-
European Journal of Neurology Aug 2023Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD.
METHODS
Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate.
RESULTS
Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation.
CONCLUSIONS
The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.
Topics: Humans; Parkinson Disease; Dopamine Agonists; Antiparkinson Agents; Tremor; Levodopa
PubMed: 37154268
DOI: 10.1111/ene.15823 -
Sleep Medicine Dec 2023Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation.
METHODS
We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed.
RESULTS
Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227).
CONCLUSIONS
A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.
Topics: Humans; Restless Legs Syndrome; Dopamine Agents; Levodopa; Iron; Ferritins; Observational Studies as Topic
PubMed: 37879259
DOI: 10.1016/j.sleep.2023.10.022 -
European Journal of Nuclear Medicine... Feb 2024Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method;...
BACKGROUND
Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.
METHODS
We searched the PubMed database for studies performing a head-to-head comparison between [I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([C]C-HED), F-18F-3,4-dihydroxyphenylalanine ([F]DOPA) [I]mIBG and Meta-[18F]fluorobenzylguanidine ([F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).
RESULTS
Ten studies were selected: two regarding [C]C-HED, four [F]DOPA, one [I]mIBG, and three [F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.
CONCLUSIONS
PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.
Topics: Child; Humans; 3-Iodobenzylguanidine; Dihydroxyphenylalanine; Neuroblastoma; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37962616
DOI: 10.1007/s00259-023-06486-9 -
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 -
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 -
Frontiers in Aging Neuroscience 2024Nutrition plays a pivotal role in the multidisciplinary approach to rehabilitating middle to old-aged patients with neurological diseases including movement disorders...
INTRODUCTION
Nutrition plays a pivotal role in the multidisciplinary approach to rehabilitating middle to old-aged patients with neurological diseases including movement disorders (MDs). Despite the prevalence of vitamin D deficiency in many patients with MDs, data supporting supplementation's effectiveness and safety is sparse and conflicting, therefore, our explicit objective was to provide an all-encompassing review of the subject.
METHODS
A comprehensive search of PubMed, Embase, and other scientific databases was conducted up to November 1 2023. The searches included RCTs in all languages with human participants aged 35 and above and not meeting these requirements led to exclusion.
RESULTS
Four studies on Parkinson's disease (PD) and one on restless legs syndrome (RLS) including 369 MD patients, however, none in a rehabilitation context, were found. Although three of the four PD studies showed better outcomes, such as decreasing levodopa-induced dyskinesia or enhancing physical performance in some or all domains, the RLS study did not identify symptom improvement. The one serious adverse effect observed, cerebral infarction, aroused safety concerns, however its relationship to vitamin D consumption is questionable. Structurally the studies can be characterized by large variations in patient populations, in primary outcomes, and disease severity, but typically a relatively short duration of therapy in most cases. With other limitations such as the small number of studies, major trial design heterogeneity, limited sample sizes, and a greatly variable Cochrane risk of bias (RoB) evaluation, only a qualitative synthesis was feasible.
DISCUSSION
Two main implications can be inferred from these results, which we interpret as cautiously promising but overall insufficient for firm recommendations. First, there is an urgent need for more research on the role of vitamin D in MDs in the middle- to older-aged population, particularly during rehabilitation. Second, given the benefits of vitamin D supplementation for those who are deficient, we recommend routine screening and supplementation for MD patients.
PubMed: 38343878
DOI: 10.3389/fnagi.2024.1333217 -
Clinical Neurology and Neurosurgery Jul 2024The decision to offer deep brain stimulation (DBS) to elderly patients with Parkinson's disease (PD) presents challenges due to higher perceived risks and uncertain... (Comparative Study)
Comparative Study Review
INTRODUCTION
The decision to offer deep brain stimulation (DBS) to elderly patients with Parkinson's disease (PD) presents challenges due to higher perceived risks and uncertain long-term benefits. Here, we aimed to compare the outcomes after DBS for elderly versus non-elderly patients with PD.
METHODS
We analyzed data from our institutional cohort and retrieved publicly available data through a systematic review. The exposure was age at DBS electrode insertion, which was defined as elderly (≥70 years old) and non-elderly (<70 years old). The outcomes examined were changes in the Movement Disorders Society-Parkinson's Disease Rating Scale (MDS-UPDRS) or UPDRS part III total score, levodopa-equivalent daily dose (LEDD), and adverse events.
RESULTS
The included studies and our cohort comprised a total of 527 patients, with 111 (21.1 %) classified as elderly. There was no statistically significant difference in the change in MDS-UPDRS or UPDRS part III total score and generally no statistically significant difference in the change in LEDD between the elderly and non-elderly patients. Elderly patients had a higher incidence of wound infection (elderly 5.4 % vs non-elderly 1.9 %; p = 0.087) and inadequate wound healing (elderly 3.6 % vs non-elderly 1.4 %; p = 0.230), but this difference was not statistically significant. There was no significant difference in the incidence of mortality (elderly 0 % vs non-elderly 0 %; p = 1.000), stroke (elderly 0 % vs non-elderly 0.2 %; p = 1.000), and cognitive decline between the age groups.
CONCLUSIONS
Notwithstanding the trend towards a higher risk of wound infection and inadequate wound healing, elderly patients have similar motor outcomes and levels of PD medication reduction as non-elderly patients after DBS for PD. Hence, age should not be used as the sole criterion for determining eligibility for DBS, and the decision to offer DBS to elderly patients should be personalized and made in a multidisciplinary setting, taking into consideration patient- and disease-related factors.
Topics: Humans; Deep Brain Stimulation; Parkinson Disease; Aged; Treatment Outcome; Age Factors; Middle Aged; Male; Female; Cohort Studies; Aged, 80 and over
PubMed: 38723583
DOI: 10.1016/j.clineuro.2024.108319 -
Cureus Mar 2024Amblyopia is a neurodevelopmental disorder of the visual system that impairs the vision of millions of children worldwide. Amblyopia is best treated within the sensitive... (Review)
Review
Amblyopia is a neurodevelopmental disorder of the visual system that impairs the vision of millions of children worldwide. Amblyopia is best treated within the sensitive period of visual development when a child is up to seven years of age. Currently, the gold standard for early treatment of childhood amblyopia is patching, with new treatments emerging in recent years. We aim to evaluate the effectiveness of these newly developed treatments for amblyopia in children aged seven years and younger while comparing them to the current industry standard of patching. We searched online databases including PubMed, Google Scholar, and Cochrane Library for randomized controlled trials (RCTs), systematic reviews, meta-analyses, and narrative reviews relating to amblyopia treatment in children aged seven and younger. We only included articles and studies completed within the last five years and those written in the English language. After compiling a list of 297 articles, we removed duplicates, articles without an available full text, and those not relevant to our topic. Of the remaining 51 articles, we were left with 22 after reading abstracts and removing further irrelevant articles. We did a quality assessment on the remaining 22 articles and were left with 14 articles for our systematic review after removing eight low-quality articles. Of the 14 articles, we had eight RCTs, two systematic reviews, one comparative interventional study, and three narrative reviews. Seven of the articles contained data reinforcing the effectiveness of patching while comparing it to other treatment modalities. Three of the articles had data supporting spectacle correction, including a novel form called alternative flicker glass which delivers occlusion therapy via a spectacle frame with unique lenses, and ultimately deemed it at least as effective or more than patching. Data from three articles supported the use of surgery to successfully correct the angle of strabismus. Findings from five articles backed the use of pharmacologic therapy, specifically atropine when used alongside patching as a more effective alternative to patching solely. However, levodopa plus patching had no advantage over patching alone. Additionally, seven articles addressed the use of virtual reality (VR) and dichoptic therapy as prospective treatments for childhood amblyopia. VR therapy proved beneficial when used within one week after strabismus surgery. Dichoptic training was also effective in improving amblyopic-eye visual acuity when used on its own or in conjunction with spectacles. Furthermore, dichoptic movie therapy was found to be more effective than patching. Thus, we found multiple highly effective treatments for childhood amblyopia that are as effective or more than patching. Future studies should consider prescribing these treatments to larger cohorts while also performing a cost-benefit analysis for each treatment. In addition, more needs to be learned about the potential adverse side effects of these treatments, especially for pharmaceutical therapy.
PubMed: 38650802
DOI: 10.7759/cureus.56705 -
Brain and Behavior Aug 2023Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. (Review)
Review
Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.
INTRODUCTION
Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions.
OBJECTIVES
The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism.
METHODS
A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review.
RESULTS
Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology.
CONCLUSION
Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.
Topics: Humans; Parkinsonian Disorders; Brain Neoplasms; Dopamine; Astrocytoma; Paraneoplastic Syndromes; Meningeal Neoplasms; Cysts
PubMed: 37433071
DOI: 10.1002/brb3.3151 -
Frontiers in Neurology 2023Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review...
Gender discrepancies and differences in motor and non-motor symptoms, cognition, and psychological outcomes in the treatment of Parkinson's disease with subthalamic deep brain stimulation.
Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review data on gender discrepancies and gender differences in clinical outcomes in PD patients treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). Included were original studies that specifically examined gender discrepancies or gender differences in PD patients with STN-DBS. Men receive more DBS than women, for various indications. The decision-making process for DBS in women compared to men is more influenced by personal preferences and external factors. Motor symptoms improve in both genders, but bradykinesia improves more in men. The postoperative reduction of the levodopa equivalent daily dose seems to be more pronounced in men. Men show more cognitive deterioration and less improvement than women after STN-DBS. Women show more depressive symptoms before surgery, but they improve similarly to men. Men show more improvement in impulsivity and less decrease in impulsive behaviour symptoms than women. Anxiety and personality traits remain unchanged in both genders. Voice quality improves more in men and deteriorates less often than in women. Men gain fat-free mass and fat mass, but women only gain fat mass. Regarding sexual function the evidence is inconsistent. More urinary symptoms improve in women than in men. Pain and restless leg syndrome seems to improve more in men. Regarding quality of life, the evidence seems to be inconsistent, and activities of daily living seems to improve in both genders. Better prospective controlled studies, focusing directly on gender differences in PD patients treated with STN-DBS, are needed to better explain gender differences in STN-DBS for PD.
PubMed: 38259647
DOI: 10.3389/fneur.2023.1257781