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Cureus Jan 2024Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that... (Review)
Review
Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that drastically affect the patient's quality of life (QoL). Although there is no cure for PD, its symptoms can be significantly improved and even resolved through different treatments. Mainstay treatments for PD include levodopa combined with carbidopa, dopamine agonists, and even deep brain stimulation (DBS) of the subthalamic nucleus. New treatment methods have emerged, such as botulinum toxin (BoNT), which further improve symptoms and, thus, the QoL of patients with PD. Botulinum toxin is a potent neurotoxin produced by that typically causes descending paralysis by suppressing acetylcholine secretion. Serotypes used to treat various disorders include serotype A (BoNT-A) and serotype B (BoNT-B). This paper aims to evaluate the outcomes of BoNT injection on different symptoms associated with PD. An extensive review using PubMed, ScienceDirect, and ProQuest articles concerning 'botulinum toxin and Parkinson's disease' was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in 23,803 articles. After applying strict inclusion and exclusion criteria, the total number of articles was finally 41. The results showed that movement disorders were a common occurrence in PD, consisting of tremors, dystonia, and freezing of gait (FOG), with tremors being the most common symptom. Tremors and dystonia were significantly improved following BoNT-A, correlating with significant improvements in various scales subjectively and objectively evaluating the symptoms and QoL. In contrast, FOG was not significantly improved by either BoNT-A or BoNT-B. Pain is associated with movement disorders such as PD and was the primary indication for the administration of BoNT; studies found pain and QoL were significantly improved following BoNT injection. Quality of life can also be affected by sialorrhea and overactive bladder, which often occur as the disease progresses. Injections of BoNT-A and BoNT-B were shown to significantly improve saliva production, flow rate, drooling frequency, voiding frequency, and urinary urge incontinence. Across all studies analyzed, it is evident that BoNT may have a significant effect on improving the QoL of patients suffering from PD. While research continues to find a cure or stop the progression of PD, it remains critical to continue focusing on improving patients' QoL. Future research should evaluate whether BoNT can be used to successfully treat other symptoms of PD, such as epiphora or constipation.
PubMed: 38435899
DOI: 10.7759/cureus.53309 -
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 -
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 -
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 -
Movement Disorders : Official Journal... Jan 2024Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known.
OBJECTIVE
We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD.
METHODS
We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD.
RESULTS
The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning.
CONCLUSION
Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Female; Parkinson Disease; Cross-Sectional Studies; Cognition Disorders; Cognitive Dysfunction; Cognition
PubMed: 38173220
DOI: 10.1002/mds.29649 -
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 -
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 -
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 -
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 -
Movement Disorders Clinical Practice Oct 2023In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy.... (Review)
Review
BACKGROUND
In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy. However, studies evaluating differences in trait impulsivity between patients with PD and healthy controls or between patients with PD with and without ICDs reported partly inconsistent findings.
OBJECTIVES
We conducted a systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) of studies comparing Barratt Impulsiveness Scale (BIS-11) scores between patients with PD and healthy controls and between patients with PD with and without ICDs.
METHODS
Eligible studies were identified through a systematic search in 3 databases. Mean differences with 95% confidence intervals (CIs) for BIS-11 total and subscale scores were separately calculated for studies comparing patients with PD and healthy controls and patients with PD with and without ICDs. Meta-regressions were performed to explore sources of heterogeneity (percentage of men, age, disease duration, and levodopa equivalent daily dose).
RESULTS
A total of 40 studies were included in the quantitative analyses. BIS-11 total scores were significantly higher in patients with PD compared with healthy controls (mean difference 2.43; 95% CI, 1.03, 3.83), and in patients with PD with active ICDs compared with patients without ICDs (6.62; 95% CI, 5.01, 8.23). No significant moderators emerged by meta-regression analyses.
CONCLUSIONS
The present meta-analysis supports that impulsivity, as a personality trait, may characterize patients with PD, even in the absence of ICDs. Moreover, these data corroborate findings of clinical studies reporting higher levels of trait impulsivity in PD patients with ICDs compared with patients without ICDs.
PubMed: 37868926
DOI: 10.1002/mdc3.13839