Search Results (512)

Beginning with a general understanding of catastrophic obstetric collapse (COC), it has been established that a catastrophic obstetric collapse is typically the result of sudden massive bleeding requiring emergency peripartum hysterectomy (EPH); this is different from historical views of what constitutes a catastrophic obstetric collapse. Current studies have found evidence that a catastrophic obstetric collapse can be the result of a longer-duration process involving gradual maternal physiological destabilization, the culmination of which creates a “maternal point of no return” for the mother. As a result of disrupting the maternal–fetal interface in placenta accreta spectrum disorders (PASDs), there are many abnormalities present in the decidua, such as: defective decidualization, fragmentation of the extracellular matrix, aberrant angiogenesis, continued hypoxic signals, and the persistence of invasive trophoblastic phenotypes. These structurally fragile vascular interfaces will eventually undergo endothelial dysfunction, oscillatory shear stress, glycocalyx injury, oxidative damage and progressive depletion of the maternal vascular adaptive reserve. Chronic inflammation will also continue to amplify immune thrombosis, alter complement function, facilitate NETosis, and cause widespread instability in diffuse microvasculature, leading to a reduced ability of the maternal system to tolerate physiological stress while maintaining macrocirculatory stability. Additionally, invasive placentation may lead to mitochondrial dysfunction, decreased oxidative phosphorylation, disrupted intracellular calcium homeostasis, ferroptotic lipid peroxidation, and redox-mediated endothelial injury, leading to a progressive limitation in the mother’s bioenergetic adaptability to hemorrhage. Ultimately, these events seem to culminate in a threshold condition where endothelial disorganization exists along with capillary transit time heterogeneity, impaired oxygen diffusion, metabolic instability, and progressive desynchrony of vascular, inflammatory, coagulative and mitochondrial networks before eventual hemodynamic collapse. Therefore, based on these findings, we propose the concept of the “Maternal Point of No Return” as a transitional state in which physiological adaptations begin to fail and irreversibly destabilize at a systems level. Lastly, we review potential applications of current technological advancements, including artificial intelligence (AI), radiomic-based placental phenotyping, exosomal biology, physiological variability analysis, spatial multi-omics, and digital twin physiology, to enable future precision-obstetrics strategies to identify a decline in maternal resilience prior to irreversible decompensation. Full article

Background and Objectives: The aim of this study was to use a modified lateral lumbar approach developed by the authors for single-level lumbar decompression and interbody fusion using intervertebral implants. Materials and Methods: A total of 38 patients with single-level L1–L5 degenerative disc disease who underwent lumbar interbody fusion were included in this study. The procedure was performed using the modified lateral lumbar surgical approach. Clinical outcomes included the assessment of functional status using the Karnofsky Performance Scale and Oswestry Disability Index (ODI), quality of life using the EuroQol Visual Analogue Scale (EQ-VAS), and pain intensity using Visual Analogue Scale (VAS). Preoperative and postoperative radiographic parameters assessed on magnetic resonance imaging (MRI) were compared. Results: Significant improvement in functional status, quality of life, and pain reduction was observed in all patients. Radiographic outcomes also improved significantly. Mean disc height increased from 8.2 mm preoperatively to 12.2 mm postoperatively (p < 0.05). The cross-sectional area of the spinal canal increased significantly following surgery. Furthermore, a reduction in disc herniation width and enlargement of the intervertebral foramina were observed. No neurovascular complications occurred, and endplate injury with cage subsidence was noted in 5% of patients. Conclusions: Lateral lumbar discectomy and interbody fusion increase spinal canal area, enlarge the neuroforamina, and restore intervertebral disc height. Most patients experienced substantial functional improvement and pain reduction. No neurological or vascular complications were observed, which may be due to the modified approach. The confirmation of this hypothesis requires further research and a longer follow-up period. Full article

Objectives: The facial nerve (FN) possesses one of the most intricate anatomical courses in the head and neck, traversing the brainstem, temporal bone, and parotid gland before terminating within the muscles of facial expression. Owing to its complex anatomy, marked anatomical variability, and frequent distortion by adjacent pathology, preservation of FN integrity remains a fundamental challenge in skull base, otologic, and head and neck surgery. This review aims to provide a comprehensive synthesis of the contemporary literature regarding the clinical anatomy of the FN and to examine how anatomical variation, pathology-induced distortion, surgical strategy, and emerging technologies influence nerve preservation and functional outcomes. Methods: A comprehensive narrative review of the literature was conducted using PubMed, Scopus, and Google Scholar. Publications from 1983 through 2026 were searched using combinations of keywords, including “facial nerve,” “facial nerve anatomy,” “anatomical variation,” “vestibular schwannoma,” “hemifacial spasm,” “parotid surgery,” “facial nerve injury,” “facial nerve reconstruction,” “facial reanimation,” “diffusion tensor imaging,” “intraoperative neurophysiological monitoring,” and “artificial intelligence.” Peer-reviewed anatomical, radiological, clinical, and review articles published in English were included, while conference abstracts and studies lacking direct anatomical or surgical relevance were excluded. Particular emphasis was placed on surgically relevant anatomical variations, pathology-related anatomical distortion, advanced imaging modalities, intraoperative neurophysiological monitoring, reconstructive techniques, and predictors of postoperative facial nerve function. Results: Facial nerve preservation was found to depend on the interplay between individual anatomical variability, disease-related anatomical distortion, and operative strategy. In vestibular schwannoma surgery, nerve displacement, capsular adhesion, and cystic tumor degeneration were consistently associated with increased surgical complexity and less favorable postoperative facial function. In hemifacial spasm, successful microvascular decompression relied on precise identification of neurovascular conflict at the root exit zone. Within the parotid gland, substantial variability in branching architecture and surgical landmarks contributed to an increased risk of iatrogenic injury. Advanced imaging techniques, particularly diffusion tensor imaging tractography, improved preoperative prediction of FN location, while intraoperative neurophysiological monitoring enabled real-time assessment of neural integrity and functional preservation. Emerging artificial intelligence-based predictive models demonstrated potential to enhance patient-specific surgical planning and prognostication. Conclusions: Contemporary facial nerve surgery has evolved toward an individualized, anatomy-driven, and function-preserving paradigm supported by advanced imaging, intraoperative monitoring, and reconstructive strategies. Detailed understanding of both normal FN anatomy and pathology-induced anatomical distortion remains essential for optimizing surgical decision-making, maximizing nerve preservation, and improving long-term functional outcomes. Future developments integrating multimodal imaging, predictive analytics, and artificial intelligence may further refine patient-specific management and enhance postoperative facial function. Full article

Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers. Full article

Background & Objectives: Endovascular embolization has matured into a sophisticated, precision-guided discipline that is central to the management of complex neurovascular pathologies. This review synthesizes contemporary treatment strategies, evaluating the advanced material characteristics of conventional inert liquid polymers, specifically non-adhesive ethylene vinyl alcohol (EVOH) copolymers and adhesive cyanoacrylates, alongside their targeted clinical applications in brain arteriovenous malformations (bAVMs), dural arteriovenous fistulas (dAVFs), hypervascular intracranial tumors, and chronic subdural hematomas (CSDHs). Furthermore, it examines the critical material and hemodynamic constraints that limit these agents in cerebral aneurysm repair. Methods: A comprehensive literature synthesis through 3 July 2026 was integrated with peer-reviewed clinical illustrations to evaluate both procedural mechanics and the necessity of post-procedural physiological management. Review Findings: Embolization serves a critical dual role: as a definitive curative therapy and as an essential preoperative or radiosurgical adjunct. As demonstrated by recent clinical validations, technical angiographic success must be closely coupled with vigilant neurocritical oversight to manage profound, localized hemodynamic shifts. While these conventional methods represent established clinical practice, the field is evolving away from inert mechanical occlusion toward a highly integrated approach. The convergence of stimuli-responsive “smart” hydrogels and endovascular robotics is being evaluated for potential roles in transforming these interventions into dynamic, bioactive platforms capable of modulating disease-specific mechanisms, such as Rat Sarcoma-Mitogen-Activated Protein Kinase (RAS-MAPK) and Bone Morphogenetic Protein (BMP) signaling in bAVMs or the Von Hippel-Lindau/Vascular Endothelial Growth Factor (VHL/VEGF) axis in hypervascular tumors. This review further analyzes landmark data, including the Squid Trial For the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) trial for CSDH, providing a synthesis for translating these advanced material sciences into standardized, multidisciplinary neurointerventional care. Full article

Background/Objectives: Type 2 diabetes is increasingly recognized as a systemic disorder driven not only by chronic hyperglycemia and insulin resistance, but also by dysregulated interorgan communication. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as biologically active carriers of proteins, lipids, and microRNAs capable of modulating gene expression in recipient cells. This narrative review integrates clinical, experimental, and translational evidence on EV-associated microRNAs as candidate biomarkers and potential mediators of diabetic complications, with emphasis on diabetic neuropathy, diabetic kidney disease, diabetic retinopathy, and metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This review was aligned with the SANRA framework and focused on biological plausibility, evidence from tissue and biofluids, biomarker potential, therapeutic implications, and barriers to clinical translation. Studies were additionally interpreted according to biological matrix, EV-carrier specificity, analytical platform, study design, and level of functional validation. Results: Across complications, EV-associated microRNAs appear to participate in shared pathogenic processes, including oxidative stress, inflammation, endothelial dysfunction, fibrosis, angiogenesis, neurodegeneration, and metabolic memory. In diabetic neuropathy, microRNAs such as miR-146a, miR-155, miR-21-5p, and miR-148a-3p have been linked to neuroinflammation, Schwann-cell dysfunction, axonal injury, and neuropathic pain. In diabetic kidney disease, miR-21, miR-29, miR-30, and miR-126 are implicated in podocyte injury, tubulointerstitial fibrosis, albuminuria, and microvascular dysfunction. In diabetic retinopathy, microRNAs including miR-146a, miR-155, miR-21, miR-126, and miR-200b contribute to neurovascular injury, inflammation, barrier disruption, and angiogenesis. In MASLD associated with diabetes, hepatocyte-derived EVs carrying microRNAs such as miR-1 and miR-126a-3p may link hepatic lipotoxicity to endothelial inflammatory and β-cell dysfunction. Conclusions: Although EV-associated microRNAs offer promising opportunities for biomarker discovery, risk stratification, and targeted therapies, clinical translation remains limited by heterogeneity in EV isolation, microRNA quantification, biological matrices, and outcome definitions. Distinguishing EV-associated miRNAs from total circulating extracellular miRNAs remains essential for biological interpretation. Standardized, longitudinal, and externally validated studies are required before these signals can be implemented as actionable tools in precision diabetes care. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease primarily affecting upper and lower motor neurons. Although cerebrovascular disease (CVD) and ALS have traditionally been studied as distinct entities, a growing body of evidence indicates meaningful epidemiological, pathophysiological, and clinical overlap between the two conditions. This narrative review synthesizes current evidence on the coexistence of ALS and cerebrovascular disease, examines shared mechanistic pathways, addresses diagnostic challenges, including stroke mimicry, considers clinical management implications, and identifies priorities for future research. A search of PubMed, Scopus, Web of Science, and EMBASE was conducted through February 2026 using the terms “amyotrophic lateral sclerosis,” “motor neuron disease,” “cerebrovascular disease,” “stroke,” “ischemic stroke,” “blood-brain barrier,” “neuroinflammation,” and “neurovascular coupling,” alone and in combination. Peer-reviewed original research, systematic reviews, meta-analyses, population-based studies, registry analyses, and expert consensus statements were included. Studies were assessed for methodological quality and relevance to the review objectives. This review is reported as a narrative synthesis. Population-based data demonstrate a bidirectional relationship between ALS and cerebrovascular events. ALS patients face an approximately 2.6-fold elevated risk of ischemic stroke, and prior cerebrovascular injury modestly increases subsequent ALS risk. Shared pathophysiological mechanisms include neuroinflammation with microglial M1/M2 polarization imbalance, pro-inflammatory cytokine cascades mediated via NF-κB signaling, oxidative stress and SOD1 pathway dysregulation, glutamate excitotoxicity, blood–brain barrier (BBB) dysfunction, and impaired neurovascular coupling. Diagnostic confusion arises because upper motor neuron–predominant ALS can closely mimic acute ischemic stroke. Concurrent cerebrovascular disease appears to accelerate functional decline and reduce survival in ALS. Resource-limited settings face compounded challenges from diagnostic misclassification, restricted EMG access, and limited specialist availability. The ALS–cerebrovascular overlap is clinically relevant, biologically plausible, and systematically understudied. Integrated multidisciplinary management, prospective longitudinal cohort studies, and linked registry analyses are urgently needed to clarify causal relationships, characterize shared disease mechanisms, and improve patient outcomes. Full article

Oxidative stress contributes to retinal neurovascular injury through inflammation, mitochondrial dysfunction, blood–retinal barrier (BRB) disruption, microcirculatory impairment, and regulated cell death. Hydroxysafflor yellow A (HSYA), a water-soluble quinochalcone C-glycoside derived from safflower (Carthamus tinctorius L.), modulates oxidative and inflammatory signaling, apoptosis, mitochondrial injury, endothelial barrier dysfunction, and neurovascular damage in experimental ischemic, inflammatory, and metabolic disorders. This review critically evaluates the direct ocular evidence for HSYA in diabetic retinopathy and examines the systemic-to-ocular pharmacokinetic and delivery barriers that constrain its ophthalmic translation. Current ocular evidence is limited and concentrated mainly in DR models, in which HSYA attenuates oxidative stress, inflammation, BRB disruption, and apoptosis, potentially through Nrf2/HO-1 signaling. Evidence in retinal photic injury is limited, whereas the proposed relevance of HSYA to retinal ischemia–reperfusion injury, glaucoma, and AMD remains largely hypothesis-generating. The principal translational challenge is whether HSYA can achieve pharmacologically relevant exposure in ocular target tissues. Future studies should integrate dose, plasma and ocular exposure, target engagement, retinal structure, local safety, and visual function in disease-specific models. Accordingly, evidence from non-DR models is discussed primarily to define mechanistic hypotheses and experimental priorities rather than to establish ophthalmic efficacy. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline, reflecting widespread brain dysfunction across multiple neural systems. Early detection of pathological changes is critical for enabling timely intervention, improved management, and better therapeutic outcomes. Methods: Using non-transgenic AD rats (Samaritan) and sham rats (Long–Evans), we explored structural and functional differences with multimodal MRI and multi-unit activity (MUA). Results: Diffusion tensor imaging (DTI) revealed no significant changes in mean diffusivity of water, but AD-related microstructural alterations of fractional anisotropy were confined to subcortical regions with cortical areas and white matter tracts remaining intact. We used functional MRI (fMRI) with blood oxygenation level-dependent (BOLD) contrast in rest-state (R-fMRI) and task-based (T-fMRI) paradigms. R-fMRI revealed much stronger functional connectivity in subcortical vs. cortical areas in AD rats, implicating AD-related functional changes in subcortical areas in agreement with DTI data. T-fMRI with sensory stimulation revealed reproducible fMRI responses in both groups; however, AD rats exhibited reduced BOLD response amplitude and spatial activation extent, which was accompanied by attenuated stimulus-evoked MUA responses. These suggest that attenuated evoked BOLD response reflects diminished neuronal activity in AD, rather than impaired neurovascular and/or neurometabolic coupling. Conclusions: Together these findings suggest that AD-induced anatomical and functional changes in subcortical areas are related to altered cortical responses, highlighting multimodal MRI as a sensitive tool for early AD-related brain changes. Full article

Muscle wasting associated with gastric cancer represents a complex, multifactorial systems disorder involving inflammatory, anabolic, mechanosensory, calcium-regulatory, mitochondrial, and proteostatic disruption. This review synthesizes current evidence regarding the cellular and physiological mechanisms involved in skeletal muscle dysfunction in gastric cancer and provides a unifying framework centered on loss of signaling coherence. Specifically, it examines IL-6/STAT3 and NF-κB inflammatory signaling, the myostatin–activin–ACVR2B–SMAD pathway, PI3K/Akt/mTOR signaling, mechanotransduction, excitation–metabolism coupling, calcium homeostasis, mitochondrial function, and proteostasis. Although individual components of these pathways have been implicated in muscle wasting associated with chronic disease, current evidence suggests that they interact through positive feedback loops. Inflammation, anabolic resistance, impaired force-to-signal conversion, mitochondrial stress, altered intracellular calcium homeostasis, and disrupted protein quality control may reinforce one another, contributing to metabolic, structural, and transcriptional instability. Within this context, muscle wasting reflects not only loss of muscle mass or strength, but also loss of functional integrity resulting from disrupted integration of mechanical, metabolic, inflammatory, and anabolic signals. Given the systemic nature of these effects, this review proposes kinesitherapy as a potentially useful nonpharmacological adjunctive strategy that may modulate inflammation, restore responsiveness to mechanical stimuli, support calcium homeostasis and mitochondrial function, improve anabolic sensitivity, and maintain protein quality control. Overall, this review presents a systems-biology model of gastric cancer-associated muscle wasting and supports further investigation of exercise-based therapies for this condition. Full article

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency. While brain pathology has been extensively studied, the retina remains underexplored. This study investigated retinal structural, functional, vascular, and cellular changes in a Scn1a^+/− rat model of DS. Anatomical quantification revealed thinning of the retinal nerve fiber layer and thickening of the outer plexiform layer. Electroretinography (ERG) showed selectively reduced oscillatory potential amplitudes, suggesting dysfunction of neurovascular coupling. Consistent with these findings, immunohistochemistry demonstrated aberrant vascular morphology, including increased vessel curvature and reduced branching density. In addition, we observed robust microglial activation in the outer and inner plexiform layers; however, astrocyte morphology remained largely unchanged. Fenfluramine, an approved anti-seizure drug for DS, attenuated microglial activation but failed to rescue retinal structural or vascular deficits, indicating a dissociation between its anti-inflammatory and disease-modifying effects. Our findings suggest that multimodal retinal assessment could serve as a noninvasive biomarker platform for monitoring disease progression and therapeutic response in DS. Full article

Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate contemporary evidence regarding emerging and established treatment approaches for rosacea. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, and Web of Science were searched for studies published between 2016 and 2025. Original human studies evaluating therapeutic interventions for rosacea were included. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. Results: Fifteen studies involving 537 patients with rosacea and 77 controls (614 participants in total) met the eligibility criteria. Evaluated interventions included vascular-targeted therapies, topical anti-inflammatory agents, systemic and immunomodulatory treatments, and microbiome-oriented approaches. Oxymetazoline, pulsed-dye laser, platelet-rich plasma, ivermectin, azelaic acid, dapsone, sulfur preparations, and metronidazole demonstrated clinical benefits in reducing erythema, inflammatory lesions, or overall disease severity. Emerging therapies, including tofacitinib and oral ivermectin, showed promising results in refractory disease. Microbiome-related interventions, particularly Demodex-targeted therapies and Helicobacter pylori eradication, were also associated with clinical improvement. Risk-of-bias assessment identified two studies with low risk of bias, twelve with moderate risk of bias, and one study with high risk of bias. Conclusions: Current evidence supports a multimodal and mechanism-based approach to rosacea management, integrating vascular, inflammatory, immunological, and microbiological targets. However, the available evidence remains limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and a predominance of non-randomized study designs. Large, well-designed randomized controlled trials are needed to establish optimal evidence-based treatment strategies and define the long-term efficacy and safety of emerging therapies. Full article

Background and Objectives: The labyrinthine artery (LA) is a small but surgically important vessel encountered during procedures involving the cerebellopontine angle (CPA). Variations in its number, origin, and relationship to the facial–vestibulocochlear nerve complex may increase the risk of vascular injury during CPA surgery. The aim of this cadaveric microdissection study was to evaluate the number, origin, and course of the LA within the CPA and to characterize its relationship to the anterior inferior cerebellar artery (AICA) and the facial–vestibulocochlear nerve complex. Materials and Methods: Microsurgical dissections were performed bilaterally in 45 formalin-fixed adult cadavers (90 CPAs) using an operating microscope and vascular injection. The number, origin, and course of the LA were analyzed together with its relationship to the AICA and the facial–vestibulocochlear nerve complex. Results: The LA was identified in all specimens. A single LA was observed in 57.8% of CPAs, whereas multiple LAs were identified in 42.2%. The artery most commonly originated from the AICA (65.6%), followed by a common trunk shared with the AICA (21.1%) and direct origin from the basilar artery (13.3%). In specimens with bifurcated AICAs forming double loops, multiple LAs frequently arose from both loops. Considerable variability was observed in the course of the LA relative to the facial–vestibulocochlear nerve complex, including superior, inferior, and interposed courses. Bilateral asymmetry was identified in 15.6% of cadavers. Conclusions: The LA demonstrates substantial anatomical variability within the CPA regarding its number, origin, and neurovascular relationships. Although the artery most commonly arises from the apex or medial aspect of the AICA loop, its subsequent course may vary considerably. Careful microsurgical inspection remains essential during CPA surgery, as the configuration of the AICA alone is insufficient to reliably predict the distal trajectory of the LA. Full article

Background: Trigeminal neuralgia (TN), a facial pain disorder classically characterized by recurrent brief electric-shock-like paroxysms in one or more trigeminal divisions, frequently traverses dental pathways before specialist evaluation. Conversely, dental extraction, endodontic treatment, implant procedures, and third-molar surgery may injure the inferior alveolar, superior alveolar, mental, or lingual nerves and generate painful post-traumatic trigeminal neuropathy. We sought to define the diagnostic interface between classical TN and post-dental/alveolar nerve-related trigeminal pain in a tertiary referral cohort. Methods: We performed a retrospective single-center diagnostic-pathway study using a clinical dataset comprising 672 unique patients. A dental-interface trigeminal candidate cohort was assembled from aggregated patient-level source notes and adjudicated into five prespecified phenotypes: confirmed alveolar neuropathy, post-extraction neuropathic onset, odontogenic diagnostic misclassification, mixed/uncertain dental-interface pain, and clean classical TN. Extracted variables included demographics, trigeminal branch documentation, sensory deficit, dental procedure history, post-extraction onset, MRI and neurovascular conflict language, secondary structural disease, TN-directed medication exposure, invasive treatment exposure, documented outcomes, and time from first specialist documentation to first dated invasive treatment. Results: Among 201 dental-interface trigeminal candidates, 19 patients (9.5%) had confirmed alveolar neuropathy, 31 (15.4%) had post-extraction neuropathic onset, 20 (10.0%) represented odontogenic diagnostic misclassification, 115 (57.2%) remained mixed/uncertain, and 16 (8.0%) fulfilled a clean classical TN phenotype. Overall, 114 patients (56.7%) carried explicit TN terminology somewhere in the chart. Non-classical alveolar/post-dental syndromes comprised 70 patients (34.8%). Compared with clean classical TN, this non-classical group had higher rates of documented oral sensory deficit (38.6% vs. 0.0%, p = 0.002), post-extraction onset (52.9% vs. 0.0%, p < 0.001), extraction history (61.4% vs. 0.0%, p < 0.001), and secondary structural disease (22.9% vs. 0.0%, p = 0.035). Neurovascular conflict or vascular-loop language did not distinguish non-classical alveolar/post-dental syndromes from clean classical TN (38.6% vs. 37.5%, p = 1.000). Conclusions: A substantial minority of tertiary dental-interface trigeminal referrals represented alveolar/post-dental syndromes rather than clean classical TN, even while carrying TN labels and accumulating TN-directed treatment exposure. Post-extraction onset, lower-lip/chin or intraoral sensory change, and pain persisting despite extraction should prompt careful phenotyping before classical TN-directed escalation. The alveolar–trigeminal interface can be operationalized as a recognizable diagnostic pathway with direct implications for multidisciplinary facial-pain evaluation. Full article

Diabetic peripheral neuropathy (DPN) remains a leading cause of disability in diabetes, yet current care is largely symptomatic and does not directly address early neurovascular-immune pathology. This narrative review synthesizes clinical, redox, vascular, and immunological evidence into a peripheral nerve neurovascular unit (PNVU)/blood–nerve barrier (BNB)-centered framework for DPN. First, the review outlines the diagnostic and translational endpoint landscape of DPN, emphasizing that commonly used clinical, neurophysiological, small-fiber, and imaging-based tools capture important disease domains but do not directly assess early BNB dysfunction. It then reviews the anatomical and functional basis of the PNVU and BNB, including endoneurial microvascular endothelial cells, pericytes, basement membrane components, immune cells, and tight-junction proteins. Next, it discusses how chronic hyperglycemia and dyslipidemia drive metabolic-to-vascular coupling, redox imbalance, antioxidant defense failure, advanced glycation end products (AGEs), receptor for AGEs (RAGE), and nuclear factor-κB (NF-κB) signaling, endothelial activation, leukocyte recruitment, macrophage polarization, and junctional disassembly, culminating in increased BNB permeability and exposure of peripheral nerves to pro-inflammatory and neurotoxic mediators. Finally, it evaluates incretin-based therapies—including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors, DPP-4is), and emerging multi-agonists—as potential modulators of oxidative and inflammatory stress within this framework. Although semaglutide and related agents show mechanistic plausibility and preclinical promise, direct evidence for incretin-mediated BNB stabilization in human DPN remains limited. By reframing DPN as a redox-driven neurovascular-immune disorder, this review highlights barrier-focused biomarkers, translational endpoints, and hypothesis-generating therapeutic opportunities that require clinical validation. Full article