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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 -
Neurosurgical Review Oct 2022Deep brain stimulation (DBS) has become a well-established treatment modality for Parkinson's disease (PD), especially regarding motor fluctuations, dyskinesias, and... (Meta-Analysis)
Meta-Analysis Review
Deep brain stimulation (DBS) has become a well-established treatment modality for Parkinson's disease (PD), especially regarding motor fluctuations, dyskinesias, and tremor. Although postural abnormalities (i.e., Camptocormia [CC] and Pisa syndrome [Pisa]) are known to be a major symptom of PD as well, the influence of DBS on postural abnormalities is unclear. The objective of this study is to analyze the existing literature regarding DBS for PD-associated postural abnormalities in a systematic review and meta-analysis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review and meta-analysis of 18 studies that reported the effect of DBS regarding postural abnormalities. After screening of 53 studies, a total of 98 patients (44 female, 53 males, 1 not reported; mean age: 62.3, range 30-83 years) with postural abnormalities (CC n = 98; Pisa n = 11) were analyzed from 18 included studies. Of those patients, 94.9% underwent STN-DBS and 5.1% had GPi as DBS target area. A positive outcome was reported for 67.8% with CC and 72.2% with Pisa. In the meta-analysis, younger age and lower pre-operative UPDRS-III (ON/OFF) were found as positive predictive factors for a positive effect of DBS. DBS might be a potentially effective treatment option for PD-associated postural abnormalities. However, the level of evidence is rather low, and definition of postoperative outcome is heterogenous between studies. Therefore larger, prospective trials are necessary to give a clear recommendation.
Topics: Adult; Aged; Aged, 80 and over; Deep Brain Stimulation; Female; Humans; Male; Middle Aged; Muscular Atrophy, Spinal; Parkinson Disease; Prospective Studies; Spinal Curvatures; Subthalamic Nucleus
PubMed: 35790655
DOI: 10.1007/s10143-022-01830-3 -
NeuroImage. Clinical 2023Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity... (Review)
Review
BACKGROUND
Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive.
OBJECTIVES
Providing a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures.
METHODS
A systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes.
RESULTS
Most articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described.
CONCLUSION
Key brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes.
Topics: Humans; Tremor; Myoclonus; Tics; Dystonia; Magnetic Resonance Imaging; Chorea; Hyperkinesis; Brain; Brain Mapping; Dystonic Disorders; Ataxia; Neural Pathways
PubMed: 36669351
DOI: 10.1016/j.nicl.2022.103302 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
Journal of Parkinson's Disease 2022Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy.
OBJECTIVE
We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa.
METHODS
We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups.
RESULTS
Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments.
CONCLUSION
Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35180134
DOI: 10.3233/JPD-213057 -
BMJ Neurology Open 2024The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists...
BACKGROUND
The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications.
METHODS
In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.
RESULTS
74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile.
CONCLUSIONS
COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.
PubMed: 38352047
DOI: 10.1136/bmjno-2023-000573 -
Clinical Microbiology and Infection :... May 2022Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. (Review)
Review
BACKGROUND
Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described.
OBJECTIVES
To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study.
DATA SOURCES
Medline, Embase, Scopus, Cochrane library.
STUDY ELIGIBILITY CRITERIA
There was no discrimination on study type, time of publication or language.
PARTICIPANTS
Review: All articles with definite LNB and confirmed/possible encephalitis.
COHORT
LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis.
METHODS
Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies.
COHORT
Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered.
RESULTS
Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died.
COHORT
Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died.
CONCLUSIONS
This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.
Topics: Aged; Ataxia; Cohort Studies; Encephalitis; Humans; Lyme Neuroborreliosis; Retrospective Studies
PubMed: 34768019
DOI: 10.1016/j.cmi.2021.11.001 -
Tremor and Other Hyperkinetic Movements... 2023To describe the state of literature regarding prevalence, clinical types of tremor in Multiple Sclerosis and associated disability. (Review)
Review
OBJECTIVE
To describe the state of literature regarding prevalence, clinical types of tremor in Multiple Sclerosis and associated disability.
BACKGROUND
Tremor has long been recognized as an important symptom of multiple sclerosis. This can be intention and postural tremor that affects the upper limbs. Patients with multiple sclerosis who experience tremor of any severity typically retire early or lose their jobs due to disability.
METHODS
This systematic review was performed up to September 9, 2022. Article selection was performed by searching the MEDLINE (PubMed) and EMBASE electronic bibliographic databases. The search strategy was not limited by study design but only for articles in the English language.
RESULTS
A total of nine full-text articles were included in the analysis. Six studies were cross-sectional studies; one each was a prospective observational study, a case-control study, a community-based cohort. The prevalence of tremor in the multiple sclerosis (MS) population among studies ranged widely, between 12.5% and 68.9%. The presence of severe tremor ranged from 3% to 33%. Younger age was a significant predictor of tremor in two studies. The most common tremor subtype was action tremor. Upper extremities were the most common site involved in the majority of our studies, followed by head and neck.
CONCLUSIONS
Prevalence of tremor ranged from 12.5% to 68.9% in the MS population with severe tremor being an infrequent complication. Severity of tremor correlated with increasing disability. Upper limb action tremor was the most common with rare occurrences of resting and rubral tremor.
Topics: Humans; Case-Control Studies; Multiple Sclerosis; Prevalence; Tremor; Head; Observational Studies as Topic
PubMed: 37719089
DOI: 10.5334/tohm.776 -
Single-Nucleotide Polymorphisms as Biomarkers of Antipsychotic-Induced Akathisia: Systematic Review.Genes Feb 2023Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to... (Review)
Review
Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to move, resulting in repetitive movements of the limbs and torso, while taking antipsychotics (APs). In recent years, there have been some associative genetic studies of the predisposition to the development of AIA. : The goal of our study was to review the results of associative genetic and genome-wide studies and to systematize and update the knowledge on the genetic predictors of AIA in patients with schizophrenia (Sch). We searched full-text publications in PubMed, Web of Science, Springer, Google Scholar, and e-Library databases from 1977 to 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) quality scale was used for the critical selection of the studies. We identified 37 articles, of which 3 were included in the review. Thus, the C allele of rs1800498 (59414 C>T) and the A allele of rs1800497 (17316 G>A) (TaqIA) from the gene as well as the TT genotype rs13212041 (77461407 C>T) from the gene were found to be associated with AIA. : Uncovering the genetic biomarkers of AIA may provide a key to developing a strategy for the personalized prevention and treatment of this adverse neurological drug reaction of APs in patients with Sch in real clinical practice.
Topics: Humans; Antipsychotic Agents; Psychomotor Agitation; Polymorphism, Single Nucleotide; Schizophrenia; Biomarkers
PubMed: 36980888
DOI: 10.3390/genes14030616 -
Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis.Frontiers in Neurology 2021Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available...
Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD. Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms. A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included. Ten studies ( = 236) were included in meta-analysis and 25 studies ( = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III - motor aspects (MD = -0.98%, 95% CI = -10.03 to 8.07, = 0.83, = 0%), UPDRS IV - dyskinesias (MD = -0.89%, CI 95% = -3.82 to 2.03, = 0.55, = 0%) and motor fluctuations (MD = -0.67%, CI 95% = -2.45 to 1.11, = 0.46, = 0%), timed up and go - gait (MD = 0.14%, CI 95% = -0.72 to 0.99, = 0.75, = 0%), Berg Balance Scale - balance (MD = 0.73%, CI 95% = -1.01 to 2.47, = 0.41, = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III - motor aspects (MD = 2.05%, CI 95% = -1.96 to 6.06, = 0.32, = 0%) and gait (SMD = -0.05%, 95% CI = -0.28 to 0.17, = 0.64, = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = -1.7, SE = 1.51, z-score = -1.18, = 0.2, IC = -4.75 to 1.17) and cumulative time (estimate = -0.07, SE = 0.07, z-score = -0.99, = 0.31, IC = -0.21 to 0.07) had no significant association. There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.
PubMed: 35082749
DOI: 10.3389/fneur.2021.794784