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Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL‐1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP‐mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R‐mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation. [ABSTRACT FROM AUTHOR]

Bone mineralization is an orchestrated process by which mineral crystals are deposited by osteoblasts; however, the detailed mechanisms remain to be elucidated. The presence of P2X7 receptor (P2X7R) in immature and mature bone cells is well established, but contrasting evidence on its role in osteogenic differentiation and deposition of calcified bone matrix remains. To clarify these controversies in the present study, we investigated P2X7R participation in bone maturation. We demonstrated that the P2X7R is expressed and functional in human primary osteoblasts, and identified in the P2RX7 promoter several binding sites for transcription factors involved in bone mineralization. Of particular interest was the finding that P2X7R expression is enhanced by nuclear factor of activated T cells cytoplasmic 1 (NFATc1) overexpression, and accordingly, NFATc1 is recruited at the P2RX7 gene promoter in SaOS2 osteoblastic‐like cells. In conclusion, our data provide further insights into the regulation of P2X7R expression and support the development of drugs targeting this receptor for the therapy of bone diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Computed tomography (CT) is the actual gold standard diagnostic tool for monitoring patients after decompressive craniectomy. It is validated and provides a wide number of information. However, it takes time, expensive, and requires patient transportation. Transcranial sonography (TCS) could represent an alternative diagnostic tool in these patients. The aim of this study is to compare TCS versus CT scan after decompressive craniectomy in terms of diagnosing complications and costs evaluation. METHODS: We prospectively enrolled 10 craniectomized patients who were monitored with sonography and CT. Ventricular measurements and possible complications were evaluated by two independent observers. The two methods were compared using Fisher's exact test and Spearman's Rho coefficient. A costs analysis was also conducted. RESULTS: A good correlation coefficient (ρ) between CT and TCS was found for frontal horn dimensions (ρ.9929), median cella (ρ.9516), and third ventricle (ρ.8989). All results were statistically significant (P <.0001) and Bland‐Altman plots showed no systemic biases. Fisher's exact test showed no statistically significant differences between TCS and CT for all the studied predefined complications. Cost analysis showed a 68% cost reduction in favor of TCS. CONCLUSIONS: TCS could be a reliable alternative diagnostic tool for major complications in patients undergoing decompressive craniectomy. It could limit the number of CT scans per patient overcoming several limitations, such as costs, radiation exposure, and need to move the patient. [ABSTRACT FROM AUTHOR]

Epithelioid sarcoma is a rare tumor originating from mesenchymal cells, usually involving the extremities of young adults and is found only sporadically in the head and neck region. Only one case involving the central nervous system has been described so far.We report a 5 year-old boy with a large solid, osteolytic lesion of the clivus with a wide soft tissue component expanding into the intracranial compartment and obliterating the prepontine cistern. Histopathological examination revealed epithelioid neoplastic cells with abundant eosinophilic cytoplasm, rounded nuclei and prominent nucleoli. Areas of geographic necrosis and numerous mitoses were present. Neoplastic cells immunostained for vimentin, cytokeratin, and epithelial membrane antigen (EMA). No immunostaining was observed for glial fibrillary associated protein (GFAP), S-100, PLAP, α-fetoprotein, CD 117, CD 34, CD 31, BAF-47 (INI1). The Ki67 proliferation index exceeded 40%. These histological findings favor a diagnosis of epithelioid sarcoma. This report adds epithelioid sarcoma to the differential diagnosis of both clival tumors and pediatric skull base tumors. [ABSTRACT FROM AUTHOR]

Background: After surgical resection, the residual, invasive glioblastoma (GBM) cells give rise to a recurrent tumor, which, in 96% of patients, arises adjacent to the resection margin.Methods: In this study, the authors prospectively enrolled 25 patients with GBM who underwent gross total resection followed by adjuvant radiochemotherapy (with temozolomide). Tumor removal was achieved with resection margins that included the neighboring, apparently normal tissue (between 1 cm and 2 cm from the tumor border [B area]) and the tumor.Results: Patients who had an absence of tumor cells in the neighboring, apparently normal white matter (B area) had better survival than patients who had the presence of tumor cells in the B area (21 months vs 12 months). This difference was statistically significant in univariate analysis (P = .005) and in multivariate analysis (P = .01).Conclusions: Aggressive tumor removal may improve survival, but the current results indicated that biologic commitment of 'penumbra' cells appear to be the most relevant factor for tumor recurrence and accounts for the fatal outcome of the disease. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE The bilateral foramina of Monro occlusion is an extremely rare event in adults. To date, only six cases of adult hydrocephalus due to idiopatic obstruction of the bilateral foramina of Monro (including our patient) have been reported. METHODS The authors describe the case of a 41-year-old man with a recent onset of motor hindrance which occurred specially while jumping or playing basketball, together with recent memory impairment, deceleration of thought, and asthenia. The patient was studied with fast spin echo (FSE) and steady-state free precession high-resolution 3D sequences (SSFP) together with a ventricular infusion test, and subsequently treated with endoscopic foraminoplasty. RESULTS The presenting symptoms completely resolved. Follow-up magnetic resonance imaging (MRI) showed the patency of right Monro foramen, with gradually decreasing ventricular size and increase of subarachnoid spaces. CONCLUSIONS These patients should be accurately studied before treatment. In fact, MRI has made it possible to know what a surgeon will exactly find on the operative field. In that way a correct surgical planning can be achieved. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Subdural empyema represents a loculated infection between the dura and the arachnoid. It has been described either intracranially or in the spinal canal, the latter localization being quite rare. While treatment guidelines for a single (either brain or spinal) localization of a subdural empyema are more or less established, its management when a massive involvement of CNS is evident represents a challenge. METHODS The authors describe a unique case of a 65-year-old woman having a massive involvement of the entire CNS with multiple localizations, both intracranial and spinal. Early diagnosis was obtained through brain CT scans followed by cranio-spinal contrast enhanced MRI scans. Patient was treated with external ventricular drainage and suboccipital craniectomy, while on antibiotic therapy. RESULTS Patient's neurological condition gradually improved. By the end of the eighth hospital week, she was discharged without any neurological deficit. CONCLUSIONS Spinal subdural empyema and brain subdural empyema are not always, as in our case, two different entities. Prompt diagnosis and treatment constitute the major variables affecting outcome. [ABSTRACT FROM AUTHOR]