Search Results (1,818)

Post-stroke epilepsy (PSE) is one of the most common long-term neurological complications of stroke and represents a major contributor to disability, reduced quality of life, and increased healthcare burden. Although numerous risk factors and biomarkers have been proposed, many current risk models still emphasize lesion-related predictors and do not fully account for the temporal evolution of post-stroke network excitability. This narrative review aims to examine post-stroke epileptogenesis as a dynamic process of network reconfiguration and to summarize current evidence on biological, neurophysiological, imaging, and clinical biomarkers across different stages following stroke. A structured narrative review of the literature was performed using major biomedical databases. Studies addressing mechanisms of post-stroke epileptogenesis, biomarkers, network dysfunction, neuroinflammation, EEG findings, neuroimaging correlates, and longitudinal monitoring strategies were evaluated and synthesized qualitatively. Evidence suggests that post-stroke epileptogenesis is driven by complex interactions among structural injury, neuroinflammation, blood–brain barrier dysfunction, neurotransmitter imbalance, maladaptive plasticity, and large-scale network reorganization. Importantly, many biomarkers demonstrate substantial temporal variability, and their clinical significance depends on the stage of recovery and the evolving state of brain networks. Emerging data indicate that sleep disturbances, stress, mood disorders, metabolic factors, and other state-dependent influences may further modulate seizure susceptibility after stroke. Post-stroke epileptogenesis may be better conceptualized as a dynamic process of network instability rather than a fixed consequence of focal brain damage. It is proposed that the post-stroke brain can transiently or persistently enter an “irritable brain state”, characterized by increased vulnerability to pathological synchronization under the influence of biological and behavioral modulators. This framework may facilitate the development of longitudinal biomarker strategies and personalized monitoring approaches in future research. However, it should be emphasized that the “irritable brain state” remains a conceptual and hypothesis-generating construct; no validated diagnostic criteria exist, and prospective evidence demonstrating that interventions targeting this state reduce the incidence of post-stroke epilepsy is currently lacking. Full article

Hepatic encephalopathy (HE) is a complex of pathological processes in the brain caused by liver failure or portosystemic shunting. Even though ammonia (In this review, the term “ammonia” refers to total ammonia (ammonia gas and ammonium ion)) is widely recognized as the primary neurotoxin responsible for triggering the cerebral energy crisis and subsequent neurological manifestations of HE, its broader systemic effects are often overlooked. Meanwhile, the brain, which features the highest level of oxidative metabolism and extremely low energy reserves requires a constant supply of highly oxygenated and glucose-rich blood. Therefore, ammonia-induced disruptions in interorgan metabolic communication, leading to a restriction of vital energy substrates reaching the brain, are highly likely involved in this pathology. Currently, ammonia-related impairment of the metabolic relationship between the brain and extracerebral tissues is underestimated. This review summarizes generally accepted concepts and focuses on recent advances detailing how ammonia pathologically disrupts the highly integrated metabolic pathways in the liver and erythrocytes, thereby impairing the delivery of vital energy substrates to the brain. Additionally, the role of glutamate NMDA receptors in these metabolic disorders is discussed. The gathered information provides a deeper understanding of the indirect mechanisms by which ammonia compromises brain energy homeostasis, thereby ultimately leading to encephalopathy. Simultaneous measurement of plasma and erythrocyte ammonia is required to avoid measurement artifacts. Full article

Background: Tuberculous meningitis (TBM) is the most severe form of central nervous system tuberculosis, associated with high mortality and neurological sequelae. Microglia-driven neuroinflammation is a key contributor to TBM pathogenesis; however, its specific effects on ependymal cells—critical for cerebrospinal fluid dynamics and barrier function—and potential therapeutic strategies remain unclear. Methods: A murine TBM model was established by tail vein injection of BCG. Although the virulence of BCG, an attenuated strain of Mycobacterium bovis, is different from that of clinically isolated human Mycobacterium tuberculosis, its induced phenotypes such as periventricular inflammatory infiltration, microglia activation, and ependymal dysfunction highly reproduce the key histopathological features of human TBM. Primary ependymal cells were cultured and treated either directly with BCG or indirectly with conditioned medium from BCG-stimulated BV2 microglial cells (BCG+BV2-CM). Transcriptomic profiling was conducted via RNA sequencing, with validation by qPCR and Western blot. Functional outcomes, including ciliary morphology and apoptosis, were assessed using immunofluorescence and flow cytometry. The therapeutic effect of sodium butyrate (NaB) was evaluated through pretreatment experiments. Results: BCG infection induced characteristic TBM pathology, with persistent bacteria in the brain and lungs, ventricular inflammation, and pulmonary damage. Transcriptomic analysis showed that direct BCG treatment altered the expression of 1036 genes in ependymal cells, whereas BCG+BV2-CM treatment induced 3558 differentially expressed genes, highlighting microglia’s role in amplifying ependymal injury. Integrated analysis identified 64 consistently dysregulated genes across in vitro and in vivo models, enriched in immune and metabolic pathways. BCG challenge significantly downregulated Hmgcs2, leading to ciliary shortening and increased apoptosis. Sodium butyrate treatment restored Hmgcs2 expression, preserved ciliary structure, and reduced apoptosis. Conclusion: Microglia profoundly exacerbate transcriptional dysregulation in ependymal cells during TBM. Sodium butyrate confers protection against BCG-induced ependymal damage by upregulating Hmgcs2, revealing a novel therapeutic target for tuberculous meningitis. Full article

Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disorder caused by mutations in the SMPD1 gene, resulting in sphingomyelin accumulation. With a birth prevalence of 0.25–0.6 per 100,000, it is more prevalent in Ashkenazi Jewish and Middle Eastern populations. The disease features a clinical spectrum ranging from severe, early-onset neurodegeneration (infantile neurovisceral ASMD) to chronic, non-neurological visceral involvement (chronic visceral ASMD) and intermediate forms (chronic neurovisceral ASMD). The chronic visceral form is characterized by liver dysfunction, respiratory symptoms, and hepatosplenomegaly, which can lead to secondary thrombocytopenia. The majority of patients exhibit thrombocytopenia and/or mild bleeding manifestations, most commonly easy bruising and epistaxis, whereas clinically significant bleeding events, including gastrointestinal or variceal hemorrhage, occur less frequently. Systematic platelet-function studies in patients with ASMD are currently lacking. Evidence retrieved from biological models indicates that ASMD contributes to platelet dysfunction, including impaired secretion and thrombin generation, mediated by complex pathological mechanisms. These findings underscore the importance of hematological monitoring and further research in patients with this condition and could potentially offer new therapeutic possibilities. Full article

Equine grass sickness (EGS or equine dysautonomia) is a predominantly fatal multi-system neuropathy affecting grazing horses, likely caused by a neurotoxic phospholipase A2 (nPLA2) derived from a plant or microorganism. We studied neuronal tissue gene and protein expression patterns in EGS to elucidate the possible mechanisms of neurotoxicity and neurodegeneration. Tissue from the cranial cervical ganglion of eight EGS horses and six controls was examined histologically and used for transcriptomic analysis. These transcriptomic data were compared with previously published EGS-related proteomic datasets from different horses. Results were visualized using the network analysis tool BioLayout and Ingenuity Pathway Analysis. The cranial cervical ganglia from all affected horses showed pathology typical of EGS. They also showed distinct gene and protein expression profiles that were different from the controls. The EGS signature consisted ofreduced expression of genes and proteins involved in neurological function (including ion-channel and synaptic-function genes and genes encoding mitochondrial proteins) and increased expression of genes and proteins indicative of cellular stress, cell death and inflammation. This signature likely reflects more generalized neurodegeneration. This study thus improves our understanding of the molecular changes likely to be associated with a neurotoxic neurodegenerative process. Full article

Disease variants in GABR genes encoding γ-aminobutyric acid type A receptor (GABA_AR) subunits are major causes of developmental and epileptic encephalopathies (DEEs). There is no effective treatment for these DEEs, although the GABA_AR is a major target for antiseizure drugs. We previously identified the therapeutic effect of 4-phenylbutyrate (PBA) in Gabrg2^+/Q390X knockin DEE mice and in this study tested the effect of the drug in GABRA1 variants that encode the α1 subunit of GABA_AR. We used a multidisciplinary approach including in silico structural modeling, flow cytometry, patch-clamp recordings and biochemistry in conjunction with differential tagging of the wildtype (WT) and the mutant alleles to evaluate the effect of PBA on rescue of GABA_AR subunit expression, surface trafficking, and function in vitro in a heterologous HEK293T cell model and in vivo in Gabra1^+/A322D mice. We found that the α1 subunit expression at both the total level and the cell surface was reduced when the variant α1 protein was present, suggesting reduced functional receptor availability on the cell membrane and synapse. Patch-clamp recordings identified that α1 variants reduced GABA-evoked current amplitude. In silico prediction indicated reduced protein stability for GABRA1 variants by negative ∆∆G values. PBA increased both total and surface expression of WT α1 and α1 variants and improved expression of both WT and variant α1 alleles when these were co-expressed. Importantly, PBA also increased the GABA_AR expression in the cortex and thalamus of the Gabra1^+/A322D mice. This study indicates that PBA is a promising treatment option for DEEs associated with GABRA1 mutations. Our previous work has demonstrated that PBA improves proteostasis by enhancing expression of the WT allele, repairing the mutant allele, and reducing endoplasmic reticulum stress in other DEEs associated with GABRG2 and SLC6A1 mutations. Importantly, it can mitigate seizures and improve neurobehavioral phenotypes at behavioral levels. Based on this and our previous work on GABRG2 and SLC6A1 mutations, we propose that PBA holds promise as a common medicine for multiple genetic neurologic disorders that share the proteostasis pathology with a broad clinical application in DEEs. Full article

Background: The eye provides a valuable window for the identification of neurological diseases, as pathological changes may involve both the retina and the optic nerve. Standard imaging of the retina and the optic nerve are non-invasive and are useful tools in investigating the integrity of the visual pathways. With population aging and the increasing burden of neuro-ophthalmic diseases, there is a growing need for tools that can assist clinicians in achieving rapid and reliable diagnoses. AI may facilitate the detection of specific neuro-ophthalmological conditions. Methods: This article presents a narrative review of previously published studies addressing the current applications of AI in selected neuro-ophthalmic conditions, with emphasis on their advantages, limitations, and challenges in screening, diagnosis, and disease progression assessment. Results: AI-based approaches provide valuable opportunities for the screening, characterization, and monitoring of optic nerve head abnormalities in neuro-ophthalmology. Recent advancements, particularly in deep learning and convolutional neural networks, have shown notable potential in interpreting fundus photography, optical coherence tomography and magnetic resonance imaging, supporting a comprehensive assessment of optic nerve structure and function. These systems are particularly promising because they can extract quantitative information from routine imaging modalities and may assist clinicians in detecting structural damage that is difficult to identify through conventional evaluation alone. Conclusions: AI-assisted ophthalmic imaging has shown promising diagnostic performance in identifying ONH abnormalities and retinal or optic nerve changes associated with neurological disease. At present, however, most applications remain within research, retrospective validation, or proof-of-concept settings, and evidence that AI consistently improves early diagnosis or clinical outcomes beyond conventional assessment remains limited. Accordingly, AI should currently be regarded as a complementary tool that may support screening, image interpretation, disease characterization, and referral decisions rather than replace established clinical evaluation. Full article

Introduction: Acute subdural hematoma (aSDH) represents one of the most lethal and debilitating forms of traumatic brain injury (TBI) encountered in neurosurgical emergency settings, carrying high mortality rates and severe long-term functional deficits. Historically, the timing of surgical decompression has been considered a critical modifiable prognostic factor. However, contemporary evidence regarding the relationship between time to surgery and clinical outcomes remains inconsistent. This systematic review and meta-analysis evaluates the impact of surgical timing on mortality and functional status in adult patients undergoing evacuation for acute subdural hematoma. Methods: A systematic review was conducted according to the PRISMA 2020 guidelines and registered in PROSPERO. A database search was performed across PubMed, Scopus, Embase and Web of Science for relevant studies published between 2009 and 2026. Peer-reviewed cohort studies and clinical trials including adults (>18 years) with CT- or MRI-confirmed aSDH were included. Data extraction focused on baseline characteristics, surgical timing thresholds, and primary outcomes of mortality and functional status assessed using the Glasgow Outcome Scale (GOS). Methodological quality was assessed using the Newcastle-Ottawa Scale. Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: The search identified 1815 records, of which six studies, including 926 patients, met the inclusion criteria. Meta-analysis found no statistically significant association between time to surgery and mortality (RR 1.01, 95% CI [0.69, 1.48], p = 0.96; RD −0.02, 95% CI [−0.19, 0.15]). High statistical heterogeneity was observed (I² = 80%) across the included cohorts. Most studies indicated that patients who underwent rapid neurosurgical intervention frequently presented with significantly worse baseline neurological status, which acts as a primary confounding factor and drives poorer prognostic trends. Conclusions: While historical paradigms emphasize a 4h period for subdural hematoma evacuation, our meta-analysis indicates that a straightforward linear relationship between time to intervention and improved survival or functional outcome is absent in contemporary clinical studies. Surgical timing thresholds must be interpreted cautiously, as the decision-making process is heavily guided by clinical triage bias, where rapidly deteriorating patients are prioritized for urgent decompression. Crude timing thresholds do not reflect a lack of causal benefit of early intervention but rather highlight the profound confounding by indication embedded in contemporary neurotrauma literature. Future multicenter investigations adjusting for admission severity, pupillary reactivity, associated intracranial pathology and other confounding factors are crucial to isolate the true prognostic value of surgical timing in aSDH. Full article

The glymphatic system is a recently defined perivascular waste elimination pathway responsible for the efficient clearance of metabolic waste and neurotoxic proteins in the central nervous system. This system facilitates the entry of cerebrospinal fluid (CSF) into the brain parenchyma via arterial perivascular spaces and its interaction with interstitial fluid (ISF) via glial cell-associated aquaporin-4 (AQP4) channels. It functions particularly actively during sleep. Impairment of glymphatic flow contributes to nerve cell damage and neuroinflammation in various pathologies such as Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, subarachnoid hemorrhage, and neurological tumors. In neurosurgical practice, surgical positioning, anesthesia regimen, and intracranial pressure changes play a decisive role in glymphatic function, and perioperative modulation of the system can affect postoperative recovery and cognitive outcomes. Today, non-invasive imaging techniques and molecular biological approaches are deepening our understanding of the functioning of the glymphatic system in humans, and this system is emerging as a potential target in the diagnosis and treatment of neurological diseases. This review comprehensively addresses the basic anatomical and physiological principles of the glymphatic system, its role in pathological processes, and its clinical significance in neurosurgical applications. Full article

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis affecting predominantly small vessels, typically associated with PR3-ANCA positivity. Central nervous system involvement beyond cranial nerve palsies is rare, with intracerebral granulomas being exceptionally rare and lacking specific imaging characteristics, often mimicking malignancies or other intracranial pathologies. This significantly complicates the diagnostic process, particularly in the absence of active systemic disease. We report a case of a 71-year-old woman in whom neurological symptoms and magnetic resonance imaging revealed intracerebral granulomas and led to the diagnosis of GPA. Early recognition of tumor-like brain lesions in GPA and prompt initiation of immunosuppressive and anti-edematous therapy are crucial to prevent progression and potentially life-threatening compressive complications. Full article

Perineural invasion (PNI) is a distinct route of cancer spread associated with neuropathic pain, local recurrence, and poor survival across many solid tumours. Increasing evidence shows that PNI is not only a structural pattern of invasion but also a dynamic biological process involving neurodegeneration, nociceptor sensitisation, and marked local immunosuppression. This narrative review synthesises experimental, translational, and clinical data on the molecular, neurological, and immunological mechanisms of PNI in solid malignancies. PNI arises through complex crosstalk between tumour cells, Schwann cells, macrophages, fibroblasts, and neurotrophic pathways, leading to peripheral nerve remodelling, axonal degeneration, and abnormal regeneration. These changes promote neuropathic pain through ion-channel dysregulation, neurotrophin-driven sensitisation, and pathological neuroplasticity. At the same time, PNI creates an immunosuppressive microenvironment enriched in Tregs, M2 macrophages, and myeloid-derived suppressor cells, shaped by cholinergic, adrenergic, and neuropeptidergic signalling, which may contribute to immune exclusion and resistance to immunotherapy. We propose that PNI should be understood as a neuro-immuno-metabolic process and that recognising the PNI–pain–immunosuppression triad may support the development of targeted neuroprotective, analgesic, and immunomodulatory therapies. Full article

Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) remains difficult when presentation is non-specific, blood cultures are negative, or initial biopsy is non-diagnostic. The two entities differ substantially in antimicrobial strategies, resistance testing requirements, public health interventions, and surgical thresholds, yet diagnostic delay is associated with neurological deficits, spinal instability, and permanent deformity. This narrative review maps the non-imaging evidence most useful for frontline differentiation between TS and PS across five domains: epidemiology and risk stratification, clinical presentation, laboratory markers, tissue acquisition and histopathology, and molecular diagnostics. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified Boolean search terms; a secondary Scopus search identified no additional eligible records. Following screening, approximately 90 records were included in this synthesis. Priority was given to comparative TS-versus-PS cohorts, biopsy-yield and culture-negative studies, pathology series, pediatric data, and recent molecular diagnostics literature. Epidemiological TB (tuberculosis) risk, longer symptom duration, constitutional symptoms, deformity, and a less intense acute-phase response increase the probability of TS, whereas healthcare exposure, bacteraemia, recent spinal procedures, and brisk neutrophilic inflammation favor PS. In stable patients, the highest-yield strategy is early blood cultures followed by image-guided biopsy with parallel tissue allocation for bacterial culture, mycobacterial studies, histopathology, and selected molecular assays. No single laboratory marker reliably distinguishes TS from PS without tissue confirmation. Per a 2023 systematic review and meta-analysis, image-guided percutaneous biopsy achieves microbiological confirmation in approximately one-third of cases. Histopathology demonstrating caseating granulomatous inflammation supports TS, although a substantial minority of confirmed cases lack classic features. Supported by cohort prospective data, Xpert MTB/RIF Ultra has the clearest first-line molecular role when TS is plausible and should be requested at the time of first biopsy rather than reserved for salvage testing; broader or targeted next-generation sequencing is best reserved for selected unresolved cases. Imaging differentiation is addressed in the companion manuscript, Part II. Full article

Objective: The present study aimed to investigate the neuroprotective effects of agomelatine in a rat model of cerebral ischemia/reperfusion injury, a major pathological event underlying ischemic stroke. Methods: Male Sprague Dawley rats included in the study were divided into four groups (n = 10/group): sham, CI/R, CI/R + 20 mg/kg Agm and CI/R + 40 mg/kg Agm. Sixty minutes of ischemia was induced in all groups except the sham group. One hour after ischemia, hydroxyethyl cellulose was administered intraperitoneally to the CI/R group, while 20 and 40 mg/kg agomelatine was administered to CI/R + Agm groups. During the three-day reperfusion period, the rats underwent neurological deficit score (NDS), rotarod, adhesive removal, and grip strength tests. At the end of the experiment, animals were decapitated and brain tissues were collected. In the collected brain tissues, infarct area was determined by TTC staining, and levels of apoptosis (Bcl-2, Bax) and autophagy (Beclin-1, ATG5, ATG7, p62) proteins were determined by Western blot. Statistical analysis of the obtained data was performed. Results: Compared with the CI/R group, agomelatine-treated groups showed significantly lower NDSs and adhesive removal times, as well as higher rotarod retention times and grip strength values (p < 0.05). Infarct area was significantly reduced following agomelatine treatment (p < 0.05). Agomelatine increased Bcl-2, Beclin-1, ATG5, and ATG7 protein levels while decreasing Bax and p62 expression compared with the CI/R group (p < 0.05). Conclusions: Agomelatine attenuated neurological deficits and infarct formation following CI/R injury. These neuroprotective effects may be associated with suppression of apoptosis and enhancement of autophagy-related pathways. Full article

The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent—and at times opposing—roles, attenuating dopaminergic neurotoxicity in Parkinson’s disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms. Full article

Background/Objectives: Degenerative cervical myelopathy (DCM) is the leading cause of non-traumatic spinal cord dysfunction in adults. Both anterior and posterior surgical approaches are widely used for its treatment, yet their comparative impact on clinical outcomes and complication profiles remains clinically relevant. This study aimed to describe early and one-year postoperative outcomes between anterior and posterior surgical strategies in a consecutive single-center cohort. Methods: We conducted a retrospective single-center study of 102 consecutive adult patients surgically treated for DCM between 2013 and 2024, with complete datasets and a minimum one-year follow-up. Surgical approaches were classified as anterior, posterior, or combined. Clinical outcomes were assessed using the modified Japanese Orthopaedic Association scale (mJOA), Neck Disability Index (NDI), and Numeric Rating Scale for arm pain (NRS-arm) preoperatively, at 4–6 weeks and at one year. Complications were systematically recorded and stratified by approach. Nonparametric tests were used for all comparisons (significance threshold p < 0.05). Results: Anterior procedures were performed in 82 patients (80.4%), posterior in 18 (17.6%), and combined in 2 (2.0%). No significant between-group differences were observed in neurological, functional, or pain outcomes at either time point (ΔmJOA p = 0.268; ΔNDI p = 0.632; ΔNRS p = 0.562 at one year). Complications occurred in 13 patients (12.7%), with approach-specific profiles: anterior surgery was associated with hematoma, dysphagia, and dysphonia, posterior surgery with CSF leak, wound infection, and kyphosis. No C5 palsy was recorded. Conclusions: Both anterior and posterior surgical approaches were followed by neurological and functional improvement at one year. Given the descriptive nature of the study and the baseline differences between groups, these findings should not be read as a formal comparison of effectiveness, but they reinforce the importance of individualized, pathology-driven surgical planning in DCM. Full article