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Formation of toxic α-synuclein oligomers appears to be a key underlying pathological mechanism of synucleinopathies such as Parkinson's disease or multiple system atrophy (MSA). Given that Epigallocatechin-gallate has been shown to inhibit α-synuclein aggregation, it might represent a causal treatment option. Therefore, we set out to evaluate the safety, tolerability and a potential disease-modifying effect of Epigallocatechin-gallate in patients with MSA after 48 weeks of treatment. Power calculation was performed on existing natural history data on the progression of the Unified MSA Rating Scale as primary readout parameter. To assess the efficacy of Epigallocatechin-gallate versus placebo regarding the reduction of disease progression measured during the study period (80 % power, 5 % p level, 50 % effect size) 36 patients per group are needed. Considering a drop-out rate of 20 % a total of 86 patients will be recruited in this multicentre study. These data provide a solid rationale to investigate whether supplementation of Epigallocatechin-gallate can delay the progression of the MSA-related disability.

Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder characterized by both motor and non-motor symptoms resulting from the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and noradrenergic neurons in the locus coeruleus (LC). The current diagnosis of PD primarily relies on motor symptoms, often leading to diagnoses in advanced stages, where a significant portion of SNpc dopamine neurons has already succumbed. Therefore, the identification of imaging biomarkers for early-stage PD diagnosis and disease progression monitoring is imperative. Recent studies propose that neuromelanin-sensitive magnetic resonance imaging (NM-MRI) holds promise as an imaging biomarker. In this review, we summarize the latest findings concerning NM-MRI characteristics at various stages in patients with PD and those with atypical parkinsonism. In conclusion, alterations in neuromelanin within the LC are associated with non-motor symptoms and prove to be a reliable imaging biomarker in the prodromal phase of PD. Furthermore, NM-MRI demonstrates efficacy in differentiating progressive supranuclear palsy (PSP) from PD and multiple system atrophy with predominant parkinsonism. The spatial patterns of changes in the SNpc can be indicative of PD progression and aid in distinguishing between PSP and synucleinopathies. We recommend that patients with PD and individuals at risk for PD undergo regular NM-MRI examinations. This technology holds the potential for widespread use in PD diagnosis., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

F. Geser, J. A. Malunda, H. I. Hurtig, J. E. Duda, G. K. Wenning, S. Gilman, P. A. Low, V. M.?Y. Lee and J. Q. Trojanowski (2011) Neuropathology and Applied Neurobiology 358-365 ? The ??synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43?kDa transactive response DNA?binding protein (TDP?43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico?pathological features. Consequently, we examined MSA for evidence of TDP?43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. TDP?43 pathology was generally rare, and there were no FUS lesions. The TDP?43 lesions were located predominantly in medio?temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP?43 or FUS pathology, but rather from widespread white matter ??synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary ??synuclein?mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP?43. [ABSTRACT FROM AUTHOR]

We investigated the potency of riluzole, an anti-glutamatergic drug, to affect ongoing neuronal death process following combined MPTP?+?3-nitropropionic acid (3-NP) intoxication producing combined striatal and nigral degeneration (SND) in mice. We used a “neuronal rescue” strategy by administering riluzole after the end of intoxication. The motor disorder, its recovery, behavioral performances at motor and sensorimotor integration tasks and histopathological outcome were compared in the saline and riluzole groups (10?mg/kg and 20?mg/kg), matched by triplets for motor severity. While riluzole did not produce any effect on the gross motor disorder nor on rotarod task, open-field kinetic variables or on the traversing beam task, it had a subtle effect on the performances at the pole test. The histopathological outcome was significantly better in the riluzole-treated mice regarding both nigral and dorsolateral striatal cell loss and astroglial activation, with a dose-effect relationship. Thus, riluzole has limited “neuronal rescue” properties from an histopathological point of view with a subtle motor behavior improvement in a MPTP?+?3-NP-induced SND in mice. [ABSTRACT FROM AUTHOR]

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False-positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis. © 2003 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Iron deposition has been observed in Parkinsonism and is emerging as a diagnostic marker for movement disorders. Brain functional network disruption has also been detected in parkinsonism, and is believed to be accountable for specific symptoms in parkinsonism. However, how iron deposition influences brain network remains to be elucidated. Methods: We recruited 16 Parkinson's disease (PD), 8 multiple system atrophy (MSA) and 7 progressive supranuclear palsy (PSP) patients. T1-weighted, susceptibility weighted images and resting-state functional MRI (rs-fMRI) were acquired. Quantitative susceptibility mapping (QSM) analysis was performed to quantify iron deposition in substantia nigra, putamen and dentate nucleus. Cerebellar network, sensorimotor network, default mode network and language networks were segregated using independent analysis. Network and iron deposition status were evaluated in relation to diagnostic groups, motor and non-motor symptoms. The relationship between quantitative iron deposition and brain network status was further interrogated. To further validate the findings, 13 healthy controls and 37 PD patients who had available T1 and rs-fMRI scans were selected from Parkinson's progression markers initiative (PPMI) database, and network analysis was performed. Results: In local cohort, compared to PD, MSA patients showed greater iron deposition in putamen, while PSP patients had greater iron deposition in caudate nucleus and thalamus. Cerebellar and language networks showed significant difference across diagnostic groups, while default mode network and sensorimotor network did not. MSA patients had significantly impaired cerebellar network and language networks compared to PD patients. Cerebellar network was positively associated with motor symptom scores while language network was positively associated with MoCA scores in the patients. Iron deposition was negatively associated with both networks' activity in the patients. In PPMI cohort, impairment was found in both cerebellar and language networks in PD. Cerebellar and language networks correlated with motor and cognitive impairment, respectively. Conclusion: Cerebellar network and language networks are differently influenced in MSA, PD and PSP, which can serve as potential diagnostic marker. Impairment of cerebellar network and language network are associated with motor symptoms and cognitive impairment, respectively. Moreover, dysfunction of the networks is associated with iron deposition in deep nuclei (SN, DN, Putamen). [ABSTRACT FROM AUTHOR]

Objectives: COVID-19 lockdowns were introduced to control the pandemic, however, they resulted in a global disruption of daily life and of individual and global health. Reduced accessibility of health services, unavailability of food and drugs, and mental health challenges had a huge impact on older people and on people living with disabling conditions such as Parkinson's disease (PD). We assessed whether and to what extent the more disabled and vulnerable people with Parkinson's (PwP) were affected by lockdowns. Method: We analysed responses collected through a web-based survey of PwP according to their self-sufficiency [self-sufficient (SS); nearly self-sufficient (nSS); non-self-sufficient, cared for by family (NSS/F); non-self-sufficient, needs professional care (NSS/PC)]. Results: Fears due to COVID-19 and difficulties with food supply were highest in NSS/F PwP. Difficulties with the supply of Parkinson's medication or other drugs were apparently not an issue, while problems accessing primary care physicians and neurologists were similar across all patient groups. On the contrary, difficulties with daily and motor activities were higher in NSS/F and NSS/PC PwP. PwP symptoms worsened in all groups, with NSS/F and NSS/PC participants experiencing the worst deterioration. Notably, the deterioration of PwP symptoms was specifically related to changes in daily and motor activities, with participants who reported less engagement in daily and motor activities experiencing the worst deterioration. Conclusion: Findings strongly support the need for decision-makers and healthcare providers to carefully re-evaluate the risk–benefit ratio of limiting healthcare accessibility for PwP, since evidence shows that lockdown measures primarily impact the groups who are most fragile and vulnerable. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association of four bone metabolism biomarkers (osteoprotegerin, osteopontin, sclerostin, and osteocalcin) with cardiovascular events in people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized clinical trial evaluating the cardiovascular (CV) safety and efficacy of once-weekly exenatide for patients with T2D. Candidate biomarker data were selected from proteomic profiling performed at baseline and 12 months after randomization samples by SomaScan assay in 5,473 trial participants. The primary composite outcome was the first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (major cardiovascular events [MACE]). Cox proportional hazards models controlling for confounders were used for time-to-event analyses to calculate hazard ratios (HRs) with 95% CI for a 1 SD increase in the biomarker concentrations. RESULTS: The primary outcome occurred in 813 participants (14.9%). Higher levels of osteoprotegerin (HR 1.11; 95% CI 1.03-1.20; P = 0.0047) and osteopontin (HR 1.10; 95% CI 1.02-1.18; P = 0.0095) were associated with an increased risk of MACE. The addition of osteoprotegerin and osteopontin to a clinical predictive model containing traditional CV risk factors provided minimal incremental value for MACE prediction (C-index 0.629 vs. 0.638; likelihood ratio test P < 0.001). Osteocalcin and sclerostin were not associated with MACE. Osteocalcin had a nonlinear association with all-cause death and with CV death. CONCLUSIONS: Higher levels of osteoprotegerin and osteopontin are associated with an increased risk of CV events in people with T2D, supporting the hypothesis that pathways involved in bone metabolism play a role in CV disease. [ABSTRACT FROM AUTHOR]

Background: Multiple system atrophy-cerebellar subtype (MSA-C) is a predominance of cerebellar ataxia and autonomic failure. MSA-C has a rapid progression, with average 9 years from symptom onset to death. Despite its prevalence, there is still a lack of effective treatments. In recent years, it has been established that taVNS has significant therapeutic effects on epilepsy, depression, migraine, insomnia, and other diseases. Hence, we performed taVNS treatment for one MSA-C patient to explore whether taVNS could alleviate patient's motor and non-motor symptoms. Case presentation: A 65-year-old woman diagnosed with MSA-C received taVNS treatment for the following duration and course: once a day, 40 min a time, 20 times a month continually for 12 months. Meanwhile, she received assessments of motor and non-motor symptoms at baseline, 4-weeks and 12-months after taVNS treatment. Motor symptoms assessments was made by Scale for the Assessment and Rating of Ataxia (SARA) and Unified Multiple System Atrophy Rating Scale (UMSARS), non-motor symptoms assessment by Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). After 4-weeks and 12-months of taVNS treatment, compared to baseline assessments, SARA scores decreased from 13 to 11 and then to 10.5, UMSARS scores from 28 to 24 and then to 23, PSQI scores from 19 to 13 and then to 6, HAMA scores from 13 to 3 and then remained unchanged, and HAMD scores from 7 to 4 and then remained unchanged. Conclusion: In the case, we found that short-term taVNS treatment can alleviate ataxia, sleep problem, anxiety and depression of the MSA-C patient. The effects can be maintained and some symptoms may be further improved after receiving long-term treatment. Our case report supports the feasibility and effectiveness of taVNS treatment in MSA-C patients. [ABSTRACT FROM AUTHOR]

Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology. hiPSCs derived from accessible patient somatic cells can produce various neural cell types and tissues; current efforts to increase the complexity of these models, incorporating region-specific neural tissues and non-neural cell types of the brain microenvironment, are providing increasingly relevant insights into human-specific neurobiology. Continued advances in tissue engineering combined with innovations in genomics, high-throughput screening and imaging strengthen the physiological relevance of hiPSC models and thus their ability to uncover disease mechanisms, therapeutic vulnerabilities, and tissue and fluid-based biomarkers that will have real impact on neurological disease treatment. True physiological understanding, however, necessitates integration of hiPSC-neural models with patient biophysical data, including quantitative neuroimaging representations. We discuss recent innovations in cellular neuroscience that can provide these direct connections through generative AI modeling. Our focus is to highlight the great potential of synergy between these emerging innovations to pave the way for personalized medicine becoming a viable option for patients suffering from neuropathologies, particularly rare epileptic and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). This phenomenon often precedes the onset of other clinical symptoms, suggesting its potential utility as an early marker or prodromal symptom of neurodegenerative diseases. This review provides a vast literature overview on the current knowledge of OD in PD, AD, ALS, and HD in order to evaluate its potential as a biomarker, particularly in the early and prodromal stages of these diseases. We summarize the most common methods used to measure olfactory function and delve into neuropathological correlations and the alterations in neurotransmitter systems associated with OD in those neurodegenerative diseases, including differences in genetic variants if applicable, and cater to current pitfalls and shortcomings in the research. [ABSTRACT FROM AUTHOR]

The main characteristics of Parkinson's disease (PD) are the loss of dopaminergic (DA) neurons and abnormal aggregation of cytosolic proteins. However, the exact pathogenesis of PD remains unclear, with ferroptosis emerging as one of the key factors driven by iron accumulation and lipid peroxidation. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as supportive cells in the central nervous system (CNS), but their abnormal activation can lead to DA neuron death and ferroptosis. This paper explores the interactions between glial cells and DA neurons, reviews the changes in glial cells during the pathological process of PD, and reports on how glial cells regulate ferroptosis in PD through iron homeostasis and lipid peroxidation. This opens up a new pathway for basic research and therapeutic strategies in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objective: In developed countries, stroke is the fifth cause of death, with a high mortality rate, and with recovery to normal neurological function in one-third of survivors. Atherosclerotic occlusive disease of the extracranial part of the internal carotid artery and related embolic complications are common preventable causes of ischemic stroke (IS), attributable to 7–18% of all first-time cases. Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor (TNFR) superfamily, is considered a modulator of vascular calcification linked to vascular smooth muscle cell proliferation and collagen production in atherosclerotic plaques. Therefore, OPG emerges as a potential biomarker (BM) of calcified carotid plaques and carotid artery stenosis (CAS). Methods: We performed a literature search of PubMed on OPG in CAS and atherosclerosis published until 2024. Results: Increased levels of serum OPG were reported in both patients with symptomatic and asymptomatic CAS, and higher values were observed in those with unstable atherosclerotic plaques. Notably, increased OPG levels were observed regardless of the location of atherosclerosis, including coronary and other peripheral arteries. In addition, chronic kidney disease, the most significant confounder disturbing the association between vascular damage and circulating OPG levels, decreases the usefulness of OPG as a BM in CAS. Conclusions: Osteoprotegerin may be considered an emerging BM of global rather than cerebrovascular atherosclerosis. Its diagnostic significance in identifying patients with asymptomatic CAS and their monitoring is limited. [ABSTRACT FROM AUTHOR]

Purpose: To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. Methods: In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples. Results: All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach. Conclusion: This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings. [ABSTRACT FROM AUTHOR]

Background: Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. Schisandra chinensis has various pharmacologic effects such as antioxidant and anti-inflammatory activities. However, the neuroprotective value of seed oil of S. chinensis (SOSC) has not been elucidated yet. The purpose of this study was to determine neuroprotective effects of SOSC by supercritical fluid extraction against 3-nitropropionic acid (3-NPA)-induced HD-like symptoms and neuropathology in an experimental mouse model. Methods: SOSC (75, 150, and 300 mg/kg/day) was orally pre-administration once daily at 1 hour before 3-NPA intoxication. Results: SOSC ameliorated movement dysfunction and lethality following 3-NPA intoxication in connection with reduction of lesion area, neurodegeneration/apoptosis, microglial migration/activation, and mRNA expression of pro-inflammatory cytokines/enzymes in the striatum. SOSC inhibited the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways but stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the striatum after 3-NPA intoxication. Schizandrin, a main component of SOSC, reduced protein expression levels of Iba-1 and p-NF-κB in 3-NPA-induced BV2 cells (murine microglia cell line). BV2 cell's conditioned medium inhibited cleaved caspase-3 in 3-NPA-induced SH-SY5Y cells (a neuroblastoma cell line). Conclusion: SOSC might ameliorate movement dysfunction by inhibiting neuropathology through its anti-inflammatory and antioxidant activities in the striata of 3-NPA-intoxicated mice. These findings suggest that SOSC could serve as a promising therapeutic candidate for HD-like symptoms, providing a foundation for future treatment strategies targeting neuroinflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Individuals with Parkinson's disease (PD) exhibit a variety of impairments in nonmotor symptoms including emotional processing and cognitive control that have implications for speech production. The present study sought to investigate whether impairments in cognitive processing in individuals with PD impact emotional sentence production as indicated by changes in speech rate. Thirty-six individuals (20 individuals with PD, 16 healthy controls) completed subtests 8A and 8B of the Florida Emotional Expressive Battery (FEEB) to elicit speech samples in five different emotional tones (happy, sad, angry, fear, and neutral). Sentences contained either semantically emotional or neutral information, resulting in conditions of congruency (same semantics-tone) and incongruency (different semantics-tone). Speech rate was impacted by the emotional tone of all participants. Individuals with PD demonstrated faster speech rates under conditions of conflicting semantic information than healthy older adults. Changes in speech rate under emotional conditions were not influenced by global measures of cognition or depression. The results of this study indicate that individuals with PD struggle to manage irrelevant information present during emotional speech production. Speech rate is a simple, easy-to-measure metric that may reflect cognitive processing impairments in PD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Parkinson's disease (PD) is a neurodegenerative disorder, characterised by cardinal motor features and a multitude of non-motor manifestations. Among them, cognitive impairment in PD has been recognised as a defined clinical entity, and it might lead to an increased risk of developing dementia. Consequently, the present review aimed to ascertain the available interventions for the training of cognitive abilities in persons with PD (PwPD). Methods: PRISMA guidelines were followed to select studies in the following databases: PubMed, PsycINFO, and Web of Science. Two independent reviewers conducted the different phases of the review, and a third expert was called in to address any doubts/conflicts. Randomised controlled trials and randomised clinical trials concerning cognitive training with cognitive outcomes in PwPD were selected. Results: A total of 28 articles were included. The considered studies applied various experimental interventions for the training of cognitive functions in PwPD: computer-based platforms, exergames, paper-and-pencil programmes, dual-task or treadmill training with action observation therapy, motor imagery, and virtual reality components, interventions targeting precise cognitive domain, tele-rehabilitation, transcranial direct current stimulation, structured cognitive training, and multimodal treatments. Cognitive functions were assessed employing neuropsychological tests, self-report questionnaires, and computerised batteries. Conclusions: Overall, the review reported better performances in the experimental groups compared to the control groups, in several cognitive domains. Structured cognitive training emerged as the most effective strategy to enhance cognitive functioning in PwPD. However, further studies are necessary to determine the most appropriate and useful training and to develop interventions that also consider patients' quality of life. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease (PD) is a complex neurodegenerative disease with unclear pathogenesis. Some recent studies have shown that there is a close relationship between PD and ferroptosis. We aimed to identify the ferroptosis-related genes (FRGs) and construct competing endogenous RNA (ceRNA) networks to further assess the pathogenesis of PD. Methods: Expression of 97 substantia nigra (SN) samples were obtained and intersected with FRGs. Bioinformatics analysis, including the gene set enrichment analysis (GSEA), consensus cluster analysis, weight gene co-expression network analysis (WGCNA), and machine learning algorithms, were employed to assess the feasible differentially expressed genes (DEGs). Characteristic signature genes were used to create novel diagnostic models and construct competing endogenous RNA (ceRNA) regulatory network for PD, which were further verified by in vitro experiments and single-cell RNA sequencing (scRNA-seq). Results: A total of 453 DEGs were identified and 11 FRGs were selected. We sorted the entire PD cohort into two subtypes based on the FRGs and obtained 67 hub genes. According to the five machine algorithms, 4 features (S100A2, GNGT1, NEUROD4, FCN2) were screened and used to create a PD diagnostic model. Corresponding miRNAs and lncRNAs were predicted to construct a ceRNA network. The scRNA-seq and experimental results showed that the signature model had a certain diagnostic effect and lncRNA NEAT1 might regulate the progression of ferroptosis in PD via the NEAT1/miR-26b-5p/S100A2 axis. Conclusion: The diagnostic signatures based on the four FRGs had certain diagnostic and individual effects. NEAT1/miR-26b-5p/S100A2 axis is associated with ferroptosis in the pathogenesis of PD. Our findings provide new solutions for treating PD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide, necessitating accurate and timely diagnostic methods for effective disease management. This study proposes a novel approach for PD detection using deep features extracted from magnetic resonance imaging (MRI) scans, employing a pattern recognition neural network architecture based on DenseNet201. The developed model demonstrated exceptional performance, achieving validation and test accuracies of 99.4% and 99.2%, respectively, indicating its robustness and efficacy in distinguishing between patients with PD and healthy individuals. Furthermore, the model achieved a precision of 99.5%, recall of 99.3%, and an F1 score of 99.4%. For the test set, the accuracy was 99.2%, with precision at 99.3%, recall at 99.1%, and an F1 score of 99.2%. The rapid convergence of the model during training further underscores its efficiency in learning discriminative features from MRI images. These findings underscore the promising role of deep learning techniques, particularly convolutional neural networks (CNNs), in medical image analysis for disease diagnosis. The proposed approach holds significant potential for assisting clinicians in early PD diagnosis and personalized treatment planning, ultimately improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Background: Cueing interventions, which utilize external auditory, visual, or somatosensory stimuli, are increasingly used to improve motor performance in individuals with Parkinson's disease (PD). This review explores the effectiveness of cueing on gait, balance, and quality of life outcomes in PD. Methods: A scoping review of six studies was conducted, focusing on the impact of cueing interventions on gait parameters, balance stability, and functional outcomes in PD patients. Studies were evaluated for methodological quality using the PEDro scale, and risk of bias was assessed with RoB 2. Results: Cueing interventions consistently improved gait parameters, with five studies showing significant increases in step length. The results for walking speed were more varied, with some studies reporting statistically significant gains while others found non-significant or mixed outcomes. Balance improvements were noted in dynamic balance measures, though static balance effects were less consistent. Two studies observed long-term benefits at follow-up, particularly when interventions were structured and supervised. The quality of life improvements were limited, with only one study measuring this outcome and showing no significant changes. Conclusions: Cueing interventions demonstrate potential for enhancing gait and dynamic balance in PD, though effects on quality of life remain uncertain. Early and structured implementation of cueing, especially with auditory stimuli, may support functional gains in PD management. Further research is required to establish optimal cueing protocols and long-term benefits. [ABSTRACT FROM AUTHOR]

Background: Cell loss and mitochondrial dysfunction are key pathological features of idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). It remains unclear whether disease-specific changes in plasma circulating cell-free nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) occur in patients with PD and MSA. In this study, we investigated whether plasma cf-nDNA, cf-mtDNA levels, as well as cf-mtDNA integrity, are altered in patients with PD and MSA. Methods: TaqMan probe-based quantitative PCR was employed to measure plasma cf-nDNA levels, cf-mtDNA copy numbers, and cf-mtDNA deletion levels in 171 participants, including 76 normal controls (NC), 62 PD patients, and 33 MSA patients. A generalized linear model was constructed to analyze differences in circulating cell-free DNA (cfDNA) biomarkers across clinical groups, while a logistic regression model was applied to assess the predictive values of these biomarkers for developing PD or MSA. Spearman correlations were used to explore associations between the three cfDNA biomarkers, demographic data, and clinical scales. Results: No significant differences in plasma cf-nDNA levels, cf-mtDNA copy numbers, or cf-mtDNA deletion levels were observed among the PD, MSA, and NC groups (all P > 0.05). Additionally, these measures were not associated with the risk of developing PD or MSA. In PD patients, cf-nDNA levels were positively correlated with Hamilton Anxiety Rating Scale scores (Rho = 0.382, FDR adjusted P = 0.027). In MSA patients, cf-nDNA levels were positively correlated with International Cooperative Ataxia Rating Scale scores (Rho = 0.588, FDR adjusted P = 0.011) and negatively correlated with Montreal Cognitive Assessment scores (Rho = −0.484, FDR adjusted P = 0.044). Subgroup analysis showed that PD patients with constipation had significantly lower plasma cf-mtDNA copy numbers than those without constipation (P = 0.049). MSA patients with cognitive impairment had significantly higher cf-nDNA levels compared to those without (P = 0.008). Conclusion: Plasma cf-nDNA level, cf-mtDNA copy number, and cf-mtDNA deletion level have limited roles as diagnostic biomarkers for PD and MSA. However, their correlations with clinical symptoms support the hypothesis that cell loss and mitochondrial dysfunction are involved in PD and MSA development. [ABSTRACT FROM AUTHOR]

Central nervous system disorders impact over 1.5 billion individuals globally, with neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases being particularly prominent. These conditions, often associated with aging, present debilitating symptoms including memory loss and movement difficulties. The growing incidence of neurological disorders, alongside a scarcity of effective anti-amyloidogenic therapies, highlights an urgent need for innovative treatment methodologies. Nanoparticles (NPs), derived from medicinal plants and characterized by their favorable pharmacological properties and minimal side effects, offer a promising solution. Their inherent attributes allow for successful traversal of the blood–brain barrier (BBB), enabling targeted delivery to the brain and the modulation of specific molecular pathways involved in neurodegeneration. NPs are crucial in managing oxidative stress, apoptosis, and neuroinflammation in ND. This study reviews the efficacy of green-synthesized nanoparticles in conjunction with various medicinal plants for treating neurodegenerative diseases, advocating for further research to refine these formulations for enhanced clinical applicability and improved patient outcomes. [ABSTRACT FROM AUTHOR]

If the billions of oligodendrocytes (OLs) populating the central nervous system (CNS) of patients could express their feelings, they would undoubtedly tell gene therapists about their frustration with the other neural cell populations, neurons, microglia, or astrocytes, which have been the favorite targets of gene transfer experiments. This review questions why OLs have been left out of most gene therapy attempts. The first explanation is that the pathogenic role of OLs is still discussed in most CNS diseases. Another reason is that the so-called ubiquitous CAG, CBA, CBh, or CMV promoters—widely used in gene therapy studies—are unable or poorly able to activate the transcription of episomal transgene copies brought by adeno-associated virus (AAV) vectors in OLs. Accordingly, transgene expression in OLs has either not been found or not been evaluated in most gene therapy studies in rodents or non-human primates. The aims of the current review are to give OLs their rightful place among the neural cells that future gene therapy could target and to encourage researchers to test the effect of OL transduction in various CNS diseases. [ABSTRACT FROM AUTHOR]

Purpose: Restless Legs Syndrome (RLS) is a widespread condition that affects sleep leading to daytime sleepiness, depression, and reduced quality of life. This study aims to determine and describe how patients with RLS experience their everyday life, with a focus on facilitators and barriers related to Maslow's hierarchical theory of human needs. Method: Semi-structured interviews were analysed with qualitative content analysis resulting in facilitators and barriers affecting the fulfilment of the five human needs. Results: Addressing RLS symptoms through medications and a quiet sleep environment fulfils psychological needs. Control over RLS symptoms, engagement in activities, trust in treatments, and social support meet safety and security needs. Social inclusion, close relationships, and meaningful interactions fulfil a sense of belongingness and love needs despite RLS. Competence in managing RLS, effective self-care strategies, confident communication, and trust-building support esteem needs. Finally, comprehensive understanding through person-centred interventions and coping fulfils the self-actualization needs in managing RLS. Conclusion: Holistic and person-centred interventions, including facilitators for the fulfilment of physiological, psychological, and social needs could help healthcare professionals to provide holistic care. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD), the second most prevalent neurological illness, is treated with pharmacologic and nonpharmacologic techniques, including medicinal plants and their extracts. Purpose: We assessed the anti-neurodegenerative properties of aridanin against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD in mice. Materials and Methods: In the current investigation, the neuroprotective potential of aridanin in the MPTP-induced PD animal model via behavioral analysis, oxidative stress, pro-inflammatory cytokines, and histopathology was determined. Results: The results showed that mice treated with MPTP had mobility, motor issues, and behavioral dysfunctions. When mice were challenged with MPTP, they had low antioxidant levels. The levels of malondialdehyde (MDA) and pro-inflammatory cytokines were high in MPTP-treated mice. There are signs of PD based on these results. Behavioral effects were improved, antioxidant levels increased, and MDA and proinflammatory cytokines levels decreased in animals treated with aridanin. Conclusion: Thus, in combination, aridanin therapy guards against MPTP-induced neuronal loss, neuroinflammation, oxidative stress, and motor dysfunction in PD mice. [ABSTRACT FROM AUTHOR]

Purpose: Speakers with primary progressive apraxia of speech (PPAOS) have an insidious onset of motor speech planning/programming difficulties. As the disease progresses, the apraxia of speech (AOS) becomes more severe and a co-occurring dysarthria often emerges. Here, longitudinal data from speakers with phonetic- and prosodic-predominant PPAOS are used to characterize the progression of their motor speech impairment, including the development of dysarthria and mutism. Method: Data are presented from 52 speakers who had PPAOS at enrollment (i.e., progressive AOS in the absence of aphasia, cognitive, or other neurologic symptoms). Twenty-one had predominantly phonetic features, whereas 31 had primarily prosodic features. All participants underwent a comprehensive motor speech evaluation at their enrollment visit and each annual return visit, with a median of three visits per participant. Results: Almost 25% of the speakers with PPAOS presented with dysarthria at their enrollment visit (median disease duration of 3.65 years), whereas more than 70% of them had developed dysarthria by their last visit (median disease duration of 6.85 years). Neither the likelihood to develop dysarthria nor the disease duration at which it was detected differed significantly between the phonetic and prosodic groups. However, muteness emerged sooner for speakers with phonetic-predominant PPAOS; the median disease duration at which they became mute was 1.5 years shorter than for their prosodic counterparts. Conclusions: Clinically, these results facilitate more accurate prognostication of motor speech symptoms in speakers with PPAOS, allowing for timely introduction of alternative means of communication. The results also support the differentiation between progressive AOS and dysarthria as distinct motor speech disorders that often co-occur in these individuals. [ABSTRACT FROM AUTHOR]

Purpose: Orthostatic hypotension (OH) is a common manifestation of Parkinson's disease (PD). Factors including autonomic dysfunction from the disease, use of PD medications, comorbidities, and aging can contribute to an increased risk of OH, which can be detrimental to patients' quality of life. Maintaining a fine balance to prevent harm related to OH and retain the benefit medications used to treat PD is crucial. The current article reviews various considerations in selecting and adjusting pharmacotherapy for OH in patients with PD. Method: Current evidence and guidance on pharmacological strategies of OH in patients with PD were reviewed. Results: Current strategies include medication regimen review and adjustment of patient's medication regimen and single or combination pharmacotherapy (midodrine, droxidopa, fludrocortisone, pyridostigmine) used in addition to nonpharmacological strategies. Conclusion: A patient-specific approach is needed to address OH in PD. Larger studies on safety and management of OH in PD are recommended given paucity of studies. [Journal of Gerontological Nursing, 50(12), 5–10.] [ABSTRACT FROM AUTHOR]

Aim Diagnosing movement disorders can be challenging owing to their similar clinical presentations with other neurodegenerative and basal ganglia disorders, like idiopathic Parkinson's disease (IPD), essential tremors (ET), vascular parkinsonism, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Technetium-99m labeled tropane derivative (99mTc-TRODAT-1) imaging can help in diagnosing Parkinson's disease at an early stage to help early initiation of the treatment. The current study aimed to evaluate the role of 99mTc-TRODAT-1 imaging in differentiating IPD and Parkinson-plus syndromes (PPS). Material and Methods We have analyzed 38 patients, referred to our department for 99mTc-TRODAT imaging. These patients were thoroughly evaluated in the movement disorder clinic at our institute and had a possible/ probable diagnosis of IPD, Hoehn and Yahr (H&Y) stage I/II (n = 28) or PPS (PSP [ n = 06] and MSA [ n = 04]). Striatal uptake ratio (SUR) was calculated in all the patients and data was statistically analyzed. Results The mean age of IPD, PSP, and MSA groups was 56.5 ± 12.15, 65.2 ± 11.1, and 51.2 ± 3.9 years, respectively. On qualitative evaluation, all patients had reduced striatal uptake on 99mTc-TRODAT imaging, with 31/38 patients showed a greater reduction in putaminal uptake compared with the caudate nucleus. On semiquantitative evaluation, mean total SUR was 0.58 ± 0.27, 0.53 ± 0.31, and 0.91 ± 0.20 in IPD, PSP, and MSA groups, respectively. The total SUR was lowest in the PSP group followed by IPD, but MSA had relatively higher SUR, although the difference was not statistically significant. Among the IPD patient group, 25/28 patients (89.3%) experienced a greater reduction in SUR values in the striatum contralateral to the side, where motor symptoms first manifested at disease onset. Conclusion 99mTc-TRODAT is a potential imaging biomarker for the evaluation of presynaptic dopaminergic dysfunction in patients with movement disorders. In our study cohort, mean SUR values were lowest for the PSP group followed by IPD and MSA group, which was in concordance with previous studies. However, the difference between SUR values in these two groups was not statistically significant. The present study emphasizes that the capacity of 99mTc-TRODAT-1 imaging alone for diagnosing IPD from PPS is constrained, although it offers a precise approach for distinguishing patients with IPD from those with essential tremors, drug-induced, or psychogenic parkinsonism. Consequently, more specific imaging biomarkers are needed to effectively differentiate between patients with IPD and those with PPS. [ABSTRACT FROM AUTHOR]

Parkinsonism is a clinical syndrome characterized by akinesia/bradykinesia, muscle rigidity, resting tremor, and postural instability. Within the group of parkinsonisms is Parkinson's disease, also known as neurodegenerative parkinsonian syndrome. The group of atypical parkinsonisms was established due to the existence of sporadic parkinsonisms that do not share the exact etiology of Parkinson's disease. Additionally, parkinsonisms that arise from causes other than neurodegeneration have been classified as secondary parkinsonisms. With this in mind, given the diversity of etiologies that can trigger parkinsonism, it is crucial to understand the symptomatology and its relationship with the basal ganglia (including damage to the nigrostriatal pathway, neuroinflammation, and neuronal damage). Only then will it be possible to propose appropriate treatments for each variant of parkinsonism. [ABSTRACT FROM AUTHOR]

Creativity and the production of artwork can have an impact on the course and treatment of comorbid severe mental illness and neurodegeneration. We report on a 70-year-old male patient with highly original artistic behavior, who suffered from lifelong recurrent major depression and subsequently developed symptoms of progressive bulbar palsy (PBP). In the context of a systematic literature review, we detail the patient's personal and artistic biographies and portray artwork from his artistic portfolio together with his disease history, clinical examination, psychopathological and neuropsychological evaluations, blood and cerebrospinal fluid analyses, neuroimaging, neurophysiological testing, and psychotherapeutic treatment. The patient's 1–2-year history of primarily bulbar motor symptoms and signs aligned with electromyography, showing widespread signs of continuing denervation/chronic neurogenic changes. Slight impairments in semantic fluency, executive control, and visuoconstructive abilities were observed in neuropsychological testing, in conjunction with right-sided medial temporal lobe atrophy in an MRI. He was prescribed medication, including extended-release venlafaxine, trazodone, pramipexole, and zolpidem, and took his medication regularly, usually at high doses. For most of his life, the patient had attributed professional "success" and artistic output to, at times, excessive alcohol consumption. Later, however, his interest in creative work continued despite alcohol reduction and cessation. Psychotherapy grounded him in reality via goal-centered behaviors, making him realize that his physical and mental ailments rather hindered his creative output. In summary, creative behavior can be utilized in the treatment of patients with psychiatric conditions (affective or addictive disorders) and/or neurodegenerative diseases. In the reported case, specific psychopharmacology and psychotherapy that address goal-directed self-efficacy experiences of reality were critical to the patient's treatment. [ABSTRACT FROM AUTHOR]