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Frontiers in Neurology 2019Pregnancy in Parkinson's disease is a rare occurrence, and to date, clinical experience with its management is rather limited. In clinical practice, doubts concern...
Pregnancy in Parkinson's disease is a rare occurrence, and to date, clinical experience with its management is rather limited. In clinical practice, doubts concern mainly the impact of PD on gestation, labor, and delivery as well as the safety of dopaminergic drugs. We report the case of a 40-year-old woman with an 8-year history of PD. In the first trimester of her pregnancy, her motor status was similar to the pre-conceptional period. In gestation week 16, her motor status dramatically worsened and she complained of predictable "off" periods in the afternoon. For this reason, her dose of L-DOPA/carbidopa was increased up to 500/125 mg per day. At 39 gestational weeks, she gave birth to a healthy girl with an Apgar score of 9 by an uncomplicated cesarean delivery. The child was not breast fed to avoid exposure to antiparkinsonian drugs. The L-DOPA/carbidopa dosage remained constant during the postpartum period. We performed a systematic review of the literature using Ovid Medline, Scopus, and PubMed (including Cochrane database). We used the search terms "Parkinson disease" AND "pregnancy." We identified 20 studies of PD in pregnancy with a total of 37 pregnant women with PD. The most important available data concern the safety of L-DOPA therapy during pregnancy. There seems to be some risk of worsening of the condition or upcoming of new PD symptoms during or shortly after pregnancy. More data concerning the safety of antiparkinsonian drugs in PD treatment, as well as the effect of pregnancy on parkinsonian symptoms are needed. According to the current state of the art, L-DOPA therapy should be considered preferable to other drugs during pregnancy.
PubMed: 32140133
DOI: 10.3389/fneur.2019.01349 -
Medicine Nov 2021Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.
BACKGROUND
Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.
RESULTS
Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).
CONCLUSIONS
P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.
Topics: Antiparkinson Agents; Combined Modality Therapy; Humans; Levodopa; Multicenter Studies as Topic; Parkinson Disease; Pramipexole; Treatment Outcome
PubMed: 34871213
DOI: 10.1097/MD.0000000000027511 -
Journal of Neuromuscular Diseases 2021Parkinson's disease (PD) is a disabling neurological condition characterized by the loss of dopaminergic neurons. Currently, the treatment for PD is symptomatic and...
Parkinson's disease (PD) is a disabling neurological condition characterized by the loss of dopaminergic neurons. Currently, the treatment for PD is symptomatic and compensates for the endogenous loss of dopamine production. In cases where the pharmacological therapy is only partly beneficial or results in major wearing-off complications, surgical interventions such as deep brain stimulation may be an alternative treatment. The disease cause often remains unknown, but in some patients, a monogenic cause can be identified. Mutations in at least six genes, LRRK2, SNCA, and VPS35 (dominant forms) or Parkin/PRKN, PINK1, and DJ1/PARK7 (recessive forms) have been unequivocally linked to PD pathogenesis. We here systematically screened 8,576 publications on these monogenic PD forms. We identified 2,226 mutation carriers from 456 papers. Levodopa was the most widely applied treatment; only 34 patients were indicated to be untreated at the time of reporting. Notably, detailed treatment data was rarely mentioned including response quantification (good, moderate, minimal) in 951 and/or dose in 293 patients only. Based on available data, levodopa showed an overall good outcome, especially in LRRK2, VPS35, Parkin, and PINK1 mutation carriers ("good" response in 94.6-100%). Side effects of levodopa therapy were reported in ∼15-40%of levodopa-treated patients across genes with dyskinesias as the most frequent one. Non-levodopa medication was indicated to be administered to <200 patients with mainly good outcome. Only a few reports were available on outcomes of brain surgery. Here, most mutation carriers showed a good response. Importantly, none of the available treatments is harmful to one genetic form but effective in another one. In the light of different medication schemes, the progressive nature of PD, and side effects, an improvement of therapeutic options for PD is warranted including a treatabolome database to guide clinicians in treatment decisions. Further, novel disease-cause-modifying drugs are needed.
Topics: Antiparkinson Agents; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Levodopa; Mutation; Parkinson Disease; Protein Deglycase DJ-1; Protein Kinases; Ubiquitin-Protein Ligases; Vesicular Transport Proteins; alpha-Synuclein
PubMed: 33459660
DOI: 10.3233/JND-200598 -
RSC Advances Feb 2022A review article has been published recently (, 2021, , 22159-22198) describing flavonoids as inhibitors of tyrosinase. However, many compounds included in this review...
Comment on "Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review" by R. Obaid, E. Mughal, N. Naeem, A. Sadiq, R. Alsantali, R. Jassas, Z. Moussa and S. Ahmed, , 2021, , 22159.
A review article has been published recently (, 2021, , 22159-22198) describing flavonoids as inhibitors of tyrosinase. However, many compounds included in this review have been previously shown to act as substrates of this enzymes or antioxidants reducing tyrosinase-generated -quinones. Products of their oxidation absorb light in a range different than dopachrome, the oxidation product of l-tyrosine or l-dopa, whose concentration is measured spectrophotometrically in the standard enzymatic assay to monitor the activity of this enzyme. This effect is interpreted as enzyme inhibition, which, in fact, is only apparent and results from inadequate methodology.
PubMed: 35425534
DOI: 10.1039/d1ra08162d -
Frontiers in Pharmacology 2023Polypharmacy is common in patients with dysphagia. Routinely used drugs may influence swallowing function either improving or worsening it. We aimed to explore the...
Polypharmacy is common in patients with dysphagia. Routinely used drugs may influence swallowing function either improving or worsening it. We aimed to explore the potential effects of three commonly used drug classes on dysphagia and aspiration pneumonia through a systematic review and a real-world data analysis to probe the possibility of drug repurposing for dysphagia treatment. Five electronic databases were searched. Studies on adults at risk for dysphagia, treated with Dipeptidyl-Peptidase IV Inhibitors (DPP-4i), Adrenergic Beta-Antagonists (beta-blockers), or Angiotensin-Converting Enzyme Inhibitors (ACEi), and reporting outcomes on dysphagia or aspiration pneumonia were included. A nested case/non-case study was performed on adverse events recorded in the FDA Adverse Event Reporting System (FAERS) on patients >64 years. Cases (dysphagia or aspiration pneumonia) were compared between patients only treated with Levodopa and patients who were concomitantly treated with the drugs of interest. Twenty studies were included in the review (17 on ACEi, 2 on beta-blockers, and 1 on DPP-4i). Contrasting findings on the effects of ACEi were found, with a protective effect mainly reported in Asian studies on neurological patients. Beta-blockers were associated with a reduced dysphagia rate. The study on DPP-4i suggested no effect on dysphagia and an increased risk of aspiration pneumonia. The FAERS analysis showed a reduction of the risk for dysphagia/aspiration pneumonia with ACEi, beta-blockers, and DPP-4i. Our study explores the potential drug repurposing of ACEi, beta-blockers and DPP-4i in neurological patients with dysphagia to improve swallowing function and reduce aspiration pneumonia risk. Future randomized controlled studies should confirm these results and clarify the underlying mechanisms of action.
PubMed: 36937893
DOI: 10.3389/fphar.2023.1057301 -
Journal of Clinical Medicine Oct 2023We question whether bradyphrenia, slowing of cognitive processing not explained by depression or a global cognitive assessment, is a nosological entity in idiopathic...
We question whether bradyphrenia, slowing of cognitive processing not explained by depression or a global cognitive assessment, is a nosological entity in idiopathic parkinsonism (IP). The time taken to break contact of an index finger with a touch-sensitive plate was measured, with and without a warning in the alerting signal as to which side the imperative would indicate, in 77 people diagnosed with IP and in 124 people without an IP diagnosis. The ability to utilise a warning, measured by the difference between log-transformed reaction times (unwarned minus warned), was termed 'cognitive efficiency'. It was approximately normally distributed. A questionnaire on self- and partner perception of proband's bradyphrenia was applied. A multivariable model showed that those prescribed levodopa were less cognitively efficient (mean -5.2 (CI -9.5, -1.0)% per 300 mg/day, = 0.02), but those prescribed the anti-muscarinic trihexyphenidyl were more efficient (14.7 (0.2, 31.3)% per 4 mg/day, < 0.05) and those prescribed monoamine oxidase-B inhibitor (MAOBI) tended to be more efficient (8.3 (0.0, 17.4)%, = 0.07). The variance in efficiency was greater within IP (F-test, = 0.01 adjusted for any demographic covariates: coefficient of variation, with and without IP, 0.68 and 0.46, respectively), but not so after adjustment for anti-parkinsonian medication ( = 0.13: coefficient of variation 0.62). The within-participant follow-up time, a median of 4.8 (interquartile range 3.1, 5.5) years (101 participants), did not influence efficiency, irrespective of IP status. Perception of bradyphrenia did not usefully predict efficiency. We conclude that both bradyphrenia and 'tachyphrenia' in IP appear to have iatrogenic components, of clinically important size, related to the dose of antiparkinsonian medication. Levodopa is the most commonly prescribed first-line medication: co-prescribing a MAOBI may circumvent its associated bradyphrenia. The previously reported greater efficiency associated with (low-dose) anti-muscarinic was confirmed.
PubMed: 37892637
DOI: 10.3390/jcm12206499 -
Movement Disorders Clinical Practice Feb 2020A good response to levodopa is a key feature of Parkinson's disease (PD), and a poor response suggests an alternative diagnosis, but the extent of variation in the...
BACKGROUND
A good response to levodopa is a key feature of Parkinson's disease (PD), and a poor response suggests an alternative diagnosis, but the extent of variation in the levodopa response in definite PD is not well defined.
LITERATURE REVIEW
A systematic review of articles reporting pathologically confirmed PD and levodopa responsiveness from 1971 to 2018 was performed using the medical subheadings "postmortem," "Parkinson's disease," "levodopa," and "l-dopa" in PubMed, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS) databases.
CASES
A total of 12 articles described 445 PD cases: 61.7% male, age at disease onset 64.0 years (SD 9.6), age at death 77.1 years (SD 7.2). Levodopa responsiveness was reported in 399 cases (89.7%) either as a graded or a binary response. In the 280 cases (70.2%) describing a graded response, it was excellent in 37.5%, good in 45.7%, moderate in 12.1%, and poor in 4.6%. In the 119 cases describing a binary response (29.8%), 73.1% were levodopa responsive, and 26.9% were nonresponsive. Comorbid brain pathology was present in 137 of 235 cases assessed, being cerebrovascular in 46.0% and Alzheimer's disease in 37.2% of these, but its contribution to levodopa responsiveness was unclear.
CONCLUSIONS
The levodopa motor response varies in definite PD. Explanations other than diagnostic inaccuracy should be explored.
PubMed: 32071945
DOI: 10.1002/mdc3.12885 -
Frontiers in Neuroscience 2021Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis...
Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis (NMA) aimed to compare the efficacy and safety of different drugs. After literature searching and screening, 46 trials, including 10,674 participants are included in this NMA. The pooled results showed that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. Cabergoline decreases IRLS scores to the greatest extent among all drugs (MD -11.98, 95% CI -16.19 to -7.78). Additionally, pramipexole is superior to ropinirole in alleviating symptoms of RLS (MD -2.52, 95% CI -4.69 to -0.35). Moreover, iron supplement alleviates RLS symptoms significantly compared with placebo in patient with iron deficiency (MD -5.15, 95% CI -8.99 to -1.31), but not for RLS patients with normal serum ferritin level (MD -2.22, 95% CI -6.99 to 2.56). For primary RLS, these drugs are also effective, while there is insufficient data to analyze drug efficacy in secondary RLS. We analyzed risk of common adverse effects of drugs including nausea, somnolence, fatigue, headache and nasopharyngitis. Alpha-2-delta ligands and DAs are favorable choices for both primary and secondary RLS because of their significant efficacy and good tolerability. Iron supplement can significantly alleviate symptoms of RLS patients with iron deficiency than placebo. We recommend gabapentin, gabapentin enacarbil, and pregabalin for clinicians for first consideration mainly because that they rarely cause augmentation. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with above drugs.
PubMed: 34764852
DOI: 10.3389/fnins.2021.751643 -
Stereotactic and Functional Neurosurgery 2024Deep brain stimulation (DBS) is a well-established surgical therapy for patients with Parkinsons' Disease (PD). Traditionally, DBS surgery for PD is performed under... (Meta-Analysis)
Meta-Analysis Comparative Study
INTRODUCTION
Deep brain stimulation (DBS) is a well-established surgical therapy for patients with Parkinsons' Disease (PD). Traditionally, DBS surgery for PD is performed under local anesthesia, whereby the patient is awake to facilitate intraoperative neurophysiological confirmation of the intended target using microelectrode recordings. General anesthesia allows for improved patient comfort without sacrificing anatomic precision and clinical outcomes.
METHODS
We performed a systemic review and meta-analysis on patients undergoing DBS for PD. Published randomized controlled trials, prospective and retrospective studies, and case series which compared asleep and awake techniques for patients undergoing DBS for PD were included. A total of 19 studies and 1,900 patients were included in the analysis.
RESULTS
We analyzed the (i) clinical effectiveness - postoperative UPDRS III score, levodopa equivalent daily doses and DBS stimulation requirements. (ii) Surgical and anesthesia related complications, number of lead insertions and operative time (iii) patient's quality of life, mood and cognitive measures using PDQ-39, MDRS, and MMSE scores. There was no significant difference in results between the awake and asleep groups, other than for operative time, for which there was significant heterogeneity.
CONCLUSION
With the advent of newer technology, there is likely to have narrowing differences in outcomes between awake or asleep DBS. What would therefore be more important would be to consider the patient's comfort and clinical status as well as the operative team's familiarity with the procedure to ensure seamless transition and care.
Topics: Deep Brain Stimulation; Humans; Parkinson Disease; Wakefulness; Anesthesia, General; Treatment Outcome; Anesthesia
PubMed: 38636468
DOI: 10.1159/000536310 -
Frontiers in Aging Neuroscience 2024This meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson's disease(PD).
OBJECTIVE
This meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson's disease(PD).
METHODS
Four databases (Medline, Embase, Web of Science and CENTRAL) were searched from establishment of database to 23 March 2024, for articles studying robot-assisted DBS in patients diagnosed with PD. Meta-analyses of vector error, complication rate, levodopa-equivalent daily dose (LEDD), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, and UPDRS IV were performed.
RESULTS
A total of 15 studies were included in this meta-analysis, comprising 732 patients with PD who received robot-assisted DBS. The pooled results revealed that the vector error was measured at 1.09 mm (95% CI: 0.87 to 1.30) in patients with Parkinson's disease who received robot-assisted DBS. The complication rate was 0.12 (95% CI, 0.03 to 0.24). The reduction in LEDD was 422.31 mg (95% CI: 68.69 to 775.94). The improvement in UPDRS, UPDRS III, and UPDRS IV was 27.36 (95% CI: 8.57 to 46.15), 14.09 (95% CI: 4.67 to 23.52), and 3.54 (95% CI: -2.35 to 9.43), respectively.
CONCLUSION
Robot-assisted DBS is a reliable and safe approach for treating PD. Robot-assisted DBS provides enhanced accuracy in contrast to conventional frame-based stereotactic techniques. Nevertheless, further investigation is necessary to validate the advantages of robot-assisted DBS in terms of enhancing motor function and decreasing the need for antiparkinsonian medications, in comparison to traditional frame-based stereotactic techniques.: PROSPERO(CRD42024529976).
PubMed: 38882524
DOI: 10.3389/fnagi.2024.1419152