Search Results (6,201)

Pediatric episodic vestibular syndrome (pEVS) is a frequent source of diagnostic uncertainty because recurrent vertigo, dizziness, and unsteadiness in children may arise from disorders with markedly different mechanisms, prognostic implications, and management pathways. Symptom descriptions are often imprecise, interictal examination may be normal, and similar recurrent attack patterns may reflect spontaneous, triggered, neurologic, autonomic, audiovestibular, or extravestibular conditions. This Perspective proposes a clinician-oriented, phenotype-first framework for the practical evaluation of pEVS, grounded in the International Classification of Vestibular Disorders and Bárány Society consensus criteria where available. The proposed approach begins with structured history taking and focused bedside examination, emphasizing the core symptom category, attack duration, trigger profile, and associated migraine, auditory, autonomic, and neurologic features. Recurrent attacks are then organized into clinically recognizable phenotypes, including spontaneous non-migraine and migraine-related presentations, auditory phenotypes, ultrabrief stereotyped attacks, trigger-related attacks, orthostatic/autonomic phenotypes, motion- or visually-triggered dizziness, episodic vertigo with transient neurologic signs, and anxiety-related presentations. Rather than providing an exhaustive etiologic review, this framework is intended to support bedside classification, guide selective ancillary testing, and facilitate longitudinal reassessment, as diagnostic reclassification may occur over time. A phenotype-driven approach may improve diagnostic reasoning, support more rational use of ancillary testing, and facilitate earlier recognition of both common and less frequent but clinically important disorders. Full article

Ankle–foot orthoses (AFOs) are widely used in the rehabilitation of patients with neurological or musculoskeletal disorders. However, treatment outcomes may be influenced by incorrect use of the device or by inappropriate orthosis selection. Since many types of AFOs are available, differing in materials, stiffness, and geometry, an objective evaluation tool can support clinical decision-making. This work presents the design, development, and characterization of an instrumented AFO able to quantify relevant gait parameters in an objective way. The proposed device integrates three measurement modalities in a compact wearable structure. Two longitudinal strain gauges estimate ankle plantar- and dorsiflexion angles. Two force-sensitive elements detect foot–ground contact and allow identification of stance and swing phases of the gait cycle. A single inertial measurement unit (IMU) is used to measure lateral shank inclination. The strain-gauge-based angle estimation was validated against a gold-standard motion capture system, achieving a root mean square error of approximately 1.6 degrees and showing higher accuracy than the IMU for plantar/dorsiflexion measurement, while maintaining a simple electronic architecture. The force sensors were validated using a force platform and demonstrated reliable detection of loading and unloading events. Monitoring lateral inclination through the single IMU provides additional information related to balance and potential fall risk. Data are transmitted via Bluetooth Low Energy (BLE) to a custom Python-based application for real-time visualization and recording. Overall, the results validate the electronic instrumentation and demonstrate reliable system performance, indicating that the proposed instrumented AFO represents a promising platform for objective gait assessment and future clinical applications. Full article

Background: Functional somatic symptoms (FSSs) represent a significant clinical challenge in pediatric populations, with prevalence estimates ranging from 10 to 30%. The COVID-19 pandemic introduced unprecedented psychosocial stressors that may have influenced the presentation and precipitating factors of these conditions. This article aimed to characterize the clinical presentations, precipitating factors, and temporal patterns of functional somatic disorders in children admitted to a tertiary pediatric hospital in Bucharest, Romania, across pre-pandemic (2017–2019), pandemic (2020–2022), and post-pandemic (2023–2025) periods. Methods: This retrospective study included 1043 patients aged 3–17 years admitted with somatic symptoms without identifiable organic pathology. Data were extracted using ICD-10 diagnostic codes and confirmed through individual chart review. Variables analyzed included demographics, symptoms, precipitating factors, symptom duration, and family psychiatric history. Results: Female patients predominated (67.0%), with a median age of 14 years. Cardiovascular symptoms were most frequent (43.9%), followed by neurological (30.4%), digestive (19.0%), and respiratory (6.3%) manifestations. Family-related factors (38.6%) and school-related stress (32.7%) were the primary precipitating factors. Significant pandemic-related differences emerged: medical-related precipitating factors increased during the pandemic (18.5% vs. 10.7% pre-pandemic, p < 0.001), respiratory symptoms were more frequent (9.8% vs. 5.9% pre-pandemic), and symptom duration before admission was significantly longer (median 1 vs. 1 pre-pandemic and 0 months post-pandemic; p < 0.001). Conclusions: The COVID-19 pandemic substantially influenced pediatric somatic presentations, with increased health anxiety, respiratory symptoms, and delayed healthcare-seeking behavior. Post-pandemic patterns suggest the persistent influence of traditional stressors alongside pandemic-related effects. Full article

Background/Objectives: TCIRG1-associated infantile osteopetrosis is a severe hereditary disorder caused by impaired osteoclast function, leading to osteosclerosis, hematological abnormalities, neurological complications, and early mortality. Early diagnosis and intervention are critical. Methods: A literature-based analysis was performed on clinical manifestations, outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), immunomodulatory therapy, and experimental gene therapy and cell-based approaches, including lentiviral vectors and patient-derived induced pluripotent stem cells (iPSCs). Results: Allogeneic HSCT is the only established curative therapy, restoring osteoclast function and preventing severe complications. Early transplantation with HLA-matched donors and myeloablative conditioning provides optimal outcomes. Interferon γ1b can transiently enhance osteoclast activity but is not curative and shows variable efficacy. Preclinical studies demonstrate that lentiviral TCIRG1 delivery and transgenic correction in patient-derived iPSCs restore osteoclast function and bone resorption, with stable gene expression and minimal toxicity. Base and prime editing approaches offer potential for precise correction of single-nucleotide TCIRG1 variants, minimizing risks associated with double-strand DNA breaks. Conclusions: Allogeneic HSCT remains the standard therapy for TCIRG1-associated infantile osteopetrosis. Gene therapy and cell-based strategies represent promising adjuncts or alternatives, potentially avoiding immune-related complications and expanding therapeutic options. Further studies are needed to ensure safety, stable engraftment, and long-term efficacy, supporting translation of gene therapy into clinical practice. Full article

Background: Short-term morbidities and mortality decreased significantly in the past decade at preterm born < 25 weeks of gestation. Severe lifelong morbidities affect an important part of these patients. Objective: to investigate the in-hospital morbidity, mortality, and short-term complications of preterm neonates born ≤25 weeks of gestation. Methods: A prospective longitudinal cohort study was conducted in children born 2021–2024, ≤25 weeks of gestation, admitted to a 3rd-level unit, and care till discharge. Pregnancy complications’ effect on neonatal evolution was analyzed, six main in-hospital morbidities specific for preterm birth and other aggravating circumstances, with a possible effect on the evolution were analyzed, as follows: inflammatory syndrome, early pulmonary or digestive hemorrhages, and early inotropic support. The neurological development in the first year of life was analyzed through theparticipation of premature infants in the follow-up program after discharge. Results: Forty-nine premature infants were enrolled, with a mean gestational age of 24.37 ± 0.76 weeks and an average weight of 665 ± 143 g. Most newborns required intubation at birth (42/49), and 33/49 received 2-dose surfactant therapy postnatally. NEC was present in 26.5% of the group, being more common in patients with inflammatory syndrome—increase in procalcitonin (PCT), and those who received a higher number of blood transfusions. The BPD and ROP, as well as the severity of the latter, correlated with the oxygen requirement on the 28th day of life. BPD was more common in infants associated with PDA requiring combination treatment. ROP increased with the number of transfusions required by patients. At the follow-up at the first timepoint evaluation, were 51% of the study group, and 30.6% of them had normal neurological development. At 12 months of age, however, the neurological examination was normal in only three patients (23.08%) but only 36.5% of the study group attended the follow-up. Neurodevelopmental disorders were present in 10 of the patients, one with spastic diplegia. Conclusions: In the hospital, the morbidity and survival rate of the group was like other studies. The small number of follow-up participants does not allow the generalization of the data, but as far as neurological development is concerned, it is like that of other studies. Full article

Flunarizine is a calcium channel blocker widely used in neurological disorders; however, its low aqueous solubility may influence formulation stability and drug dispersion in polymer-based systems. The present study aimed to evaluate the compatibility of flunarizine with selected excipients and to investigate its incorporation into polymeric hydrogel matrices. Binary mixtures of flunarizine with excipients such as hydroxypropyl-β-cyclodextrin, polyethylene glycol (PEG 6000), Tween 20, gelatin, and citric acid were prepared and characterized using Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG/DTG), and high-performance liquid chromatography (HPLC). The FTIR spectra of the analyzed samples do not reveal the appearance of new absorption bands that may indicate chemical interactions; instead, minor spectral variations were observed due to weak intermolecular interactions within the polymer network. Thermal analysis revealed decomposition patterns consistent with those of the individual components, suggesting the absence of significant incompatibilities. A validated RP-HPLC method enabled sensitive and reliable quantification of flunarizine in the analyzed systems, with a limit of detection (LOD) of 0.05 µg/mL and a limit of quantitation (LOQ) of 0.16 µg/mL. Accuracy testing showed average recovery rates of 100% across 80–120% spiking levels. Overall, the results support the compatibility of flunarizine with the investigated excipients and the suitability of the studied hydrogels as potential drug delivery matrices. Full article

As modern society grows increasingly complex, access to essential services such as healthcare, legal aid, tailored education, and psychological support remains heavily gated by socio-economic, neurological, and systemic barriers. This paper explores the transformative potential of Large Language Models (LLMs) and Generative Artificial Intelligence not merely as industrial productivity enhancers, but as vital “social scaffolds” capable of fostering a more inclusive society. Crucially, we propose a paradigm shift in the concept of Ethical Computing—moving from a passive defensive framework of non-maleficence (“do no harm”) to an active mandate of beneficence, where AI systems are explicitly developed to serve marginalized and un(der)served populations. Through this expanded ethical lens, we systematically analyze the democratizing impact of AI across four primary axes of inclusivity: socio-economic (providing zero-cost medical triage and legal translation for undocumented populations), neurospicy (acting as a non-judgmental communicative bridge for individuals with Autism Spectrum Disorder), pedagogical (delivering hyper-personalized executive function support for Special Educational Needs), and psychological (serving as an accessible, first-level triage system for mental health crises). By framing LLMs as a modern social safety net, we outline a clear trajectory for future research, advocating for an “ethical-by-design” development paradigm that explicitly prioritizes equity, accessibility, and the active dismantling of historical barriers for the digitally and socially disenfranchised. Full article

Pompe disease (PD) is a neuromuscular autosomal recessive disorder caused by mutation in the GAA gene, which encodes acid α-glucosidase (GAA), an enzyme responsible for hydrolyzing glycogen to glucose. Deficiency of this enzyme leads to pathological accumulation of glycogen in almost all tissues of the body, with the most pronounced effects in cardiac and skeletal muscle, as well as in the central nervous system. Two major clinical forms of PD are recognized: infantile-onset PD, characterized by almost complete absence of GAA activity and severe cardiomyopathy and neurological abnormalities, and late-onset PD, which primarily presents with impairment of respiratory and motor function. Since 2006, enzyme replacement therapy with recombinant GAA has been used to treat PD, improving survival and quality of life. However, this approach has several limitations: the need for lifelong infusions, the risk of immune responses, and the inability of the enzyme to cross the blood–brain barrier, which is particularly critical for infantile-onset PD. Consequently, alternative strategies are being developed, including gene therapy using adeno-associated virus vectors for GAA delivery to target tissues; these approaches are currently in phase I/II clinical trials. Transplantation of genetically modified hematopoietic stem cells also represents a promising therapeutic strategy, offering a single-intervention treatment with long-lasting effects. This review discusses the molecular mechanisms of PD, current and emerging disease models, and therapeutic approaches, which together open prospects for the development of potentially one-time curative treatments, despite persistent challenges such as immunogenicity and the need for long-term efficacy monitoring. Full article

Recent advancements in neuroproteomics have enabled detailed analysis of protein expression in the human brain, yet resolving synaptic dysfunction—a central feature of many neurological and psychiatric disorders—requires careful methodological consideration. Leveraging the high sensitivity of modern liquid chromatography-tandem mass spectrometry (LC-MS/MS), we evaluated the utility of whole-tissue lysates versus enriched synaptosome preparations for detecting synaptic protein signatures. First, we optimized and standardized a sample preparation protocol for frozen human gray matter (GM) by refining the suspension trapping (sTRAP) digestion method using thin human tissue sections. We accomplished low technical variation by minimizing sample handling and achieved a highly reproducible sample preparation workflow by rigorously applying standardization and randomization across dissection, processing, and LC-MS/MS runs. Second, comparative LC-MS/MS analysis showed that while whole-tissue lysates provide a high-throughput survey of the synaptic proteome, synaptosome isolation is required to investigate synapse-specific proteins to detect alterations at the terminal that are obscured in the soma. Because these methods offer distinct but synergistic levels of information, we recommend a tiered neuroproteomics strategy. This approach utilizes whole-tissue lysates for broad disease-associated screening and consistent quantification in large cohorts, followed by targeted synaptosome proteomics to provide a unique window of insight into synaptic composition and stability. This integrated workflow respects the biological necessity of spatial resolution while maintaining the reproducibility required for robust human brain proteomics. Furthermore, initial tissue-level analysis provides the necessary context to correctly interpret synaptosome data in cases of global synapse loss or gain. Full article

The use of neuroprotective nutraceuticals as a strategy against neurodegenerative diseases such as Parkinson’s disease (PD) has gained considerable traction in recent years. In this review, we highlight ergothioneine (ET)—a naturally occurring thiol/thione derivative abundant in mushrooms—as a promising candidate, given its long half-life, blood–brain barrier penetration, and high bioavailability. Numerous population studies have linked low blood ET levels with increased risk and progression of neurological and other age-related disorders in humans, suggesting that dietary ET may confer neuroprotective benefits. Supporting this, several studies have demonstrated the efficacy of ET treatment in reducing PD-associated molecular damage across various pre-clinical models such as C. elegans, Drosophila, rodent models and human neuronal cultures, leading to marked improvements in disease phenotypes. Here, we summarize some of the proposed mechanisms by which ET may exert neuroprotection in PD, including the reduction of protein aggregation, enhancement of mitochondrial function, mitigation of oxidative stress, and attenuation of apoptosis and neuroinflammation. We also highlight recent clinical trials demonstrating the safety and potential efficacy of ET and propose future research to facilitate the translation of ET into the clinic. Full article

Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain’s primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid–interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood–brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH. Full article

Abnormal gait associated with neuromuscular and musculoskeletal disorders represents a growing clinical burden, particularly in aging populations. This study presents a modular, low-cost Smart Rehabilitation Walker (SRW) that integrates multimodal sensing and real-time haptic feedback to enable simultaneous gait monitoring and corrective intervention in both clinical and home environments. The system combines force-sensing resistors for bilateral load symmetry assessment, inertial measurement units for fall detection, and surface electromyography (sEMG) for neuromuscular activity monitoring within a closed-loop assistive feedback architecture. A 15-day pilot study involving ten individuals with rheumatoid arthritis and clinically observed neurological gait abnormalities demonstrated measurable improvements in gait biomechanics. The Force Symmetry Index (FSI), calculated using the Robinson symmetry metric, decreased from an average of 0.9691 to 0.2019, corresponding to a 79.26% average reduction in inter-limb load asymmetry. Concurrently, sEMG measurements showed a substantial increase in neuromuscular activation (ΔEMG = 4.28), with statistical analysis confirming a significant improvement across participants (paired t-test: t(9) = 13.58, p < 0.001). To model rehabilitation trajectories, a nonlinear predictive framework based on Gaussian Process Regression achieved high predictive accuracy (R² ≈ 0.9, with a mean RMSE of 0.0385), while providing uncertainty-aware trend estimation. Validation using an independent amyotrophic lateral sclerosis gait dataset further demonstrated the transferability of the analytical pipeline. These results highlight the potential of sensor-enabled assistive walkers as scalable platforms for quantitative gait rehabilitation, adaptive feedback, and long-term mobility monitoring. Full article

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have also identified various associated comorbidities such as vascular dysfunction, metabolic alterations, and neuroinflammatory changes. Positive airway pressure (PAP) therapy has been associated with cognitive improvement in some studies, but its long-term effects on cognitive function remain uncertain. This study employs a prospective, observational, longitudinal cohort design to examine longitudinal associations between disease severity, PAP therapy and cognition. Additionally, we aim to examine the relationships between cognitive dysfunction, brain structure and associated OSA-related risk factors. A total of 100 eligible participants with mild to severe OSA will be recruited. All participants will undergo comprehensive assessments at baseline and after 12 months, including neurological, pulmonary, and ear, nose and throat clinical examinations, polysomnography, neuropsychological testing, brain magnetic resonance imaging with volumetry, anthropometric measurements, blood and saliva sampling for the assessment of the selected laboratory parameters, gut microbiome analysis, and evaluation of endothelial function and baroreflex sensitivity. This study may improve understanding of how PAP therapy and OSA-related pathophysiological processes influence cognitive outcomes. Full article

In the contemporary era, nanotechnology has become a central pillar in numerous domains, particularly in cosmetics, nanoelectronics, nanomedicine, and nanobiotechnology. Defined by its focus on materials with dimensions ranging from 0.1 to 100 nm, nanotechnology offers unique physicochemical properties—such as enhanced reactivity, conductivity, and permeability—attributable to the nanoscale. These properties facilitate greater interaction with biological systems, notably improving cellular uptake and functional efficacy. The increasing demand for eco-friendly and biocompatible nanomaterials has driven interest in green synthesis routes, particularly those utilising plant extracts. These methods stand out due to their low toxicity and environmental impact, positioning it as a safer alternative to conventional chemical or microbial methods. Plant-extract-mediated nanoparticles demonstrate promising applications in diagnostics, drug delivery, regenerative medicine, and neurotherapeutics. Their role in precision medicine, including gene and drug delivery and the imaging of neurological disorders, underscores green nanotechnology’s transformative potential. This review highlights recent advances in the synthesis, functionality, and biomedical applications of plant-based nanoparticles, emphasizing their relevance in in vitro models and prospective clinical settings. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article