Osteocalcin-expressing neutrophils from skull bone marrow exert immunosuppressive and neuroprotective effects after TBI.

Neutrophils from skull bone marrow (Nskull) are activated under some brain stresses, but their effects on traumatic brain injury (TBI) are lacking. Here, we find Nskull infiltrates brain tissue quickly and persistently after TBI, which is distinguished by highly and specifically expressed osteocalcin (OCN) from blood-derived neutrophils (Nblood). Reprogramming of glucose metabolism by reducing glycolysis-related enzyme glyceraldehyde 3-phosphate dehydrogenase expression is involved in the antiapoptotic and proliferative abilities of OCN-expressing Nskull. The transcription factor Fos-like 1 governs the specific gene profile of Nskull including C-C motif chemokine receptor-like 2 (CCRL2), arginase 1 (Arg1), and brain-derived neurotrophic factor (BDNF) in addition to OCN. Selective knockout of CCRL2 in Nskull demonstrates that CCRL2 mediates its recruitment, whereas high Arg1 expression is consistent with its immunosuppressive effects on Nblood, and the secretion of BDNF facilitating dendritic growth contributes to its neuroprotection. Thus, our findings provide insight into the roles of Nskull in TBI.

Artificial Intelligence Application in Skull Bone Fracture with Segmentation Approach.

This study aims to evaluate an AI model designed to automatically classify skull fractures and visualize segmentation on emergent CT scans. The model's goal is to boost diagnostic accuracy, alleviate radiologists' workload, and hasten diagnosis, thereby enhancing patient outcomes. Unique to this research, both pediatric and post-operative patients were not excluded, and diagnostic durations were analyzed. Our testing dataset for the observer studies involved 671 patients, with a mean age of 58.88 years and fairly balanced gender representation. Model 1 of our AI algorithm, trained with 1499 fracture-positive cases, showed a sensitivity of 0.94 and specificity of 0.87, with a DICE score of 0.65. Implementing post-processing rules (specifically Rule B) improved the model's performance, resulting in a sensitivity of 0.94, specificity of 0.99, and a DICE score of 0.63. AI-assisted diagnosis resulted in significantly enhanced performance for all participants, with sensitivity almost doubling for junior radiology residents and other specialists. Additionally, diagnostic durations were significantly reduced (p < 0.01) with AI assistance across all participant categories. Our skull fracture detection model, employing a segmentation approach, demonstrated high performance, enhancing diagnostic accuracy and efficiency for radiologists and clinical physicians. This underlines the potential of AI integration in medical imaging analysis to improve patient care.

Subgaleal and Epidural Hematomas Secondary to Calvarial Infarcts: An Uncommon Presentation of Sickle Cell Disease.

We present the case of a 13-year-old male with sickle cell disease (SCD) who presented to the emergency department with a severe headache secondary to calvarial infarcts with associated epidural and subgaleal hematomas. This case was complicated by external compression of the superior sagittal sinus by the hematomas as seen on magnetic resonance imaging. Management included supportive treatment of pain and swelling. This case emphasizes skull infarctions with associated hematomas as a possible differential diagnosis for patients with SCD presenting with headaches and scalp swellings.

Extra-pulmonary Cutaneous Sarcoidosis Presenting With Granulomatous Cranial Lesions and Cardiac Complications: A Case Report.

Sarcoidosis is a non-caseating granulomatous disorder affecting multiple organs. Although the lungs are the most common site of presentation, extra-pulmonary manifestations involving the skin and heart can occur. Sarcoidosis affecting skull bone is uncommon and involvement of skin, heart, and skull bone all together, without pulmonary manifestations, is extremely rare. We report a 63-year-old Caucasian woman with a past history of cutaneous sarcoidosis and granulomatous skull bone lesions who presented with recurrent syncope. An ambulatory cardiac monitor detected intermittent high-grade atrioventricular block and cardiac MRI confirmed the diagnosis of cardiac sarcoidosis. This case represents an extremely unique journey of sarcoidosis and suggests potential consideration for cardiac sarcoidosis screening in patients with a history of extra-cardiac manifestations.

Lateralized response of skull bone marrow via osteopontin signaling in mice after ischemia reperfusion.

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.

Explanted Skull Flaps after Decompressive Hemicraniectomy Demonstrate Relevant Bone Avitality-Is Their Reimplantation Worth the Risk?

BACKGROUND: Reimplantations of autologous skull flaps after decompressive hemicraniectomies (DHs) are associated with high rates of postoperative bone flap resorption (BFR). We histologically assessed the cell viability of explanted bone flaps in certain periods of time after DH, in order to conclude whether precursors of BRF may be developed during their storage. METHODS: Skull bone flaps explanted during a DH between 2019 and 2020 were stored in a freezer at either -23 °C or -80 °C. After their thawing process, the skulls were collected. Parameters of bone metabolism, namely PTH1 and OPG, were analyzed via immunohistochemistry. H&E stain was used to assess the degree of avital bone tissue, whereas the repeated assays were performed after 6 months. RESULTS: A total of 17 stored skull flaps (8 at -23 °C; 9 at -80 °C) were analyzed. The duration of cryopreservation varied between 2 and 17 months. A relevant degree of bone avitality was observed in all skull flaps, which significantly increased at the repeated evaluation after 6 months (p < 0.001). Preservation at -23 °C (p = 0.006) as well as longer storage times (p < 0.001) were identified as prognostic factors for higher rates of bone avitality in a linear mixed regression model. CONCLUSIONS: Our novel finding shows a clear benefit from storage at -80° C, which should be carefully considered for the future management and storage of explanted skull flaps. Our analysis also further revealed a significant degree of bone avitality, a potential precursor of BFR, in skull flaps stored for several weeks. To this end, we should reconsider whether the reimplantation of autologous skull flaps instead of synthetic skull flaps is still justified.

Immune compartments at the brain's borders in health and neurovascular diseases.

Recent evidence implicates cranial border immune compartments in the meninges, choroid plexus, circumventricular organs, and skull bone marrow in several neuroinflammatory and neoplastic diseases. Their pathogenic importance has also been described for cardiovascular diseases such as hypertension and stroke. In this review, we will examine the cellular composition of these cranial border immune niches, the potential pathways through which they might interact, and the evidence linking them to cardiovascular disease.

Low skull bone density is associated with poor motor prognosis in women with Parkinson's disease.

Parkinson's disease (PD) and osteoporosis are degenerative diseases that have shared pathomechanisms. To investigate the associations of skull bone density with nigrostriatal dopaminergic degeneration and longitudinal motor prognosis in female patients with PD. We analyzed the data of 260 drug-naïve female PD patients aged ≥50 years old who were followed-up for ≥3 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. We measured skull bone density as a surrogate marker for systemic bone loss by calculating the Hounsfield unit (HU) in computed tomography scans. A Cox proportional hazard model was built to compare the rates of levodopa-induced dyskinesia (LID) or wearing-off according to skull HU. Longitudinal changes in levodopa-equivalent dose (LED) during a 3-year follow-up were assessed using a linear mixed model. A lower skull HU was associated with lower baseline DAT availability in striatal subregions; however, this relationship was not significant after adjusting for age, disease duration, body mass index, and white matter hyperintensities. After adjusting for confounding factors, a lower skull HU was significantly associated with an increased risk of LID development (hazard ratio = 1.660 per 1 standard deviation decrease, p = 0.007) and wearing-off (hazard ratio = 1.613, p = 0.016) in younger (<67 years) but not in older patients. Furthermore, a lower skull HU was associated with a steeper increase in LED during follow-up in younger patients only (ß = -21.99, p < 0.001). This study suggests that baseline skull bone density would be closely linked to motor prognosis in drug naïve women with PD.

Central Skull Base Osteomyelitis: Multimodality Imaging and Clinical Findings from a Large Indian Cohort.

Background: Central or atypical skull base osteomyelitis (CSBO) often presents with severe unrelenting headache and progressive mono or polyneuritis cranialis. MRI and CT are used as initial imaging techniques but have a poor specificity and sensitivity. Objective: To analyze our cohort of CSBO. Materials and Methods: Over a 5-year period [2015-2020], we retrospectively analyzed the records of all patients with CSBO who had undergone a 3T MRI Brain, MR angiography, regional FDG PET-CT, and skeletal scintigraphy with 99mTc MDP/SPECT-CT. Surgical biopsy specimens were sent for bacterial and fungal cultures. Results: In total, 17 patients with CSBO were identified. Typically, 88% of patients presented with severe unilateral headache. All patients had at least a cranial mono or polyneuritis. The majority of patients were diabetic [64%]. MRI was normal in 42% of patients, whereas PET-CT and with 99mTc MDP scan and SPECT-CT were abnormal in all patients. Conclusion: Our series of CSBO showed a 40% mortality rate with significant morbidity and relentless progression. Patients required repeated PET CT and bone scans to detect regression of disease activity. The average duration of IV therapy ranged from 3 weeks to 9 months and oral therapy for around 2-3 months. Cure was defined after taking into account the original diagnosis, symptom resolution, and concordant reduction of tissue uptake on PET CT and 99mTc bone scan. The combination of MRI, FDG PET CT, and 99mTc bone scan with concurrent SPECT CT was able to detect disease and disease progression in all patients.

The emergence of the calvarial hematopoietic niche in health and disease.

The diploë region of skull has recently been discovered to act as a myeloid cell reservoir to the underlying meninges. The presence of ossified vascular channels traversing the inner skull of cortex provides a passageway for the cells to traffic from the niche, and CNS-derived antigens traveling through cerebrospinal fluid in a perivascular manner reaches the niche to signal myeloid cell egress. This review will highlight the recent findings establishing this burgeoning field along with the known role this niche plays in CNS aging and disease. It will further highlight the anatomical routes and physiological properties of the vascular structures these cells use for trafficking, spanning from skull to brain parenchyma.

Microbiological profile and infection potential of different cryopreserved skull flaps after decompressive hemicraniectomy. Is cryopreservation at - 80 ℃ better?

OBJECTIVE: Patterns of cryopreservation of explanted skull bone flaps have long been a matter of debate, in particular the appropriate temperature of storage. To the best of our knowledge no study to date has compared the microbiological profile and the infection potential of skull bone flaps cryostored at the same institution at disparate degrees for neurosurgical purposes. In the context of our clinical trial DRKS00023283, we performed a bacterial culture of explanted skull bone flaps, which were cryopreserved lege artis at a temperature of either - 23 °C or - 80 °C after a decompressive hemicraniectomy. In a further step, we contaminated the bone fragments in a s uspension with specific pathogens (S. aureus, S. epidermidis and C. acnes, Colony forming unit CFU 103/ml) over 24 h and conducted a second culture. RESULTS: A total of 17 cryopreserved skull flaps (8: - 23 °C; 9: - 80 °C) explanted during decompressive hemicraniectomies performed between 2019 and 2020 as well as 2 computer-aided-designed skulls (1 vancomycin-soaked) were analyzed. Median duration of cryopreservation was 10.5 months (2-17 months). No microorganisms were detected at the normal bacterial culture. After active contamination of our skull flaps, all samples showed similar bacterial growth of above-mentioned pathogens; thus, our study did not reveal an influence of the storage temperature upon infectious dynamic of the skulls.

Transcranial attenuation in bone conduction stimulation.

In bone conduction (BC) stimulation, the sound travels from the site of stimulation to the ipsilateral and contralateral cochlea. A frequency dependent reduction in BC hearing sensitivity occurs when sound travels to the contralateral cochlea as compared to the ipsilateral cochlea. This effect is called transcranial attenuation (TA) that is affected by several factors. Experimental and clinical studies describe TA and the factors that have an effect on it. These factors include stimulus location, coupling of a bone conduction hearing aid to the underlying tissue, and the properties of the head (such as geometry of the head, thickness of the skin and/or skull, changes due to aging, iatrogenic changes such as bone removal in mastoidectomy, and occlusion of the external auditory canal). While TA has an effect of the patient's benefit of BCHAs, there seems to be a discrepancy between experimental measurements and clinical relevance. The effects are small and the interindividual variability, in comparison, is rather large. However, a better understanding of these factors may help to determine the site of attachment, the coupling mode, and possibly the fitting of a BCHA, depending on its indication.

Case Report: Simultaneous Resection of Bone Tumor and CAD/CAM Titanium Cranioplasty in Fronto-Orbital Region.

Background: Simultaneous resection of bone tumors in the fronto-naso-orbital region is a great challenge due to the need for adequate reconstruction of the facial skeleton. Pre-operative virtual planning of resection margins and the simultaneous fabrication of the cranioplasty using computer-aided design/computer-aided manufacturing (CAD/CAM) technology could allow combining the tumor resection and cosmetic restoration steps into a single procedure. Methods: We present five consecutive cases of patients with bone tumors of the fronto-naso-orbital region. The indications for surgery included: (1) the presence of a major cosmetic defect; (2) progressive tumor growth. The histological examination revealed vascular malformation, hemangioma, and fibrous dysplasia in two cases. Tumor resection was performed with the help of a drilling template in form of a tumor. The computer-designed cranioplasty formed based on the non-involved side of the skull of the patient was manufactured. In one patient, the reconstruction was performed using two separate implants. Results: The position of the implant fits in with pre-operative planning in two cases; in those cases, the additional trimming of the implant or bone defect was required. Good cosmetic outcomes were noted in all patients, and no complications occurred. No repeat surgery was necessary. The template has proved to have high application potential. Conclusion: Simultaneous resection and CAD/CAM cranioplasty in the case of bone tumors in the fronto-orbital region is a promising technique with the aim of minimizing operation time and achieving a good esthetic outcome.

Transforming Growth Factor-ß3/Recombinant Human-like Collagen/Chitosan Freeze-Dried Sponge Primed With Human Periodontal Ligament Stem Cells Promotes Bone Regeneration in Calvarial Defect Rats.

Patients with a skull defect are at risk of developing cerebrospinal fluid leakage and ascending bacterial meningitis at >10% per year. However, treatment with stem cells has brought great hope to large-area cranial defects. Having found that transforming growth factor (TGF)-ß3 can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), we designed a hybrid TGF-ß3/recombinant human-like collagen recombinant human collagen/chitosan (CS) freeze-dried sponge (TRFS) loading hPDLSCs (TRFS-h) to repair skull defects in rats. CFS with 2% CS was selected based on the swelling degree, water absorption, and moisture retention. The CS freeze-dried sponge (CFS) formed a porous three-dimensional structure, as observed by scanning electron microscopy. In addition, cytotoxicity experiments and calcein-AM/PI staining showed that TRFS had a good cellular compatibility and could be degraded completely at 90 days in the implantation site. Furthermore, bone healing was evaluated using micro-computed tomography in rat skull defect models. The bone volume and bone volume fraction were higher in TRFS loaded with hPDLSCs (TRFS-h) group than in the controls (p < 0.01, vs. CFS or TRFS alone). The immunohistochemical results indicated that the expression of Runx2, BMP-2, and collagen-1 (COL Ⅰ) in cells surrounding bone defects in the experimental group was higher than those in the other groups (p < 0.01, vs. CFS or TRFS alone). Taken together, hPDLSCs could proliferate and undergo osteogenic differentiation in TRFS (p < 0.05), and TRFS-h accelerated bone repair in calvarial defect rats. Our research revealed that hPDLSCs could function as seeded cells for skull injury, and their osteogenic differentiation could be accelerated by TGF-ß3. This represents an effective therapeutic strategy for restoring traumatic defects of the skull.

Multifocal Osteolytic Lesions in Skull Bone with Mycobacterium Tuberculosis: A Case Report.

BACKGROUND: Bone Tuberculosis of the skull base as well as maxillofacial and oral cavity involvement can rarely and only occur in about 3% of the cases with systemic diseases or in case of pulmonary involvement. CASE PRESENTATION: A 37-year-old patient with fever and swelling in his face and neck referred to our center. After MRI and CT scan, it was revealed that multiple erosions and destructions are seen in the Hard Palate bones, as well as the pre-maxillary process, alveolar ridge, and the floor of maxillary sinus on both sides. In the Ziel Nelson staining, there were 5 Acid-fast bacilli in each field. The patient received standard anti-tuberculosis and clarithromycin therapy. In the follow-up three months later, the patient's condition improved and MRI showed significant remission. CONCLUSION: The present case confirms that tuberculosis may occur in patients with skull bone involvement and osteolytic lesions whose early diagnosis and treatment can result in gaining good outcomes.

Patient-Specific Three-Dimensional Printing Guide for Single-Stage Skull Bone Tumor Surgery: Novel Software Workflow with Manufacturing of Prefabricated Jigs for Bone Resection and Reconstruction.

OBJECTIVE: To describe a novel system workflow to design and manufacture patient-specific three-dimensional (3D) printing jigs for single-stage skull bone tumor excision and reconstruction and to present surgical outcomes of 14 patients. METHODS: A specific computer-aided design/computer-aided manufacturing software and hardware system was set up, including a virtual surgical planning subsystem and a 3D printing-associated manufacturing subsystem. Computed tomography data of the patient's skull were used for 3D rendering of the skull and tumor. The output of patient-specific designing included a 3D printing guide for tumor resection and a 3D printing model of the bone defect after tumor excision. A polymethyl methacrylate implant was fabricated preoperatively and used for repair. RESULTS: The specific 3D printing guide was used to design intraoperative jigs and implants for 14 patients (age range, 1-72 years) with skull bone tumors. In all cases, the cutting jig allowed precise excision of tumor and bone, and implants were exact fits for the defects created. All operative results were successful, without intraoperative or postoperative complications. Postoperative computed tomography scans were obtained for analysis. Postoperative 3D measurement of the skull symmetry index (cranial vault asymmetry index) showed significant improvement of head contour after surgery. CONCLUSIONS: The computer-aided design/computer-aided manufacturing system described allows definitive preoperative planning and fabrication for treatment of skull bone tumors. Apparent benefits of the method include more accurate determination of surgical margins and better oncological outcomes.

Cranial intraosseous angiolipoma: case report and literature review.

Angiolipomas are slow-growing, soft tissue tumors consisting of mature adipocytes and thin-walled blood vessels. While most angiolipomas are subcutaneous lesions in the trunk and upper extremities, intraosseous angiolipomas are rare at cranial site. We present the case of a 61-year-old female with an enlarging lesion in the left frontoparietal skull following minor head trauma. Radiography confirmed an expansile, enhancing, spiculated bony lesion in the left frontoparietal calvarium with extension outside the cortex into the soft tissues. She underwent a craniectomy for complete resection of the calvarial mass, which was histologically composed of mature adipocytes and disorganized blood vessels highlighted by an immunophenotype positive for S100 and CD34, respectively, consistent with a cranial intraosseous angiolipoma. The review of the literature that reported five cases of cranial intraosseous angiolipoma with our case representing the sixth case is discussed.

Polycomb Repressive Complex 2: a Dimmer Switch of Gene Regulation in Calvarial Bone Development.

PURPOSE OF REVIEW: Epigenetic regulation is a distinct mechanism of gene regulation that functions by modulating chromatin structure and accessibility. Polycomb Repressive Complex 2 (PRC2) is a conserved chromatin regulator that is required in the developing embryo to control the expression of key developmental genes. An emerging feature of PRC2 is that it not only allows for binary ON/OFF states of gene expression but can also modulate gene expression in feed-forward loops to change the outcome of gene regulatory networks. This striking feature of epigenetic modulation has improved our understanding of musculoskeletal development. RECENT FINDINGS: Recent advances in mouse embryos unravel a range of phenotypes that demonstrate the tissue-specific, temporal, and spatial role of PRC2 during organogenesis and cell fate decisions in vivo. Here, we take a detailed view of how PRC2 functions during the development of calvarial bone and skin. Based on the emerging evidence, we propose that PRC2 serves as a "dimmer switch" to modulate gene expression of target genes by altering the expression of activators and inhibitors. This review highlights the findings from contemporary research that allow us to investigate the unique developmental potential of intramembranous calvarial bones.

Investigation of the Effect of the Skull in Transcranial Photoacoustic Imaging: A Preliminary Ex Vivo Study.

Although transcranial photoacoustic imaging (TCPAI) has been used in small animal brain imaging, in animals with thicker skull bones or in humans both light illumination and ultrasound propagation paths are affected. Hence, the PA image is largely degraded and in some cases completely distorted. This study aims to investigate and determine the maximum thickness of the skull through which photoacoustic imaging is feasible in terms of retaining the imaging target structure without incorporating any post processing. We identify the effect of the skull on both the illumination path and acoustic propagation path separately and combined. In the experimental phase, the distorting effect of ex vivo sheep skull bones with thicknesses in the range of 0.7~1.3 mm are explored. We believe that the findings in this study facilitate the clinical translation of TCPAI.