD in change in levodopa equivalent daily dose (LEDD) was 1.14 for the MER group and 0.65 for non-MER group (p < 0.01). Insufficient data were available for comparative analysis of PDQ-39 and complications.
CONCLUSION
The change in motor symptoms from baseline to follow-up did not differ between studies that used MER and those that did not. The postoperative reduction in LEDD from baseline to follow-up was greater in the MER-group. In the absence of high-quality studies comparing both methods, there is a clear need for a well-designed comparative trial.
Topics: Deep Brain Stimulation; Humans; Levodopa; Microelectrodes; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome
PubMed: 35912752
DOI: 10.3233/JPD-223333 -
Neurological Sciences : Official... Nov 2022Levodopa is the most commonly used first-line drug for Parkinson's disease. However, during the period of medication, the generation of motor fluctuations affects the... (Meta-Analysis)
Meta-Analysis Review
High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson disease for the treatment of OFF episodes: a meta-analysis of randomized controlled trials.
BACKGROUND
Levodopa is the most commonly used first-line drug for Parkinson's disease. However, during the period of medication, the generation of motor fluctuations affects the life quality of patients. CVT-301, as an inhaled levodopa for the treatment of OFF episodes, rose in response to this condition.
METHODS
We systematically searched Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov for relevant randomized controlled trials, from the earliest available date to February 12, 2022, to evaluate the efficacy of high and low dose of inhaled levodopa in patients with Parkinson's disease.
RESULTS
A total of six multicenter, randomized controlled trials with 1166 patients were included. Compared with placebo, CVT-301 has a statistically significant effect on the treatment of Parkinson's patients with OFF episodes of medication interval. The UPDRS Part III score decreased more significantly in the high-dose group 30 minutes after administration than the low-dose group (WMD = - 4.51; 95% CI, - 7.34 to - 1.68; p = 0.002). More patients in the high-dose group achieved and maintained an on state up to 60 min after receiving study medication (RR = 1.17; 95% CI, 1.08 to 1.27; p < 0.001). And more patients were proved with improved PGIC scores in the high-dose group (RR = 1.13; 95% CI, 1.05 to 1.21; p = 0.001).
CONCLUSIONS
High doses CVT-301 can improve the motor function of the patient to some extent. There seems no risk of increasing adverse reactions.
Topics: Humans; Antiparkinson Agents; Levodopa; Multicenter Studies as Topic; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35907110
DOI: 10.1007/s10072-022-06298-z -
Journal of Neural Transmission (Vienna,... Oct 2022Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based... (Review)
Review
Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based point of view for patients and physicians, we performed a systematic review of randomized controlled trials (RCT) on the use of cannabinoids in MD. The seven RCTs found on PD used different cannabis formulations. No improvement of motor symptoms was shown in any of the two RCTs with this as primary outcome (PO), but in the nabilone group, an improvement in quality of life was documented. Of the three RCTs having levodopa-induced dyskinesia as PO, only one using nabilone showed a reduction. Anxiety and anxiety-induced tremor could be reduced in the cannabidiol group as well as anxiety and sleeping problems in the nabilone group in another RCT. In two RCTs with Tourette syndrome, an improvement in tics was revealed. From three RCTs on Huntington's disease only one found symptoms relief using nabilone. No reduction of dystonia could be shown in the two included RCTs. The limited number of available but small and inhomogeneous RCTs precludes reliable conclusions. Therefore, more and smartly designed RCTs are urgently needed.
Topics: Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Hallucinogens; Humans; Randomized Controlled Trials as Topic; Tourette Syndrome
PubMed: 35859051
DOI: 10.1007/s00702-022-02529-x -
Journal of Comparative Effectiveness... Aug 2022To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A... (Meta-Analysis)
Meta-Analysis Review
To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A systematic review and meta-analysis were conducted. Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Topics: Adult; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Double-Blind Method; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 35758044
DOI: 10.2217/cer-2022-0031 -
Neurology. Clinical Practice Apr 2022To investigate the efficacy and safety of CVT-301 in treating motor fluctuation in patients with Parkinson disease (PD). (Review)
Review
PURPOSE OF REVIEW
To investigate the efficacy and safety of CVT-301 in treating motor fluctuation in patients with Parkinson disease (PD).
RECENT FINDINGS
This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (odds ratio [OR] = 2.68; 95% confidence interval [CI]: 1.86-3.86; < 0.00001). Moreover, CVT-301 had also shown to improve motor function by Unified Parkinson Disease Rating Scale part III score (standardized mean difference = 3.83; 95% CI: 2.44-5.23; < 0.00001) and promote an overall improvement of PD by Patient Global Impression of Change self-rating (OR = 2.95; 95% CI: 1.78-4.9; < 0.00001). The most common adverse events encountered were respiratory symptoms (OR = 12.18; 95% CI: 5.01-29.62; < 0.00001) and nausea (OR = 3.95; 95% CI: 1.01-15.41; = 0.05).
SUMMARY
CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in patients with PD.
PubMed: 35747892
DOI: 10.1212/CPJ.0000000000001143 -
Maturitas Sep 2022The aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled...
OBJECTIVE
The aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled trials (RCTs) on humans and animal studies with PD models.
DESIGN
Systematic review of in vivo studies.
METHODS
Studies related to the research question were identified through searches in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and the gray literature, from inception until November 2021. Rayyan was employed to screen and identify all studies fulfilling the inclusion criteria. Cochrane's revised Risk of Bias 2.0 and SYRCLE tools evaluated bias in RCTs and animal studies, respectively. An effect direction plot was developed to synthesize the evidence of the RCTs.
RESULTS
Twelve studies were identified and included in the qualitative synthesis (4 RCTs and 8 animal trials). Interventions included ketogenic diets (KDs), supplementation with medium-chain triglyceride (MCT) oil, caprylic acid administration and ketone ester drinks. The animal research used zebrafish and rodents, and PD was toxin-induced. Based on the available RCTs, ketogenic therapy does not improve motor coordination and functioning, cognitive impairment, anthropometrics, blood lipids and glycemic control, exercise performance or voice disorders in patients with PD. The evidence is scattered and heterogenous, with single trials assessing different outcomes; thus, a synthesis of the evidence cannot be conclusive regarding the efficacy of ketogenic therapy. On the other hand, animal studies tend to demonstrate more promising results, with marked improvements in locomotor activity, dopaminergic activity, redox status, and inflammatory markers.
CONCLUSIONS
Although animal studies indicate promising results, research on the effect of ketogenic therapy in PD is still in its infancy, with RCTs conducted on humans being heterogeneous and lacking PD-specific outcomes. More studies are required to recommend or refute the use of ketogenic therapy in PD.
Topics: Animals; Cognitive Dysfunction; Humans; Parkinson Disease
PubMed: 35714419
DOI: 10.1016/j.maturitas.2022.06.001 -
Cureus Apr 2022Stroke is a leading cause of death and disability, especially in certain ethnic groups. Impaired consciousness is a common outcome in stroke patients, serving as a... (Review)
Review
Stroke is a leading cause of death and disability, especially in certain ethnic groups. Impaired consciousness is a common outcome in stroke patients, serving as a predictor of prognosis and mortality. Lately, there has been increased interest in drugs such as Levodopa (LD), which have been found to promote wakefulness. To further appreciate this association, we gathered updated evidence of this novel therapeutic approach and compared it, evaluating its clinical use in an acute stroke setting. We carried out a systematic review of clinical trials conducted exclusively on stroke patients who received levodopa. Four clinical trials were reviewed and analyzed after applying the inclusion/exclusion criteria. The use of levodopa showed positive results in four of the clinical trials, and statistically significant results in 3/4 of the studies; however, more studies need to be conducted to corroborate these results.
PubMed: 35651458
DOI: 10.7759/cureus.24529 -
Journal of Geriatric Psychiatry and... Mar 2023Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID.
METHOD
In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG).
RESULTS
The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models.
CONCLUSION
The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.
Topics: Humans; Catechol O-Methyltransferase; Dyskinesias; Genetic Predisposition to Disease; Genotype; Levodopa; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 35603896
DOI: 10.1177/08919887221103580 -
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 -
RSC Advances Jun 2021Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two... (Review)
Review
Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two key steps of melanogenesis: tyrosine's hydroxylation to dihydroxyphenylalanine (DOPA), and oxidation of the latter species to dopaquinone. Melanin guards against the destructive effects of ultraviolet radiation which is known to produce considerable pathological disorders such as skin cancer, among others. Moreover, the overproduction of melanin can create aesthetic problems along with serious disorders linked to hyperpigmented spots or patches on skin. Several skin-whitening products which reduce melanogenesis activity and alleviate hyperpigmentation are commercially available. A few of them, particularly those obtained from natural sources and that incorporate a phenolic scaffold, have been exploited in the cosmetic industry. In this context, synthetic tyrosinase inhibitors (TIs) with elevated efficacy and fewer side effects are direly needed in the pharmaceutical and cosmetic industries owing to their protective effect against pigmentation and dermatological disorders. Furthermore, the biological significance of the chromone skeleton and its associated medicinal and bioactive properties has drawn immense interest and inspired many researchers to design and develop novel anti-tyrosinase agents based on the flavonoid core (2-arylchromone). This review article is oriented to provide an insight and a deeper understanding of the tyrosinase inhibitory activity of an array of natural and bioinspired phenolic compounds with special emphasis on flavonoids to demonstrate how the position of ring substituents and their interaction with tyrosinase could be correlated with their effectiveness or lack thereof against inhibiting the enzyme.
PubMed: 35480807
DOI: 10.1039/d1ra03196a