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Toxins May 2024Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's... (Review)
Review
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
Topics: Humans; Parkinson Disease; Botulinum Toxins; Neuromuscular Agents; Spinal Curvatures; Posture
PubMed: 38787080
DOI: 10.3390/toxins16050228 -
European Journal of Investigation in... May 2024Parkinson's disease (PD) is a neurological disorder caused by the loss of dopamine-producing cells in the substantia nigra and characterized by motor and non-motor... (Review)
Review
Parkinson's disease (PD) is a neurological disorder caused by the loss of dopamine-producing cells in the substantia nigra and characterized by motor and non-motor symptoms. Boxing is a type of complementary therapy to improve symptoms in PD. The purpose of the present study was to examine the effect of boxing training on the functionality and quality of life of patients with PD. The literature search was performed on PubMed, Scopus, PEDro, Cochrane Library, and Google Scholar search engines. The PEDro scale was used to assess the methodological quality of the studies. This systematic review included three studies that examined disease severity, mobility, physical activity, balance, and quality of life. According to the PEDro scale criteria, the three articles included were of high methodological quality. Statistically significant improvements after the implementation of boxing training was shown for balance and quality of life in contrast to the other variables. Boxing training intervention programs had a positive effect on balance and quality of life in patients with PD; however, the results are conflicting regarding certain functionality variables. Therefore, it is necessary to conduct further research to examine the effectiveness of boxing training on the functionality and quality of life of patients with Parkinson's disease.
PubMed: 38785583
DOI: 10.3390/ejihpe14050085 -
Current Issues in Molecular Biology Apr 2024Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in... (Review)
Review
Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.
PubMed: 38785512
DOI: 10.3390/cimb46050244 -
Clinical Neurology and Neurosurgery Jul 2024Parkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found throughout the central nervous system. There is growing interest in investigating the potential diagnostic and therapeutic utility of OXA in PD. To date, studies have reported a wide range of OXA concentrations in patients with PD. In this review, we discuss the current understanding of the dysregulation of OXA in PD and analyze its levels in the CSF.
METHODS
We searched six databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, and EBSCOHost) and preprint servers using a predetermined search strategy through 4th March 4, 2023. The search keywords included "Parkinson's disease", "Orexin-A", "Hypocretin-1", "cerebrospinal fluid", and "CSF". Studies that reported OXA/Hypocretin-1 levels in the CSF of patients with PD were included. Two researchers independently reviewed the records and extracted data.
FINDINGS
Eighteen studies involving 244 patients were analyzed. CSF Orexin-A concentrations were lower in patients with Parkinson's disease than in controls, with a mean difference of -59.21 (95 % CI: -89.10 to -29.32). The mean OXA levels were 281.52 (95 % CI: 226.65-336.40).
CONCLUSION
Our analysis reveals lower concentrations of orexin-A in the cerebrospinal fluid of Parkinson's disease patients compared to controls, but within the normal range. These findings suggest a potential, but not significant, disruption in the orexinergic system associated with the disease.
Topics: Orexins; Humans; Parkinson Disease
PubMed: 38781804
DOI: 10.1016/j.clineuro.2024.108320 -
Epilepsy & Behavior Reports 2024Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the... (Review)
Review
Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the effectiveness of exercise in improving sleep in epilepsy is less clear. The purpose of this report is to identify the published literature regarding exercise interventions in people with epilepsy to determine 1) what proportion of published clinical trials assess sleep as an outcome, and 2) what benefits of exercise interventions on sleep have been observed. We searched the PubMed, PsycINFO, and SCOPUS electronic databases using the search terms "epilepsy AND [exercise OR physical activity]" and identified 23 articles reporting on 18 unique clinical trials. Nine studies were conducted in adults, five in children, and four in adults and children with active seizures, controlled seizures, or both. Exercise modalities included aerobic exercise, strength training, walking, and yoga, among others, and some also included educational and motivational components. Exercise effects on sleep were tested in four studies, two of which only included indirect measures of sleep- and rest-related fatigue, with mixed results. Of the two reports assessing sleep directly, one reported marginal non-significant improvements in subjective sleep quality and no improvements in objective sleep quality in children after twelve weeks of walking, and the other reported no benefits in subjective sleep quality after twelve weeks of combined aerobic, strength, and flexibility training in adults. Given the health benefits of sleep and detrimental effects of sleep deprivation in epilepsy, epilepsy researchers need to assess the effects of exercise interventions on sleep.
PubMed: 38779424
DOI: 10.1016/j.ebr.2024.100675 -
BMJ Mental Health May 2024Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the...
BACKGROUND
Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the literature on HS in patients with neurological disorders. We conducted a systematic review to identify studies that reported HS in neurological disorders. HS was defined as a condition characterized by excessive and persistent preoccupation with sexual thoughts, urges, and behaviors that cause significant distress or impairment in personal, social, or occupational functioning. Data on demographics, assessment techniques, associated elements, phenotypic manifestations, and management strategies were also extracted. The final analysis included 79 studies on HS, encompassing 32 662 patients across 81 cohorts with neurological disorders. Parkinson's disease was the most frequently studied condition (55.6%), followed by various types of dementia (12.7%). Questionnaires were the most common assessment approach for evaluating HS, although the techniques varied substantially. Alterations in the dopaminergic pathways have emerged as contributing mechanisms based on the effects of medication cessation. However, standardized treatment protocols still need to be improved, with significant heterogeneity in documented approaches. Critical deficiencies include risks of selection bias in participant sampling, uncontrolled residual confounding factors, and lack of blinded evaluations of reported outcomes. Despite growth in the last decade, research on HS remains limited across neurological conditions, with lingering quality and methodological standardization deficits. Key priorities include advancing assessment tools, elucidating the underlying neurobiology, and formulating management guidelines.
PROSPERO REGISTRATION NUMBER
CRD42017036478.
Topics: Humans; Nervous System Diseases; Sexual Dysfunctions, Psychological; Male; Female; Parkinson Disease; Sexual Behavior
PubMed: 38777563
DOI: 10.1136/bmjment-2024-300998 -
Clinical Neuropharmacology May 2024Alpha-synucleinopathies are incurable neurodegenerative diseases. Abelson tyrosine kinase inhibitors (Abl TKIs) may be disease-modifying therapies. This systematic...
BACKGROUND
Alpha-synucleinopathies are incurable neurodegenerative diseases. Abelson tyrosine kinase inhibitors (Abl TKIs) may be disease-modifying therapies. This systematic review, meta-analysis, and meta-regression evaluated the use of Abl TKIs in their treatment.
METHODS
We searched PubMed, Embase, and Cochrane databases for trials using Abl TKIs in patients with Parkinson's disease and Lewy body dementia published until July 2023. The outcome was the change in the MDS-UPDRS-III (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale III). DerSimonian-Laird random-effects model was used to calculate the pooled effect estimates. Leave-one-out forest plots were used for the sensitivity analysis, and meta-regression (restricted maximum likelihood) was performed.
RESULTS
Five studies (197 patients) were included. Nilotinib 300 mg had an effect size of -1.154 (95% confidence interval [CI], -3.000 to 0.692). Nilotinib 150 mg and bosutinib 100 mg versus placebo yielded 0.82 (95% CI, -3.76 to 5.41). Sensitivity analysis showed that 1 trial changed the significance of the nilotinib 300 mg single-arm analysis (MD = -1.723; 95% CI, -2.178 to -1.268). Meta-regression revealed that lower age (EC = -0.9103, SE = 0.2286, P < 0.0001) and higher baseline MDS-UPDRS-III scores (EC = 0.1210, SE = 0.0168, P < 0.0001) could explain the inefficacy of nilotinib 300 mg.
CONCLUSIONS
Nilotinib (300 mg) proved effective postsensitivity analysis, unlike lower doses and bosutinib in Parkinson's disease/Lewy body dementia. Abl TKIs showed reduced efficacy in younger, more impaired patients, indicating the need for further testing with higher-potency drugs in patients who have diseases that are in the early stage but with a later onset.
PubMed: 38776533
DOI: 10.1097/WNF.0000000000000597 -
BMC Geriatrics May 2024Dysphagia affects about 40% of patients admitted to acute geriatric wards, as it is closely associated with diseases that rise in prevalence with advancing age, such as...
BACKGROUND
Dysphagia affects about 40% of patients admitted to acute geriatric wards, as it is closely associated with diseases that rise in prevalence with advancing age, such as stroke, Parkinson's disease, and dementia. Malnutrition is a highly associated predictive factor of dysphagia as well as one of the most common symptoms caused by dysphagia. Thus, the two conditions may exist simultaneously but also influence each other negatively and quickly cause functional decline especially in older adults. The purpose of this review was to determine whether institutions have established a protocol combining screenings for dysphagia and malnutrition on a global scale. If combined screening protocols have been implemented, the respective derived measures will be reported.
METHODS
A scoping review was conducted. A systematic database search was carried out in January and February 2024. Studies were included that examined adult hospitalized patients who were systematically screened for dysphagia and malnutrition. The results were managed through the review software tool Covidence. The screening of titles and abstracts was handled independently by two reviewers; conflicts were discussed and resolved by consensus between three authors. This procedure was retained for full-text analysis and extraction. The extraction template was piloted and revised following feedback prior to extraction, which was carried out in February 2024.
RESULTS
A total of 2014 studies were found, 1075 of which were included for abstract screening, 80 for full text screening. In the end, 27 studies were extracted and reported following the reporting guideline PRISMA with the extension for Scoping Reviews.
CONCLUSION
Most of the studies considered the prevalence and association of dysphagia and malnutrition with varying outcomes such as nutritional status, pneumonia, oral nutrition, and swallowing function. Only two studies had implemented multi-professional nutrition teams.
Topics: Aged; Humans; Deglutition Disorders; Geriatric Assessment; Hospitalization; Malnutrition; Mass Screening
PubMed: 38773449
DOI: 10.1186/s12877-024-05070-6 -
Journal of Neurology May 2024Gaucher disease (GD) is classically divided into three types, based on the presence or absence of neurological signs and symptoms. However, presentation can be highly... (Review)
Review
INTRODUCTION
Gaucher disease (GD) is classically divided into three types, based on the presence or absence of neurological signs and symptoms. However, presentation can be highly variable in adulthood, and this aspect has not been adequately addressed in the literature so far. We performed a systematic literature review to analyze the entire spectrum of neurological manifestations in adult patients previously classified as GD type I, II, or III, evaluating the role of variants in different neurological manifestations.
METHODS
We searched databases for studies reporting clinical data of adult GD patients (age ≥ 18). Data extraction included GD types, GBA1 variants, age at disease onset and diagnosis, duration of GD, and age at onset and type of neurological symptoms reported.
RESULTS
Among 4190 GD patients from 85 studies, 555 exhibited neurological symptoms in adulthood. The median age at evaluation was 46.8 years (IQR 26.5), age at neurological symptoms onset was 44 years (IQR 35.1), and age at GD clinical onset was 23 years (IQR 23.4). Parkinsonism, including Parkinson's disease and Lewy Body dementia, was the most reported neurological manifestation. Other symptoms and signs encompassed oculomotor abnormalities, peripheral neuropathy, seizures, myoclonus, and cerebellar, cognitive and psychiatric symptoms. The genotype N370S/N370S mostly presented with Parkinsonism and the L444P variant with severe and earlier neurological symptoms.
CONCLUSION
The findings of this systematic review highlight: (1) the relevance of a comprehensive neurological assessment in GD patients, and (2) the importance of considering possible undiagnosed GD in adult patients with mild systemic symptoms presenting unexplained neurological symptoms.
PubMed: 38771384
DOI: 10.1007/s00415-024-12439-5 -
JMIR Medical Informatics May 2024With the increasing availability of data, computing resources, and easier-to-use software libraries, machine learning (ML) is increasingly used in disease detection and... (Review)
Review
BACKGROUND
With the increasing availability of data, computing resources, and easier-to-use software libraries, machine learning (ML) is increasingly used in disease detection and prediction, including for Parkinson disease (PD). Despite the large number of studies published every year, very few ML systems have been adopted for real-world use. In particular, a lack of external validity may result in poor performance of these systems in clinical practice. Additional methodological issues in ML design and reporting can also hinder clinical adoption, even for applications that would benefit from such data-driven systems.
OBJECTIVE
To sample the current ML practices in PD applications, we conducted a systematic review of studies published in 2020 and 2021 that used ML models to diagnose PD or track PD progression.
METHODS
We conducted a systematic literature review in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in PubMed between January 2020 and April 2021, using the following exact string: "Parkinson's" AND ("ML" OR "prediction" OR "classification" OR "detection" or "artificial intelligence" OR "AI"). The search resulted in 1085 publications. After a search query and review, we found 113 publications that used ML for the classification or regression-based prediction of PD or PD-related symptoms.
RESULTS
Only 65.5% (74/113) of studies used a holdout test set to avoid potentially inflated accuracies, and approximately half (25/46, 54%) of the studies without a holdout test set did not state this as a potential concern. Surprisingly, 38.9% (44/113) of studies did not report on how or if models were tuned, and an additional 27.4% (31/113) used ad hoc model tuning, which is generally frowned upon in ML model optimization. Only 15% (17/113) of studies performed direct comparisons of results with other models, severely limiting the interpretation of results.
CONCLUSIONS
This review highlights the notable limitations of current ML systems and techniques that may contribute to a gap between reported performance in research and the real-life applicability of ML models aiming to detect and predict diseases such as PD.
PubMed: 38771237
DOI: 10.2196/50117