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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 -
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 -
Parkinsonism & Related Disorders Mar 2021Levodopa-induced dyskinesia frequently complicates long-term Parkinson's disease. More in-depth knowledge regarding the role of genetic factors in dyskinesia development... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Levodopa-induced dyskinesia frequently complicates long-term Parkinson's disease. More in-depth knowledge regarding the role of genetic factors in dyskinesia development may be important to identify parkinsonian patients who are more prone to developing dyskinesia and clarify the molecular mechanisms underlying this condition. For this reason, we systematically reviewed studies investigating genetic factors involved in dyskinesia.
METHODS
A systematic search of genetic factors in Parkinson's disease dyskinesia was performed using the MEDLINE (through PubMed up to June 2019) and EMBASE databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was conducted using a random effect model.
RESULTS
The literature search retrieved 33 studies assessing genes and variants possibly associated with dyskinesia in Parkinson's disease. The studies were published between 1984 and 2019 and included a total of 27,092 subjects of different ethnicities. Overall, 37 genes were analyzed in the studies reviewed, of which 22 were possibly associated with dyskinesia. The studies reported a total of 158 variants, of which 94 were possibly related to dyskinesia.
CONCLUSION
The studies reviewed demonstrated inconsistent results, possibly due to differences in screening methods and in the comparison of clinical data in a large variety of genetically- and ethnically-diverse populations. The meta-analysis failed to demonstrate any association between the rs6280 in the DRD3 gene, rs1799836 in the MAO-B, rs4680 in the COMT gene, rs34637584 in the LRRK2 gene and LID susceptibility. The role of genetic factors in LID susceptibility is still unclear and further studies are required.
Topics: Dopamine Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 33561612
DOI: 10.1016/j.parkreldis.2021.01.020 -
Nutritional Neuroscience Oct 2022The clinical symptoms and nutritional status of patients with Parkinson's disease (PwP) are interrelated, and the clinical outcomes in malnourished patients are often... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The clinical symptoms and nutritional status of patients with Parkinson's disease (PwP) are interrelated, and the clinical outcomes in malnourished patients are often poor. Only a few studies have reviewed the prevalence of malnutrition and nutrition-related risk factors in PwP.
OBJECTIVE
To explore the prevalence of malnutrition/ malnutrition risk among PwP, and estimate nutrition-related risk factors.
METHODS
PubMed, EMBASE, and Cochrane Library were systematically searched. Literatures published between 1 January 1995 and 1 November 2020, subjects were patients with idiopathic PD underwent Mini Nutritional Assessment (MNA) were included.
RESULT
Sixteen articles, including 1650 PwP from 13 countries/regions, were included in the meta-analysis. The prevalence of malnutrition and malnutrition risk were 8.8% (Confidence interval [CI] 95%, 5.3%-12.2%) and 35.3% (CI 95%, 29.0%-41.7%), and the prevalence of nutritional disorders was 42.3% (CI 95%, 33.7%-51%). The prevalence of malnutrition in developing countries was higher than that in the developed countries. Meta-analysis reveals there were significant differences in the course of the disease (0.88 years; 95% CI, 0.26-1.50), levodopa equivalent daily dose (LEDD; 60.77 mg/day; 95% CI, 2.7-118.8), Hoehn and Yahr (H&Y) staging (0.323; CI 95%, 0.164-0.482), and unified Parkinson's disease rating scale (UPDRS) scores (total: 13.66, CI 95%: 10.57-16.75 and part III: 5.52, CI 95%: 3.79-7.25) between normal and nutritional disorder groups.
CONCLUSIONS
Malnutrition/malnutrition risk prevalence in PwP are high. The duration of the disease, LEDD, H&Y staging, and UPDRS score (part III and total) may be nutrition-related risk factors in PwP.
Topics: Humans; Levodopa; Malnutrition; Nutrition Assessment; Nutritional Status; Parkinson Disease; Prevalence; Risk Factors
PubMed: 34238139
DOI: 10.1080/1028415X.2021.1948655 -
Tremor and Other Hyperkinetic Movements... 2019Orthostatic tremor (OT) is defined as tremor in the legs and trunk evoked during standing. While the classical description is tremor of ≥13 Hz, slower frequencies are...
BACKGROUND
Orthostatic tremor (OT) is defined as tremor in the legs and trunk evoked during standing. While the classical description is tremor of ≥13 Hz, slower frequencies are recognized. There is disagreement as to whether the latter represents a slow variant of classical OT, or different tremor disorder(s) given frequent coexistent neurological disease.
METHODS
A systematic literature search of PubMed was performed in February 2019 for "slow orthostatic tremor" and related terms which generated 573 abstracts, of which 61 were included.
RESULTS
Between 1970 and 2019, there were 70 cases of electrophysiologically confirmed slow OT. Two-thirds were female, of mean age 60 years (range 26-86), and mean disease duration 6 years (range 0-32). One-third of cases were isolated, and two-thirds had a coexistent disorder(s), including parkinsonism (30%), ataxia (12%), and dystonia (10%). Postural arm tremor was present in 34%. Median tremor frequency was 6-7 Hz (range 3-12). Tremor bursts ranged from 50 to 150 ms duration, and were alternating or synchronous in antagonistic and/or analogous muscles. Low and high coherences were reported. Five cases (7%) had coexistent classical OT. Clonazepam was the most effective medication across all frequencies, and levodopa was effective for 4-7 Hz OT with coexistent parkinsonism. Two cases resolved with the treatment of Graves' disease. Electrophysiology and imaging predominantly support a central tremor generator.
DISCUSSION
While multiple lines of evidence separate slow OT from classical OT, clinical and electrophysiological overlap may occur. Primary and secondary causes are identified, similar to classical OT. Further exploration to clarify these slow OT subtypes, clinically and neurophysiologically, is proposed.
Topics: Dizziness; Electromyography; Evidence-Based Medicine; Humans; Posture; Tremor
PubMed: 31832265
DOI: 10.7916/tohm.v0.721 -
Frontiers in Aging Neuroscience 2022Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side... (Review)
Review
BACKGROUND
Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson's disease.
METHODS
We first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices.
RESULTS
Our review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark.
CONCLUSION
Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
PubMed: 35462692
DOI: 10.3389/fnagi.2022.807909 -
Annals of Medicine and Surgery (2012) Aug 2022There remains a scarcity of literature regarding COVID-19 and its neurological sequelae. This study highlights Parkinsonism as a post-COVID-19 sequela and helps us... (Review)
Review
BACKGROUND
There remains a scarcity of literature regarding COVID-19 and its neurological sequelae. This study highlights Parkinsonism as a post-COVID-19 sequela and helps us understand a possible link between the two.
METHODS
A literature search covering relevant databases was conducted for studies reporting the development of Parkinsonism in patients recovering from COVID-19 infection. A quality assessment tool developed by The Joanna Briggs Institute Critical Appraisal tools for the assessment of case reports was utilized. Fisher's exact test was used to explore the factors associated with COVID-19 and Parkinsonism as its complication.
RESULTS
Ten studies were included in our study. The median age of patients was 60.0, with an interquartile range of 42.5-72.0. There were 8 males (61.5%) patients, and 53.8% of cases were reported to have at least one comorbidity. Cogwheel rigidity was the most common symptom of Parkinsonism in 11 patients. While the most standard treatment modality used was Levodopa in 76.9% of cases. Using the Fisher's Exact test, it was identified that 10 patients (76.9%) with bradykinesia made a full recovery.
CONCLUSION
Despite presumed "recovery" from COVID-19, patients still face a wide range of neurological complications. One of these complications presenting as Parkinsonism requires health care professionals to be on the lookout for the long-term effects of COVID-19. Hence, our study provides information on the possible likely hood of a link between COVID-19 and the development of Parkinsonism as post-COVID neurological sequelae.
PubMed: 35971509
DOI: 10.1016/j.amsu.2022.104281 -
Neurological Sciences : Official... Jun 2022Dopamine replacement therapy remains the gold standard for symptomatic management of Parkinson's disease worldwide. However, most patients will develop debilitating... (Meta-Analysis)
Meta-Analysis
Polymorphisms of the dopamine metabolic and signaling pathways are associated with susceptibility to motor levodopa-induced complications (MLIC) in Parkinson's disease: a systematic review and meta-analysis.
BACKGROUND
Dopamine replacement therapy remains the gold standard for symptomatic management of Parkinson's disease worldwide. However, most patients will develop debilitating motor levodopa-induced complications (MLIC) in the form of levodopa-induced dyskinesia (LID) and/or motor fluctuations (MF). This study aimed to conduct a systematic review and meta-analysis on the pharmacogenetic association between LID and MF with common genetic variants of the dopamine metabolic and signaling pathways.
METHODS
A meta-analysis was conducted according to the PRISMA guidelines. Extracted studies include case-control studies evaluating the association between SLC6A3/DAT rs28363170 and rs393795; COMT rs4680 and rs4633; MAO-B rs1799836, BDNF rs6265, DRD1 rs4532, DRD2 rs1800497, DRD3 rs6280, and DRD5 rs6283 polymorphisms; and the overall risk of MLIC and its subtypes LID or MF. Genotypic frequency were tested for deviation from the Hardy-Weinberg equilibrium (HWE), and the genetic association was examined using the allelic (a vs. A), recessive (aa vs. Aa + AA), dominant (aa + Aa vs. AA), overdominant (Aa vs. aa + AA), homozygous (aa vs. AA), and heterozygous (Aa vs. AA and aa vs. aA) models.
RESULTS
Fourteen studies were included in the meta-analysis. A significant association was found between COMT rs46809 polymorphisms with LID but not MF, with the association observable in Asians but not Caucasians. In Asians, the COMT rs4633 was significantly associated with the occurrence of both LID and MF. The MAO-B rs1799836 was associated with both MF and LID. Among all the dopamine receptor genes analyzed, only DRD2 exhibited an association with LID. No association was observed between the SLC6AT/DAT and BDNF genes with either LID or MF.
CONCLUSION
Strong associations were observed between polymorphisms of genes regulating dopamine metabolism with the occurrence of LID and/or MF. The MAO-B rs1799836 may be potential for use as a general pharmacogenetic marker of MLIC, while the COMT rs4680 and rs4633 may be used as markers of LID in Asian ethnicities.
Topics: Brain-Derived Neurotrophic Factor; Dopamine; Dyskinesias; Humans; Levodopa; Monoamine Oxidase; Parkinson Disease; Signal Transduction
PubMed: 35079903
DOI: 10.1007/s10072-021-05829-4 -
International Journal of Environmental... Dec 2021Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia.... (Review)
Review
Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016-2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg ( = 0.0138) and 100 mg ( = 0.0006) have improved the Unified Parkinson's Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression-Change (CGI-C), Clinical Global Impression-Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson's Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Pharmaceutical Preparations; Psychotic Disorders; United States
PubMed: 35010624
DOI: 10.3390/ijerph19010364 -
The Journal of Prosthetic Dentistry May 2022Various factors are responsible for sleep bruxism; however, whether the dopaminergic agonist group of drugs is effective in the treatment of sleep bruxism is unclear. (Review)
Review
STATEMENT OF PROBLEM
Various factors are responsible for sleep bruxism; however, whether the dopaminergic agonist group of drugs is effective in the treatment of sleep bruxism is unclear.
PURPOSE
The purpose of this systematic review was to evaluate the effect of the dopaminergic agonist group of drugs in controlling sleep bruxism in comparison with no treatment or placebo-controlled treatment.
MATERIAL AND METHODS
Two electronic databases, PubMed and Cochrane Central, were searched by using the keywords bruxism, sleep bruxism, dopamine, and dopamine agonist. After screening titles and abstracts, only those articles which met predefined inclusion criteria were selected for full-text assessment. Clinical trials using the dopaminergic agonist group of drugs as a treatment approach to sleep bruxism were included.
RESULTS
The literature search yielded a total of 64 articles from the 2 electronic databases (PubMed, 53; Cochrane Central, 11). After removal of the duplicates (n=8), the initial screening of titles and abstracts was performed by 2 independent reviewers, removing 46 articles. A total of 10 articles were selected for full-text reading, and 4 studies were included for qualitative analysis.
CONCLUSIONS
Levodopa (L-DOPA) and Bromocriptine showed decrease in root mean square value in electromyography per bruxism burst (P<.001) and 20% to 30% reduction of bruxism episodes during sleep in 2 different studies. However, treatment with bromocriptine led to conflicting result in another study in terms of frequency of bruxism episodes and amplitude of muscle contractions in electromyography (EMG). Bruxism bursts and episodes were also not significantly improved with another dopaminergic agonist group of drugs, Pramipexole (P>.001). Based on the limited evidence and conflicting results, significant conclusions cannot be generated, and further studies are required.
Topics: Bromocriptine; Bruxism; Dopamine Agonists; Electromyography; Humans; Sleep; Sleep Bruxism
PubMed: 33455727
DOI: 10.1016/j.prosdent.2020.11.028