Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?

Spinal tumor (ST) surgery carries the risk of new neurological deficits in the postoperative period. Intraoperative neurophysiological monitoring and mapping (IONM) represents an effective method of identifying and monitoring in real time the functional integrity of both the spinal cord (SC) and the nerve roots (NRs). Despite consensus favoring the use of IONM in ST surgery, in this era of evidence-based medicine, there is still a need to demonstrate the effective role of IONM in ST surgery in achieving an oncological cure, optimizing patient safety, and considering medicolegal aspects. Thus, neurosurgeons are asked to establish which techniques are considered indispensable. In the present study, the authors focused on the rationale for and the accuracy (sensitivity, specificity, and positive and negative predictive values) of IONM in ST surgery in light of more recent evidence in the literature, with specific emphasis on the role of IONM in reducing the incidence of postoperative neurological deficits. This review confirms the role of IONM as a useful tool in the workup for ST surgery. Individual monitoring and mapping techniques are clearly not sufficient to account for the complex function of the SC and NRs. Conversely, multimodal IONM is highly sensitive and specific for anticipating neurological injury during ST surgery and represents an important tool for preserving neuronal structures and achieving an optimal postoperative functional outcome.

Cerebral venous sinus thrombosis (CVST) associated with SARS-CoV-2 vaccines: clues for an immunopathogenesis common to CVST observed in COVID-19.

Severe acute respiratory syndrome coronavirus type 2 has been responsible for an unprecedented pandemic, and nowadays, several vaccines proved to be effective and safe, representing the only available strategy to stop the pandemic. While millions of people have safely received vaccine, rare and unusual thrombotic events have been reported and are undergoing investigations to elucidate their nature. Understanding initial trigger, underlying pathophysiology and the reasons for specific site localization of thrombotic events are a matter of debate.We here propose that rare cases of cerebral venous sinus thrombosis, a clinical event that may rapidly evolve to brain death, reported after COVID-19 vaccine, might be consequent to an immune response resulting in inflamed/damaged endothelium, an event similar to that described for cases of cerebral venous sinus thrombosis reported during COVID-19 and not necessarily related to anti-Platelets Factor 4 antibodies, as recently described. Remarkably, in the two patients presenting at our hospital with cerebral venous sinus thrombosis and evolved to brain death, proper tissue perfusion and function maintenance allowed organ donation despite extensive thrombosis in the organ donors, with favorable outcome at 6 months.Increased vigilance, close multidisciplinary collaboration, and further prospective research will help to better elucidate a very rare and still not fully understood pathophysiological event associated with vaccines for severe acute respiratory syndrome coronavirus 2.

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain.

OBJECTIVE: This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS). SETTINGS: Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016. SUBJECTS: Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months. MATERIALS AND METHODS: All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months. RESULTS: Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07-4.72±0.9 by the end of the study duration (12 months) (P<0.001). CONCLUSION: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.

TLR-4/Wnt modulation as new therapeutic strategy in the treatment of glioblastomas.

PURPOSE: Glioblastomas are highly aggressive brain tumors. Various pathways are involved in gliomagenesis, among which the Wingless (Wnt) signaling. Dickkopf protein-related protein 3 (Dkk-3) interacts with proteins of Wnt pathwayas inhibitor. The Wnt signaling contributes to activity of the claudins, that are critical components of tight junctions, whose expression was altered selectively in cerebral microvessels of glioblastoma. The aim of this study was to determine the role of Wnt pathways in the regulation of tumor growth, apoptosis process by targeting Dkk-3, tight junctions alteration involving claudin-5, suggesting possible therapeutic interactions involving Wnt/Toll-like receptors (TLRs) pathways. RESULTS: We showed a significant decreasing of Dkk-3 and claudin-5 in human glioblastoma cell lines, as well as in U-87 MG xenograft tumors and in glioblastoma human patient's tissues, with an involvement of the apoptosis process. Also, an interesting TLR-4/Wnt modulation highlighted that the absence of TLR-4 determined resistance to the tumor onset. CONCLUSIONS: We concluded that combined modulation of Wnt/Dkk-3/claudin-5 and TLR-4 pathways, simultaneously targeting apoptosis and survival signaling defects, might shift the balance from tumor growth stasis to cytotoxic therapeutic responses, flowing in greater therapeutic benefits. METHODS: In the present study we investigated the expression of Dkk-3, claudin-5, apoptosis markers and TLR-4 receptor protein levels in in vitro studies on U-138MG, A-172, LN-18 and LN-229 human glioblastoma cell lines, and in vivo study using TLR-4 KO mice and in glioblastoma human patient's tissues.

Modulation of Dkk-3 and claudin-5 as new therapeutic strategy in the treatment of meningiomas.

Meningiomas are the most common tumors of the central nervous system, where the incidence is around 25% of all primary brain tumors. The optimal treatment is represented by total resection accompanied by the removal of the dura mater and bone when infiltrated by the tumor. The histological grading is the most important prognostic factor in the outcome. However, recurrences do occur in a significant proportion (10-25%) of cases, representing the most relevant clinical complication. Molecular therapies are providing to give different opportunities in the development of new treatments. The Dickkopf-related family of proteins includes four secretory proteins. The expression of the REIC/Dkk-3 gene is down-regulated in many tumor cell lines and could contribute to the immunomodulatory properties of the tissue microenvironment. An important role in carcinogenesis is played by Dickkopf protein-related protein 3, which is involved in embryonic development through its interaction and modulation of the pathway of the Wnt signal transduction. The mutations of this pathway are of clinical importance, because they lead to the onset of several cancers, including brain tumors, being also involved in tumor angiogenesis. The claudin-5, is an integral membrane protein, which regulate the permeability of the blood-brain barrier. In various pathological processes, including inflammation, trauma and tumor, claudin 5 regulate the change in endothelial or epithelial permeability, therefore, modification in claudin-5 expression may play a role in malignant transformation. The aim of our study is to demonstrate the role of Dkk-3 and claudin-5 in the pathogenesis of meningiomas. A more correct identification of the role of these proteins might suggest interesting and new molecular targets for future therapeutic protocols.