Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model.

In neurosurgical interventions, effective closure of the dura mater is essential to prevent cerebrospinal fluid leakage and minimize post-operative complications. Biodegradable synthetic materials have the potential to be used as dura mater grafts owing to their regenerative properties and low immunogenicity. This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The stained slides were graded based on the brain-specific reactions. The results showed no damage to the underlying brain tissue for either the ArtiFascia or control implants. Neither inflammation nor neuronal loss was evident, corroborating the safety of the ArtiFascia. This approach, combined with previous histopathological analyses, strengthens the safety profile of ArtiFascia and sets a benchmark for biodegradable material assessment in dura graft applications. This study aligns with the Food and Drug Administration guidelines and offers a comprehensive evaluation of the potential neural tissue effects of synthetic dura mater grafts.

Space invaders: Reassessing the histology of hyperostosis frontalis interna.

Hyperostosis frontalis interna (HFI) is a human skeletal lesion characterized by nodules of hyperplastic bone and thickening of the frontal bone's inner surface. Despite its prevalence in the general population and its long history of observation-it is one of the most frequently observed pathologies in gross anatomy laboratories-HFI's etiology and pathogenesis remain poorly understood. This is largely due to the lack of a thorough survey of its histology across the various stages of its development. Our study has three major aims: (1) assess HFI histology from incipient to advanced lesions; (2) elucidate lamellar and trabecular structure in HFI; and (3) clarify impacts/roles of the dura mater in HFI. Sections of nondecalcified bone provide evidence for two different categories of lesions: (1) stratum lesions, characterized by lamellar-based overall thickening of the internal table, and (2) eruptive lesions, characterized by nodular formations of initially lamellar bone that appear to form the bulk of bone mass in advanced stages. Sections of nondecalcified bone also suggest that for both lesion types, HFI growths begin as deposits of lamellar bone, which are later remodeled into woven bone deposits; our data do not support the hypothesis that lesions begin as a "diploization" of cortical bone as suggested by prior studies. Trichrome-stained sections provide evidence that growing lesions erode through and engulf the dura mater, effectively destroying this tissue layer as they grow laterally and inwardly. Our results indicate possible avenues of research to better understand the root causes of this disorder.

Iatrogenic cerebral amyloid angiopathy in older adults.

BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.

Cerebral tumor with hemi-dural enhancement as unique presentation of multiple myeloma: A case report.

Introduction: Intracranial multiple myeloma (MM) is a rare manifestation of MM, a malignant plasma cell disorder that primarily affects bone marrow. Dural involvement in MM is even rarer and can manifest as a dural mass. We present a case of MM presenting as an intracranial dural tumor with primary hemi-dural involvement. Research question: This case report aims to investigate the clinical presentation, diagnostic challenges, and treatment approaches for intracranial multiple myeloma, with a focus on the extensive hemi-dural thickening and enhancement seen in this case. Material and methods: A 73-year-old male presented with progressive dysphasia and weakness. MRI revealed a solid left frontal mass with significant mass-effect. Hemi-dural thickening and enhancement was present along with invasion of the skull. The patient underwent surgical resection of the tumor with dural and bone reconstruction. Results: Histopathological examination confirmed MM diagnosis. Chemotherapy was started. Follow-up MRI showed complete tumor resection, but extensive hemi-dural thickening and enhancement persisted. Postoperative radiation therapy was considered. Discussion and conclusion: MM with primary dural involvement is rare and poses diagnostic challenges. Postoperative treatment involves chemotherapy, the role of surgery and radiotherapy is not established. The extensive hemi-dural thickening and enhancement observed in this case require further investigation, and a wait-and-scan policy was recommended instead of radiotherapy.

Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF.

Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1ß and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure.

An Incidental Finding of Idiopathic Hypertrophic Pachymeningitis: A Case Report.

In this case report, we discuss and explore the clinical, laboratory, and imaging findings, as well as the treatment options and follow-up measures, in an 83-year-old patient with idiopathic hypertrophic pachymeningitis (IHP), a rare disorder characterized by fibrosing, hypertrophic inflammation that thickens the dura mater. An 83-year-old female with a medical history of hypertension and hyperlipidemia presented with speech arrest and was taken to the emergency department, where she received a stroke code, a CT scan, and an MRI. The MRI results showed a temporal lobe meningioma and a pan-cranial pachymeningitis encasing the entire brain and cerebellum and extending into the upper cervical spine. Multiple unsuccessful attempts at a lumbar puncture were made, so a dural biopsy specimen was obtained, which revealed no malignant process. A cerebral spinal fluid specimen (CSF) from the biopsy showed minimal white blood cells (WBCs) which ruled out infection. Idiopathic hypertrophic pachymeningitis was the given diagnosis based on the apparent MRI findings. The patient was treated in the hospital for four days with IV methylprednisolone and discharged on oral methylprednisolone for four to six weeks.

Biosubstitutes for dural closure: Unveiling research, application, and future prospects of dura mater alternatives.

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.

Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization.

OBJECTIVE: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. METHODS: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. RESULTS: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. CONCLUSION: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.

Bovine Pericardium Treated with Polyethylene Glycol and Ethanol Versus Pericranium for Duraplasty: A Pilot Study in Supratentorial Neurosurgery.

BACKGROUND: Watertight closure of dura mater after intracranial surgery can avoid cerebrospinal fluid leakage and central nervous system infection and herniation. When primary closure is not possible, the pericranium is the preferential choice. When it is not available, a dural substitute becomes necessary. Bovine pericardium treated with polyethylene glycol and ethanol is herein tested as a dural substitute. METHODS: A pilot study comparing bovine pericardium with pericranium in supratentorial neurosurgery was performed. RESULTS: Twenty patients were initially allocated into a bovine pericardium group (group 1) or a pericranium group (group 2). Three patients from group 1 and 2 from group 2 had a loss of follow-up, being excluded. In the remaining 15 patients, epidemiological analysis demonstrated a male:female ratio of 3:4 and 4:4 for groups 1 and 2. Ages varied from 28 to 68 (Mean = 49.6) in group 1 and 40-80 (Mean = 61.2) in group 2, with a mean difference of 11.68 years (P = 0.09). Two cases of surgical site infection and 1 of hydrocephalus were observed. Although the calculated relative risk for complications was higher in group 1 (Relative Risk = 1.08), Fisher exact test demonstrated no statistically significant difference between groups (P = 1.00). Procedure mean time was 23 minutes and 11 seconds in group 1 versus 27 minutes and 55 seconds in group 2 (P = 0.47). Mean graft area was 13.17 and 6.23 cm2 in groups 1 and 2 (P = 0.02). CONCLUSIONS: Bovine pericardium treated with polyethylene glycol and ethanol was comparable to pericranium as a dural substitute. More studies are encouraged to certify our findings.

Effects of surface profile on porcine dural mechanical properties.

BACKGROUND: Cerebrospinal fluid leakage through the spinal meninges is difficult to diagnose and treat. Moreover, its underlying mechanism remains unknown. Considering that the dura mater is structurally the strongest and outermost membrane among the three-layered meninges, we hypothesized that a dural mechanical tear would trigger spontaneous cerebrospinal fluid leakage, especially when a traumatic loading event is involved. Thus, accurate biomechanical properties of the dura mater are indispensable for improving computational models, which aid in predicting blunt impact injuries and creating artificial substitutes for transplantation and surgical training. METHOD: We characterized the surface profile of the spinal dura and its mechanical properties (Young's moduli) with a distinction of its inherent anatomical sites (i.e., the cervical and lumbar regions as well as the dorsal and ventral sides of the spinal cord). FINDINGS: Although the obtained Young's moduli exhibited no considerable difference between the aforementioned anatomical sites, our results suggested that the wrinkles structurally formed along the longitudinal direction would relieve stress concentration on the dural surface under in vivo and supraphysiological conditions, enabling mechanical protection of the dural tissue from a blunt impact force that was externally applied to the spine. INTERPRETATION: This study provides fundamental data that can be used for accurately predicting cerebrospinal fluid leakage due to blunt impact trauma.

Magnetic resonance imaging-based classification of the myodural bridge complex and its influencing factors.

Cerebrospinal fluid (CSF) circulation is considered the third circulation of the human body. Recently, some scholars have proposed the myodural bridge (MDB) as a novel power source for CSF flow. Moreover, the suboccipital muscles can exert a driving force on the CSF via the MDB. This hypothesis is directly supported by head rotation and nodding movements, which can affect CSF circulation. The MDB has been validated as a normal structure in humans and mammals. In addition, the fusion of MDB fibers of different origins that act in concert with each other forms the MDB complex (MDBC). The MDBC may be associated with several CSF disorder-related neurological disorders in clinical practice. Therefore, the morphology of the MDBC and its influencing factors must be determined. In this study, T2-weighted imaging sagittal images of the cervical region were analyzed retrospectively in 1085 patients, and magnetic resonance imaging (MRI) typing of the MDBC was performed according to the imaging features of the MDBC in the posterior atlanto-occipital interspace (PAOiS) and posterior atlanto-axial interspace (PAAiS). The effects of age and age-related degenerative changes in the cervical spine on MRI staging of the MDBC were also determined. The results revealed four MRI types of the MDBC: type A (no MDBC hyposignal shadow connected to the dura mater in either the PAOiS or PAAiS), type B (MDBC hyposignal shadow connected to the dura mater in the PAOiS only), type C (MDBC hyposignal shadow connected to the dura mater in the PAAiS only), and type D (MDBC hyposignal shadow connected to the dura mater in both the PAOiS and PAAiS). The influencing factors for the MDBC typing were age (group), degree of intervertebral space stenosis, dorsal osteophytosis, and degenerative changes in the cervical spine (P < 0.05). With increasing age (10-year interval), the incidence of type B MDBC markedly decreased, whereas that of type A MDBC increased considerably. With the deepening of the degree of intervertebral space stenosis, the incidence of type C MDBC increased significantly, whereas that of type A MDBC decreased. In the presence of dorsal osteophytosis, the incidence of type C and D MDBCs significantly decreased, whereas that of type A increased. In the presence of protrusion of the intervertebral disc, the incidence of type B, C, and D MDBCs increased markedly, whereas that of type A MDBC decreased considerably, with cervical degenerative changes combined with spinal canal stenosis. Moreover, the incidence of both type C and D MDBCs increased, whereas that of type A MDBC decreased. Based on the MRI signal characteristics of the dural side of the MDBC, four types of the MDBC were identified. MDBC typing varies dynamically according to population distribution, depending on age and cervical degeneration (degree of intervertebral space stenosis, vertebral dorsal osteophytosis formation, simple protrusion of intervertebral disc, and cervical degeneration changes combined with spinal canal stenosis, except for the degree of protrusion of the intervertebral disc and the degree of spinal canal stenosis); however, it is not influenced by sex.

Investigation of direction- and age-dependent prestretch in mouse cranial dura mater.

Cranial dura mater is a dense interwoven vascularized connective tissue that helps regulate neurocranial remodeling by responding to strains from the growing brain. Previous ex vivo experimentation has failed to account for the role of prestretch in the mechanical behavior of the dura. Here we aim to estimate the prestretch in mouse cranial dura mater and determine its dependency on direction and age. We performed transverse and longitudinal incisions in parietal dura excised from newborn (day [Formula: see text]4) and mature (12 weeks) mice and calculated the ex vivo normalized incision opening (measured width over length). Then, similar incisions were simulated under isotropic stretching within Abaqus/Standard. Finally, prestretch was estimated by comparing the ex vivo and in silico normalized openings. There were no significant differences between the neonatal and adult mice when comparing cuts in the same direction, but adult mice were found to have significantly greater stretch in the anterior-posterior direction than in the medial-lateral direction, while neonatal dura was essentially isotropic. Additionally, our simulations show that increasing curvature impacts the incision opening, indicating that flat in silico models may overestimate prestretch.

Mast-cell-specific receptor mediates alcohol-withdrawal-associated headache in male mice.

Rehabilitation from alcohol addiction or abuse is hampered by withdrawal symptoms including severe headaches, which often lead to rehabilitation failure. There is no appropriate therapeutic option available for alcohol-withdrawal-induced headaches. Here, we show the role of the mast-cell-specific receptor MrgprB2 in the development of alcohol-withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces headache behaviors, including facial allodynia, facial pain expressions, and reduced movement, which are symptoms often observed in humans. Those behaviors were absent in MrgprB2-deficient mice during alcohol withdrawal. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia (TG) neurons in alcohol-withdrawal WT mice, but not in alcohol-withdrawal MrgprB2-deficient mice. Increased mast cell degranulation by alcohol withdrawal in dura mater was dependent on the presence of MrgprB2. The results indicate that alcohol withdrawal causes headache via MrgprB2 of mast cells in dura mater, suggesting that MrgprB2 is a potential target for treating alcohol-withdrawal-related headaches.

Menthol dural application alters meningeal arteries tone and enhances excitability of trigeminocervical neurons in rats.

Headaches, including migraines, can have a causal relationship to exposure to cold, and this relationship may be both positive and negative, as cold can both provoke and alleviate cephalgia. The role of thermoreceptors responsible for transduction of low temperatures belongs to the transient receptor potential cation channel subfamily melastatin member 8 (TRPM8). These channels mediate normal cooling sensation and have a role in both cold pain and cooling-mediated analgesia; they are seen as a potential target for principally new anti-migraine pharmaceuticals. Using a validated animal migraine models, we evaluated effects of menthol, the TRPM8-agonist, on trigeminovascular nociception. In acute experiments on male rats, effects of applied durally menthol solution in various concentrations on the neurogenic dural vasodilatation (NDV) and firing rate of dura-sensitive neurons of the trigeminocervical complex (TCC) were assessed. Application of menthol solution in concentrations of 5 % and 10 % was associated with NDV suppression, however amplitude reduction of the dilatation response caused not by the vascular dilatation degree decrease, but rather due to the significant increase of the meningeal arterioles' basal tone. In electrophysiological experiments the 1 % and 30 % menthol solutions intensified TCC neuron responses to the dural electrical stimulation while not changing their background activity. Revealed in our study excitatory effects of menthol related to the vascular as well as neuronal branches of the trigeminovascular system indicate pro-cephalalgic effects of TRPM8-activation and suggest feasibility of further search for new anti-migraine substances among TRPM8-antagonists.

Peptidomics insights: neutrophil extracellular traps (NETs) related to the chronic subdural hemorrhage.

Chronic subdural hemorrhage (CSDH) refers to a hematoma with an envelope between the dura mater and the arachnoid membrane and is more common among the elderly. It was reported that the dura mater, which is highly vascularized with capillary beds, precapillary arterioles and postcapillary venules play an important role in the protection of the central nervous system (CNS). Numerous evidences suggests that peptides play an important role in neuroprotection of CNS. However, whether dura mater derived endogenous peptides participate in the pathogenesis of CSDH remains undetermined. In the current study, the peptidomic profiles were performed in human dura of CSDH (three patients) and the relative control group (three non-CSDH samples) by LC-MS (liquid chromatography-mass spectrometry). The results suggested that a total of 569 peptides were differentially expressed in the dura matter of CSDH compared with relative controls, including 217 up-regulated peptides and 352 down-regulated peptides. Gene Ontology (GO) analysis demonstrated that the precursor proteins of those differentially expressed peptides were involved in the various biological processes. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that NETs participated in the pathogenies of CSDH. Further investigate showed that H3Cit was significantly elevated in the dural and hematoma membranes of patients with CSDH compared to patients without CSDH. Taken together, our results showed the differentially expressed peptides in human dura mater of CSDH and demonstrated that NETs formation in the dural and hematoma membranes might be involved in the pathogenesis of CSDH. It is worth noting that pharmacological inhibition of NETs may have potential therapeutic implications for CSDH.

A Case Series of DuraMatrix-Onlay® Plus in Cranial Surgery Is Associated With a Low Complication Profile.

BACKGROUND: DuraMatrix-Onlay® Plus is a collagen dura membrane derived from purified bovine Achilles tendon. The matrix provides a scaffold for collagen synthesis and is intended to be used as an onlay without the need for dural sutures. The study aims to describe our experience with 33 consecutive patients who underwent a duraplasty procedure using the novel DuraMatrix-Onlay® Plus collagen dura membrane. METHODS: This is a retrospective case series of 33 patients who underwent a duraplasty procedure at a single academic hospital in Los Angeles, CA, USA between May 2016 and March 2017. The primary outcome was the incidence rate of cerebrospinal fluid (CSF) leak. Secondary outcomes included rates of patient infection, dural substitute complication, and removal. RESULTS: Thirty-three patients underwent a duraplasty procedure using the DuraMatrix-Onlay® Plus material. The average age of the patients was 41.12±7.34 years (range 2-75 years). There were 18 (54.5%) females and 15 (45.5%) males. The majority of procedures were elective operations for the resection of a lesion (n=19, 58%), and the average graft size was 17.69±4.73 cm². At an average follow-up of 3 months, there were no postoperative CSF leaks. The rates of patient infection, dural substitute complication, and removal were 6%, 6%, and 3%, respectively. CONCLUSION: DuraMatrix-Onlay® Plus is associated with a low rate of postoperative CSF leakage and an acceptable complication profile. This result supports the use of collagen matrices for dural closure in general neurosurgical procedures.

Spinal dural arteriovenous fistula masquerading as a herniated disc: illustrative case.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a rare disorder with an unknown etiology. Often, the clinical presentation and imaging findings are misleading, causing this condition to be mistaken for other entities, such as demyelinating or degenerative spinal lesions. OBSERVATIONS: The authors report a challenging case of SDAVF in which the patient's symptoms were initially thought to be attributable to a herniated disc based on his imaging studies at another institution. He sought the authors for a second opinion, which yielded a confirmed diagnosis of SDAVF. Due to his rapidly progressive neurological manifestations, he underwent a surgical division of the fistula using intraoperative video angiography via indocyanine green injections. His symptoms progressively improved over a 3-month period. He regained full sphincter control by 4 months, which gave him a better recovery than seen in other patients with SDAVFs, who do not generally fully regain sphincter control. LESSONS: SDAVF is a critical spinal vascular pathology that should not be overlooked in the differential diagnosis of any patient presenting with signs of progressive myelopathy. Despite its associated vague initial clinical symptoms, SDAVF typically, but not always, demonstrates a characteristic imaging appearance on magnetic resonance (MR) imaging studies; therefore, MR angiography is still required for definitive diagnosis. Surgical treatment for SDAVF is almost always definitive and curative.

Differences in invasiveness and recurrence rate among nonfunctioning pituitary neuroendocrine tumors depending on tumor subtype.

PURPOSE: To clarify the invasiveness to surrounding structures and recurrence rate of each subtype of nonfunctioning pituitary neuroendocrine tumor (Pit-NETs) according to the WHO 2022 classification. METHODS: This retrospective study utilized data from 292 patients with nonfunctioning Pit-NETs treated with initial transsphenoidal surgery. Recurrence was evaluated on 113 patients who were available for a magnetic resonance imaging follow-up ≥ 60 months. All tumors were assessed by immunohistochemical staining for Pit-1, T-PIT, and GATA3. Invasiveness to surrounding structures was evaluated based on intraoperative findings. RESULTS: Cavernous sinus invasion was found in 47.5% of null cell tumors, 50.0% of Pit-1 lineage tumors, 31.8% of corticotroph tumors, and 18.3% of gonadotroph tumors. Dura mater defects in the floor of sellar turcica, indicating dural invasion, were found in 44.3% of null cell tumors, 36.4% of corticotroph tumors, 16.7% of Pit-1 lineage tumors, and 17.3% of gonadotroph tumors. In logistic regression analysis, Pit-1 (OR 5.90, 95% CI 1.71-20.4, P = 0.0050) and null tumors (OR 4.14, 95% CI 1.86-9.23, P = 0.0005) were associated with cavernous sinus invasion. Recurrence was found in 8 (4.9%) patients, but without significant differences between tumor subtypes. The presence of cavernous sinus invasion was correlated with recurrence (HR = 1.95, 95% CI 1.10-3.46, P = 0.0227). CONCLUSION: Among nonfunctioning Pit-NETs, Pit-1 lineage tumors tend to invade the cavernous sinus, corticotroph tumors may produce dura mater defects, and null cell tumors tend to cause both. Pit-NETs with cavernous sinus invasion require a careful attention to recurrence.

Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: An in vitro dural model and the application of lab-on-a-chip for EDAS.

Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1ß-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1ß stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 (p < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1ß-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors (p < 0.001). ECs co-cultured with IL-1ß-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1ß-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers.

Unforeseen Complications: A Case of Subdural Anesthesia Post-epidural Insertion.

Subdural anesthesia, although rare, is a significant complication of epidural anesthesia. This case report presents a 28-year-old female patient who developed sudden unconsciousness following epidural anesthesia administration for labor pain. Despite no evident contraindications to epidural anesthesia, she lost consciousness shortly after the initial test dose, leading to an emergency cesarean section under general anesthesia. The neonate showed signs of fetal bradycardia post-epidural and required intensive care. The patient made a complete recovery with no postpartum complications. This report underlines the need for vigilant monitoring and the importance of swift interventions in case of complications arising from epidural anesthesia.