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Frontiers in Neuroscience 2021Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the...
Comparative Efficacy and Safety of Dopamine Agonists in Advanced Parkinson's Disease With Motor Fluctuations: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials.
Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.
PubMed: 34776841
DOI: 10.3389/fnins.2021.728083 -
Journal of Cannabis Research Mar 2022We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms... (Review)
Review
AIM
We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms associated with neurocognitive disorders.
METHODS
We conducted a PRISMA-guided systematic review to identify studies using cannabis-based medicine to treat behavioral, psychological, and motor symptoms among individuals with Alzheimer's disease (AD) dementia, Parkinson's disease (PD), and Huntington's disease (HD). We considered English-language articles providing original data on three or more participants, regardless of design.
FINDINGS
We identified 25 studies spanning 1991 to 2021 comprised of 14 controlled trials, 5 pilot studies, 5 observational studies, and 1 case series. In most cases, the cannabinoids tested were dronabinol, whole cannabis, and cannabidiol, and the diagnoses included AD (n = 11), PD (n = 11), and HD (n = 3). Primary outcomes were motor symptoms (e.g., dyskinesia), sleep disturbance, cognition, balance, body weight, and the occurrence of treatment-emergent adverse events.
CONCLUSIONS
A narrative summary of the findings from the limited number of studies in the area highlights an apparent association between cannabidiol-based products and relief from motor symptoms in HD and PD and an apparent association between synthetic cannabinoids and relief from behavioral and psychological symptoms of dementia across AD, PD, and HD. These preliminary conclusions could guide using plant-based versus synthetic cannabinoids as safe, alternative treatments for managing neuropsychiatric symptoms in neurocognitive vulnerable patient populations.
PubMed: 35287749
DOI: 10.1186/s42238-022-00119-y -
Experimental Brain Research Feb 2022Tourette syndrome (TS) is a neurodevelopmental condition characterised by tics, which are stereotyped movements and/or vocalisations. Tics often cause difficulties in... (Review)
Review
Tourette syndrome (TS) is a neurodevelopmental condition characterised by tics, which are stereotyped movements and/or vocalisations. Tics often cause difficulties in daily life and many with TS express a desire to reduce and/or gain control over them. No singular effective treatment exists for TS, and while pharmacological and behavioural interventions can be effective, the results are variable, and issues relating to access, availability and side effects can be barriers to treatment. Consequently, over the past decade, there has been increasing interest into the potential benefits of non-invasive brain stimulation (NIBS) approaches. This systematic review highlights work exploring NIBS as a potential treatment for TS. On balance, the results tentatively suggest that multiple sessions of stimulation applied over the supplementary motor area (SMA) may help to reduce tics. However, a number of methodological and theoretical issues limit the strength of this conclusion, with the most problematic being the lack of large-scale sham-controlled studies. In this review, methodological and theoretical issues are discussed, unanswered questions highlighted and suggestions for future work put forward.
Topics: Humans; Motor Cortex; Tic Disorders; Tics; Tourette Syndrome; Transcranial Magnetic Stimulation
PubMed: 34643763
DOI: 10.1007/s00221-021-06229-y -
Neuropsychology Review Mar 2024Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than... (Review)
Review
Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than motor symptoms in cervical dystonia (CD). Some cognitive impairments have been reported; however, findings are inconsistent, and described across mixed groups of dystonia. The current review aimed to examine the evidence for cognitive impairments in CD. MEDLINE, EMBASE, PsychINFO and Web of Science databases were searched. Studies were included if they met the following criteria (i) cross-sectional or longitudinal studies of adults with CD, (ii) where the results of standardised measures of cognitive or neuropsychological function in any form were assessed and reported, (iii) results compared to a control group or normative data, and (iv) were published in English. Results are presented in a narrative synthesis. Twenty studies were included. Subtle difficulties with general intellectual functioning, processing speed, verbal memory, visual memory, visuospatial function, executive function, and social cognition were identified while language, and attention and working memory appear to be relatively spared. Several methodological limitations were identified that should be considered when interpreting the evidence to describe a specific profile of cognitive impairment in CD. Clinical and research implications are discussed.
Topics: Adult; Humans; Torticollis; Quality of Life; Cross-Sectional Studies; Cognition; Memory, Short-Term
PubMed: 36696021
DOI: 10.1007/s11065-022-09558-z -
Brain and Behavior Jun 2023Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically... (Review)
Review
BACKGROUND
Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear.
OBJECTIVES
This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques.
METHODS
A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211).
RESULTS
All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers.
CONCLUSIONS
Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.
Topics: Humans; Dystonia; Dystonic Disorders; Molecular Chaperones; Neuroimaging
PubMed: 37165749
DOI: 10.1002/brb3.3023 -
Frontiers in Aging Neuroscience 2023Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most... (Review)
Review
Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson's disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients' caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient's nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM's symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients' suffering.
PubMed: 38076536
DOI: 10.3389/fnagi.2023.1264143 -
Frontiers in Physiology 2023Neurological disorders with dyskinesia would seriously affect older people's daily activities, which is not only associated with the degeneration or injury of the...
Neurological disorders with dyskinesia would seriously affect older people's daily activities, which is not only associated with the degeneration or injury of the musculoskeletal or the nervous system but also associated with complex linkage between them. This study aims to review the relationship between motor performance and cortical activity of typical older neurological disorder patients with dyskinesia during walking and balance tasks. Scopus, PubMed, and Web of Science databases were searched. Articles that described gait or balance performance and cortical activity of older Parkinson's disease (PD), multiple sclerosis, and stroke patients using functional near-infrared spectroscopy were screened by the reviewers. A total of 23 full-text articles were included for review, following an initial yield of 377 studies. Participants were mostly PD patients, the prefrontal cortex was the favorite region of interest, and walking was the most popular test motor task, interventional studies were four. Seven studies used statistical methods to interpret the relationship between motor performance and cortical activation. The motor performance and cortical activation were simultaneously affected under difficult walking and balance task conditions. The concurrent changes of motor performance and cortical activation in reviewed studies contained the same direction change and different direction change. Most of the reviewed studies reported poor motor performance and increased cortical activation of PD, stroke and multiple sclerosis older patients. The external motor performance such as step speed were analyzed only. The design and results were not comprehensive and profound. More than 5 weeks walking training or physiotherapy can contribute to motor function promotion as well as cortices activation of PD and stroke patients. Thus, further study is needed for more statistical analysis on the relationship between motor performance and activation of the motor-related cortex. More different type and program sports training intervention studies are needed to perform.
PubMed: 37051020
DOI: 10.3389/fphys.2023.1153469 -
BioMed Research International 2022Clinical data has recently shown an association between Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and zonisamide. The purpose of this study was to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Clinical data has recently shown an association between Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and zonisamide. The purpose of this study was to thoroughly evaluate the efficacy and safety of zonisamide in PD and DLB.
METHODS
Pubmed, the Cochrane Library, Web of Science, and Embase databases were searched for all randomized clinical trials (RCTS) on the role of zonisamide in PD and DLB that were completed by April 18, 2022. UPDRS II (off) total score, UPDRS III total score, Daily "off" time, and UPDRS Part IV, Nos. 32, 33, and 34 were used as clinical efficacy endpoints. Adverse events reported in the RCTs will be considered in the final safety analysis. To better understand the effect of zonisamide on the efficacy and safety of PD and DLB, the UPDRS III total score and the six overlapping adverse events were examined in subgroups. Either a fixed effects model analysis (OR) or a random effects model analysis (MD) is used to figure out the mean difference (MD) and the relative risk.
RESULTS
Seven articles involving 1749 patients (916 PD and 833 DLB) were included in this study. Compared to the control group, zonisamide could significantly reduce the UPDRS III total score in patients with PD and DLB (WMD-2.27 [95% CI: -3.06, -1.48], < 0.0001). For patients with PD, compared to the control group, zonisamide could significantly reduce the UPDRS II (off) total score (WMD-0.81 [95% CI: -1.36, -0.26], = 0.004), daily "off" time (WMD-0.67 [95% CI: -1.10, 0.24], = 0.002), and UPDRS part IV, No. 32 worsen (OR-3.48 [95% CI: 1.20, 10.10], = 0.02). In terms of safety, compared with the control group, for patients with DLB, zonisamide could significantly increase the incidence of contusion (OR-0.60 [95% CI: 0.38, 0.96], = 0.03) and may increase the probability of reduced appetite (OR-3.13 [95% CI: 1.61, 6.08], = 0.0008). And for patients with PD, zonisamide may increase the probability of somnolence (OR-2.17 [95% CI: 1.25, 3.76], = 0.006).
CONCLUSIONS
For the analysis of the current study results, our results show that zonisamide could improve the motor function in patients with PD and DLB and improve the activities of daily living (off) and wearing off and decrease the duration of dyskinesia in patients with PD. In terms of safety, the use of zonisamide significantly increases the probability of contusion in patients with DLB and may increase the probability of reduced appetite in patients with DLB and somnolence in patients with PD. Zonisamide appears to be a new treatment option for patients with PD and DLB. However, the effectiveness and safety of zonisamide in the treatment of PD and DLB need to be further investigated.
Topics: Contusions; Humans; Lewy Body Disease; Parkinson Disease; Sleepiness; Zonisamide
PubMed: 36132085
DOI: 10.1155/2022/4817488 -
PloS One 2023Parkinson's disease (PD) is a common neurological disease affecting around 1% of people above sixty years old. It is characterised by both motor and non-motor symptoms...
BACKGROUND
Parkinson's disease (PD) is a common neurological disease affecting around 1% of people above sixty years old. It is characterised by both motor and non-motor symptoms including tremor, slow movement, unsteady gait, constipation and urinary incontinence. As the disease progresses, individuals living with the disease are likely to lose their independence and autonomy, subsequently affecting their quality of life. People with PD should be supported to live well within their communities but there has been limited research regarding what the public know about PD. This review aims to develop an understanding of how the public view people living with PD, which has the potential to aid the development of an educational resource for the future to improve public awareness and understanding of PD. The purpose of this scoping review is to review and synthesise the literature on the public perception and attitudes towards people living with PD and identify and describe key findings.
AIM
This scoping review aims to explore public perceptions and awareness of Parkinson's Disease among diverse populations, encompassing beliefs, knowledge, attitudes, and the broader societal context influencing these perceptions.
METHODS
A scoping review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for ScR (PRISMA-ScR). Four electronic databases were searched systematically (CINAHL Plus, Medline, PsycINFO and International Bibliography of the Social Sciences). The Joanna Briggs Institute Critical Appraisal Tools (JBI) were used to assess the quality of primary studies, however, all relevant studies were considered regardless of their methodological quality. The 'Population-Concept-Context' framework was used in the screening process to identify eligible papers.
RESULTS
A total of 23 studies were included in the review representing global research in quantitative (n = 12) and mixed methods approaches (n = 11). All 23 studies adopted some aspect of cross-sectional design. Three themes emerged from the studies, the first being public knowledge of symptoms, causes and treatment of PD and this highlighted a lack of understanding about the disease. Secondly, the review identified public attitudes towards PD, highlighting the social consequences of the disease, including the association between PD and depression, isolation and loss of independence. Finally, the third theme highlighted that there was a paucity of educational resources available to help increase public understanding of PD.
CONCLUSION
Findings from this scoping review have indicated that public awareness of PD is a growing area of interest. To our knowledge, this is the first scoping review on this topic and review findings have indicated that public knowledge and attitudes towards PD vary internationally. The implications of this are that people with PD are more likely to be a marginalised group within their communities. Future research should focus on understanding the perception of the public from the perspective of people with PD, the development of interventions and awareness campaigns to promote public knowledge and attitude and further high-quality research to gauge public perceptions of PD.
Topics: Humans; Middle Aged; Cross-Sectional Studies; Parkinson Disease; Public Opinion; Quality of Life; Tremor; Aged
PubMed: 37713383
DOI: 10.1371/journal.pone.0291357 -
European Journal of Neurology Nov 2022Structural magnetic resonance techniques have been widely applied in neurological disorders to better understand tissue changes, probing characteristics such as volume,... (Review)
Review
BACKGROUND AND PURPOSE
Structural magnetic resonance techniques have been widely applied in neurological disorders to better understand tissue changes, probing characteristics such as volume, iron deposition and diffusion. Dystonia is a hyperkinetic movement disorder, resulting in abnormal postures and pain. Its pathophysiology is poorly understood, with normal routine clinical imaging in idiopathic forms. More advanced tools provide an opportunity to identify smaller scale structural changes which may underpin pathophysiology. This review aims to provide an overview of methodological approaches undertaken in structural brain imaging of dystonia cohorts, and to identify commonly identified pathways, networks or regions that are implicated in pathogenesis.
METHODS
Structural magnetic resonance imaging studies of idiopathic and genetic forms of dystonia were systematically reviewed. Adhering to strict inclusion and exclusion criteria, PubMed and Embase databases were searched up to January 2022, with studies reviewed for methodological quality and key findings.
RESULTS
Seventy-seven studies were included, involving 1945 participants. The majority of studies employed diffusion tensor imaging (DTI) (n = 45) or volumetric analyses (n = 37), with frequently implicated areas of abnormality in the brainstem, cerebellum, basal ganglia and sensorimotor cortex and their interconnecting white matter pathways. Genotypic and motor phenotypic variation emerged, for example fewer cerebello-thalamic tractography streamlines in genetic forms than idiopathic and higher grey matter volumes in task-specific than non-task-specific dystonias.
DISCUSSION
Work to date suggests microstructural brain changes in those diagnosed with dystonia, although the underlying nature of these changes remains undetermined. Employment of techniques such as multiple diffusion weightings or multi-exponential relaxometry has the potential to enhance understanding of these differences.
Topics: Brain; Diffusion Tensor Imaging; Dystonia; Dystonic Disorders; Humans; Iron; Magnetic Resonance Imaging
PubMed: 35785410
DOI: 10.1111/ene.15483