Clinical, Radiological, and Etiological Aspects of Pachymeningitis: A Study of 24 Cases.

Introduction and importance Hypertrophic pachymeningitis (HP) is an uncommon disorder with varied etiological origins and heterogeneous clinical presentation. Establishing the etiological diagnosis poses a challenge, but prompt identification provides a treatment window, potentially leading to a reversal of symptoms. MRI is the reference examination, allowing not only the early diagnosis of pachymeningitis but also the assessment of its extent and importance, detection of possible complications, and suggestion of etiology. Case presentation We conducted a retrospective study involving 24 patients recruited over 5 years for who brain imaging had revealed the presence of pachymeningitis. The average age of the patients was 40 years, with a male-to-female ratio of 0.6. Clinical discussion Headache was present in 54.17% of patients. All the patients underwent MRI examinations utilizing different sequences, with subsequent Gadolinium injection showing localized and asymmetrical meningeal thickening in 13 cases, and diffuse in the rest. The cerebrospinal fluid study unveiled an inflammatory fluid characterized by a lymphocytic predominance and hyperproteinorrhea, noted in 50% of the patients. The histopathological analysis of a stereotactic biopsy conducted on an individual patient revealed non-diagnostic results. The etiological investigation was dominated by tuberculosis, which was detected in 33.3% of cases. Idiopathic origin was identified in 16.7% of patients. Conclusion Meningeal thickening is rare, and the multitude of potential causes makes the etiological investigation challenging unless they fall within the scope of secondary meningeal disorders; otherwise, a dural biopsy becomes necessary, and the prompt initiation of treatment, along with determining the etiology influences the prognosis.

A novel perspective of calvarial development: the cranial morphogenesis and differentiation regulated by dura mater.

There are lasting concerns on calvarial development because cranium not only accommodates the growing brain, but also safeguards it from exogenous strikes. In the past decades, most studies attributed the dynamic expansion and remodeling of cranium to the proliferation of osteoprecursors in cranial primordium, and the proliferation of osteoprogenitors at the osteogenic front of cranial suture mesenchyme. Further investigations identified series genes expressed in suture mesenchymal cells as the markers of the progenitors, precursors and postnatal stem cells in cranium. However, similar to many other organs, it is suggested that the reciprocal interactions among different tissues also play essential roles in calvarial development. Actually, there are increasing evidence indicating that dura mater (DM) is indispensable for the calvarial morphogenesis and osteogenesis by secreting multiple growth factors, cytokines and extracellular matrix (ECM). Thus, in this review, we first briefly introduce the development of cranium, suture and DM, and then, comprehensively summarize the latest studies exploring the involvement of ECM in DM and cranium development. Eventually, we discussed the reciprocal interactions between calvarium and DM in calvarial development. Actually, our review provides a novel perspective for cranium development by integrating previous classical researches with a spotlight on the mutual interplay between the developing DM and cranium.

Biomimetic and Nonbiomimetic Approaches in Dura Substitutes: The Influence of Mechanical Properties.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid (CSF) leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.

[Clinical analysis of resection and dura skull base reconstruction of cranionasal communication tumor in 31 cases].

Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions（one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor） and 14 malignant lesions（one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma） . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases（fascia lata in 5 cases and nasal mucosa in 3 cases）. Twenty-three cases were repaired with pedicled flaps（septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases）. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.

Dura mater and survival time determination in individuals who died after traumatic brain injury: a preliminary study.

BACKGROUND: Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among young people and is a matter of concern for forensic pathologists. Many authors have tried to estimate a person's survival time (ST) after TBI using different approaches. OBJECTIVE: The present study aimed to present an innovative workflow to estimate the ST after TBI by observing the inflammatory reaction of the dura mater (DM). METHODS: The authors collected DM samples from 36 cadavers (20 with TBI and 16 with no history or signs of TBI). Each sample was labelled via immunohistochemistry with three different primary antibodies, CD15, CD68, and CD3, yielding 108 slides in total. The slides were digitalized and analysed using QuPath software. RESULTS: The DM is involved in the inflammatory response after TBI. CD15 immunoreactivity allowed us to distinguish between subjects who died immediately after TBI and those with an ST of minutes or hours. CD3 immunoreactivity can be used to differentiate subjects with an ST of days from those with other STs. Moreover, the DM samples showed an acceptable diagnostic yield even in samples with signs of putrefaction.

Meningioma originating from the superior petrosal vein without dural attachment: A case report.

BACKGROUND: Meningioma in the cerebellopontine angle (CPA) without dural attachment is extremely rare. We report a unique case of meningioma derived from the superior petrosal vein without dural attachment. CASE SUMMARY: A 44-year-old right-handed woman presented with a two-month history of headache and tinnitus. Brain magnetic resonance imaging showed a well-defined contrast-enhancing lesion in the right CPA without a dural tail sign. Tumor resection was performed using a right retro sigmoid approach. A dural attachment was not seen at the tentorium or posterior surface of the petrous pyramid. The tumor was firmly adherent to the superior petrosal vein. The origin site was cauterized and resected with the preservation of the superior petrosal vein. A diagnosis of meningothelial meningioma was made. The patient's headache and tinnitus gradually disappeared, and a recurrence was not observed five years after the surgery. CONCLUSION: The rare occurrence of meningioma without dural attachment makes it difficult to determine dural attachment before surgery. The absence of dural attachment makes it easy to completely resect such tumors. Vessels related to tumors should be removed carefully, considering the possible presence of tumor stem cells in the microvessels.

High incidence of dural tears with 3-column osteotomies: a systematic review of adult spinal deformity surgery literature for the past decade.

PURPOSE: Dural tear (DT) is a well-known complication of spinal surgery. We aimed to systematically review the literature from the past decade and determine the incidence and risk factors for DT in the adult spinal deformity (ASD) population to improve both the surgical strategy and counseling of patients undergoing ASD correction. METHODS: A systematic review from 2013 to 2023 utilizing PRISMA guidelines was performed. The MEDLINE database was used to collect primary English language articles. The inclusion criterion for patients was degenerative ASD. Pediatric studies, animal studies, review articles, case reports, studies investigating minimally invasive surgery (MIS), studies lacking data on DT incidence, and articles pertaining to infectious, metastatic or neoplastic, traumatic, or posttraumatic etiologies of ASD were excluded. RESULTS: Our results demonstrate that the incidence of DT in ASD surgery ranges from 2.0% to 35.7%, which is a much broader range than the reported incidence for non deformity surgery. Moreover, the average rate of DT during ASD surgery stratified by surgical technique was greater for osteotomy overall (19.5% +/- 7.9%), especially for 3-column osteotomy (3CO), and lower for interbody fusion (14.3% +/- 9.9%). Risk factors for DT in the ASD surgery cohort included older age, revision surgery, chronic severe compression, higher-grade osteotomy, complexity of surgery, rheumatoid arthritis (RA), and higher Anesthesiology Society of America (ASA) grade. CONCLUSION: To our knowledge, this is the first systematic review discussing the incidence of and risk factors for DT in the ASD population. We found that the risk factors for DT in ASD patients were older age, revision surgery, chronic severe compression, a greater degree of osteotomy, complexity of surgery, RA, and a higher ASA grade. These findings will help guide spine surgeons in patient counseling as well as surgical planning.

The Impact of VEGF-C-Induced Dural Lymphatic Vessel Growth on Ischemic Stroke Pathology.

Timely relief of edema and clearance of waste products, as well as promotion of anti-inflammatory immune responses, reduce ischemic stroke pathology, and attenuate harmful long-term effects post-stroke. The discovery of an extensive and functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural lymphatic vessel (dLV) growth via a single injection of a vector encoding vascular endothelial growth factor C (VEGF-C). In the present study, we aimed to improve post-stroke outcomes by inducing dLV growth in mice. We injected mice with a single intracerebroventricular dose of adeno-associated viral particles encoding VEGF-C before subjecting them to transient middle cerebral artery occlusion (tMCAo). Behavioral testing, Gadolinium (Gd) contrast agent-enhanced magnetic resonance imaging (MRI), and immunohistochemical analysis were performed to define the impact of VEGF-C on the post-stroke outcome. VEGF-C improved stroke-induced behavioral deficits, such as gait disturbances and neurological deficits, ameliorated post-stroke inflammation, and enhanced an alternative glial immune response. Importantly, VEGF-C treatment increased the drainage of brain interstitial fluid (ISF) and cerebrospinal fluid (CSF), as shown by Gd-enhanced MRI. These outcomes were closely associated with an increase in the growth of dLVs around the region where we observed increased vefgc mRNA expression within the brain, including the olfactory bulb, cortex, and cerebellum. Strikingly, VEGF-C-treated ischemic mice exhibited a faster and stronger Gd-signal accumulation in ischemic core area and an enhanced fluid outflow via the cribriform plate. In conclusion, the VEGF-C-induced dLV growth improved the overall outcome post-stroke, indicating that VEGF-C has potential to be included in the treatment strategies of post-ischemic stroke. However, to maximize the therapeutic potential of VEGF-C treatment, further studies on the impact of an enhanced dural lymphatic system at clinically relevant time points are essential.

Classical monocyte ontogeny dictates their functions and fates as tissue macrophages.

Classical monocytes (CMs) are ephemeral myeloid immune cells that circulate in the blood. Emerging evidence suggests that CMs can have distinct ontogeny and originate from either granulocyte-monocyte- or monocyte-dendritic-cell progenitors (GMPs or MDPs). Here, we report surface markers that allowed segregation of murine GMP- and MDP-derived CMs, i.e., GMP-Mo and MDP-Mo, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP-Mo yielded an equal increase in homeostatic CM progeny, such as blood-resident non-classical monocytes and gut macrophages; however, these cells differentially seeded various other selected tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo differentiated into distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse that differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.

"The novel dura substitute: a revolutionary advancement in neurosurgery".

This Article provides a concise summary of the comprehensive exploration into the dura mater, dural tears, and the groundbreaking medical device, ArtiFascia® Dura Substitute. The neuroanatomy of the dura mater is elucidated, emphasizing its resilience and susceptibility to tears during spinal surgery. Dural repair methods are scrutinized, with research findings revealing the efficacy of primary closure with or without a patch.The introduction of ArtiFascia®, a nanofiber-based resorbable dural repair graft, represents a pivotal moment in neurosurgery. Obtaining 510(k) clearance from the FDA, ArtiFascia® demonstrates exceptional biological benefits, including enhanced cellular adhesion and tissue regeneration. The device's safety is affirmed through chemical analysis and toxicological risk assessment.The NEOART study, a randomized clinical trial involving 85 subjects across prominent European medical centers, validates ArtiFascia®'s superiority over existing dural substitutes. Noteworthy findings include exceptional graft strength, durability, and its ability to withstand physiological pressures.In conclusion, ArtiFascia® marks a revolutionary era in neurosurgery, promising safer and more effective solutions. This innovative device has the potential to elevate standards of care, offering both patients and surgeons an improved experience in navigating the complexities of neurosurgical procedures. The abstract encapsulates the key elements of the research, emphasizing the transformative impact of ArtiFascia® in the field.

A Wireless Battery-Free Implant With Optical Telemetry for In Vivo Cortical Stimulation.

We present a 100 µm-thick, wireless, and battery-free implant for brain stimulation through a U.S. Food and Drug Administration-approved collagen dura substitute without contact with the brain's surface, while providing visible-light spectrum telemetry to track the onset of stimulation. The device is fabricated on a 16 × 6.67 mm2 biocompatible parylene/PDMS substrate and is encapsulated with a 2 µm-thick transparent parylene layer that enables the relay of the LED brightness. The in vivo rodent testing confirmed the implant's ability to trigger motor response while generating observable brightness through the skin. The results reveal the prospect of wireless stimulation with enhanced safety by eliminating contact between the implant and the brain, with optical telemetry for facilitated tracking.

The meninges.

The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical findings and meningeal damage. Galen proposed that the dura was attached only at the sutures, and he was the first to describe the pia in humans. In the Middle Ages, new interest in the management of meningeal injuries arose, with renewed interest in relating clinical changes to intracranial injuries. These associations were neither consistent nor accurate. The Renaissance brought little change. It was in the 18th century that it became clear that the indication for opening the cranium following trauma was to relieve pressure from hematomas. Moreover, the important clinical findings on which to base an indication for intervention were changes in the level of consciousness.

The pericranium.

The purpose of this chapter is to present how past surgeons have viewed the pericranium and how they have reacted to its appearances. In ancient times, the membrane was considered formed by the dura through the sutures and it retained a relationship with the dura via vessels in the sutures. It was considered advisable to strip it totally from any area to be examined for fissure fractures and also for any area to be trepanned, as pericranial injury was thought to lead to fever and inflammation. In the 18th century, a new idea arose that posttraumatic spontaneous separation of the pericranium from the bone was a reliable indicator of the development of intracranial suppuration. This idea was subsequently refuted. For over two millennia, the pericranium was considered to be an important membrane requiring the close attention of the surgeon. It is no longer required to receive more than minimal attention.

Incidental dural tears during pediatric posterior spinal fusions.

PURPOSE: To characterize the frequency of incidental dural tears in pediatric spine surgery, their treatment, complications, and results of long-term follow-up. METHODS: A retrospective review of all pediatric patients who underwent a posterior spinal fusion (PSF) between 2004-2019 at a tertiary children's hospital was conducted. Electronic medical records were reviewed for patient demographics, intra-operative data, presence of an incidental dural tear, repair method, and patient outcomes. RESULTS: 3043 PSFs were reviewed, with 99 dural tears identified in 94 patients (3.3% overall incidence). Mean follow-up was 35.7 months (range 0.1-142.5). When the cause of the dural tear was specified, 69% occurred during exposure, 5% during pedicle screw placement, 4% during osteotomy, 2% during removal of implants, and 2% during intra-thecal injection of morphine. The rate of dural tears during primary PSF was significantly lower than during revision PSF procedures (2.6% vs. 6.2%, p < 0.05). 86.9% of dural tears were repaired and/or sealed intraoperatively, while 13.1% had spontaneous resolution. Postoperative headaches developed in 13.1% of patients and resolved at a mean of 7.6 days. There was no difference in the incidence of headaches in patients that were ordered bedrest vs. no bedrest (p > 0.99). Postoperative infections occurred in 9.5% of patients and 24.1% patients were identified to have undergone a revision surgery. CONCLUSIONS: Incidence of intra-operative dural tears in pediatric spine surgery is 3.3%. Although complications associated with the dural tear occur, most resolve over time and there were no long-term sequelae in patients with 2 years of follow up. LEVEL OF EVIDENCE: Level IV.

Double Skull Sign After Cranioplasty: A Case Report.

The double skull sign (DSS) is a unique image on the outside of the brain that looks like two skulls. Whereas congenital and acquired types of DSS have been reported, the etiology of both of them is calcified hematomas. We encountered a case of a 46-year-old woman with a history of subarachnoid hemorrhage followed by cranioplasty at 43 years old. She developed right hemiparalysis and motor aphasia suddenly. Brain computed tomography and magnetic resonance imaging revealed not only cerebral infarction but also DSS incidentally. After detailed analysis, we concluded that the DSS in this case was not due to calcification of the hematoma but was related to the cranioplasty. In this report, we present an interesting case and discuss etiologies of the development of DSS after cranioplasty.

Cranial sutures.

Cranial sutures are not of great concern to the modern neurosurgeon, except when abnormalities interfere with the skull's shape and its ability to expand during childhood. It is a commonplace that a craniotomy may cross a variety of sutures without providing any extra difficulty to the operator. The sagittal suture does remain useful as a definition of the midline of the cranium and as an indicator of the underlying sinus. Galen for reasons that are far from clear, "observed" relationships between the sutures, the meninges and the pericranium which led him to advise avoidance of any surgical proximity to the sutures. The result of this proscription was a severe limit of the access surgeons considered was appropriate and thus limited their ability to care for their patients.

Models of Trigeminal Activation: Is There an Animal Model of Migraine?

Migraine, recognized as a severe headache disorder, is widely prevalent, significantly impacting the quality of life for those affected. This article aims to provide a comprehensive review of the application of animal model technologies in unraveling the pathomechanism of migraine and developing more effective therapies. It introduces a variety of animal experimental models used in migraine research, emphasizing their versatility and importance in simulating various aspects of the condition. It details the benefits arising from the utilization of these models, emphasizing their role in elucidating pain mechanisms, clarifying trigeminal activation, as well as replicating migraine symptoms and histological changes. In addition, the article consciously acknowledges the inherent limitations and challenges associated with the application of animal experimental models. Recognizing these constraints is a fundamental step toward fine-tuning and optimizing the models for a more accurate reflection of and translatability to the human environment. Overall, a detailed and comprehensive understanding of migraine animal models is crucial for navigating the complexity of the disease. These findings not only provide a deeper insight into the multifaceted nature of migraine but also serve as a foundation for developing effective therapeutic strategies that specifically address the unique challenges arising from migraine pathology.

Imaging evaluation and volumetric measurement of the space surrounding the diploic veins.

PURPOSE: The diploic veins have been suggested to be involved in the excretion of cerebrospinal fluid and intracranial waste products; however, to date, there have been no reports evaluating the space surrounding the diploic veins. Therefore, we aimed to visualize the distribution of gadolinium-based contrast agent (GBCA) in the space surrounding the diploic veins and to evaluate the spatial characteristics. MATERIALS AND METHODS: Ninety-eight participants (aged 14-84 years) were scanned 4 h after intravenous GBCA injection at Nagoya University Hospital between April 2021 and December 2022. The volume of the space surrounding the diploic veins where the GBCA was distributed was measured using contrast-enhanced T1-weighted images with the application of three-axis motion-sensitized driven equilibrium. The parasagittal dura (PSD) volume adjacent to the superior sagittal sinus was also measured using the same images. Both volumes were corrected for intracranial volume. The correlation between age and the corrected volume was examined using Spearman's rank correlation coefficient; the relationship between the corrected volume and sex was assessed using the Mann-Whitney U test. RESULTS: A significant weak negative correlation was observed between the volume of the space surrounding the diploic veins and age (r = -0.330, p < 0.001). Furthermore, there was a significant weak positive correlation between the PSD volume and age (r = 0.385, p < 0.001). Both volumes were significantly greater in men than in women. There was no correlation between the volume of the space surrounding the diploic veins and the volume of the PSD. CONCLUSION: The volume of the space surrounding the diploic veins was measurable and, in contrast to the volume of the PSD, was greater in younger participants. This space may be related to intracranial excretory mechanisms and immune responses during youth, requiring further research.

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.

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.