Search Results (4,355)

Parkinson’s disease (PD) is a progressive and heterogeneous neurodegenerative disorder and one of the fastest-growing causes of neurological disability worldwide. Although historically defined by motor manifestations resulting from nigrostriatal dopaminergic degeneration, PD is now recognized as a multisystem disorder. Non-motor features—including autonomic dysfunction, neuropsychiatric symptoms, cognitive impairment, and sleep-related disorders—frequently precede motor onset by years or even decades, delineating a clinically meaningful prodromal phase. The aetiology of PD reflects a complex interplay between genetic susceptibility and environmental exposures. Approximately 20% of cases are linked to identifiable pathogenic variants, most commonly in LRRK2, GBA1, and SNCA, whereas the majority arise from cumulative interactions among environmental factors, lifestyle determinants, and common genetic risk variants rather than from single causal mechanisms. Despite substantial advances in understanding disease biology, current therapies remain fundamentally symptomatic. Dopaminergic pharmacotherapy and device-aided interventions improve motor function and, in selected contexts, functional outcomes, but they do not modify disease progression. Non-motor symptoms remain a dominant driver of disability and reduced quality of life. Recent conceptual frameworks propose redefining PD as a biologically defined α-synucleinopathy. Emerging biomarkers, including α-synuclein seed amplification assays in cerebrospinal fluid and peripheral tissues, offer unprecedented opportunities to define biological disease, enable early detection, and stratify patients. However, biomarker positivity currently informs diagnosis and classification rather than prognostication or therapeutic selection, and validated intermediate endpoints linking biomarker change to sustained functional benefit remain lacking. Consequently, translation into disease-modifying therapies has been constrained by late-stage intervention, reliance on clinically defined populations, limited trial generalizability, and marked global inequities in access to advanced diagnostics and treatments. This narrative review synthesizes current evidence on PD epidemiology, diagnosis, aetiology, progression, and treatment, emphasizing gene–environment interactions, convergence on shared pathogenic pathways, limitations of existing therapeutic paradigms, and the as-yet unrealized potential of biologically informed precision care. Full article

Eye movement classification, particularly the identification of fixations and saccades, plays a vital role in advancing our understanding of neurological functions and cognitive processing. Conventional modalities of data, such as RGB webcams, often face limitations such as motion blur, latency and susceptibility to noise. Neuromorphic Vision Sensors, also known as event cameras (ECs), capture pixel-level changes asynchronously and at a high temporal resolution, making them well suited for detecting the swift transitions inherent to eye movements. However, the resulting data are sparse, which makes them less well suited for use with conventional algorithms. Spiking Neural Networks (SNNs) are gaining attention due to their discrete spatio-temporal spike mechanism ideally suited for sparse data. These networks offer a biologically inspired computational paradigm capable of modeling the temporal dynamics captured by event cameras. This study validates the use of Spiking Neural Networks (SNNs) with event cameras for efficient eye movement classification. We manually annotated the EV-Eye dataset, the largest publicly available event-based eye-tracking benchmark, into sequences of saccades and fixations, and we propose a convolutional SNN architecture operating directly on spike streams. Our model achieves an accuracy of 94% and a precision of 0.92 across annotated data from 10 users. As the first work to apply SNNs to eye movement classification using event data, we benchmark our approach against spiking baselines such as SpikingVGG and SpikingDenseNet, and additionally provide a detailed computational complexity comparison between SNN and ANN counterparts. Our results highlight the efficiency and robustness of SNNs for event-based vision tasks, with over one order of magnitude improvement in computational efficiency, with implications for fast and low-power neurocognitive diagnostic systems. Full article

Background/Objectives: Primary metabolic diseases including mitochondrial encephalomyopathies (ME), glycolytic enzymopathies, and disorders of lipid and amino acid metabolism can manifest with severe neurological and neuromuscular symptoms. Conversely, it is increasingly appreciated that primary neurodegenerative diseases can have metabolic etiology and pathophysiology. Pharmacological treatments have limited benefit for these classes of diseases, but dietary therapy is increasingly recognized as a tool for bolstering metabolic processes that can ameliorate neurological symptoms. The ketogenic diet is the best-established example, having long been used as a therapy for epilepsy. Replenishing metabolic intermediates (anaplerosis) especially substrates of the citric acid cycle (CAC) is currently being explored, with ongoing clinical trials of simple metabolic intermediates such as oxaloacetate or NAD+ to treat neurodegenerative diseases. We have shown ketogenic and anaplerotic therapies to be effective in a Drosophila model of ME; however, the full therapeutic potential and role of the CAC in neuronal health is still not well understood. Methods: Here, we have used genetic, behavioral, and dietary approaches to elucidate critical links between the CAC and neurological function. Results: We have found that stimulating the CAC can improve and sustain neurological health in the face of severe metabolic disease, and that its functions include a previously unrecognized role in maintaining normal circadian rhythms, whose disruption is often an early indicator or complicating factor in neurological and neurodegenerative disease. We investigated the hypothesis that the production of GTP by the CAC may be an important mechanistic contributor to the role of the CAC in neurological health and disease, and may underlie its therapeutic potential. Conclusions: Overall, our findings expand our understanding of the role of the CAC in neurological health and disease, support its development as a therapeutic target, and provide a foundation for further studies investigating the intersection between neurological disease and metabolic function. Full article

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all cell types into the extracellular space, acting as important mediators of intercellular communication by transferring proteins, lipids, and nucleic acids horizontally. EVs are generally classified into small EVs (<200 nm), medium/large EVs (>200 nm), microvesicles, and apoptotic bodies, with current classification methods focusing on physical properties, molecular composition, and cellular origin, as detailed in the MISEV2023 guidelines. EVs are highly promising for diagnostic and therapeutic applications due to their intrinsic biocompatibility, stability in biological fluids, capacity to carry diverse molecular cargo, and potential for drug delivery and functionalization to enable targeted delivery and tissue repair. This narrative review discusses the emerging roles of EVs across various medical fields, including obstetrics and gynecology, ophthalmology, otorhinolaryngology, urology, oncology, orthopedics, neurology, immunology, wound healing, chronic pain management, dermatology, and cardiology. In each discipline, EVs show potential as biomarkers for diagnosing physiological or pathological conditions and as carriers for targeted drug delivery and regenerative treatments. Exosomes, a major type of small EVs, have especially attracted attention as versatile nanocarriers for precision medicine. However, translation into clinical practice requires addressing key pitfalls, including the standardization of isolation and characterization protocols, dose definition, GMP-compliant large-scale production, and regulatory approval. Ongoing interdisciplinary collaboration across disciplines and thorough clinical testing will be essential to unlock the full biomedical potential of EVs and establish them as transformative tools in personalized healthcare. Full article

Background and Clinical Significance: Hypoglossal nerve palsy is an uncommon neurological complication of infectious mononucleosis and is only rarely reported. Putative mechanisms include virus-triggered neuritis (Epstein–Barr virus (EBV) or Cytomegalovirus (CMV)) and/or mechanical compression related to cervical lymphadenopathy. Case Presentation: We report two children with infectious mononucleosis and transient unilateral hypoglossal nerve palsy. Case 1 was a 15-year-old boy with 7 days of fever and typical mononucleosis features who developed leftward tongue deviation accompanied by sialorrhea, dysarthria, and dysphagia. Laboratory testing showed marked hepatocellular injury and EBV-specific IgM positivity. Case 2 was a 9-year-old girl with a 24 h history of bilateral lateral cervical lymphadenopathy with overlying inflammatory signs; examination revealed rightward tongue deviation with similar associated symptoms. CMV-specific IgM antibodies were detected on serological testing. Both patients received systemic corticosteroids and empiric intravenous antibiotics, with supportive care. Hypoglossal nerve function fully recovered within 2–4 weeks of treatment initiation. Conclusions: These cases underscore that isolated hypoglossal nerve palsy may complicate EBV- or CMV-associated mononucleosis in children. Although the prognosis is generally favorable, the presentation warrants careful evaluation to exclude alternative causes of lower cranial neuropathies and close follow-up until complete neurological resolution. Full article

Background: Severe lower urinary tract dysfunction (LUTD) in neurologically and anatomically normal children is uncommon and frequently underdiagnosed. When severe, functional voiding disorders may closely mimic obstructive or reflux pathology, leading to diagnostic errors, unnecessary invasive procedures, and potential risk to the upper urinary tract. Case presentation: We present three pediatric cases (aged 3–10 years) referred for recurrent febrile urinary tract infections, incontinence, or acute urinary retention in the absence of neurological or structural abnormalities. Urodynamic evaluation identified three distinct severe functional phenotypes: detrusor overactivity with reduced bladder capacity, poor compliance with detrusor–sphincter dyssynergia and secondary high-grade vesicoureteral reflux (Hinman syndrome), and detrusor underactivity with significant post-void residual volumes. All patients demonstrated marked bladder wall remodeling on cystoscopy, including trabeculation and pseudopolypoid mucosal changes. Case discussion: Despite similar clinical severity, the cases illustrated substantial functional heterogeneity and differing risks of upper urinary tract involvement. Urodynamic phenotyping proved central to diagnosis, differentiation from structural disease, and treatment planning. Multimodal conservative management—including urotherapy, pelvic floor biofeedback, targeted pharmacologic therapy, and, when indicated, clean intermittent catheterization or antibiotic prophylaxis—led to resolution of recurrent infections and meaningful improvement in bladder function during medium-term follow-up, although symptom recurrence occurred in one patient after treatment withdrawal. Conclusions: These cases highlight the heterogeneity and potential reversibility of severe functional LUTD in otherwise healthy children. Early functional recognition based on urodynamic assessment is essential to avoid misdiagnosis, prevent unnecessary surgical intervention, and protect renal function. Conservative, function-oriented management remains the cornerstone of effective treatment. The findings are discussed in the context of the existing literature on severe non-neurogenic LUTD and Hinman syndrome. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic neurological disorder causing physical, cognitive, and psychological impairments that affect daily functioning and quality of life (QoL). Psychological distress, cognitive deficits, and reduced physical activity often co-occur, yet their associations with QoL across disability levels are unclear. This study examined these relationships in people with relapsing–remitting MS, stratified by disability severity. Materials and Methods: This cross-sectional study included 149 adults with RRMS. Disability severity was classified as mild, moderate, or severe using the Patient-Determined Disease Steps (PDDS) scale. Psychological distress was assessed using the Depression, Anxiety, and Stress Scale–21 (DASS-21), cognitive function using the Montreal Cognitive Assessment (MoCA), and physical activity using the International Physical Activity Questionnaire (IPAQ). QoL was evaluated using the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire. Stratified comparative analyses were conducted to examine differences in overall and domain-specific QoL according to levels of psychological distress, cognitive function, and physical activity within disability categories. Results: In participants with mild and moderate disability, higher levels of depression, anxiety, and stress were associated with lower QoL scores, particularly in domains related to activities of daily living, psychological well-being, and symptoms. Higher cognitive function and greater physical activity were associated with more favorable QoL across several domains. In those with severe disability, associations between psychological distress and QoL were less consistent, although stress remained associated with selected QoL domains. Conclusions: Psychological distress, cognitive function, and physical activity show distinct patterns of association with daily functioning and QoL across disability levels in RRMS. Although causal inferences cannot be drawn from this cross-sectional design, disability-stratified analyses provide clinically relevant insights into how these factors co-vary with QoL at different stages of disease severity. Full article

White matter injury (WMI) and blood–brain barrier (BBB) disruption contribute to neurological and cognitive deficits in intracerebral hemorrhage (ICH), with no effective pharmacological treatments available. Puerarin, with anti-inflammatory, anti-apoptotic, and antioxidant properties, exhibits neuroprotective potential. Here, mice subjected to ICH were treated with puerarin for 14 days. Neurological function, cerebral perfusion, and BBB integrity were assessed using behavioral tests, laser speckle imaging, Evans blue assays, immunofluorescence, Western blotting, and MRI. Integrated transcriptomics, machine learning, network pharmacology, molecular docking, and dynamics simulations were used to identify key targets. Puerarin improved neurological outcomes, reduced BBB permeability, enhanced microvascular perfusion, and attenuated WMI. Twenty-six hub genes were identified, with PARP1 and AKT1 correlated with OLIG2 and MBP, enriched in the cGAS-STING and AKT1-mTOR pathways. Molecular simulations indicated stable puerarin–cGAS interactions, validated experimentally: puerarin suppressed cGAS-STING activation, reduced oligodendrocyte apoptosis, and promoted remyelination. These results provide new insights into ICH pathogenesis and support puerarin as a potential therapeutic agent for BBB disruption and WMI. Full article

Background: Obsessive–compulsive disorder (OCD) is a heterogeneous psychiatric condition with substantial heritability. Early genetic studies were often underpowered and produced limited reproducibility, but recent large-scale genomic and multi-omic approaches are beginning to elucidate the genetic architecture of OCD. Objectives: This review aims to synthesise current evidence from recent genomic and epigenomic studies on OCD and their implications for molecular pathways of pathogenesis, including endophenotypes. Methods: We reviewed peer-reviewed literature and preprints published in recent years, focusing on multiple genetic approaches, including genome-wide association studies (GWAS), whole exome sequencing (WES), whole genome sequencing (WGS), and methylome-wide association studies (MWAS). We then integrated the results with endophenotypic evidence at the biochemical, physiological, structural, functional, and executive/cognitive levels. Results: Recent large-scale genomic studies provide strong evidence of a highly polygenic contribution from common variants, while rare coding and structural variants also contribute measurably, with enriched signals in pathways relevant to neurodevelopment and, in some cohorts, early-onset presentations. Epigenomic studies have moved from scattered findings to more replicable methylation patterns, including loci influenced by nearby genetic variation and indications of sex-dependent effects. Although convergence at the single-gene level remains limited, cross-study and cross-omics signals increasingly point to biological domains involving synaptic organisation and plasticity, neurological development and chromatin regulation, immune/stress pathways, and cellular homeostasis. Conclusions: The biology of OCD risk is best represented by an integrative model combining polygenic load, contributions from rare variants, and regulatory (epigenetic) mechanisms that influence intermediate phenotypes at the circuit and cognitive levels. The current findings are not yet clinically applicable for individual diagnosis; however, they may inform future multidisciplinary research frameworks and, in the longer term, contribute to the development of more personalised approaches in OCD. Full article

Introduction: Neurological injuries significantly impair quality of life by disrupting neural transmission. Traditional implantable stimulators often rely on internal batteries, which limit device longevity and necessitate repeated surgical interventions. Objective: This study presents the experimental validation of a battery-free, RFID-powered neural platform for peripheral nerve signal acquisition and stimulation, targeting TRL-6 validation. Methods: The prototype incorporates an adjustable analog front-end with gains up to 93 dB and a biphasic current-controlled stimulator. Validation was performed through benchtop testing, biological tissue assessments using porcine tissue, and functional in vivo trials in adult Wistar rats (n = 3) over a three-month period. Results: Benchtop evaluation confirmed gain accuracy with errors below 2.2 dB and precise stimulation timing. The system maintained a stable 3.3 V wireless power link through 20 mm of biological tissue using RFID. In vivo experiments indicated a 100% functional success rate (51/51 trials) in eliciting gross motor responses via wireless stimulation. Thermal safety was confirmed, with a maximum operating temperature of 28 °C, remaining well below physiological limits. Conclusions: The results demonstrate the functional feasibility of a battery-free, RFID-powered neural interface for wireless signal acquisition and stimulation, supporting system-level validation of this architecture. Full article

Adaptive locomotion requires the integration of cognitive and motor processes and is challenged in neurological disorders. Dual-task (DT) training may improve cognitive–motor coordination, but its feasibility across heterogeneous clinical populations is uncertain. This pilot study aimed to understand if the effects of a secondary motor or cognitive task added to a walking task depend on the functional walking abilities of the subjects. We enrolled 30 participants with neurological disorders not related to traumatic events, 5 for each one of the following groups: healthy young subjects (HeY), healthy control subjects (HeC), subjects with stroke (ictus, IC), Parkinson’s disease (PD), multiple sclerosis (MS), and Long-COVID sequelae (LC). Spatiotemporal gait parameters were recorded using a wearable inertial magnetic unit, and subjective workload was assessed with the visual analog scale (VAS) and NASA-Task Load Index. Regression models revealed strong baseline–DT coupling for stride duration (slopes 1.11–1.37; R² 0.85–0.97), stride length (slopes 0.93–0.94; R² 0.86–0.93), walking speed (slopes 0.87–0.98; R² 0.78–0.93), and gait ratio (stance/swing, slopes 0.38–0.60; R² 0.21–0.52). Mixed-effects analyses identified significant group effects for walking speed (F(5) = 7.218, p < 0.001), stride length (F(5) = 4.834, p = 0.001), gait cycle duration (F(5) = 5.630–5.664, p < 0.001), Walking Quality (F(5) = 4.340–4.373, p = 0.001), and propulsion index (F(5) = 5.668–6.843, p < 0.001). The incongruent DT condition was the most sensitive in differentiating clinical groups. NASA-TLX indicated higher perceived workload in IC and MS compared with non-clinical groups. The protocol was completed by all participants without adverse events, supporting the feasibility of the procedure in this pilot sample. Its predictable scaling across baseline gait metrics supports its use as a personalized rehabilitation tool for diverse neurological populations. (ClinicalTrials.gov NCT07254377). Full article

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus with suboptimal outcomes despite standard management. Emerging evidence suggests that thiamine (vitamin B1) deficiency may play an under-recognized role in DKA pathophysiology and clinical course. This narrative review synthesizes current evidence regarding thiamine deficiency in diabetes and DKA, examining molecular mechanisms, clinical implications, and the rationale for thiamine supplementation as adjunctive therapy. Thiamine deficiency is highly prevalent in diabetes, with plasma concentrations reduced by approximately 75% compared to healthy controls. In DKA specifically, 25–35% of patients present with thiamine deficiency, which often worsens during insulin therapy. The primary mechanism involves hyperglycemia-induced downregulation of renal thiamine transporters (THTR-1 and THTR-2), resulting in 16–24-fold increased renal clearance and massive urinary losses. Thiamine pyrophosphate serves as an essential cofactor for three critical enzymes in glucose metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency impairs these pathways, causing pyruvate accumulation with conversion to lactate (resulting in lactic acidosis), compromised TCA cycle function (reducing ATP production by 40–48%), and decreased NADPH generation (increasing oxidative stress). Clinical manifestations include persistent metabolic acidosis despite standard therapy, myocardial dysfunction with elevated cardiac biomarkers, neurological impairment, and prolonged recovery times. Cellular studies demonstrate that thiamine supplementation significantly improves mitochondrial oxygen consumption in DKA patients. The high prevalence of thiamine deficiency in DKA, compelling biochemical rationale, excellent safety profile, and preliminary mechanistic evidence support the urgent need for large-scale randomized controlled trials examining thiamine supplementation to definitively establish efficacy, optimal dosing, and patient selection criteria. Full article

Flaveria trinervia (Spreng) C. Mohr is a plant traditionally used in Mexican medicine. In this study, gas chromatography–mass spectrometry (GC–MS) combined with network pharmacology was employed to characterize volatile and semi-volatile metabolites from F. trinervia leaves and to explore their potential system-level mechanisms of action in inflammatory and tumor-related disorders. A dual extraction strategy (hexane/dichloromethane and acetone/chloroform) was applied, followed by GC–MS-based compound identification. Putative molecular targets were predicted using established pharmacological databases, and protein–protein interaction networks were constructed to identify topological features and enriched biological pathways. A total of 11 bioactive compounds were tentatively identified with an identity level of ≥80%, with seven shared between both extracts, including phytol, germacrene D, caryophyllene oxide, pinene isomers, squalene, and 2,2′:5′,2″-terthiophene, metabolites previously reported to exhibit antioxidant, anti-inflammatory, and cytotoxic activities. Network topology analysis identified ESR1, RXRA/B/G, NCOA2, and CYP19A1 as central nodes, reflecting convergence on signaling axes involved in apoptosis, cell proliferation, immune modulation, and transcriptional regulation pathways. Functional enrichment analysis revealed significant associations with KEGG pathways related to immune modulation, neuroendocrine regulation, and cancer-associated pathways. Collectively, these findings suggest a multitarget biological and multipathway pharmacological profile for F. trinervia, consistent with previously reported biological activities. The concordance between in silico predictions and existing experimental evidence strengthens the pharmacological relevance of the identified metabolites and supports their prioritization for further experimental validation, including mechanistic and pharmacokinetic studies, in metabolic, immune, neurological, and cancer-related contexts. Full article

Trace elements are widely involved in fundamental physiological processes, including enzymatic reactions, neurotransmitter metabolism, and redox homeostasis, and their balanced regulation plays an important role in maintaining normal brain development and neurological function. Depression is a complex psychiatric disorder characterized primarily by mood disturbances, with its onset and progression arising from long-term interactions among genetic susceptibility, neurobiological alterations, and environmental factors. A substantial body of epidemiological and clinical evidence indicates that dysregulation of trace elements—such as zinc, selenium, iron, and magnesium—is closely associated with the risk of depression and the severity of depressive symptoms. Mechanistic studies further demonstrate that trace elements influence depression-related pathophysiology through multi-target and multi-pathway mechanisms, including modulation of monoaminergic neurotransmission, neuroinflammation, oxidative stress, mitochondrial energy metabolism, and hypothalamic–pituitary–adrenal axis function. Network pharmacology analyses have additionally identified systemic hub targets, such as albumin (ALB), insulin (INS), and TP53, as well as key pathways including calcium signaling, neuroactive ligand–receptor interactions, and the HIF-1 signaling pathway. These findings suggest that trace elements may regulate depression-related pathological processes through coordinated network-level effects. Collectively, these integrative insights provide a theoretical basis for the application of trace elements in depression risk assessment, the development of precision intervention strategies, and future mechanistic investigations. Full article

Background: Thoracic endovascular aortic repair (TEVAR) has evolved the management of descending thoracic aortic disease, but neurological complications—particularly spinal cord ischemia (SCI), stroke, and postoperative delirium—remain among the most feared adverse events, adversely affecting survival, quality of life, and functional independence. Objectives: The aim of this study was to provide a contemporary narrative synthesis (2000–2025) of the incidence, mechanisms, risk factors, prevention, and management of neurological complications after TEVAR, emphasizing how current evidence supports individualized and risk-adapted strategies for prevention and management. Methods: A narrative, non-systematic search (PubMed/MEDLINE, Scopus, Cochrane Library; 2000–2025) was conducted using terms related to TEVAR, SCI, cerebrovascular events, delirium, and cognitive dysfunction. Priority was given to large registries, cohort studies, and systematic reviews in adult TEVAR populations. Results: Perioperative stroke occurs in ~2–6% of TEVAR cases, with higher rates in arch/zone 0–2 procedures and when the left subclavian artery (LSA) is covered without revascularization. SCI incidence ranges from ~2–9%, influenced by aortic extent and urgency; Vascular Quality Initiative data report SCI in 3.7% of procedures, with markedly reduced 1-year survival. Major SCI risk factors include extensive thoracic coverage, prior aortic repair, vertebral or hypogastric occlusion, emergency presentation, low perioperative mean arterial pressure, anemia, and chronic kidney disease. Postoperative delirium occurs in ~13% of TEVAR-treated type B dissections and correlates with longer hospitalization and early complications. Emerging nomograms for SCI and delirium enable individualized risk stratification. Conclusions: Neurological complications after TEVAR remain clinically significant. Contemporary evidence supports personalized prevention—selective cerebrospinal fluid (CSF) drainage, LSA revascularization, staging, neuromonitoring, and tailored hemodynamic targets—guided by anatomical complexity, comorbidities, collateral network integrity, and prior aortic history. Further research should refine prediction tools, standardize definitions, and evaluate individualized neuroprotective bundles. Full article