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Disruptions in gait function are common after concussion in adolescents; however, the neuromotor control deficits driving these gait disruptions are not well known. Fifteen concussed (age mean [SD]): 17.4 [0.6], 13 females, days since injury: 26.3 [9.9]) and 17 uninjured (age: 18.0 [0.7], 10 females) adolescents completed 3 trials each of single-task gait and dual-task gait (DT). During DT, participants simultaneously walked while completing a serial subtraction task. Gait metrics and variability in instantaneous mean frequency in lower extremity muscles were captured by inertial sensors and surface electromyography, respectively. A 2-way analysis of covariance was used to compare gait metrics across groups and conditions. Functional principal components analysis was used to identify regions of variability in instantaneous mean frequency curves. Functional principal component scores were compared across groups using a Welch statistic. Both groups displayed worse performance on gait metrics during DT condition compared to single-task, with no differences between groups (P <.001). Concussed adolescents displayed significantly greater instantaneous mean frequency, indicated by functional principal component 1, in the tibialis anterior, biceps femoris, and semitendinosus (P <.05) during single-task and DT compared with uninjured adolescents. Our observations suggest that concussed adolescents display inefficient motor unit recruitment lasting longer than 2 weeks following injury, regardless of the addition of a secondary task. [ABSTRACT FROM AUTHOR]

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted the essential role of RNA splicing, a key mechanism of alternative RNA processing, in establishing connections between genetic variations and disease. Genetic loci influencing RNA splicing variations show considerable influence on complex traits, possibly surpassing those affecting total gene expression. Dysregulated RNA splicing has emerged as a major potential contributor to neurological and psychiatric disorders, likely due to the exceptionally high prevalence of alternatively spliced genes in the human brain. Nevertheless, establishing direct associations between genetically altered splicing and complex traits has remained an enduring challenge. We introduce Spliced-Transcriptome-Wide Associations (SpliTWAS) to integrate alternative splicing information with genome-wide association studies to pinpoint genes linked to traits through exon splicing events. We applied SpliTWAS to two schizophrenia (SCZ) RNA-sequencing datasets, BrainGVEX and CommonMind, revealing 137 and 88 trait-associated exons (in 84 and 67 genes), respectively. Enriched biological functions in the associated gene sets converged on neuronal function and development, immune cell activation, and cellular transport, which are highly relevant to SCZ. SpliTWAS variants impacted RNA-binding protein binding sites, revealing potential disruption of RNA-protein interactions affecting splicing. We extended the probabilistic fine-mapping method FOCUS to the exon level, identifying 36 genes and 48 exons as putatively causal for SCZ. We highlight VPS45 and APOPT1, where splicing of specific exons was associated with disease risk, eluding detection by conventional gene expression analysis. Collectively, this study supports the substantial role of alternative splicing in shaping the genetic basis of SCZ, providing a valuable approach for future investigations in this area.

INTRODUCTION: Protective associations of greenspace with Parkinsons disease (PD) have been observed in some studies. Visual exposure to greenspace seems to be important for some of the proposed pathways underlying these associations. However, most studies use overhead-view measures (e.g., satellite imagery, land-classification data) that do not capture street-view greenspace and cannot distinguish between specific greenspace types. We aimed to evaluate associations of street-view greenspace measures with hospitalizations with a PD diagnosis code (PD-involved hospitalization). METHODS: We created an open cohort of about 45.6 million Medicare fee-for-service beneficiaries aged 65 + years living in core based statistical areas (i.e. non-rural areas) in the contiguous US (2007-2016). We obtained 350 million Google Street View images across the US and applied deep learning algorithms to identify percentages of specific greenspace features in each image, including trees, grass, and other green features (i.e., plants, flowers, fields). We assessed yearly average street-view greenspace features for each ZIP code. A Cox-equivalent re-parameterized Poisson model adjusted for potential confounders (i.e. age, race/ethnicity, socioeconomic status) was used to evaluate associations with first PD-involved hospitalization. RESULTS: There were 506,899 first PD-involved hospitalizations over 254,917,192 person-years of follow-up. We found a hazard ratio (95% confidence interval) of 0.96 (0.95, 0.96) per interquartile range (IQR) increase for trees and a HR of 0.97 (0.96, 0.97) per IQR increase for other green features. In contrast, we found a HR of 1.06 (1.04, 1.07) per IQR increase for grass. Associations of trees were generally stronger for low-income (i.e. Medicaid eligible) individuals, Black individuals, and in areas with a lower median household income and a higher population density. CONCLUSION: Increasing exposure to trees and other green features may reduce PD-involved hospitalizations, while increasing exposure to grass may increase hospitalizations. The protective associations may be stronger for marginalized individuals and individuals living in densely populated areas.

CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4+ T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4+ T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4+ T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4+ T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4+ T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the Aberrant Cell Cycle Disease (ACCD) due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Spasticity is a common impairment within pediatric neuromusculoskeletal disorders. How spasticity contributes to gait deviations is important for treatment selection. Our aim was to evaluate the pathophysiological mechanisms underlying gait deviations seen in children with spasticity, using predictive simulations. A cluster analysis was performed to extract distinct gait patterns from experimental gait data of 17 children with spasticity to be used as comparative validation data. A forward dynamic simulation framework was employed to predict gait with either velocity- or force-based hyperreflexia. This framework entailed a generic musculoskeletal model controlled by reflexes and supraspinal drive, governed by a multiobjective cost function. Hyperreflexia values were optimized to enable the simulated gait to best match experimental gait patterns. Three experimental gait patterns were extracted: (1) increased knee flexion, (2) increased ankle plantar flexion, and (3) increased knee flexion and ankle plantar flexion when compared with typical gait. Overall, velocity-based hyperreflexia outperformed force-based hyperreflexia. The first gait pattern could mostly be explained by rectus femoris and hamstrings velocity-based hyperreflexia, the second by gastrocnemius velocity-based hyperreflexia, and the third by gastrocnemius, soleus, and hamstrings velocity-based hyperreflexia. This study shows how velocity-based hyperreflexia from specific muscles contributes to different spastic gait patterns, which may help in providing targeted treatment. [ABSTRACT FROM AUTHOR]

Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Emerging evidence indicates that neurological disorders play a significant role in the etiology of PCOS, highlighting the complex interplay between the central nervous system (CNS) and ovarian function. Yulinzhu, a traditional Chinese medicine (TCM) formulation, has been traditionally used to regulate menstrual cycles and improve fertility. This study aims to investigate the efficacy and mechanisms of Yulinzhu in treating PCOS induced by neurological disorders. METHODS: An extensive literature search was performed across electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI), covering publications up to 1 June 2024. The review included randomized controlled trials (RCTs) that compared Yulin Zhu with placebo, standard care, or other active treatments in patients with PCOS. Two reviewers independently carried out data extraction and quality assessment. Meta-analyses were conducted using both fixed and random-effects models, with heterogeneity evaluated using the I2 statistic. RESULTS: We screened 891 records and included 6 studi es in the meta-analysis. The meta-analysis revealed that Yulinzhu about effective rate [RR = 1.19, 95% CI (1.10, 1.29), p < 0.0001], pregnancy rate [RR = 2.80, 95% CI (1.65, 4.76), p < 0.0001] and ovulation rate [RR = 1.33, 95% CI (1.10, 1.62), p = 0.04]. Meta-analysis shows the results of follicle estrogen [WMD = 0.69, 95% CI (-0.39, 1.78), p = 0.21], luteinizing hormone [WMD = -2.27, 95% CI (-3.86, -0.67), p = 0.005], testosterone [WMD = -0.44, 95% CI (-0.64, -0.25), p < 0.0001], estradiol [WMD = 16.20, 95% CI (2.74, 29.67), p < 0.0001]. CONCLUSION: This study demonstrates that plant medicine compund Yulinzhu may effectively treats PCOS including hormonal regulation, anti-inflammatory actions, and neuroprotection. We expect further research with larger, well-designed clinical trials to substantiate our conclusions.

Background: Multiple Sclerosis (MS) is a debilitating neurological disease affecting the central nervous system and significantly impacting patients' quality of life. MS is known as an autoimmune disease affecting the white matter. The disease involves inflammation, demyelination, and neurodegeneration, causing irreversible disabilities. Current treatments for MS target the inflammatory phase, with limited effects on long-term disability. While neuronal damage significantly contributes to MS pathology, mechanisms of neurodegeneration are not well studied. Methods: This study evaluated neurodegenerative changes in the retina during disease progression, using data collected from an experimental MS model (Experimental Autoimmune Encephalomyelitis, EAE). Utilizing Hematoxylin and Eosin-stained retinal sections and assessment using Optical Coherence Tomography (OCT), the study investigated the neurodegenerative changes, such as loss of cells in the retinal ganglion cell layer (GCL) and retinal thinning in the retina of the EAE model and the control groups. Results: Our results showed a significant reduction in the number of cells in the GCL of the EAE retina at two different time points studied, suggesting loss of neurons compared to the control group. Thickness measurements showed a reduction in the total retina and inner retinal layer thicknesses in the EAE retina compared to the controls. Our results indicate evidence of neurodegenerative changes in the retina of the experimental model of MS. No significant differences were observed between the percent losses of cells between the two time points studied. The pattern of cell loss suggests that neurodegeneration occurs at an earlier stage of disease progression. Conclusions: Overall, the retina is an excellent model to investigate neurodegeneration in MS, and possibly, loss of cells in the GCL could be used as an early indicator of neurodegeneration in MS and to identify novel therapeutic agents to treat the disease. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive examination of recent developments in both neurofeedback and brain-computer interface (BCI) within the medical field and rehabilitation. By analyzing and comparing results obtained with various tools and techniques, we aim to offer a systematic understanding of BCI applications concerning different modalities of neurofeedback and input data utilized. Our primary objective is to address the existing gap in the area of meta-reviews, which provides a more comprehensive outlook on the field, allowing for the assessment of the current landscape and developments within the scope of BCI. Our main methodologies include meta-analysis, search queries employing relevant keywords, and a network-based approach. We are dedicated to delivering an unbiased evaluation of BCI studies, elucidating the primary vectors of research development in this field. Our review encompasses a diverse range of applications, incorporating the use of brain-computer interfaces for rehabilitation and the treatment of various diagnoses, including those related to affective spectrum disorders. By encompassing a wide variety of use cases, we aim to offer a more comprehensive perspective on the utilization of neurofeedback treatments across different contexts. The structured and organized presentation of information, complemented by accompanying visualizations and diagrams, renders this review a valuable resource for scientists and researchers engaged in the domains of biofeedback and brain-computer interfaces. [ABSTRACT FROM AUTHOR]

Psychiatric disorders exhibit a shared neuropathology, yet the diverse presentations among patients necessitate the identification of transdiagnostic subtypes to enhance diagnostic and treatment strategies. This study aims to unveil potential transdiagnostic subtypes based on personalized gray matter morphological abnormalities. A total of 496 patients with psychiatric disorders and 255 healthy controls (HCs) from three distinct datasets (one for discovery and two for validation) were enrolled. Individualized gray matter morphological abnormalities were determined using normative modeling to identify transdiagnostic subtypes. In the discovery dataset, two transdiagnostic subtypes with contrasting patterns of structural abnormalities compared to HCs were identified. Reproducibility and generalizability analyses demonstrated that these subtypes could be generalized to new patients and even to new disorders in the validation datasets. These subtypes were characterized by distinct disease epicenters. The gray matter abnormal pattern in subtype 1 was mainly linked to excitatory receptors, whereas subtype 2 showed a predominant association with inhibitory receptors. Furthermore, we observed that the gray matter abnormal pattern in subtype 2 was correlated with transcriptional profiles of inflammation-related genes, while subtype 1 did not show this association. Our findings reveal two robust transdiagnostic biotypes, offering novel insights into psychiatric nosology. • We identify two robust transdiagnostic subtypes based on individualized gray matter morphological abnormalities. • These subtypes exhibiting contrasting patterns of structural abnormalities relative to healthy controls. • The identified subtypes are validated using independent datasets and can be extended to unseen disorders. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non‐uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH‐responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo‐crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2‐mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair. [ABSTRACT FROM AUTHOR]

Epilepsy is referred to as a neurological disorder, which is detected via examination and manual comprehension of Electroencephalogram (EEG) signals. In deep learning schemes, various enhancements have emerged to efficiently address complex issues by end-to-end learning. The major objective of this research is to propose a new seizure detection approach from EEG signals using a deep learning-based classification technique. The pre-processing is the initial stage, where denoising is performed using a Short-Time Fourier Transform (STFT). Subsequently, the statistical features, time-domain features and spectral features are extracted from the pre-processed signal. Finally, an efficient optimization approach, named Adadelta-Chameleon Swarm Algorithm (Adadelta-CSA), is proposed and employed to train Deep Neural Network (DNN) to carry out the precise seizure prediction. Here, the integration of the Adadelta concept in the Chameleon Swarm Algorithm (CSA) has resulted in Adadelta-CSA. At last, the performance of the Adadelta-CSA scheme-based DNN is compared with the existing techniques by considering accuracy, sensitivity and specificity, and it is found to produce better values of 0.951, 0.966, and 0.935, respectively. [ABSTRACT FROM AUTHOR]

Moringa is a type of plant that is used both for medicinal and food. Moringa seed (MS) are rich in volatile oil and have initially been employed to treat diseases of the nervous system. Insomnia, a prevalent neurological disorder, has led to this study's aim: to extract the essential oil from MS and analyze its potential to improve sleep. This study utilized petroleum ether for the thermal extraction of the essential oil from MS, which was then subjected to compositional analysis using Gas Chromatograph Mass Spectrometer (GC–MS). P‐chlorophenyl alanine (PCPA) was used to induce an insomnia model in Sprague–Dawley (SD) rats. Following the successful establishment of the model, the MS essential oil was administered at concentrations of 10%, 5%, and 2.5% to investigate its sedative and hypnotic effects. The efficacy of the MS essential oil was assessed by observing the general condition of rats in each group, conducting an open field test, a pentobarbital sodium righting test, and measuring the serum 5‐HT (5‐hydroxytryptamine) levels and hypothalamic GABA (γ‐aminobutyric acid) content. GC–MS analysis of the MS essential oil revealed a rich composition, including oleic acid, palmitoleic acid, stigmasterol, and γ‐stigmasterol, among other substances. Through the assessment of the rats' general condition, behavioral tests, and blood biochemical assays, it was inferred that MS essential oil aromatherapy can reduce the rat's locomotor activity, increase their interest in activity and exploration, enhance the serum 5‐HT levels, and elevate hypothalamic GABA content. Consequently, it can be concluded that MS essential oil has a sedative and hypnotic effect. [ABSTRACT FROM AUTHOR]

In recent years, researchers have highly observed that neurological disorders (NSDs) with the aging of the population are a global health burden whose prevalence is increasing every year. Previous evidence suggested that the occurrence of neurological disorders is correlated with predisposing factors such as inflammation, aging, and injury. Particularly, the neuronal cells are susceptible to oxidative stress, leading to lesions caused by high oxygen-consuming properties. Oxidative stress (OS) is a state of peroxidation, which occurs as a result of the disruption of the balance between oxidizing and antioxidizing substances. The oxidative intermediates such as free radicals, hydrogen peroxide (H2O2), and superoxide anion (O2-) produced by OS promote disease progression. Curcumin, a natural diketone derived from turmeric, is a natural antioxidant with a wide range of neuroprotective, anti-inflammatory, anti-tumor, anti-aging, and antioxidant effects. Fortunately, curcumin is recognized for its potent antioxidant properties and is considered a promising candidate for the prevention and treatment of neurological diseases. Consequently, this review elucidates the mechanisms by which curcumin mitigates oxidative stress and emphasizes the potential in treating nervous system disorders, including depression, Alzheimer's disease, Parkinson's disease, epilepsy, subarachnoid hemorrhage, and glioblastoma. We aim to provide a new therapeutic option for the management of neurological diseases. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a central feature in the pathophysiology of several neurodegenerative diseases, including MS, AD, and PD. This review aims to synthesize current research on the role of inflammation in these conditions, emphasizing the potential of inflammatory biomarkers for diagnosis and treatment. We highlight recent findings on the mechanisms of neuroinflammation, the utility of biomarkers in disease differentiation, and the implications for therapeutic strategies. Advances in understanding inflammatory pathways offer promising avenues for developing targeted interventions to improve patient outcomes. Future research should focus on validating these biomarkers in larger cohorts and integrating them into clinical practice to enhance diagnostic accuracy and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Advancements in medical treatments and increased access to healthcare have significantly extended the life expectancy of children with neurological disorders. However, this has also led to a higher incidence of secondary health issues, such as nephrolithiasis. This review aims to analyze the risk factors, management, and treatment outcomes for stone disease in children with neurological disorders and focus on specific risk factors such as immobilization, urinary tract infections, and metabolic abnormalities to identify key points in the occurrence of nephrolithiasis. Methods: A comprehensive literature search was conducted across two primary databases, PubMed and Ovid Medline, to identify studies on urolithiasis in children with neurological disorders. A total of 771 articles were initially identified. After removing four duplicate articles, 729 were excluded following title and abstract screening due to irrelevance. Thirty-eight articles were selected for full-text review, and after further exclusions, 11 articles were included in this review. Results: The studies mainly consisted of small-scale, single-center investigations. Nephrolithiasis were reported in 5–54% of patients across the studies. The most commonly identified risk factors were immobilization, urinary tract infections (UTIs), and hypercalciuria. Treatment options for urinary stones included medical expulsive therapy (MET), extracorporeal shock wave lithotripsy (ESWL), endoscopic surgery (RIRS), and percutaneous nephrolithotomy (PCNL). Conclusion: Key steps in managing these patients include monitoring bone mineral density, conducting a 24-h urine analysis to assess metabolic components (despite challenges in obtaining this), and encouraging physical activity as much as the patient's condition permits. [ABSTRACT FROM AUTHOR]

In neurodegenerative diseases, the activation of microglia and the ensuing neuroinflammation are pivotal in regulating disease progression. Attenuating inflammation induced by microglial cells is considered a key strategy for slowing the progression of neurodegenerative diseases. γ‐glutamylcysteine (γ‐GC) has exhibited significant antioxidative and anti‐inflammatory effects; nevertheless, its potential role in modulating neuroinflammatory responses remains incompletely explored. The current investigation aimed to establish a neuroinflammation model by stimulating BV2 microglia cells with lipopolysaccharide (LPS) and to explore the protective effect of γ‐GC on neuroinflammation in BV2 microglia cells. The results demonstrated that γ‐GC significantly attenuated LPS‐induced oxidative damage in BV2 cells, reduced the levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), inhibited the cytoplasmic translocation of high‐mobility group box 1 protein (HMGB1), and effectively mitigated the LPS‐induced inflammatory response in BV2 cells. We further investigated the regulatory mechanism of γ‐GC on LPS‐induced BV2 neuroinflammation and found that γ‐GC significantly enhances autophagy in BV2 cells, resulting in a marked reduction in mammalian target of rapamycin (mTOR) phosphorylation levels and an increase in AMP‐activated protein kinase (AMPK) phosphorylation levels. The use of autophagy inhibitors 3‐methyladenine (3‐MA) and AMPK inhibitors further corroborates the proposition that γ‐GC promotes autophagy in BV2 cells while suppressing the LPS‐induced inflammatory response of BV2 microglia through the activation of the AMPK‐mTOR pathway. The findings indicate that γ‐GC exerts a substantial inhibitory impact on neuroinflammation, making it a promising candidate for the development of therapeutic strategies against neuroinflammatory disorders and related conditions. [ABSTRACT FROM AUTHOR]

The common cold is the primary cause of illness in the community, with over 200 viral strains identified, and rhinovirus infections being the most prevalent. Coronavirus Disease 19 (COVID-19) is also a significant cause of severe illness. The burden of acute respiratory infections has a significant impact on the economy, resulting in absenteeism from work and school. Rhinovirus infections can exacerbate asthma and other chronic diseases, leading to hospitalization. The objective of this study is to investigate the factors associated with death and survival in patients hospitalized for rhinovirus in Brazil in 2022. This is a retrospective cohort study using data from the national surveillance of Severe Acute Respiratory Syndrome (SARS) in 2022 in Brazil, with all the norrifications. We analysed and compared clinical and epidemiological factors and outcomes between survivors and deaths in patients hospitalised for rhinovirus. The absolute and relative frequencies were calculated according to the states. Bivariate analysis was performed using chi-squared test and Fisher's exact test, while multivariate analysis was performed using COX regression. Out of 8,130 cases of SARS caused by rhinovirus, 291 (3.58%) resulted in death while 7839 (96.47%) patients survived. The factors associated with death were invasive ventilation (p- < 0.001 HR 4.888 CI 95% 3.816–6.262), bocavirus (p- < 0.001 HR 4.204 CI 95% 2.595–6.812), immunodepression/Immunosuppression (p- < 0.001 HR 2.417 CI 95% 1. 544–3, 786), COVID-19 (p- < 0.001 HR 2.167 CI 95% 1.495–3.142), chronic neurological diseases (p-0.007 HR 1.610 CI 95% 1.137–2.280), abdominal pain (p-0.005 HR 1.734 CI 95% 1.186–2.537), age (p- < 0.001 HR 1.038 CI 95% 1.034–1.042). The survival factors identified in this study were dyspnea (p = 0.005; HR 0.683; CI 95% 0.524–0.889), cough (p < 0.001; HR 0.603; CI 95% 0.472–0.769), and asthma (p = 0.052; HR 0.583; CI 95% 0.339–1.004). Additionally, the study found that receiving a COVID-19 booster dose was also a significant survival factor (p = 0.001; HR 0.570; CI 95% 0.415–0.784). The factors associated with death were similar to those in the literature, and the factors associated with survival were also similar, except for the booster dose of the COVID-19 vaccine, which we didn't find in any studies. Our study is the first to associate the full course of the COVID-19 vaccine with survival in those hospitalized for rhinovirus, regardless of COVID-19 and rhinovirus co-detection. [ABSTRACT FROM AUTHOR]

Objective: Work phobic anxiety can occur as an additional problem in any somatic illness and is often associated with work capacity limitations and sick leave. This study investigates work‐related capacity limitations in patients with and without work phobic anxiety who are undergoing neurological rehabilitation. It was conducted in the rehabilitation facility Brandenburgklinik Berlin‐Brandenburg in Germany. Methods: Work phobic anxiety was assessed with the Workplace Phobia Scale (WPS). The response rate was 69.51%. Capacity limitations (Mini‐ICF‐APP) were compared between 19 patients with neurological conditions and work phobic anxiety and 209 patients with neurological conditions without work phobic anxiety. Work participation restrictions were examined and compared using the self‐ and observer rated Index for Measuring Participation (IMET, IMEP‐O). The work ability assessments regarding the patients' last occupation as well as the general labor market were conducted by the treating physicians as part of their medical reports and compared between the subgroups. The work ability was rated as less than 3 h, 3 to less than 6 h, or 6 h or more a day for more than 6 months, with the latter being an indication for prognostic work ability and potential reintegration into the labor market. This is a common classification in sociomedical assessments in Germany. Results: Independent t‐tests showed that patients with work phobic anxiety were significantly more limited in their planning and structuring of tasks (t[20.104] = 2.310, p = 0.032, d = 0.68), flexibility (t[217] = 3.586, p < 0.001, d = 0.86), assertiveness (t[19.613] = 2.151, p = 0.044, d = 0.70), group integration (t[19.534] = 2.274, p = 0.034, d = 0.76), and mobility capacities (t[16.616] = 2.198, p = 0.042, d = 0.76) and significantly more restricted in participating in work compared to patients without work phobic anxiety (IMEP‐O: t[23.549] = 2.298, p = 0.031, d = 0.40; IMET: t[27.191] = 4.581, p < 0.001, d = 0.78). Chi‐squared tests revealed no significant differences in the physicians' work ability assessments between patients with and without work phobic anxiety. Conclusions: While work phobic anxiety seems to not be decisive concerning early retirement assessments, it is associated with greater capacity limitations and work participation restrictions. The results highlight the need for identifying work phobic anxiety and associated capacity limitations in clinical practice. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Excitotoxicity is a common hallmark of epilepsy and other neurological diseases associated with elevated extracellular glutamate levels. Thus, here, we studied the protective effects of (R)‐AS‐1, a positive allosteric modulator (PAM) of glutamate uptake in epilepsy models.(R)‐AS‐1 was evaluated in a range of acute and chronic seizure models, while its adverse effect profile was assessed in a panel of standard tests in rodents. The effect of (R)‐AS‐1 on glutamate uptake was assessed in COS‐7 cells expressing the transporter. WAY 213613, a selective competitive EAAT2 inhibitor, was used to probe the reversal of the enhanced glutamate uptake in the same transporter expression system. Confocal microscopy and Western blotting analyses were used to study a potential influence of (R)‐AS‐1 on GLT‐1 expression in mice.(R)‐AS‐1 showed robust protection in a panel of animal models of seizures and epilepsy, including the maximal electroshock‐ and 6 Hz‐induced seizures, corneal kindling, mesial temporal lobe epilepsy, lamotrigine‐resistant amygdala kindling, as well as seizures induced by pilocarpine or Theiler's murine encephalomyelitis virus. Importantly, (R)‐AS‐1 displayed a favorable adverse effect profile in the rotarod, the minimal motor impairment, and the Irwin tests. (R)‐AS‐1 enhanced glutamate uptake in vitro and this effect was abolished by WAY 213613, while no influence on GLT‐1 expression in vivo was observed after repeated treatment.Collectively, our results show that (R)‐AS‐1 has favorable tolerability and provides robust preclinical efficacy against seizures. Thus, allosteric enhancement of EAAT2 function could offer a novel therapeutic strategy for treatment of epilepsy and potentially other neurological disorders associated with glutamate excitotoxicity. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Cognitive impairment is common in neurologic diseases. Precise measurement of cognitive change over time is necessary for isolating disease-related patterns from normal age-related decline. Existing measures of subjective cognition, however, focus on present status. There is, to our knowledge, no currently available self-report measure of cognitive change. We therefore developed the Cognitive Change Scale (CCS), which assesses perceived cognitive change in neurologic populations.A systematic mixed-methods process was followed for the scale design and validation. Associations of CCS responses to demographics, mood, and fatigue were examined in 131 persons with multiple sclerosis. A total of 46 participants also completed a cognitive test battery. Correlations of test scores with CCS responses were calculated.The 17-item CCS showed good reliability and validity. Results of exploratory and confirmatory factor analyses supported a four-factor structure, with items reflecting change in (1) general cognition, (2) language and executive function, (3) external feedback, and (4) use of coping strategies. Positive relationships of CCS scores with fatigue, depression, and anxiety were observed. Correlations of CCS scores with cognitive test performance did not reach significance.The CCS may be a useful cognitive outcome tool for treatment trials in neurologic populations. [ABSTRACT FROM AUTHOR]

To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra‐intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra‐intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Self‐compassion is a positive psychological factor linked to improved physical and psychological outcomes across different chronic illness populations. However, the extent to which self‐compassion contributes to reduced distress across different conditions or as a function of participant factors is not clear. The current meta‐analysis aimed to quantify the association between self‐compassion and psychological distress in different chronic illness populations and evaluate the factors that moderate this association.A systematic search of three electronic databases identified research reporting associations between self‐compassion and psychological distress in chronic illness. A random effects meta‐analysis was conducted to evaluate the association between self‐compassion and psychological distress. Moderator analyses were conducted for sample characteristics and distress types. A bespoke tool evaluated study quality.Searches yielded 51 eligible studies with 57 effect sizes. Meta‐analysis revealed that self‐compassion was negatively associated with psychological distress (r = −.516; 95% CIs [−.55, −.48]; p = .000). Moderator analyses were significant for distress type and chronic illness group, with effects being largest for stress and neurological conditions. Effects did not vary by sex, age or illness duration.Findings from this first comprehensive investigation of the link between self‐compassion and distress in chronic illness highlight the protective role of self‐compassion for chronic illness populations. These results lay the foundation for further research into understanding the processes that link self‐compassion to lower psychological distress, and that examine the effectiveness of self‐compassion interventions in chronic illness populations, to further advance knowledge and inform practice in this area. [ABSTRACT FROM AUTHOR]

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia. [Display omitted] Through a combined approach of international gene matching, deep phenotyping, and model organism functional studies, we provide evidence to establish ASTERIX (WDR83OS) loss of function as underlying a recessive human neurological disease trait with liver disease (hypercholanemia). This condition overlaps with trichohepatoneurodevelopmental syndrome caused by variants in CCDC47, a binding partner of ASTERIX. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Interpretation Peripheral neuropathy (PN) is a common neurological condition in elderly adults. Vitamin D deficiency has been associated with diabetic and chemotherapy‐induced neuropathy, but its role in idiopathic PN, in which no underlying cause of neuropathy can be identified, has not been investigated.Two hundred thirty patients with idiopathic PN enrolled in the Peripheral Neuropathy Research Registry (PNRR) at Johns Hopkins University School of Medicine had vitamin D testing information on record. Linear and logistic regressions were used to investigate the relationship between absolute vitamin D level or vitamin D insufficiency (<20 ng/mL) and both the severity of neuropathy as measured by the reduced total neuropathy score (TNSr) and severity of neuropathic pain.Sixteen (7%) patients were vitamin D insufficient (<20 ng/mL). Controlling for factors known to correlate with severity of neuropathy, there was no correlation between absolute vitamin D levels and TNSr (correlation coefficient 0.01, 95% CI −0.03 to 0.07, p = .59) and no association between vitamin D insufficiency and TNSr (correlation coefficient 0.3, 95% CI −2.8 to 3.4, p = .86). Vitamin D insufficiency was not associated with the presence of neuropathic pain (OR 4.1, 95% CI 0.6–26.0, p = .13), and there was no correlation between vitamin D levels and pain score (correlation coefficient 0.01, 95% CI −0.02 to 0.03, p = .59).In a single‐center cohort of patients with idiopathic PN, there was no correlation between vitamin D levels and the severity of neuropathy or neuropathic pain. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Blood–brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals.We scanned 50 drug‐resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE‐MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls.Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10−7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI‐visible lesions compared with non‐lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10).These findings are consistent with pre‐clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Recent advances in neural engineering have opened new ways to investigate the impact of topology on neural network function. Leveraging microfluidic technologies, it is possible to establish modular circuit motifs that promote both segregation and integration of information processing in the engineered neural networks, similar to those observed in vivo. However, the impact of the underlying topologies on network dynamics and response to pathological perturbation remains largely unresolved. In this work, we demonstrate the utilization of microfluidic platforms with 12 interconnected nodes to structure modular, cortical engineered neural networks. By implementing geometrical constraints inspired by a Tesla valve within the connecting microtunnels, we additionally exert control over the direction of axonal outgrowth between the nodes. Interfacing these platforms with nanoporous microelectrode arrays reveals that the resulting laminar cortical networks exhibit pronounced segregated and integrated functional dynamics across layers, mirroring key elements of the feedforward, hierarchical information processing observed in the neocortex. The multi-nodal configuration also facilitates selective perturbation of individual nodes within the networks. To illustrate this, we induced hypoxia, a key factor in the pathogenesis of various neurological disorders, in well-connected nodes within the networks. Our findings demonstrate that such perturbations induce ablation of information flow across the hypoxic node, while enabling the study of plasticity and information processing adaptations in neighboring nodes and neural communication pathways. In summary, our presented model system recapitulates fundamental attributes of the microcircuit organization of neocortical neural networks, rendering it highly pertinent for preclinical neuroscience research. This model system holds promise for yielding new insights into the development, topological organization, and neuroplasticity mechanisms of the neocortex across the micro- and mesoscale level, in both healthy and pathological conditions. [ABSTRACT FROM AUTHOR]

Whole-exome sequencing (WES), a ground-breaking technology, has emerged as a linchpin in neurology and neurosurgery, offering a comprehensive elucidation of the genetic landscape of various neurological disorders. This transformative methodology concentrates on the exonic portions of DNA, which constitute approximately 1% of the human genome, thus facilitating an expedited and efficient sequencing process. WES has been instrumental in advancing our understanding of neurodegenerative diseases, neuro-oncology, cerebrovascular disorders, and epilepsy by revealing rare variants and novel mutations and providing intricate insights into their genetic complexities. This has been achieved while maintaining a substantial diagnostic yield, thereby offering novel perspectives on the pathophysiology and personalized management of these conditions. The utilization of WES boasts several advantages over alternative genetic sequencing methodologies, including cost-effectiveness, reduced incidental findings, simplified analysis and interpretation process, and reduced computational demands. However, despite its benefits, there are challenges, such as the interpretation of variants of unknown significance, cost considerations, and limited accessibility in resource-constrained settings. Additionally, ethical, legal, and social concerns are raised, particularly in the context of incidental findings and patient consent. As we look to the future, the integration of WES with other omics-based approaches could help revolutionize the field of personalized medicine through its implications in predictive models and the development of targeted therapeutic strategies, marking a significant stride toward more effective and clinically oriented solutions. [ABSTRACT FROM AUTHOR]

Detecting and monitoring elevated intracranial pressure (ICP) is crucial in managing various neurologic and neuro-ophthalmic conditions, where early detection is essential to prevent complications such as seizures and stroke. Although traditional methods such as lumbar puncture, intraparenchymal and intraventricular cannulation, and external ventricular drainage are effective, they are invasive and carry risks of infection and brain hemorrhage. This has prompted the development of non-invasive techniques. Given that direct, non-invasive access to the brain is limited, a significant portion of research has focused on utilizing the eyes, which uniquely provide direct access to their internal structure and offer a cost-effective tool for non-invasive ICP assessment. This review explores the existing non-invasive ocular techniques for assessing chronically elevated ICP. Additionally, to provide a comprehensive perspective on the current landscape, invasive techniques are also examined. The discussion extends to the limitations inherent to each technique and the prospective pathways for future advancements in the field. [ABSTRACT FROM AUTHOR]

Introduction: Dementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted. Materials and methods: In this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized. Results: Our study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X. Conclusions: This study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine. Methods: This study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results. Results: Our MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings. Discussion: This study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Therapy intensity is among the most critical factors influencing neurorehabilitative outcomes. Because of its simplicity, time spent in therapy is the most commonly used measure of therapy intensity. However, time spent in therapy is only a vague estimate of how hard a patient works during therapy. Several measures have been proposed to better capture the amount of work a patient puts forth during therapy. Still, it has never been analyzed how these measures respond to changes in therapist-selected exercise intensity in children with neurological conditions. Objectives: To investigate the response and the reliability of heart rate variability (HRV), skin conductance (SC), activity counts per minute (AC/min), movement repetitions per minute (MOV/min), and perceived exertion to different therapist-tailored intensity levels of upper limb technology-assisted therapy in children with neurological conditions. Methods: In this pilot cross-sectional study, participants engaged in three personalized, randomized exergame intensity levels ("very easy", "challenging", "very difficult") for eight minutes each. We assessed all measures at each intensity level. The experiment was conducted twice on two consecutive days. We quantified reliability using intra-class correlation coefficients (ICC). Results: We included 12 children and adolescents aged 11.92 (±3.03) years. HRV, MOV/min, and perceived exertion could differentiate among the three intensity levels. HRV, MOV/min, perceived exertion, and AC/min showed moderate to excellent (0.62 ≤ ICC ≤ 0.98) test-retest reliability. Conclusion: HRV, MOV/min, and perceived exertion show potential for becoming valid and reliable intensity measures for an upper limb robotic rehabilitative setting. However, studies with larger sample sizes and more standardized approaches are needed to understand these measures' responses better. [ABSTRACT FROM AUTHOR]

Background: Migraine is a neurological condition marked by frequent headaches, which tends to be accompanied by nausea and vomiting in severe instances. Injectable therapies for migraine, such as monoclonal antibodies that target calcitonin gene-related peptide (CGRP), have proven to be effective and safe. While various oral drugs are available, none have been developed for migraines. Patients prefer oral therapies because they are easier to use, making atogepant, an orally accessible small-molecule CGRP receptor antagonist, a possible alternative. Objectives: This systematic review and meta-analysis compared the safety and effectiveness of atogepant with placebo in treating migraine. Methods: Adhering to the PRISMA guidelines, we meticulously gathered randomized controlled trials (RCTs) from databases including the Cochrane Library, PubMed, Science Direct, and ClinicalTrials.gov. Studies comparing atogepant with placebo and reporting monthly migraine days (MMDs) as the primary outcome along with secondary outcomes such as monthly headache days and acute medication use days were included. Two independent reviewers conducted the data extraction and quality assessment. Statistical analyses were carried out using RevMan, utilizing risk ratios for dichotomous outcomes and mean differences for continuous outcomes, and a random-effects model. Results: Our primary outcome was the change in MMDs over 12 weeks, which showed a significant reduction with atogepant at dosages of 10, 30, and 60 mg. Secondary outcomes, such as monthly headache days, proportion of patients achieving a ≥ 50% reduction in MMDs, acute medication use days, and patient-reported outcomes, consistently showed that atogepant outperformed placebo, highlighting its effectiveness in reducing the migraine burden. Conclusion: Higher doses of atogepant are more effective in lowering migraine and headache-related days and increasing quality of life metrics. However, this is accompanied by an increased incidence of adverse events, suggesting the need for careful dose optimization to balance the benefits and risks. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display%5frecord.php?RecordID=563395. Unique Identifier: CRD42024563395. [ABSTRACT FROM AUTHOR]

Background: The penis is a relatively uncommon organ for metastases. Secondary lesions often originate from the bladder, prostate, or rectosigmoid cancers. Only a few cases have described penile lesions secondary to lung cancers, mostly as a later complication. Case Description: We hereby report the case of an 86‐year‐old male patient who presented with a 3‐week‐long nonpainful priapism. A penile Doppler ultrasound and a chest and abdominal CT scan were performed, showing a left hilar lung mass as well as lesions in the liver, the adrenal glands, the pancreas, bone structures, and the penis. Penile metastasis is associated with a poor prognosis because of the frequent disseminated malignant lesions in other sites. Conclusion: Malignant priapism should be suspected, especially in patients with no evident risk factors for priapism (hematological diseases, drugs, alcohol, neurological diseases, or metabolic disorders). [ABSTRACT FROM AUTHOR]

Background: Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS. Case presentation: Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient's condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient's condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission. Conclusion: ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia. [ABSTRACT FROM AUTHOR]

AbstractParkinson’s disease (PD) is a neurological disorder that primarily affects movement and is often accompanied by depressive symptoms. Subthalamic nucleus (STN) deep brain stimulation (DBS) has emerged as a therapeutic intervention for PD, although its impact on depressive symptoms remains complex. This study investigates the relationship between PD, DBS, and depressive symptoms, focusing on how DBS influences cognitive function and mood among PD patients in Brazil. The study involved two cohorts: one in 2019 with 46 participants and another in 2022 with 31 patients. Distinct assessment instruments, including the Geriatric Depression Scale-15 and Beck Depression Inventory-II, were employed to evaluate depressive symptoms. The results revealed no significant correlation between participants’ gender and the presence of DBS, but substantial differences were observed in age, disease duration, and Activities of Daily Living scores. Patients undergoing DBS showed notably poorer cognitive performance compared to those treated solely with medication. Furthermore, the use of DBS was associated with higher scores on depressive symptoms scales within one of the cohorts. These findings underscore the intricate interplay among PD, DBS treatment, and depressive symptoms, highlighting the necessity for tailored approaches to patient care. [ABSTRACT FROM AUTHOR]

Raman spectroscopy (RS) is used increasingly for disease detection, including diseases of the nervous system (CNS). This Perspective presents RS basics and how it has been applied to disease detection. Research that focused on using a novel Raman-based technology—Rametrix® Molecular Urinalysis (RMU)—for systemic disease detection is presented, demonstrated by an example of how the RS/RMU technology could be used for detection and management of diseases of the CNS in companion animals. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD), as a refractory neurological disorder with complex etiology, currently lacks effective therapeutic agents. Natural products (NPs), derived from plants, animals, or microbes, have shown promising effects in PD models through their antioxidative and anti-inflammatory properties, as well as the enhancement of mitochondrial homeostasis and autophagy. The misfolding and deposition of α-Synuclein (α-Syn), due to abnormal overproduction and impaired clearance, being central to the death of dopamine (DA) neurons. Thus, inhibiting α-Syn misfolding and aggregation has become a critical focus in PD discovery. This review highlights NPs that can reduce α-Syn aggregation by preventing its overproduction and misfolding, emphasizing their potential as novel drugs or adjunctive therapies for PD treatment, thereby providing further insights for clinical translation. [ABSTRACT FROM AUTHOR]

Introduction: Currently, neurological diseases has surpassed cardiovascular diseases as the primary cause of global disease burden. Among these, headache disorders are the most prevalent and have emerged as the main cause of disability in people under 50 years old in recent years. Since the release of GBD 2021, there has been no comprehensive systematic exposition on the burden of headache among individuals under 50 years old and a forecast for future burdens. This study aims to quantify the global, regional, and national burden of headache disorders among people under 50 from 1992 to 2021 and to predict future trends in order to provide policy makers with precise and effective epidemiological evidence. Methods: This study extracted the incidence, prevalence, and DALYs data related to headache disorders in the 5–50 age group from the GBD 2021. After age-standardizing the data, we used joinpoint regression analysis and health inequity analysis to analyze the burden and temporal trend of headache disorders and predicted the future disease burden and changes based on the age-period-cohort model. Results: By 2021, the case number of global incidence, prevalence and DALYs have increased by 35, 39, and 41%, respectively, over the past 30 years. The incidence and prevalence of tension-type headache (TTH) are significantly higher than those of migraine, but migraine causes greater health burdens. The burden is higher for female than for male. In terms of age, youth aged 25–29 years had the highest incidence in 2021, with an age-standardized rate (ASR) of 13,454.64 (95%CI, 9,546.96–18,361.36) per 100,000 population. Nationally, the highest ASR of incidence and prevalence are found in Norway, and the most damaging to health is found in Belgium. Among the five sociodemographic index (SDI) categories, the middle SDI has the highest number of cases (190 million in 2021). It is worth noting that the forecast shows that by 2046 the three indicators will reach 680 million, 2.33 billion, and 41 million, respectively, indicating that the burden of headache disorders in this age group will continue to persist. Conclusion: Globally, the burden of headache disorders in people under 50 years of age remains significant and has not improved over the past 30 years, especially in regions with high SDI. Headache problems will continue to pose a serious public health challenge for this age group for some time to come. This study reveals the burden and distribution of headache disorders in this age group, providing important basis for governments and policymakers to accurately and effectively allocate health care resources, strengthen prevention and management strategies, and respond to this global health problem. [ABSTRACT FROM AUTHOR]

Background: Published best‐practice guidelines and standardized protocols for voice assessment recommend multidisciplinary evaluation utilizing a comprehensive range of clinical measures. Previous studies report variations in assessment practices when compared with these guidelines. Aims: To provide an up‐to‐date evaluation of current global multidisciplinary practice patterns and the opinions of otolaryngologist, ear, nose and throat (ENT) and speech–language pathology (SLP) clinicians on initial assessment and differential diagnosis of adults with voice disorders (VDs). Methods & Procedures: ENTs and SLPs worldwide who had worked with VDs within the last 10 years completed an anonymous online survey. Themes explored demographic information about the clinical practice, information about diagnostic assessment pathways, clinical assessments routinely used for initial voice evaluation and clinician perceived value of clinical assessments important for diagnosis. Outcomes & Results: Patterns in the clinical practice of 88 SLPs and 21 ENTs from 18 countries with 1 to more than 25 years' experience were analysed. Clinicians provided services across a range of locations, and a range of assessment pathways was available for initial evaluation. Case history, laryngoscopy and auditory–perceptual measures were the most frequently selected assessments. Most clinicians favoured formal assessment measures for auditory–perceptual evaluation. Clinicians placed equal weighting on ENT and SLP assessment to aid diagnosis for muscle tension VDs and functional neurological voice disorders (FVDs). Conclusions & Implications: Practice patterns for initial diagnostic voice assessment are largely consistent with the currently published guidelines. Decisions for the selection of assessment tools vary according to VD classification, and assessment decisions appear to be guided by case history. Clinicians are not always following established protocols for obtaining reliable standardized measures. Further research is needed to understand the barriers to adhering to standardized protocols and to develop evidence for the use of case history in the process of VD diagnosis. WHAT THIS PAPER ADDS: What is already known on the subject: Best‐practice guidelines recommend a multidisciplinary and multidimensional assessment of adults with vocal symptoms. Prior uni‐disciplinary survey studies have reported a divergence in clinical practice with the recommended guidelines. No previous studies have examined otolaryngologists and SLPs concurrently to investigate the multidisciplinary approach clinicians' use in a diagnostic voice assessment. What this paper adds to the existing knowledge: This study highlights new insights into multidisciplinary voice evaluation practice patterns with an emphasis on diagnostic assessment from a global perspective. The findings build on prior research exploring clinical assessment pathways, service utilization and clinicians' preferences when selecting clinical tools to inform a differential diagnosis. What are the potential or actual clinical implications of this work?: This paper provides insights to inform future service and resource planning to ensure the delivery of evidenced‐based diagnostic assessment pathways. This study also makes recommendations for areas of future research to understand barriers to clinicians following recommended best‐practice guidelines. [ABSTRACT FROM AUTHOR]

Background: Functional Communication Disorders (FCDs) are one specific presentation of Functional Neurological Disorder (FND). FND is characterised by neurological symptoms, such as sensory and motor symptoms, which are not explained by neurological disease. Speech and language therapists (SLTs) have expertise in managing communication disorders, including FCDs, though is not known is what clinicians do in practice to treat and manage FCDs. Aim: To explore the clinical practices of SLTs who regularly manage FCDs in the UK, including the assessment and intervention approaches taken. Methods & Procedures: An online survey was developed using Qualtrics software and piloted before dissemination. Participants were experienced SLTs working in the UK who managed at least three FCD referrals a year. The survey was developed with a mix of qualitative and quantitative questions. The survey was disseminated via social media and professional networks. Outcomes & Results: There were 73 completed responses to the survey. Participants reported working with a range of FCDs clinically, with functional stuttering and articulation disorders seen most frequently. SLTs reported working with a wide range of multidisciplinary professionals when managing patients with FCDs, though lack of access to mental health professionals was raised as an issue. SLTs reported using a combination of formal and informal communication assessments. Interventions varied, with a wide range of psychological approaches informing treatment. Lack of specific training, evidence base and negative attitudes around functional neurological disorder (FND) were raised as ongoing issues. Conclusions & Implications: Therapists encountered a wide range of FCDs as part of their clinical practice, though there was a significant disparity in the service and interventions offered. SLTs feel their input can be effective, but lack the resources, training and evidence‐based interventions to provide adequate care. WHAT THIS PAPER ADDS: What is already known on the subject: FCDs are one manifestation of FND and can present as a wide range of communication disorders. SLTs encounter FCDs as part of clinical practice, but report feeling unsure and underprepared to manage these disorders. Consensus recommendations have provided some guidance on how to manage these disorders, though what was not known was what practising SLTs are doing in practice with FCD patients: what assessment, intervention and management strategies they use, and what they feel are the facilitators and barriers to effective management. What this study adds to the existing knowledge: This is the first UK‐wide survey of FCD SLT clinical practice. The survey found that SLTs are seeing a range of FCDs as part of their clinical practice. SLTs reported that they feel their input is effective, that they had confidence in their ability to provide assessment and intervention, and that SLT for FCDs should be routine. SLTs reported using a wide variety of approaches to assessment and intervention. Barriers to effective management included a lack of resources, training, negative staff attitudes towards FND, and lack of research and evidence‐based interventions. What are the practical and clinical implications of this work?: This survey has found that SLTs working across the UK are providing input for patients with FCDs, but frequently reported feeling isolated and lacking clinical peer support. This shows the potential for networking groups to support SLTs to learn and share resources. There is a training need for SLTs and other healthcare professionals to tackle pervasive negative attitudes towards FND. Common themes in intervention approaches were found, but there was variability in the specific approach taken. This requires further research to guide SLTs on the best evidence‐based practice. [ABSTRACT FROM AUTHOR]

Handwriting analysis is a valuable tool in forensic document examination, but the interpretation of observed findings can be complicated when individuals with neurological disorders are involved. The process of handwriting necessitates complex neuro‐muscular synchronization, which requires a much more intricate connection between the brain, muscles, and nerves than simply placing pen to paper. People with neurological illnesses, including Parkinson disease, Multiple System Atrophy, Alzheimer disease, and so on, may have trouble writing by hand. These illnesses can impair writing abilities physically and cognitively, resulting in inconsistencies or erratic handwriting that may be challenging to decipher. Because these illnesses impact a person's handwriting, it becomes challenging for document examiners to make an opinion about the handwriting of the author. A literature search was performed using PubMed, ScienceDirect, and Google Scholar databases to analyze the association between neurological disorders and handwriting and their implications for handwriting analysis. This review article explores the effects of neurological disorders on handwriting. It emphasizes the importance of examining and analyzing handwriting impacted by these illnesses with care and knowledge. Document examiners, forensic professionals, and investigators must comprehend these challenges brought on by neurological illnesses. In forensic settings, specialized training, expertise, and suitable forensic handwriting examination methods (collection, analysis, interpretation, and reporting) should be adopted effectively in cases that involve people suffering from neurological disorders. This review majorly focuses on the analysis and interpretation stage of the forensic handwriting examination. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence and cumulative incidence of neuro‐retinal‐disorders (NRD) in HIV‐controllers. Design: Prospective, single‐centre, cohort study of people living with HIV (PLWH): elite‐controllers, long‐term‐non‐progressors and early diagnosed. Methods: The study compared "HIV‐controllers" (including elite‐controllers and long‐term‐non‐progressors), who were not on antiretroviral therapy (ART), and "HIV‐treatment" (HIV‐infected subjects with a recent diagnosis and on ART). A matched cohort of "non‐HIV subjects" was created. NRD was defined as at least one altered (not normal) ophthalmological parameter (functional or structural). Functional (visual acuity, contrast sensitivity, chromatic vision, visual field) and structural parameters (ganglion cells, macular nerve fibre layer, peripapillary nerve fibre layers, vascular calibre) as well as quality of life (Medical Outcomes Study‐HIV Short Form‐30) were assessed. Results: Between March 2012 and November 2015, the study included all HIV‐controllers (16 elite‐controllers, 1 long‐term‐non‐progressor), 11 HIV‐treatment and 16 non‐HIV. Prevalence of NRD at baseline was 88.2% (15/17, 95% CI: 65.7%–96.7%), 90.9% (10/11, 95% CI: 62.3%–98.4%) and 56.3% (9/16, 95% CI: 33.2%–76.9%), respectively. Cumulative incidence at 3 years was 50% (1/2), 100% (1/1) and 33.3% (2/6), respectively. None of the participants manifested ocular clinical symptoms. Three years later, prevalence of NRD was 92.3% (12/13, 95% CI: 66.7%–98.6%), 75% (6/8, 95% CI: 40.9%–92.9%) and 50.0% (7/14, 95% CI: 26.8%–73.2%), respectively. Contrast sensitivity and structural parameters were globally the most affected among PLWH. Quality of life (total score) [median (interquartile range)] at baseline and 3 years was 82 (71–89) and 74 (63.5–79.25) in HIV‐controllers and 80 (73–88) and 88 (83–92) in HIV‐treatment. Conclusions: HIV‐controllers and those individuals on ART presented a higher percentage of NRD than non‐HIV. Our results suggest that NRD could be a biomarker of ocular aging among PLWH. [ABSTRACT FROM AUTHOR]

Background and Purpose: In recent years, there has been a growing interest in the study of resting neural networks in different neurological and mental disorders. While previous studies suggest that the default mode network (DMN) may be altered in dyscalculia, the study of resting‐state networks in the development of numerical skills, especially in children with developmental dyscalculia (DD), is scarce and relatively recent. Based on this, this study examines differences in resting‐state functional connectivity (rs‐FC) data of children with DD using functional connectivity multivariate pattern analysis (fc‐MVPA), a data‐driven methodology that summarizes properties of the entire connectome. Methods: We performed fc‐MVPA on resting‐state images of a sample composed of a group of children with DD (n = 19, 8.06 ± 0.87 years) and an age‐ and sex‐matched control group of typically developing children (n = 23, 7.76 ± 0.46 years). Results: Analysis of fc‐MVPA showed significant differences between group connectivity profiles in two clusters allocated in both the right and left medial temporal gyrus. Post hoc effect size results revealed a decreased rs‐FC between each temporal pole and the DMN in children with DD and an increased rs‐FC between each temporal pole and the sensorimotor network. Conclusions: Our results suggest an aberrant information flow between resting‐state networks in children with DD, demonstrating the importance of these networks for arithmetic development. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is a common multifactorial neurological disease usually diagnosed during childhood. In this study, we present the contribution of consecutive genetic testing to the genetic diagnostic yield of childhood epilepsy. Methods: In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n = 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co‐occurring findings (including developmental delay/intellectual disability, brain malformations, macro‐/microcephaly, and dysmorphic features). Results: The overall diagnostic rate in this study was 33% (n = 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro‐/microcephaly 50% (6/12) and without macro‐/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71). Conclusion: Genotype–phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results. [ABSTRACT FROM AUTHOR]

Background/Objectives: Clinical trials have investigated the efficacy of rehabilitation robotics for various pathological conditions, but the overall impact on rehabilitation practice remains unclear. We comprehensively examined and analyzed systematic reviews (SRs) of randomized controlled trials (RCTs) investigating rehabilitative interventions with robotic devices. Methods: Four databases were searched using term combinations of keywords related to robotic devices, rehabilitation, and SRs. The SR meta-analyses were categorized into "convincing", "highly suggestive", "suggestive", "weak", or "non-significant" depending on evidence strength and validity. Results: Overall, 62 SRs of 341 RCTs involving 14,522 participants were identified. Stroke was most frequently reported (40 SRs), followed by spinal cord injury (eight SRs), multiple sclerosis (four SRs), cerebral palsy (four SRs), Parkinson's disease (three SRs), and neurological disease (any disease causing limited upper- and lower-limb functioning; three SRs). Furthermore, 38, 21, and 3 SRs focused on lower-limb devices, upper-limb devices, and both upper- and lower-limb devices, respectively. Quantitative synthesis of robotic intervention effects was performed by 51 of 62 SRs. Robot-assisted training was effective for various outcome measures per disease. Meta-analyses offering suggestive evidence were limited to studies on stroke. Upper-limb devices were effective for motor control and activities of daily living, and lower-limb devices for walking independence in stroke. Conclusions: Robotic devices are useful for improving impairments and disabilities in several diseases. Further high-quality SRs including RCTs with large sample sizes and meta-analyses of these RCTs, particularly on non-stroke-related diseases, are required. Further research should also ascertain which type of robotic device is the most effective for improving each specific impairment or disability. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the roles of microglia and macrophages in neuroinflammation and their dual impact on the progression of neurological diseases. Background: Microglia and macrophages are integral components of the central and peripheral nervous systems, where they play important roles in maintaining homeostasis, influencing disease progression, and facilitating repair mechanisms. Methods: The review integrates recent advancements in single‐cell RNA sequencing that highlight the extensive heterogeneity of microglia and macrophages, which helps in understanding their wide‐ranging roles in different neurological conditions. Results: The analysis reveals that microglia and macrophages have a dual nature, capable of both exacerbating and mitigating disease processes across various conditions, including Alzheimer's disease, multiple sclerosis, stroke, peripheral nerve disorders, and brain tumors. Conclusion: Modulating the activity of microglia and macrophages offers a promising avenue for therapeutic interventions in neurological disorders. There is a critical need for further research to fully leverage their therapeutic potential in targeting neuroinflammation to enhance patient outcomes. [ABSTRACT FROM AUTHOR]