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24 pages, 588 KB  
Review
Dural Lymphomas Unmasked: A Narrative Review of Extra-Axial Mimics and a Pragmatic Diagnostic Decision Algorithm
by Luca Zavatto, Viviana Berti, Davide Costazza, Paolo Cipriano Cecchi, Andreas Schwarz, Alessandro Spimpolo, Mohsen Farsad, Matteo Bonatti, Andrea Bernardelli, Mauro Krampera, Carlo Visco and Pier Paolo Berti
Cancers 2026, 18(15), 2369; https://doi.org/10.3390/cancers18152369 - 23 Jul 2026
Viewed by 473
Abstract
Dural-based lymphomas are rare extranodal non-Hodgkin lymphomas that span from indolent primary dural entities, most commonly the extranodal marginal zone (mucosa-associated lymphoid tissue) lymphoma, to aggressive variants that are primary or represent secondary involvement from systemic lymphoma. They overlap radiologically with benign meningiomas, [...] Read more.
Dural-based lymphomas are rare extranodal non-Hodgkin lymphomas that span from indolent primary dural entities, most commonly the extranodal marginal zone (mucosa-associated lymphoid tissue) lymphoma, to aggressive variants that are primary or represent secondary involvement from systemic lymphoma. They overlap radiologically with benign meningiomas, dural metastases, and immune-mediated pachymeningitis, creating a risk of anchoring bias, delayed diagnosis, and unnecessarily extensive resections when limited tissue sampling would be sufficient for diagnosis. We conducted a structured narrative review to synthesize the epidemiology, clinico-pathological classification, imaging phenotypes, and management principles of dural lymphomatous disease. This study will especially focus on primary dural lymphoma (PDL) with additional discussion of secondary dural involvement. Emphasis is placed on the clinical value of a multiparametric diagnostic approach that integrates computed tomography contrast-enhanced magnetic resonance imaging with functional techniques, and fluorodeoxyglucose positron emission tomography/computed tomography for systemic staging and for distinguishing truly localized primary dural lymphoma from secondary involvement. Potential diagnostic pitfalls related to somatostatin receptor–based tracer uptake will also be discussed. We introduced a pragmatic operational framework based on four clinico-biological clusters, translated into a step-by-step decision algorithm that prioritizes timely biopsy and comprehensive hematologic staging to guide surgical strategy. Given the absence of dedicated, multidisciplinary guidance for dural-based lymphomas, this algorithm is intended as a reproducible foundation for consensus recommendations and future multicenter validation. Full article
(This article belongs to the Special Issue The Development of Immunotherapies to Treat Lymphoma)
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13 pages, 3123 KB  
Case Report
Extending the Reach of the Inferior Trapezius Flap in Occipital Reconstruction: A Technical Refinement with Dorsal Scapular Artery Sacrifice—A Case Report
by Ioana-Maria Onați, Florian Dorel Bodog, Iones Afana, Isabelle-Yvette Indig, Camelia Crișan, Cristina Mihaela Brisc, Iulia Codruța Macovei, Narcis Vîlceanu and Ruxandra Florina Bodog
J. Clin. Med. 2026, 15(10), 3933; https://doi.org/10.3390/jcm15103933 - 20 May 2026
Viewed by 985
Abstract
Background/Objectives: Occipital defects with dural exposure represent a complex reconstructive challenge requiring reliable vascularized coverage to prevent severe complications. This study aims to describe a salvage reconstructive approach using a transverse cervical artery (TCA)-based inferior trapezius flap and to highlight a technical [...] Read more.
Background/Objectives: Occipital defects with dural exposure represent a complex reconstructive challenge requiring reliable vascularized coverage to prevent severe complications. This study aims to describe a salvage reconstructive approach using a transverse cervical artery (TCA)-based inferior trapezius flap and to highlight a technical modification intended to increase flap reach. Methods: We report the case of a 61-year-old male presenting with a chronic occipital defect associated with infection following cerebellar abscess evacuation. After failure of primary closure, skin grafting, and local flap reconstruction, a regional pedicled inferior trapezius musculocutaneous flap was performed. Intraoperatively, the dorsal scapular artery (DSA) was selectively sacrificed after confirmation of dominant TCA perfusion to increase the arc of rotation. Flap perfusion was assessed clinically. Results: The flap provided adequate coverage of the defect with stable perfusion. The postoperative course was favorable, with resolution of a minor donor-site seroma. At 1- and 3-month follow-up, stable coverage, preserved cervical mobility, and satisfactory aesthetic outcomes were observed. These results were maintained at 1-year follow-up, with no functional limitation or late complications. Conclusions: This single case report suggests that a TCA-based inferior trapezius flap may represent a feasible salvage option in selected occipital defects. The intentional sacrifice of the DSA appeared to increase flap reach in this case; however, its safety and reproducibility remain uncertain. Further studies are required before this approach can be routinely recommended. Full article
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15 pages, 737 KB  
Systematic Review
Surgical Techniques and Materials Used in the Treatment of Complicated Otomastoiditis: A Systematic Review
by Maria Denisa Zica, Catalina Voiosu, Andreea Rusescu, Irina Ionita, Luana Maria Gherasie, Oana Ruxandra Alius, Alexandra Bizdu Branovici, Razvan Hainarosie and Viorel Zainea
J. Clin. Med. 2026, 15(10), 3911; https://doi.org/10.3390/jcm15103911 - 19 May 2026
Viewed by 559
Abstract
Background and Objectives: Complicated cholesteatomatous otomastoiditis includes a spectrum of inflammatory, suppurative, and destructive lesions affecting the temporal bone and surrounding critical structures, including the dura mater, labyrinth, facial nerve, sigmoid sinus, and skull base. The selection of appropriate surgical techniques and closure [...] Read more.
Background and Objectives: Complicated cholesteatomatous otomastoiditis includes a spectrum of inflammatory, suppurative, and destructive lesions affecting the temporal bone and surrounding critical structures, including the dura mater, labyrinth, facial nerve, sigmoid sinus, and skull base. The selection of appropriate surgical techniques and closure materials is decisive for long-term outcomes, functional preservation, and prevention of life-threatening complications. This systematic review and meta-analysis evaluates the evidence base for surgical approaches, intraoperative technologies, and autologous and synthetic closure materials used in the management of iatrogenic and disease-related fistulas in otomastoid surgery. Materials and Methods: A PRISMA 2020-compliant search was conducted across PubMed, Cochrane Library, Embase, and Scopus (2000–2024). The review was registered in PROSPERO (CRD420261370406). After the systematic screening process, 56 eligible studies involving 4218 patients were selected for inclusion. The primary outcome measures analysed were infection rates, fistula recurrence, preservation of function, and long-term integrity of the closure. Limitations include the predominance of observational studies and the absence of prospective registration prior to data extraction. Results: Autologous materials demonstrated consistently low infection rates (<10%) in contaminated operative fields and therefore remain the preferred first-line option for the reconstruction of small to moderate defects. In contrast, synthetic materials exhibited superior mechanical durability in large sterile defects, achieving closure integrity rates of 85–92% at two-year follow-up. Hybrid reconstructive constructs provided the most favourable overall outcomes, with pooled closure integrity reaching 91.6%, suggesting a synergistic advantage when combining biologic and synthetic components. Furthermore, the adjunctive use of combined microscopic–endoscopic surgical techniques was associated with a significant reduction in residual cholesteatoma rates (OR 0.56, 95% CI 0.38–0.82), supporting the growing role of endoscopic assistance in middle ear and mastoid surgery. When biologic closure strategies were appropriately selected according to defect characteristics and contamination status, functional preservation rates exceeded 90–95%, underscoring the importance of tailored reconstructive approaches. Conclusions: The durability of long-term outcomes is most strongly influenced by complete pathological clearance and by the strategic alignment of biomaterial properties with defect dimensions, contamination status, and surrounding anatomical structures. In response to these findings, an evidence-based algorithmic framework is proposed to facilitate rational intraoperative material selection. Full article
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12 pages, 3607 KB  
Case Report
Manual Therapy-Associated Dural Tear Causing Intracranial Hypotension Treated with an Epidural Blood Patch: A Case Report
by Niklavs Nemme, Arturs Balodis, Mara Klibus, Olegs Sabelnikovs, Arina Novasa, Jolanta Osina and Marina Sarkele
J. Clin. Med. 2026, 15(10), 3860; https://doi.org/10.3390/jcm15103860 - 17 May 2026
Viewed by 524
Abstract
Background/Objectives: Intracranial hypotension is a rare and underdiagnosed serious condition characterized by low cerebrospinal fluid (CSF) pressure, often resulting from trauma to the dura mater. While manual therapy is increasingly used for musculoskeletal complaints, it is not without risk and may, in [...] Read more.
Background/Objectives: Intracranial hypotension is a rare and underdiagnosed serious condition characterized by low cerebrospinal fluid (CSF) pressure, often resulting from trauma to the dura mater. While manual therapy is increasingly used for musculoskeletal complaints, it is not without risk and may, in rare cases, result in complications such as dural tears. Although these complications are rare, they require early recognition and appropriate treatment to prevent further morbidity. This case report aims to highlight a rare presentation of multilevel dural defects in temporal association with manual therapy and to demonstrate the efficacy of epidural blood patch (EBP) treatment. Case Presentation: We report a case of a 46-year-old woman without chronic illness who developed worsening orthostatic headaches, weakness, and vomiting after multiple manual therapy sessions. Only after 6 months did the patient undergo magnetic resonance imaging (MRI), which revealed intracranial hypotension due to dural damage in the spinal dura mater at C6–T1 and T8–T10, brain sagging, and an increased risk of subdural hematoma. After excluding other causes of dural defects, EBP was performed under CT guidance at C6–C7 and T8–T9, which resulted in symptom regression. Follow-up MRI was recommended for the patient. Conclusions: This case highlights a rare but clinically significant occurrence of multilevel dural defects and intracranial hypotension in temporal association with manual therapy. This emphasizes the critical role of timely diagnosis using MRI and the clinical effectiveness of EBP as a minimally invasive procedure. Full article
(This article belongs to the Section Anesthesiology)
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9 pages, 508 KB  
Article
Anatomical Investigation of the Transverse Dural Venous Sinuses
by Jacobus J. Gates, Kirsten S. Regan, Lané Prigge and Gerda Venter
Anatomia 2026, 5(1), 8; https://doi.org/10.3390/anatomia5010008 - 23 Mar 2026
Viewed by 1119
Abstract
Background and objectives: Accurate anatomical knowledge of the transverse dural venous sinuses (TS) is essential for safe neurosurgical procedures, particularly in resource-limited settings where advanced imaging modalities may be unavailable. Despite the TS’s clinical importance, detailed cadaveric studies focusing solely on its morphology [...] Read more.
Background and objectives: Accurate anatomical knowledge of the transverse dural venous sinuses (TS) is essential for safe neurosurgical procedures, particularly in resource-limited settings where advanced imaging modalities may be unavailable. Despite the TS’s clinical importance, detailed cadaveric studies focusing solely on its morphology are scarce. This study investigated the length, width, and shape of the TS in adult human cadavers, assessing anatomical dominance and morphological variations relevant to surgical planning. Methods: A descriptive, cross-sectional study was conducted on 32 formalin-fixed adult cadavers (20 male, 12 female) at the University of Pretoria in South Africa. The TS was examined bilaterally within the dura mater and the corresponding transverse sulcus. Lengths were measured using a string and a ruler to accommodate curvature, while widths at the origin, midpoint, and termination were measured using digital calipers. Statistical analyses included Shapiro–Wilk tests, paired t-tests, and intra-class correlation to determine significance and reliability. Results: The average TS length was 72.54 mm (left) and 70.23 mm (right), with no statistically significant differences between sides. Right-sided dominance in TS width was observed in 71.88% of cases. A significant narrowing at the midpoint, followed by widening at the termination, was consistently noted, especially in males. Differences between dural and bony groove widths suggested that sulcal impressions may not accurately reflect TS dimensions. Conclusions: The TS demonstrates significant morphological variability, including asymmetry and abrupt dimensional changes. These findings underscore the importance of direct anatomical reference for surgical navigation, particularly in low-resource settings lacking advanced imaging. Full article
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25 pages, 1724 KB  
Review
Mechanisms of Dural Involvement in Cerebral Amyloid Angiopathy
by Marialuisa Zedde, Fabrizio Piazza and Rosario Pascarella
Cells 2026, 15(1), 26; https://doi.org/10.3390/cells15010026 - 23 Dec 2025
Viewed by 2070
Abstract
Cerebral Amyloid Angiopathy (CAA) is a neurovascular condition characterized by the accumulation of amyloid-beta (Aβ) in the walls of small blood vessels, particularly affecting the leptomeninges and cortical regions in elderly populations. Initially recognized for its association with spontaneous lobar intracerebral hemorrhage, recent [...] Read more.
Cerebral Amyloid Angiopathy (CAA) is a neurovascular condition characterized by the accumulation of amyloid-beta (Aβ) in the walls of small blood vessels, particularly affecting the leptomeninges and cortical regions in elderly populations. Initially recognized for its association with spontaneous lobar intracerebral hemorrhage, recent studies have highlighted the broader implications of CAA on cognitive decline and vascular health. This narrative review aims to elucidate the mechanisms of dural involvement in CAA, an aspect that has been largely overlooked in existing literature. This paper provides a detailed examination of the potential role of the dura mater and its associated lymphatic system in the clearance of interstitial amyloid and the maintenance of cerebrospinal fluid (CSF) homeostasis. Dural lymphatic vessels may facilitate the efflux of Aβ from the brain, and any impairment in this drainage system could contribute to the pathological accumulation of amyloid, exacerbating CAA and its neurological consequences. Additionally, the significant association between CAA and subdural hematoma (SDH) has been explored, indicating that the presence of SDH may complicate the clinical management of CAA patients by signaling an increased risk of hemorrhagic events. The mechanisms linking CAA and SDH, including vascular fragility and chronic inflammatory processes, are discussed to provide insight into potential pathways for therapeutic intervention. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Vascular-Related Diseases)
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16 pages, 2914 KB  
Article
Expression of Connexins 37/40 and Pannexin 1 in Early Human and Yotari (Dab1−/−) Meninges Development
by Marko Puljiz, Natalija Filipović, Nela Kelam, Anita Racetin, Yu Katsuyama and Katarina Vukojević
Biomedicines 2025, 13(12), 3088; https://doi.org/10.3390/biomedicines13123088 - 15 Dec 2025
Viewed by 720
Abstract
Background/Objectives: The meninges, the protective membranes covering the central nervous system, undergo complex developmental processes that are critical for CNS integrity and function. Connexin 37 (Cx37) and 40 (Cx40), members of the connexin family of gap junction proteins, have been implicated in [...] Read more.
Background/Objectives: The meninges, the protective membranes covering the central nervous system, undergo complex developmental processes that are critical for CNS integrity and function. Connexin 37 (Cx37) and 40 (Cx40), members of the connexin family of gap junction proteins, have been implicated in various physiological and pathological processes. They play a critical role in cell–cell communication. The aim of our study was to investigate the expression of connexins Cx37, Cx40, and Panx1 in the meninges of both human and murine models (yotari and wild type) at the 6th week/E13.5 and 8th week/E15.5 of developmental stages. Methods: Human embryonic tissues (6th–8th week, n = 4 for the 6th week and n = 4 for the 8th week) and mouse embryos (yotari Dab1/ and wild type, E13.5–E15.5) were collected and fixed in 4% paraformaldehyde. Paraffin sections were stained for Cx37, Cx40, and Panx1 using immunofluorescence. Images were analyzed in ImageJ, and statistical comparisons were performed using one-way ANOVA with Tukey’s post hoc test (p < 0.05). Results: Cx37 was consistently expressed across all developmental stages, with the highest threshold area percentage observed at E13.5 and E15.5 in murine leptomeninges, demonstrating statistically significant differences compared to controls (p < 0.05) and notably from corresponding human stages (p < 0.001). Strong Cx37 staining intensity at E13.5 was noted in both wild-type and yot mice, while human leptomeninges displayed mild staining at the 6th week of development. In contrast, both human and murine pachymeninges exhibited moderate Cx37 expression. Additionally, the expression of Cx37 in wild-type mice surpassed that of human samples at both E13.5 and E15.5 stages (p < 0.01 and p < 0.001, respectively). For the developing dura mater, Cx37 expression peaked at E15.5 in yot mice, significantly different from both wild-type and human dura mater (p < 0.01 and p < 0.05). Cx40 expression was highest in the leptomeninges at E15.5. Panx1 was similarly expressed across stages, with the highest threshold area percent observed in wild-type leptomeninges and pachymeninges at E15.5, showing significant differences compared to yot mice and human samples (p < 0.05). Both leptomeninges and pachymeninges exhibited mild Panx1 staining at E13.5, while stronger staining was observed at E15.5 in murine samples, contrasting with mild intensity in human counterparts. Conclusions: These findings highlight the implications of Dab1 deficiency for the expression of gap junction proteins during meninges development, implicating their importance in intercellular communication that is essential for normal meningeal and neurodevelopmental processes. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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25 pages, 1655 KB  
Article
LPS-Induced Neuroinflammation Increases Serotonin-Evoked Activity of Trigeminal Afferents and Aggravates Mechanical Allodynia and Photophobic Behavior in Rat Migraine Model
by Svetlana Svitko, Elisaveta Ermakova, Karina Gilizhdinova, Ksenia Bogatova, Nazgul Gaifutdinova, Dinara Nurmieva, Egor Nevsky, Anton Ananev, Olga Yakovleva, Albert Sufianov, Galina Z. Sufianova, Artyom Baev, Kseniia Shaidullova, Albert Rizvanov, Aliya Yakubova and Guzel Sitdikova
Int. J. Mol. Sci. 2025, 26(24), 11983; https://doi.org/10.3390/ijms262411983 - 12 Dec 2025
Cited by 1 | Viewed by 1510
Abstract
Migraine is characterized by severe pain and somatic symptoms like allodynia and photophobia, driven by neuroinflammation that sensitizes the trigeminal vascular system (TVS). This study investigated how neuroinflammation induced by systemic lipopolysaccharide (LPS) affects migraine-related nociceptive signaling. Using a chronic migraine model in [...] Read more.
Migraine is characterized by severe pain and somatic symptoms like allodynia and photophobia, driven by neuroinflammation that sensitizes the trigeminal vascular system (TVS). This study investigated how neuroinflammation induced by systemic lipopolysaccharide (LPS) affects migraine-related nociceptive signaling. Using a chronic migraine model in rats with nitroglycerin (NTG), we compared prenatal and acute postnatal LPS administration. Rats with prenatal LPS exhibited lower mechanical thresholds and enhanced allodynia and photophobia after NTG. Acute LPS also increased allodynia, but not photophobia. Both LPS groups showed increased mast cell degranulation in the dura mater. Plasma CGRP after NTG administration was elevated in the acute LPS group. Electrophysiology revealed enhanced trigeminal afferent responses to serotonin in both acutely and prenatally LPS-treated rats. Calcium imaging demonstrated increased neuronal responses to serotonin and capsaicin, suggesting an upregulation of serotonin and TRPV1 receptors. Our findings show that LPS-induced neuroinflammation, whether prenatal or acute, promotes sensitization of peripheral and central nociceptive pathways, involving serotoninergic mechanisms. Full article
(This article belongs to the Section Molecular Biology)
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15 pages, 999 KB  
Article
Spontaneous SSCD Auto-Plugging: Clinical, Electrophysiological and Radiological Evidence
by Pierre Reynard, Eugenia Mustea, Aïcha Ltaief-Boudrigua, Andrea Castellucci, Hung Thai-Van and Eugen C. Ionescu
J. Clin. Med. 2025, 14(22), 8054; https://doi.org/10.3390/jcm14228054 - 13 Nov 2025
Viewed by 909
Abstract
Background: Superior semicircular canal dehiscence (SSCD) is characterized by a bony defect of the superior semicircular canal (SSC), leading to vestibular and auditory symptoms. A process of spontaneous “auto-plugging,” in which the overlying dura mater progressively occludes the SSC, may replicate the effects [...] Read more.
Background: Superior semicircular canal dehiscence (SSCD) is characterized by a bony defect of the superior semicircular canal (SSC), leading to vestibular and auditory symptoms. A process of spontaneous “auto-plugging,” in which the overlying dura mater progressively occludes the SSC, may replicate the effects of surgical canal plugging but remains under-recognized. The present study reports diverse clinical, instrumental, and 3d High Resolution MRI findings in patients with SSCD and subsequently confirmed to present with spontaneous complete or partial auto-plugging. Methods: We retrospectively reviewed 11 patients with SSCD diagnosed on high-resolution CT and suspected auto-plugging based on clinical atypia and large dehiscence (>4 mm). Patients underwent comprehensive neurotological assessment, including pure-tone audiometry, vestibular testing, and HR MRI with 3D labyrinthine reconstructions to identify partial or complete auto-plugging. Auto-plugging was classified as partial (Canalis semicircularis superior depressus) or complete (absence of endolymph fluid signal; Canalis semicircularis superior obturatus). Results: Among 13 ears with auto-plugging, 6 were partial and 7 complete. The mean SSCD size in auto-plugged ears was 5.5 mm. Most ears had normal or near-normal vestibular function on VHIT, with minimal air-bone gaps and preserved VEMP responses. Imaging demonstrated varying degrees of dural contact with the SSC, confirming partial or complete canal occlusion. Conclusions: Spontaneous auto-plugging of the SSC is a plausible, under-recognized phenomenon that may reproduce functional effects of surgical plugging. Dedicated 3D labyrinthine MRI enhances detection and characterization. Prospective multimodal studies are needed to clarify the pathophysiology, progression, and clinical implications, optimizing patient selection for surgical versus conservative management. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Management of Vestibular Disorders)
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15 pages, 5143 KB  
Article
Ovariectomy Induces Selective Alterations in Dura Mater Blood and Lymphatic Microvascular Network Architecture in Mice
by Olga V. Glinskii, Imad Eddine Toubal, Leike Xie, Sunilima Sinha, Kannappan Palaniappan and Vladislav V. Glinsky
Cells 2025, 14(21), 1647; https://doi.org/10.3390/cells14211647 - 22 Oct 2025
Cited by 1 | Viewed by 1068
Abstract
Ovarian hormones are essential regulators of vascular homeostasis, yet their deficiency’s effects on the meningeal microvasculature remain incompletely understood. We used high-resolution imaging to assess the cranial dura mater (CDM) blood and lymphatic microvasculature in ovariectomized (OVX) and control (intact or sham-operated) mice, [...] Read more.
Ovarian hormones are essential regulators of vascular homeostasis, yet their deficiency’s effects on the meningeal microvasculature remain incompletely understood. We used high-resolution imaging to assess the cranial dura mater (CDM) blood and lymphatic microvasculature in ovariectomized (OVX) and control (intact or sham-operated) mice, followed by morphometric analysis of microvessel architecture. Immunofluorescent staining and Western blotting were employed to evaluate markers of vascular remodeling and profibrotic signaling. Blood microvascular quantification revealed a significant reduction in total microvessel length two weeks post-OVX, primarily due to arteriolar, but not venular, shortening. At the same time, the lengths of individual segments of both arterioles and venules were also significantly decreased, indicating microvascular fragmentation. Despite these changes, total vessel surface area remained preserved, suggesting compensatory dilation, particularly in arterioles. OVX also increased overall vessel tortuosity, again selectively affecting arterioles. Region-specific analysis of lymphatic networks associated with the coronal suture (CS) showed significantly increased surface area of podoplanin-positive lymphatic vessels. Elevated α-smooth muscle actin (α-SMA) expression in vascular and stromal compartments in OVX animals, along with increased transforming growth factor beta (TGF-β) levels, indicated early profibrotic changes. These findings highlight the selective vulnerability of arterial and lymphatic microvascular structures to hormonal deficiency post-OVX and suggest an association between hormonal status, microvascular remodeling, and profibrotic alterations in the CDM. Full article
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32 pages, 526 KB  
Review
A Practical Approach to Intracranial Dural Arteriovenous Fistulas: Pathogenesis, Classification and Management
by Karol Maciejewski, Miłosz Pinkiewicz, Bartosz Mruk, Daniel Knap, Artur Zaczyński, Jerzy Walecki and Michał Zawadzki
J. Clin. Med. 2025, 14(19), 6895; https://doi.org/10.3390/jcm14196895 - 29 Sep 2025
Cited by 6 | Viewed by 13170
Abstract
Dural arteriovenous fistulas (dAVFs) are a heterogeneous group of intracranial vascular anomalies characterized by abnormal arteriovenous shunting within the dura mater. While they are often considered acquired lesions—associated with trauma, surgery, venous sinus stenosis, or thrombosis—their precise etiology remains unclear in many cases. [...] Read more.
Dural arteriovenous fistulas (dAVFs) are a heterogeneous group of intracranial vascular anomalies characterized by abnormal arteriovenous shunting within the dura mater. While they are often considered acquired lesions—associated with trauma, surgery, venous sinus stenosis, or thrombosis—their precise etiology remains unclear in many cases. The clinical presentation of dAVFs varies widely depending on location and venous drainage patterns. Benign forms may manifest as pulsatile tinnitus or headache, whereas lesions with retrograde venous drainage and cortical venous reflux are considered aggressive and carry a heightened risk of hemorrhage and progressive neurological decline. Multiple classification systems, primarily based on angioarchitecture and venous outflow characteristics, have been developed to stratify risk and guide treatment strategies, as these features largely determine the natural history and clinical course of dAVFs. Endovascular embolization, microsurgical disconnection, and stereotactic radiosurgery (SRS) represent the mainstays of treatment, aiming to prevent hemorrhage or rebleeding and to alleviate symptoms related to venous congestion. Over the past two decades, advances in endovascular techniques have driven a paradigm shift in management, positioning embolization as the first-line therapy for most dAVFs. This review begins with a comprehensive overview of dAVF pathogenesis, classification systems, and angioarchitecture. It then focuses on the endovascular management of dAVFs, offering a detailed appraisal of current and emerging techniques, key technical considerations, and lesion-specific treatment strategies. Finally, we discuss the role of microsurgery and SRS. Full article
(This article belongs to the Special Issue Neurovascular Diseases: Clinical Advances and Challenges)
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21 pages, 2413 KB  
Article
Brain Hsp90 Inhibition Mitigates Facial Allodynia in a Rat Model of CSD Headache and Upregulates Endocannabinoid Signaling in the PAG
by Seph M. Palomino, Aidan A. Levine, Erika Liktor-Busa, Parthasaradhireddy Tanguturi, John M. Streicher and Tally M. Largent-Milnes
Pharmaceuticals 2025, 18(10), 1430; https://doi.org/10.3390/ph18101430 - 24 Sep 2025
Viewed by 1404
Abstract
Background/Objectives: The role of the molecular chaperone heat shock protein 90 (Hsp90) in pain and analgesia has been recognized; however, no study to date has investigated its role in facial allodynia during headache. In the current study, we examined the role of [...] Read more.
Background/Objectives: The role of the molecular chaperone heat shock protein 90 (Hsp90) in pain and analgesia has been recognized; however, no study to date has investigated its role in facial allodynia during headache. In the current study, we examined the role of Hsp90 and its possible connection to the endocannabinoid system utilizing a rodent model of cortical spreading depression (CSD). Methods: CSD, a physiological phenomenon associated with headache disorders, was induced by cortical injection of KCl in female Sprague Dawley rats. To selectively inhibit Hsp90, 17-AAG was applied on the dura mater 24 h before CSD induction. Periorbital allodynia was assessed by von Frey filaments, while tissue samples were subjected to LC-MS, qPCR, Western immunoblotting, and the GTPγS coupling assay. Results: Increased expression of Hsp90 was selectively observed in the periaqueductal gray (PAG) harvested 90 min after cortical KCl injection, suggesting increased cellular stress from CSD induction. Application of 17-AAG (0.5 nmol) on dura mater 24 h before CSD induction significantly prevented facial allodynia as measured by von Frey filaments. This effect was blocked by injection of the CB1R antagonist rimonabant (1 mg/kg, ip). The pretreatment with 17-AAG significantly increased the level of anandamide (AEA) in PAG 90 min after cortical insult, as measured by LC-MS. This effect was accompanied by reduced expression of FAAH and increased expression of NAPE-PLD in the same nuclei. Conclusions: These results suggest that Hsp90 inhibition positively modulates the endocannabinoid system, causing pain relief through descending pain modulation in PAG post-CSD. Full article
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20 pages, 2622 KB  
Case Report
WHO Grade II or III Solitary Fibrous Tumors (Hemangiopericytomas) of the Spine: Two Case Reports with a Comprehensive Review of the Literature
by Kazuyuki Segami, Yutaro Okamura, Syu Takahashi, Yasuo Ueda, Koji Kanzaki and Yoshifumi Kudo
J. Clin. Med. 2025, 14(17), 6068; https://doi.org/10.3390/jcm14176068 - 27 Aug 2025
Cited by 3 | Viewed by 2906
Abstract
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case [...] Read more.
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case reports and small case series. To our knowledge, 157 cases, including the current case, have been reported since Schirger’s 1958 report on spinal SFTs. This report describes two cases of WHO grade II and III SFTs in the spine and presents a review of the literature. In the first case, an extradural WHO grade II SFT recurred 6 years after the first surgery, and a second surgery was performed, including wide excision of the surrounding tissue. The patient has remained recurrence-free for 16 years since the second surgery. In the second case, an intradural extramedullary WHO grade III SFT was resected, including the dura mater, and the patient has remained recurrence-free for 3 years since the surgery. Few reports have described tumor recurrence and long-term outcomes after reoperation, as in the first case, or extensive resection including the dura, as in the second case. Furthermore, the literature review not only summarizes patients’ general and surgical information, but also indicates, based on multivariate analysis, that gross total resection (GTR) is an important factor in preventing recurrence and metastasis. This is the first study to comprehensively examine previous reports and identify risk factors for recurrence and metastasis. In addition, because recurrences have been reported long after surgery, we believe that even if GTR is performed surgically, it is important to conduct follow-ups to check for long-term recurrence. Full article
(This article belongs to the Section Orthopedics)
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17 pages, 8254 KB  
Article
Aquaporins in the Capillaries of the Dura Mater of Pigs
by Slavica Martinović, Dinko Smilović, Boris Pirkić, Petra Dmitrović, Leonarda Grandverger and Marijan Klarica
Int. J. Mol. Sci. 2025, 26(15), 7653; https://doi.org/10.3390/ijms26157653 - 7 Aug 2025
Cited by 1 | Viewed by 1355
Abstract
Dura mater plays a critical role in neurofluid homeostasis, yet comparative data on capillary network density and organization between cranial and spinal regions remain limited. This study addresses this gap by systematically analyzing capillary architecture and aquaporin (AQP) expression in porcine cranial (parietal, [...] Read more.
Dura mater plays a critical role in neurofluid homeostasis, yet comparative data on capillary network density and organization between cranial and spinal regions remain limited. This study addresses this gap by systematically analyzing capillary architecture and aquaporin (AQP) expression in porcine cranial (parietal, falx) and spinal dura mater. Immunofluorescence labeling and confocal microscopy were used to assess capillary density, spatial distribution, and AQP1/AQP4 expression patterns across over 1000 capillaries in these regions. Cranial dura exhibited a 3–4 times higher capillary density compared to spinal dura, with capillaries predominantly localized to meningeal–dural border cell interfaces in cranial regions and a more dispersed distribution in spinal dura. Both AQP1 and AQP4 were detected as discrete clusters within capillary walls, with higher expression in cranial compared to spinal dura. Lymphatic vessels (PDPN-positive) were also observed adjacent to capillaries, supporting a dual-system model for fluid and waste exchange. These findings highlight the dura’s region-specific vascular specialization, with cranial regions favoring dense, structured capillary networks suited for active fluid exchange. This work establishes a foundation for investigating capillary-driven fluid dynamics in pathological states like subdural hematomas or hydrocephalus. Full article
(This article belongs to the Special Issue Aquaporins in Brain Disease, 2nd Edition)
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Article
A Murine Model of High Dietary Histamine Intake: Impact on Histamine Contents and Release in Neural and Extraneural Tissues
by Annette Kuhn, Jana Schramm, Birgit Vogler, Mária Dux, Fernando de Mora and Karl Messlinger
Nutrients 2025, 17(11), 1851; https://doi.org/10.3390/nu17111851 - 29 May 2025
Cited by 1 | Viewed by 2638
Abstract
Background: Histamine intolerance, a disorder due to impaired degradation of dietary histamine, is frequently associated with headaches, but the underlying pathophysiology is largely unknown; the sensitization of meningeal afferents appears likely. We approached this issue by examining histamine concentrations in different tissues and [...] Read more.
Background: Histamine intolerance, a disorder due to impaired degradation of dietary histamine, is frequently associated with headaches, but the underlying pathophysiology is largely unknown; the sensitization of meningeal afferents appears likely. We approached this issue by examining histamine concentrations in different tissues and meningeal histamine release in a new mouse model of high-histamine diets. Methods: C57BL/6 mice of both sexes were fed with diets containing 3 or 9 g/kg histamine and compared to control groups. After 10–30 days, the histamine concentration was determined in plasma, samples of homogenized ileum, trigeminal ganglia, spinal medulla, and cerebellum using an ELISA. The histamine release from mast cells in the dura mater stimulated with compound 48/80 was also examined. Results: Animals supplied with high dietary histamine showed normal behavior and no signs of suffering. Compared with the controls, the histamine concentration was significantly higher in plasma and ileum of mice fed with 3 g/kg, highest in animals fed with 9 g/kg histamine. In addition, this group of animals showed also higher histamine concentrations in the trigeminal ganglion. The histamine release from the dura mater in mice supplied with 3 g/kg histamine was not significantly different to control animals, but the relative increase in stimulated release was lower in male animals of the high histamine group. Conclusions: High dietary histamine increases histamine levels in blood plasma and the gut, whereas the histamine content of neural tissues is not significantly influenced. The lowered stimulated release in animals subjected to high dietary histamine may indicate compensatory mechanisms. Full article
(This article belongs to the Section Nutrition and Neuro Sciences)
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