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European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
BMJ Clinical Evidence Aug 2007Around 1% of adults have Parkinson's disease, with a median time of 9 years between diagnosis and death. (Review)
Review
INTRODUCTION
Around 1% of adults have Parkinson's disease, with a median time of 9 years between diagnosis and death.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with early-stage Parkinson's disease? What are the effects of adding other treatments in people with Parkinson's disease who have motor complications from levodopa? What are the effects of surgery in people with later Parkinson's disease? What are the effects of nursing and rehabilitation treatments in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding a catechol-methyl transferase inhibitor, or dopamine agonist to levodopa; amantadine; dopamine agonists; levodopa (immediate-release, modified-release); monoamine oxidase B inhibitors; occupational therapy; pallidal deep brain stimulation; pallidotomy; Parkinson's disease nurse specialist interventions; physiotherapy; speech and language therapy; subthalamic nucleus deep brain stimulation; subthalamotomy; swallowing therapy; thalamic deep brain stimulation; and thalamotomy.
Topics: Deep Brain Stimulation; Globus Pallidus; Humans; Levodopa; Parkinson Disease; Subthalamic Nucleus
PubMed: 19454106
DOI: No ID Found -
Frontiers in Aging Neuroscience 2023Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and...
BACKGROUND
Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence.
METHODS
Suitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1.
RESULTS
The results of our meta-analysis, consisting of case-control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: -0.30[-0.39, -0.22], < 0.001 for Vitamin B12; SMD [95%CI]: -0.20 [-0.28, -0.13], < 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], < 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], < 0.001) rather than plasma Hcy below 15 μmol/L (SMD [95%]: -0.31 [-0.62, 0.00], = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region ( = 0.03), age ( = 0.03), levodopa therapy ( = 0.03), Hoehn and Yahr stage ( < 0.001), and cognitive impairment ( < 0.001). However, gender ( = 0.38) and sample size ( = 0.49) were not associated.
CONCLUSION
Hcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.
PubMed: 37941998
DOI: 10.3389/fnagi.2023.1254824 -
Clinical Drug Investigation Apr 2021BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The... (Meta-Analysis)
Meta-Analysis
UNLABELLED
BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes.
METHODS
PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed.
RESULTS
Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence.
CONCLUSION
Overall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.
Topics: Alanine; Antiparkinson Agents; Benzylamines; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 33674954
DOI: 10.1007/s40261-021-01011-y -
Movement Disorders : Official Journal... Nov 2014This study was undertaken to perform a systematic review and meta-analysis of studies of mortality in Parkinson's disease (PD) and to investigate which factors were... (Meta-Analysis)
Meta-Analysis Review
This study was undertaken to perform a systematic review and meta-analysis of studies of mortality in Parkinson's disease (PD) and to investigate which factors were associated with mortality. We conducted comprehensive searches of studies reporting a ratio of mortality in PD versus controls, descriptive survival measures, or factors predicting survival; assessed study quality; and extracted relevant data. Descriptive analysis, meta-analysis, and meta-regression were performed as appropriate. Eighty-eight studies were included in the review with variable study methods and quality. Almost all studies reported increased mortality in PD (vs. controls), with mortality ratios ranging from 0.9 to 3.8, with major between-study heterogeneity. Inception cohorts were more consistent with a pooled mortality ratio of approximately 1.5. Inception cohorts, measurements at longer follow-up duration, and older study recruitment year were associated with lower mortality ratios, but these findings were not robust in sensitivity analyses. Within studies, mortality ratios increased over time. No robust evidence was found that mortality has decreased after the introduction of levodopa (L-dopa). On average, PD survival reduced by approximately 5% every year of follow-up, although there was significant heterogeneity. In post-mortem studies, mean duration until death ranged from 6.9 to 14.3 years. Increasing age and presence of dementia were most commonly associated with increased mortality. Parkinson's disease is associated with increased mortality, but major heterogeneity is seen in estimates of mortality, which is probably explained by variable methodology and patient selection. Individual-patient-data meta-analysis of high-quality inception studies with long-term follow-up would be the optimal way to investigate the factors influencing mortality.
Topics: Databases, Factual; Humans; Parkinson Disease
PubMed: 24821648
DOI: 10.1002/mds.25898 -
Frontiers in Neurology 2022The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic...
BACKGROUND
The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic review and meta-analysis was to evaluate the prevalence of dysphagia in PD and to clarify its associated factors.
METHODS
Two researchers systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, SinoMed and VIP databases and manually searched references in the retrieved articles to identify potential research subjects. The last search was conducted on June 28, 2022. Finally, a total of 58 studies including 60 observations with 20,530 PD patients were included in our meta-analysis.
RESULTS
The meta-analysis estimated that the pooled prevalence rate of dysphagia in PD was 36.9% (95% CI: 30.7-43.6%) and instrumental examination showed a higher prevalence (57.3%, 95% CI: 44.3-69.1%). Oceania showed the highest prevalence of dysphagia in PD (56.3%) compared to Africa (39.5%), Asia (38.6%), Europe (36.1%) and America (28.9%). Dysphagia in PD was associated with older age, lower body mass index, longer disease duration, higher Hoehn and Yahr stage and levodopa equivalent daily dose, PIGD subtype, severe motor symptoms, drooling and higher levels of depression, and lower quality of life.
CONCLUSIONS
In conclusion, our meta-analysis showed that dysphagia occurs in more than one-third of PD patients and was associated with several demographic characteristics and PD-related characteristics, motor symptoms, non-motor symptoms, as well as decreased quality of life. It deserves early screening, diagnosis, and treatment in clinical practice to prevent serious complications from dysphagia.
PubMed: 36277913
DOI: 10.3389/fneur.2022.1000527 -
Langenbeck's Archives of Surgery Nov 2016The great spatial and temporal resolution of positron emission tomography might provide the answer for patients with primary hyperparathyroidism (pHPT) and non-localized... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The great spatial and temporal resolution of positron emission tomography might provide the answer for patients with primary hyperparathyroidism (pHPT) and non-localized parathyroid glands. We performed a systematic review of the evidence regarding all investigated tracers.
METHODS
A study was considered eligible when the following criteria were met: (1) adults ≥17 years old with non-familial pHPT, (2) evaluation of at least one PET isotope, and (3) post-surgical and pathological diagnosis as the gold standard. Performance was expressed in sensitivity and PPV.
RESULTS
Twenty-four papers were included subdivided by radiopharmaceutical: 14 studies investigated L-[C]Methionine (11C-MET), one [C]2-hydroxy-N,N,N-trimethylethanamium (11C-CH), six 2-deoxy-2-[F]fluoro-D-glucose (18F-FDG), one 6-[F] fluoro-L-DOPA (18F-DOPA), and three N-[(F)Fluoromethyl]-2-hydroxy-N,N-dimethylethanaminium (18F-FCH). The 14 studies investigating MET included a total of 327 patients with 364 lesions. Sensitivity for the detection of a lesion in the correct quadrant had a pooled estimate of 69 % (95 % CI 60-78 %). Heterogeneity was overall high with I of 51 % (p = 0.01) for all 14 studies. Pooled PPV ranged from 91 to 100 % with a pooled estimate of 98 % (95 % CI 96-100 %). Of the other investigated tracers, 18-FCH seems the most promising with high diagnostic performance.
CONCLUSIONS
The results of our meta-analysis show that 11C-MET PET has an overall good sensitivity and PPV and may be considered a reliable second-line imaging modality to enable minimally invasive parathyroidectomy. Our literature review suggests that 18F-FCH PET may produce even greater accuracy and should be further investigated using both low-dose CT and MRI for anatomical correlation.
Topics: Carbon Radioisotopes; Humans; Hyperparathyroidism, Primary; Methionine; Parathyroidectomy; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 27086309
DOI: 10.1007/s00423-016-1425-0 -
Clinical Endocrinology Oct 2021The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both... (Meta-Analysis)
Meta-Analysis
PURPOSE
The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both Ga-DOTA peptides and F-fluorodihydroxyphenyl- l-alanine ( F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data.
METHODS
PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of Ga-DOTA peptides and F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth.
RESULTS
Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed.
CONCLUSION
Both F-DOPA PET/CT and Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of F-DOPA PET/CT was observed. Thus, the use of F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.
Topics: Dihydroxyphenylalanine; Humans; Neuroendocrine Tumors; Organometallic Compounds; Peptides; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 34018606
DOI: 10.1111/cen.14527 -
Cureus Mar 2023Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of this review is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.
PubMed: 37069881
DOI: 10.7759/cureus.36211 -
Journal of Neurology Apr 2018L-Dopa represents the mainstay of therapy of Parkinson's disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
L-Dopa represents the mainstay of therapy of Parkinson's disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly, there remains a need to explore novel treatment strategies to manage the signs and symptoms of the later disease stages. The aim of the study was to evaluate the efficacy and safety of adjunctive perampanel (PER) in patients with PD through a meta-analysis of existing trials.
METHODS
Randomized, placebo-controlled, double- or single-blind, add-on studies of PER in patients with PD were identified through a systematic literature search. The following outcomes were assessed: changes from baseline to final efficacy visit in total daily OFF time, activities of daily living during OFF time and motor function during ON time, incidence of adverse events (AEs), and treatment withdrawal.
RESULTS
Four trials were included involving 2266 participants, 1449 and 817 for PER and placebo treatment groups, respectively. Four PER daily doses were tested, namely 0.5, 1, 2 and 4 mg. There were no significant differences in any efficacy outcome between PER and placebo treated patients. The risk ratios (RRs) for AEs, severe AEs and treatment withdrawal were similar between placebo and PER at 0.5, 1 and 2 mg; the 4 mg daily dose was associated with an increased risk of AEs [RR 1.118 (1.047-1.193)], and withdrawal for AEs [RR 1.345 (1.034-1.749)] and for any reason [RR 1.197 (1.020-1.406)].
CONCLUSIONS
In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.
Topics: Activities of Daily Living; Antiparkinson Agents; Clinical Trials as Topic; Double-Blind Method; Humans; Nitriles; Parkinson Disease; Pyridones; Single-Blind Method
PubMed: 29159466
DOI: 10.1007/s00415-017-8681-y