Hasil untuk "Neurology. Diseases of the nervous system"

S. Traynelis, L. Wollmuth, C. McBain et al.

Mallikarjuna Nimgampalle, Harshini Chakravarthy, Sapana Sharma et al.

Neurotransmitters serve as chemical messengers playing a crucial role in information processing throughout the nervous system, and are essential for healthy physiological and behavioural functions in the body. Neurotransmitter systems are classified as cholinergic, glutamatergic, GABAergic, dopaminergic, serotonergic, histaminergic, or aminergic systems, depending on the type of neurotransmitter secreted by the neuron, allowing effector organs to carry out specific functions by sending nerve impulses. Dysregulation of a neurotransmitter system is typically linked to a specific neurological disorder. However, more recent research points to a distinct pathogenic role for each neurotransmitter system in more than one neurological disorder of the central nervous system. In this context, the review provides recently updated information on each neurotransmitter system, including the pathways involved in their biochemical synthesis and regulation, their physiological functions, pathogenic roles in diseases, current diagnostics, new therapeutic targets, and the currently used drugs for associated neurological disorders. Finally, a brief overview of the recent developments in neurotransmitter-based therapeutics for selected neurological disorders is offered, followed by future perspectives in that area of research.

Constanza C. Corrotea-Maltez, Catalina V. Fernández-Flores, Constanza L. Gutiérrez-Neira et al.

IntroductionAdmission to neonatal or pediatric intensive care units exposes vulnerable patients to confounding environmental cues, disrupting circadian rhythms and potentially compromising physiological stability. While various circadian interventions exist, ranging from simple light cycling to complex multicomponent bundles, it remains unclear whether complex bundles offer superior clinical benefits over single-modality interventions. This systematic review evaluated the efficacy of circadian interventions on physiological parameters and sleep primarily in critically ill neonates and children, specifically comparing single versus combined strategies.MethodsA systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. We searched five major electronic databases: PubMed, ScienceDirect, CINAHL, WoS, Scopus and LILACS. Additionally, the Epistemonikos and SciELO databases were screened to identify relevant studies published in languages other than English. The search covered from inception to 2025 and was conducted during October 2025. Risk of bias was assessed using the Cochrane RoB 2 tool and ROBINS-I, while the certainty of evidence was evaluated using the GRADE approach. Data were synthesized using random-effects meta-analysis for physiological outcomes and SWiM guidelines for studies with non-parametric or incompatible data.ResultsForty-one studies (N = 2,548) met the inclusion criteria. Meta-analysis of 16 studies demonstrated that circadian interventions significantly reduced heart rate (SMD -0.70; 95% CI [−1.10, −0.30]; p < 0.001) and respiratory rate (SMD −0.75; p < 0.001), while improving oxygen saturation (SMD + 1.33; p < 0.001) and increasing sleep duration (SMD + 0.92; p < 0.001). Narrative synthesis of 16 additional studies confirmed these findings, with 81.2% reporting positive outcomes. Importantly, subgroup analysis revealed no statistically significant difference between single and multicomponent interventions across any outcome (p > 0.05). The certainty of evidence was graded as low due to the inherent inability to blind environmental interventions and statistical heterogeneity.ConclusionCircadian interventions are effective strategies for modulating physiological parameters and improving sleep quality in the NICU. Single interventions, such as cycled lighting, yielded similar outcomes to complex multicomponent bundles, but due to the lack of pediatric research, our results should be interpreted with caution. Future research should prioritize primary research in pediatric settings to deepen our understanding about circadian interventions.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/8SPZM, Identifier: CRD4201091137.

B. Chow, Chenghua Gu

Alexei Verkhratsky, Alexey Semyanov

Zhengwei Chen, Liangqun Rong, Lijie Xiao et al.

ObjectiveTo investigate changes of brain functional activity in patients with acute unilateral vestibulopathy (AUVP) using functional magnetic resonance imaging (fMRI).MethodsWe studied 32 AUVP patients and 30 healthy controls (HC) who received resting-state fMRI scanning. Methods of voxel-based amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were adopted to compare the difference in brain function between the two groups. In addition, we evaluated the associations between abnormal neuroimaging results and clinical data in AUVP patients.ResultsCompared with HC, patients with AUVP showed lower ALFF in brain regions of bilateral insular, right precentral gyrus, left inferior frontal gyrus and right middle frontal gyrus, as well as higher ALFF in left cerebellar anterior lobe. Using these abnormal brain areas as seeds, we observed decreased FC between left insular and left precuneus in AUVP patients. Furthermore, AUVP patients showed increased FC between left insular and left supplementary motor area. Results of correlation analysis indicated that ALFF value (z-value) in left insular was negatively correlated with the canal paresis value (p = 0.005, r = −0.483), and the FC (z-value) between left insular and left precuneus was negatively correlated with dizziness handicap inventory score (p = 0.012, r = −0.438) in patients with AUVP.ConclusionPatients with AUVP during acute period showed altered functional activity and connectivity in brain regions mainly involved in motor control and vestibular information processing. These changes in brain functional activity and connectivity were potentially attributed to decreased vestibular input resulting from unilateral peripheral vestibular impairment.

Vanessa Pitz, Mary B. Makarious, Sara Bandres-Ciga et al.

Abstract Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies. The meta-analysis resulted in five significant variants after Bonferroni correction, including variants in GBA1 and LRRK2. Another eight variants are strong candidate variants for their association with PD. Here, we provide the largest rare variant meta-analysis to date, providing information on confirmed and newly identified variants for their association with PD using several large databases. Additionally we also show the complexities of studying rare variants in large-scale cohorts.

Priyanshi Dixit, Saumya P Srivastava, Surya Kant Tiwari et al.

Background: Nurses frequently experience compassion fatigue and burnout, which impact their personal lives and patient care. The COVID-19 pandemic additionally caused stress, uncertainty, and fear of death among healthcare professionals. Aim: To assess professional quality of life (ProQoL) among nurses after the second wave of the COVID-19 pandemic. Material and Methods: A web-based cross-sectional study was conducted among 203 nurses using a purposive sampling technique in the month of September to December 2021. Data were collected using a self-administered ProQoL scale version 5. Statistical Analysis: Descriptive and inferential statistics were used. Kolmogorov–Smirnov test, Mann–Whitney U, and Kruskal–Wallis H test were used. Bivariate correlations were used to correlate the main variables. Multiple linear regression analysis was also performed. Results: The majority of the nurses reported a moderate level of compassion satisfaction (CS) (62.6%), burnout (BO) (66.0%), and secondary traumatic stress (STS) (63.1%). Residence and education emerged as a factor whether the nurses experienced BO or STS, respectively. Additionally, CS negatively correlated with BO (r = -0.732: P < 0.001) and STS (r = -0.141: p-0.04). Conclusions: The majority of the nurses experienced moderate levels of CS, BO, and STS after the second wave of the COVID-19 crisis and nurse patient–ratio emerged as a significant factor to predict CS, BO, or STS. Hence, effective measures need to be implemented by hospital administration to enhance the nurses' satisfaction and reduce fatigue and burnout.

Taras O. Simaniv, Anna A. Belkina, Maria N. Zakharova

Demyelinating diseases of the central nervous system and multiple sclerosis in particular are a pressing issue for medical community and society as a whole. Deve- lopment and implementation of highly effective specific therapy significantly slow the disease progression and help maintain patients' quality of life and social participation. We analyzed pathogenic mechanisms of multiple sclerosis and other B cell-mediated diseases and reviewed therapeutic options for main disease stages.

Simone Hemm, Denise Baumann, Vasco Duarte da Costa et al.

BackgroundThe Fukuda-stepping-test (FST), i.e., repetitive walking on the spot while blindfolded, has been proposed as a means to assess the integrity of the vestibular pathways. While its sensitivity to detect abnormalities in patients is limited, it may be useful in studying the physiology of the subjective-straight-ahead (SSA). Considering reported systematic shifts in SSA in humans, we hypothesize that such asymmetries arise from individual differences in the orientation/configuration of the macular organs and in central processing of vestibular input. We hypothesize that such asymmetries are stable over time in individual subjects. Alternatively, such asymmetries may arise from random noise in the sensory/motor systems involved, demonstrating low reproducibility over time.Materials and methodsTwenty-four subjects walked on the spot over 60 s while blindfolded (n = 6 trials per subject). Using an inertial measurement unit (IMU) placed at the chest, angular deviations were recorded and compared to manually-measured final positions. Both static (direction, magnitude) and dynamic (time-to-onset of deviation, pattern of deviations) parameters were retrieved from the yaw slopes.ResultsSignificant deviations were found in 15/24 participants for the manual measurements (leftwards = 8; rightwards = 7), whereas when using the IMU-sensor 13/24 participants showed significant shifts (leftwards = 9; rightwards = 4). There was a high correlation (0.98) between manually measured rotation angles (average absolute deviations = 58.0 deg ± 48.6 deg; intra-individual variability = 39 deg ± 24 deg) and sensor-based yaw slopes (1.00 deg/s ± 0.88 deg/s; 0.67 deg/s ± 0.41 deg/s). Relevant yaw deviation was detected 22.1 s ± 12.3 s (range = 5.6 s-59.2 s) after the onset of marching (no relevant yaw-deviation in 15/139 measurements), showing a mostly linear behavior over time.ConclusionWe observed significant inter-individual variability in task performance in the FST, reproducing findings from previous studies. With test-re-test reliability being moderate only, but at the same time observing a preference in the side of shifts in most trials and subjects, we conclude that likely both individually varying estimates of straight-ahead and random noise contribute to the pattern of angular deviations observed. Using an IMU-sensory based approach, additional dynamic parameters could be retrieved, emphasizing the value of such a quantitative approach over manual measurements. Such an approach may provide useful additional information to distinguish patients from healthy controls.

Mengmeng Liu, Jianling Tan, Yuhao Jiang et al.

Objectives The application of electroencephalography (EEG) to the study of major depressive disorder (MDD) is a common approach. However, there is no one-to-one correspondence between EEG and brain neural activity, and it is unclear whether single-trial EEG signals detect the cognitive neural activity of MDD. Methods Here, we used deep learning to explore this issue. Deep learning adopted in this paper was an end-to-end classification method named EEGNet which could update model parameters automatically based on the characteristics of the data and classify MDD and healthy subjects (HS) from single-trial EEG signals to obtain classification results above the chance level. Furthermore, the saliency map was used to analyze the neural network model and visualize the channels and time periods that contributed the most. Results Finally, EEGNet achieved an average classification accuracy of 61.4% in the four categories, and the result of feature visualization was consistent with the cognitive neural interpretation of existing studies. Conclusion The findings suggested that deep learning could help cognitive neuroscience explore neural activity.

Konstantin Butenko, Ningfei Li, Clemens Neudorfer et al.

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulation of neural activity.Objective: The aim of this project was to investigate correlations between patient-specific pathway activation profiles and clinical motor improvement.Methods: We used the concept of pathway activation modeling, which incorporates advanced volume conductor models and anatomically authentic fiber trajectories to estimate DBS-induced action potential initiation in anatomically plausible pathways that traverse in close proximity to targeted nuclei. We applied the method on two retrospective datasets of DBS patients, whose clinical improvement had been evaluated according to the motor part of the Unified Parkinson’s Disease Rating Scale. Based on differences in outcome and activation levels for intrapatient DBS protocols in a training cohort, we derived a pathway activation profile that theoretically induces a complete alleviation of symptoms described by UPDRS-III. The profile was further enhanced by analyzing the importance of matching activation levels for individual pathways.Results: The obtained profile emphasized the importance of activation in pathways descending from the motor-relevant cortical regions as well as the pallidothalamic pathways. The degree of similarity of patient-specific profiles to the optimal profile significantly correlated with clinical motor improvement in a test cohort.Conclusion: Pathway activation modeling has a translational utility in the context of motor symptom alleviation in Parkinson’s patients treated with DBS.

Jose M. Serra López-Matencio, Yaiza Pérez García, Virginia Meca-Lallana et al.

Background: Plasma concentration of natalizumab falls above the therapeutic threshold in many patients who, therefore, receive more natalizumab than necessary and have higher risk of progressive multifocal leukoencephalopathy.Objective: To assess in a single study the individual and treatment characteristics that influence the pharmacokinetics and pharmacodynamics of natalizumab in multiple sclerosis (MS) patients in the real-world practice.Methods: Prospective observational study to analyse the impact of body weight, height, body surface area, body mass index, gender, age, treatment duration, and dosage scheme on natalizumab concentrations and the occupancy of α4-integrin receptor (RO) by natalizumab.Results: Natalizumab concentrations ranged from 0.72 to 67 μg/ml, and RO from 26 to 100%. Body mass index inversely associated with natalizumab concentration (beta = −1.78; p ≤ 0.001), as it did body weight (beta = −0.34; p = 0.001), but not height, body surface area, age or gender Extended vs. standard dose scheme, but not treatment duration, was inversely associated with natalizumab concentration (beta = −7.92; p = 0.016). Similar to natalizumab concentration, body mass index (beta = −1.39; p = 0.001) and weight (beta = −0.31; p = 0.001) inversely impacted RO. Finally, there was a strong direct linear correlation between serum concentrations and RO until 9 μg/ml (rho = 0.71; p = 0.003). Nevertheless, most patients had higher concentrations of natalizumab resulting in the saturation of the integrin.Conclusions: Body mass index and dosing interval are the main variables found to influence the pharmacology of natalizumab. Plasma concentration of natalizumab and/or RO are wide variable among patients and should be routinely measured to personalize treatment and, therefore, avoid either over and underdosing.

Raquel Vidal, Laura Vidal, Francesc Ristol et al.

Objetivo: El objetivo de este estudio fue evaluar la eficacia de la Terapia Asistida con Perros (TAP) en niños y adolescentes con Trastorno del Espectro Alcohólico Fetal (TEAF). Método: Realizamos un ensayo piloto aleatorizado y controlado, cegado por el evaluador, en una cohorte de 33 niños y adolescentes con TEAF. Los participantes fueron asignados aleatoriamente al grupo TAP (n=17) o al tratamiento habitual (n=16). Resultados: De los 39 participantes iniciales inscritos, 33 completaron el tratamiento. Un análisis de modelo de efectos mixtos reveló que los participantes que fueron asignados al grupo TAP experimentaron mejoras significativas en habilidades sociales (SSIS-P Habilidades sociales: p = 0.02; d = 0.8), reducciones en los síntomas de externalización (CBCL Externalización p = 0.03; d = 0.56) y puntuaciones más bajas en la severidad del TEAF (CGI-S Clínico: p = 0.001; d = 0.5). Conclusiones: La TAP parece ser un tratamiento complementario prometedor para niños y adolescentes con TEAF.

Lambert M, Sanchez P, Bergmans P et al.

Martin Lambert,1 Pedro Sanchez,2,3 Paul Bergmans,4 Srihari Gopal,5 Maju Mathews,6 Annette Wooller,7 Katalin Pungor8 1Centre for Psychosis and Integrated Care, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Treatment Resistant Psychosis Unit, Hospital Psiquiatrico De &Aacute;lava, Osakidetza, Vitoria, Spain; 3School of Medicine, University of Deusto, Bilbao, Spain; 4Janssen-Cilag B.V., Biostatistics, Breda, Netherlands; 5Janssen R&amp;D LLC, Titusville, NJ, USA; 6Janssen Pharma, Global Medical Affairs, New York City, NY, USA; 7Janssen, Medical Affairs EMEA, High Wycombe, UK; 8Janssen Medical Affairs EMEA, Janssen-Cilag GmbH. Johnson and Johnson Platz 1, 41470 Neuss, GermanyCorrespondence: Katalin Pungor Tel +491724463940Email kpungor@its.jnj.comPurpose: This pragmatic clinical study aimed to assess goal attainment among patients with schizophrenia treated with paliperidone palmitate 3-monthly (PP3M) and its relation to their level of disability, and whether patients achieved symptomatic remission at the study endpoint.Patients and Methods: Goal attainment was assessed as a secondary endpoint using Goal Attainment Scaling (GAS) within a 52-week, prospective, single-arm, non-randomized, open-label, international, multicenter study evaluating the impact of transitioning stable patients with schizophrenia from paliperidone palmitate 1-monthly (PP1M) to PP3M. Additional exploratory analyses were performed to investigate the relationship between disability and functioning as measured by the World Health Organization Disability Assessment Schedule (WHODAS), Version 2.0, symptomatic remission, and goal attainment.Results: Overall, 305 patients were enrolled, of whom 281 (92.1%) provided GAS data at baseline. Of these, 160 achieved symptomatic remission at the last observation carried forward (LOCF) endpoint. The most common category of goals was &ldquo;self&rdquo; related, of which work-related was most frequent. Two-thirds of patients (67.7%) achieved at least one goal at the LOCF endpoint. Goal achievement was positively associated with lower baseline symptoms and symptomatic remission at LOCF endpoint, and with lower WHODAS scores at baseline and LOCF endpoint and greater WHODAS score improvements from baseline. Age, duration of disease, and duration of PP1M treatment before the switch did not impact goal setting and goal attainment. The proportion of patients with remunerated work status increased by 11.3% at LOCF endpoint.Conclusion: The results of this secondary endpoint analysis indicate that continued treatment of patients with schizophrenia with PP3M following stabilization with PP1M may facilitate attainment of patients&rsquo; personal goals and reduce disability, especially, but not exclusively, in patients with symptomatic remission achieved at LOCF.Keywords: GAS, goal attainment, paliperidone palmitate 1-monthly formulation, paliperidone palmitate 3-monthly formulation, schizophrenia, WHODAS

Zheng Jiang, Xinran Xu, Xiaojing Gu et al.

Background: The causal relationship between serum lipid levels and the risk of Parkinson's disease (PD) remains largely uncertain. We summarized the existing controversial evidence on this topic.Methods: We searched the electronic databases for observational studies from January 1988 to March 2020. We applied random-effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). Random-effects dose-response meta-analyses were further conducted to explore the dose-risk relationship.Results: Twelve cohort studies and three case-control studies were included in this meta-analysis. Higher levels of serum low-density lipoprotein cholesterol (LDL-C) were inversely associated with the subsequent risk of PD (RR 0.73, 95% CI 0.57–0.93), whereas, there were no associations between serum levels of total cholesterol (TC) (RR 0.91, 95% CI 0.73–1.13), high-density lipoprotein cholesterol (HDL-C) (RR 0.97, 95% CI 0.73–1.27), or triglycerides (TG) (RR 0.85, 95% CI 0.55–1.29) and the risk of PD. Further dose-response meta-analysis revealed that every 38.6 mg/dL (1mmol/L) increase in serum LDL-C correlates with a 7% decreased risk of PD.Conclusions: Our paper supports the protective effect of higher serum LDL-C on the subsequent risk of PD. More prospective cohort studies are warranted to confirm the conclusion, and further fundamental researches are needed to elucidate the underlying biological mechanisms.

Haleh Heizomi, Hamid Allahverdipour, Mohammad Asghari Jafarabadi et al.

Abstract Background Poor mental health is common among adolescents. Given the increasing burden of poor mental health among adolescents in developing countries, it seems necessary to identify the effective interventions. The main purpose of this study was to investigate the effects of a school-based mental health promotion program (SMHPP) on mental health parameters among female adolescents in Tabriz, Iran. Method In this experimental study, a random sample of female high-school students of grade nine was recruited. The subjects were then randomly allocated to intervention (n = 145) and control (n = 139) groups. The three-stage SMHPP was designed based on the shortages and unmet needs of the students as reported in the pretest stage. All subjects in the intervention group were provided with a stress management skill training program of six sessions using McNamara Model. Coincided with making environmental changes, a joyful intervention program was carried out. After 2 months, post-test data were collected. Results A total of 284 students completed their participation in the study. The groups did not differ in none of socio-demographic characteristics and mental health parameters, at baseline. The number of subjects reporting medium-level of happiness was increased by 32.6% among intervention group. Moreover, upon sign test and pre-post comparison, the group-wise distribution changed between the intervention and control groups for the parameters of life satisfaction (p ≤ 0.001) and psychological well-being (p ≤ 0.01). Conclusion The implementation of SMHPP as a low-cost, needs-based and multifaceted program, showed promise in promoting adolescents’ mental health, particularly in the parameters of happiness, life satisfaction and psychological well-being. This was an important evidence for the development and implementation of interventions and policies in the field of mental health promotion among adolescents. Our work provided means for reducing burden of poor mental health among adolescents in a non-western cultural context. Further larger studies are required to evaluate the effectiveness of such school-based mental health promotion interventions in students.

Catherine Henderson, Martin Knapp, Sharon M. Nelis et al.

Abstract Introduction We examined 3‐month service use and costs of care for people with mild‐to‐moderate dementia in Great Britain. Methods We analyzed Improving the experience of Dementia and Enhancing Active Life cohort study baseline data on paid care, out‐of‐pocket expenditure, and unpaid care from participants with dementia (N = 1547) and their carers (N = 1283). In regression analyses, we estimated per‐group mean costs of diagnostic and sociodemographic subgroups. Results Use of services apart from primary and outpatient hospital care was low. Unpaid care accounted for three‐quarters of total costs (mean, £4008 [standard error, £130] per participant). Most participants (87%) received unpaid care equating to 36 hours weekly. Estimated costs for people with Parkinson's dementia were £8609, £4359 for participants with mixed dementia, and £3484 for those with Alzheimer's disease. Total costs were lower for participants with dementia living alone than living with others (£2484 vs. £4360); costs were lower for female than for male participants (£3607 vs. £4272). Discussion Costs varied by dementia subtype, carer status, and living arrangement. Policy makers should recognize the high costs of unpaid care for people with dementia, who do not always get the support that they need or would like to receive.