Splenial Callosal Disconnection in Right Hemianopic Patients Induces Right Visual-Spatial Neglect.

Posterior cerebral artery (PCA) territory infarction involving occipital cortical damage can give rise to contralateral homonymous hemianopia. Here, we report two rare cases of patients with lesions in the left hemisphere PCA territory who developed right visuo-spatial neglect. One patient suffered right hemianopia and right visuo-spatial neglect after a stroke that damaged the left primary visual cortex and the callosal splenial fibers. The other unique case is of a patient who had a brain tumor in the posterior cerebral region in the left hemisphere and initially exhibited only right hemianopia that developed into right visuo-spatial neglect after tumor resection that included the splenial fibers. These cases indicate that, as in cases with damage in the right PCA territory, lesions in the left PCA yield visuo-spatial neglect when the damage produces contralateral hemianopia and concomitant disconnection of the splenium of the corpus callosum, which interferes with the arrival of visual inputs from the intact right to the lesioned left hemisphere. These results also emphasize the necessity of sparing the splenial fibers in surgical interventions in patients who exhibit hemianopia.

Neurosurgery on the web: an analysis of the web-visibility of the European Neurosurgical Societies.

Nowadays, internet provides a great opportunity that allows the research community to constantly increase their scientific collaboration, together with information distribution. Aim of this study is to investigate the European National Neurosurgical Societies (ENNS) web-visibility that represents the necessary basis for diffusion of neurosurgical knowledge to both patients and neurosurgeons. We evaluated the web-visibility of each Neurosurgical Society affiliated to the European Associations of Neurosurgical Societies (EANS) using 3 different parameters: 1) the availability of the full list of all Neurosurgical Centers (NCs) of the country in each ENNS website; 2) the availability of a specific English-written section on the ENNS web-site; and 3) the availability of at least one section titled "news and events" and/or "educational" and/or "patient info" on the ENNS website. The web-visibility was categorized in significant (at least 2 out of 3 items fulfilled), not significant (1 out of 3 only) and insufficient (all not fulfilled). We also evaluated the web-visibility of single NCs, and the availability on the web of society's sections dealing with specific neurosurgical topics for each ENNS. Through the EANS Website we identified 38 ENNS. The rate of ENNS with significant web-visibility was 39%, while 24% of ENNS showed to have a not-significant web-visibility, while 37% had an insufficient visibility. The most unattended criterion was the availability of an English-written section of the website. Among ENNS with a significant web-visibility, this specific criterion was fulfilled in only 53% of cases. This percentage goes down to the 22% for ENNS with a non-significant web-visibility. The full list of NCs was available in 87% of cases for significant profiles and in zero cases for not-significant ones. Finally, the web-visibility rate of single NCs among different ENNS was 80%. Specific sections focusing on specific neurosurgical topics were available in 5 out of 38 ENNS websites (13%). This study highlighted the importance of increasing the ENNS web-visibility to spread the neurosurgical knowledge for patients, neurosurgeons and trainees. This could lead to an easier ENNS interaction, increasing the international collaboration between neurosurgical centers in the clinical, research and educational settings.

TAK1 Inhibitor Enhances the Therapeutic Treatment for Glioblastoma.

Glioblastoma (GBM) is a brain tumor characterized by poor therapeutic response and overall survival. Despite relevant progress in conventional treatments represented by the clinical use of temozolomide (TMZ), a combination of approaches might be a possible future direction for treating GBM. Transforming growth factor-beta-activated kinase-1 (TAK1) is an essential component in genotoxic stresses-induced NF-κB-activation and mitogen-activated protein kinase (MAPK)-pathways; however, the role of TAK1 in GBM-chemoresistance remains unknown. This study aimed to verify, in GBM human cell lines, in an in vivo U87-xenograft model and in TMZ-treated-patients, the effect of TAK1 inhibition on the sensitivity of GBM cells to chemotherapy. In vitro model, using GBM cell lines, showed that 5Z-7-oxozeaenol augmented the cytotoxic effects of TMZ, blocking TMZ-induced NF-κB-activation, reducing DNA-damage and enhancing TMZ-induced apoptosis in GMB cell lines. We showed a reduction in tumor burden as well as tumor volume in the xenograft model following the treatment with 5Z-7-oxozaenol associated with TMZ. Our results showed a significant up-regulation in TAK1, p-p38, p-JNK and NF-κB in glioblastoma TMZ-treated-patients and denoted the role of 5Z-7-oxozeaenol in increasing the sensitivity of GBM cells to chemotherapy, proving to be an effective coadjuvant to current GBM chemotherapeutic regimens, suggesting a new option for therapeutic treatment of GBM.

Image-Guided Multisession Radiosurgery of Skull Base Meningiomas.

BACKGROUND: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. METHODS: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. RESULTS: 156 patients met the inclusion criteria. The median follow-up period was 36.2 ± 29.3 months. Progression-free survival at 2-, 5-, and 10- years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. CONCLUSION: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited.

The Value of Preoperative Planning Based on Navigated Transcranical Magnetic Stimulation for Surgical Treatment of Brain Metastases Located in the Perisylvian Area.

BACKGROUND: Brain metastases are the most common neoplasms in adults. When brain metastases are located in eloquent areas, their treatment still seems controversial and not clearly defined. It is therefore essential to provide correct preoperative planning to better define extension and characterization of brain metastasis. METHODS: We retrospectively looked for the tumor database of our institution, patients with single brain metastasis, located in the sylvian area, who underwent resection with the support of intraoperative neurophysiologic monitoring between 2008 and 2018. RESULTS: We retrieved data for 30 adults, each with a single brain metastasis that was located in the sylvian area, including the insula and the lower portion of the motor cortex. Neuronavigation and the intraoperative visualization of the navigated transcranial magnetic stimulation-based reconstruction of functional networks were used to delineate the ideal trajectory toward the lesion. The Karnofsky Performance Status significantly improved in the postoperative period. CONCLUSIONS: The correct planning of brain metastasis allows more secure removal of the neoplastic lesion, avoiding and/or reducing the appearance of neurologic deficits. Navigated transcranial magnetic stimulation represents a new method that can promote a more complete and safer resection of the metastatic lesion in eloquent areas. An optimal surgical result, in the absence of postoperative neurologic deficits, allows the patient to undertake adjuvant therapy able to prolong survival.

Minimally invasive posterior fossa decompression with duraplasty in Chiari malformation type I with and without syringomyelia.

BACKGROUND: Posterior fossa decompression (PFD), with and without duraplasty, represents a valid treatment in Chiari malformation Type I (CM-I) with and without syringomyelia. Despite a large amount of series reported in literature, several controversies exist regarding the optimal surgical approach yet. In this study, we report our experience in the treatment of CM-I, with and without syringomyelia, highlighting how the application of some technical refinements could lead to a good outcome and a lesser rate of complications. METHODS: Twenty-six patients with CM-I, with and without syringomyelia, underwent PFD through a 3 cm × 3 cm craniectomy with the removal of the most median third of the posterior arch of C1 and duraplasty. Signs and symptoms included sensory deficits, motor deficits, neck pain, paresthesias, headache, dizziness, lower cranial nerve deficits, and urinary incontinence. Postoperative magnetic resonance (MR) was performed in all patients. RESULTS: Signs and symptoms improved in 76.9% of cases. Postoperative MR revealed a repositioning of cerebellar tonsils and the restoration of cerebrospinal fluid circulation. In our experience, the rate of complication was 23% (fistula, worsening of symptoms, and respiratory impairment). CONCLUSION: PFD through a 3 cm × 3 cm craniectomy and the removal of the most median third of posterior arch of C1 with duraplasty represents a feasible and valid surgical alternative to treat patients with CM-I, with and without syringomyelia, achieving a good outcome and a low rate of complications.

Surgery of malignant motor-eloquent gliomas guided by sodium-fluorescein and navigated transcranial magnetic stimulation: a novel technique to increase the maximal safe resection.

BACKGROUND: Maximal safe resection is the goal of modern surgical treatment of high-grade gliomas (HGGs) located close to the motor cortex (M1) and/or the corticospinal tract (CST). Preoperative planning based on navigated transcranial magnetic stimulation (nTMS) and fluorescence-guided resection (FGR) using sodium-fluorescein have been separately described to increase the extent of resection (EOR) while preserving the motor pathway. We assessed the efficacy of the combination of these techniques for surgery of motor-eloquent HGGs. METHODS: We enrolled patients with motor-eloquent HGGs operated at the Departments of Neurosurgery of the University of Messina, Italy, and of the Charitè Universitatsmedizin Berlin, Germany, between 2016 and 2019. All patients underwent nTMS mapping of M1, and nTMS-based DTI tractography of CST. Tumor resection was guided by intraoperative neurophysiological mapping (IONM) supported by sodium-fluorescein fluorescence and by intraoperative visualization of the nTMS-based information through neuronavigation. EOR and new permanent motor deficits were compared with a historical control group of patients operated exclusively with IONM guidance. RESULTS: Seventy-nine patients were enrolled, while 55 patients were included as controls. The gross total resection (GTR) rate was significantly higher in patients operated using nTMS + FGR compared with controls (64.5% vs. 47.2%, P=0.04). As well, postoperative new permanent motor deficits were reduced in the study group vs. controls (11.4% vs. 20%). CONCLUSIONS: In this series, the combination of sodium-fluorescein FGR with nTMS-based planning improved surgical treatment of motor-eloquent HGGs. It represents a valuable support to IONM-guided resection, increasing the GTR rate while reducing the occurrence of permanent motor deficits.

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.

The efficacy of 90cm-long peritoneal shunt catheters in newborns and infants.

BACKGROUND: Ventriculoperitoneal (VP) shunt is one of the options for the treatment of hydrocephalus. The aim of this study is to describe the efficacy and safety of a 90cm-long peritoneal catheter in newborns and infants treated for hydrocephalus. We analyzed the incidence of distal-related complications and the need of successive surgeries for malfunction or for lengthening of the peritoneal catheter. METHODS: We reviewed medical records of neonates and infants treated with a VP shunt using a 90cm-long peritoneal catheter. Function and integrity of shunts were assessed through abdominal echographic studies, skull, neck, chest and abdomen X-rays. We compared shunt revision rates due to distal complications and insufficient length of the peritoneal catheter in the study group with an historical control group composed by newborns and infants treated with a standard VP shunt at our Institution during the last twenty years. RESULTS: Three neonates and 3 infants were treated with the insertion of the 90cm-long distal catheter into the peritoneal cavity for its total length. The mean follow-up was 7.6 years. As compared to controls, in the study group the revision rate for distal complications was not significantly increased (P=0.33), whereas revision surgeries due to insufficient peritoneal catheter length were significantly reduced (P=0.04). CONCLUSIONS: This study demonstrates for the first time that the use of 90cm-long peritoneal catheters in neonates and infants is a safe and effective procedure. It does not increase the incidence of abdominal complications, avoiding the need of revision for insufficient length of the peritoneal catheter.

Microvascular Decompression for Trigeminal Neuralgia: Technical Refinement for Complication Avoidance.

BACKGROUND: Microvascular decompression (MVD) represents the most effective and safe surgical option for the treatment of trigeminal neuralgia since it was first popularized by Jannetta 50 years ago. Despite several advances, complications such as cerebellar and vascular injury, hearing loss, muscular atrophy, cerebrospinal fluid (CSF) leak, postoperative cutaneous pain, and sensory disturbances still occur and may negatively affect the outcome. We propose some technical nuances of the surgical procedure that were used in our recent series. METHODS: We used a novel hockey stick-shaped retromastoid skin incision, preserving the major nerves of the occipital and temporal areas. Microsurgical steps were performed without the use of retractors. CSF leakage was prevented with a watertight dural closure and multilayer osteodural reconstruction. RESULTS: The refined surgical steps were perfected in the last consecutive 15 cases of our series. In these cases we did not record any cutaneous pain, sensory disturbances, or CSF leakage. The average diameter of the craniectomy was 18 mm. No patient reported major complications related to the intradural microsurgical maneuvers. In all cases the neurovascular conflict was found and solved with a good outcome in terms of pain disappearance. CONCLUSIONS: Our minimally invasive approach was demonstrated to guarantee an optimal exposure of the cerebellopontine angle and minimize the rate of complications related to skin incision and muscular dissection, microsurgical steps, and closure.

CyberKnife multisession stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for perioptic meningiomas: intermediate-term results and radiobiological considerations.

Single fraction radiosurgery is conventionally precluded for lesions lying <2-3 mm of the anterior visual pathway because of the radiosensitivity of the optic nerve. We analyzed a series of 64 patients with "perioptic" meningiomas treated by CyberKnife multisession radiosurgery and hypofractionated stereotactic radiotherapy (hSRT). Between July 2007-May 2010, patients were treated using conventional multisession Cyberknife schemes (2-5 fractions) and results were retrospectively analyzed. A radiobiological model was then developed to estimate the best tumor control probability (TCP)/ normal tissue complication probability (NTCP) for these lesions. Resulting dose/fraction schemes were applied to patients treated between May 2010 and July 2014. Data were prospectively collected Twenty-five patients were included in the retrospective part of the study. Median tumor volume was 4.95 cc; median dose was 23.0 Gy and median number of fraction was 5 (range 2-5). No patient had visual deterioration at mean follow-up of 60 ± 12 months. Tumor control was achieved in all cases. Thirty-nine patients were treated according the radiobiology model and results prospectively analyzed. Median tumor volume was 7.5 cc, median dose 25.0 Gy and mean number of fraction 5 (range 3-15). No patient had visual deterioration or tumor progression at mean follow-up of 17 ± 10 months. Conventional multisession CyberKnife treatments (2-5 fractions) provided satisfactory results. Nonetheless, our estimation of TCP suggests the use of higher doses to grant long-term disease control. To achieve higher equivalent doses without significantly increasing the NTCP, we suggest the use of a greater number of fractions, moving to hSRT, in tumors in which the encasement of optic nerves is presumed.

Human leukocyte antigen frequency in human high-grade gliomas: a case-control study in Sicily.

OBJECTIVE: Human leukocyte antigens (HLAs) are widely expressed cell surface molecules that present antigenic peptides to T lymphocytes and modulate immune response against inflammatory and malignant diseases. The aim of this study was to compare HLA distribution in patients with newly diagnosed high-grade gliomas (HGGs) and 2 control groups from a restricted geographic area (eastern Sicily). METHODS: HLA allele frequency, as determined from peripheral blood of 56 adult patients with HGGs, was compared with that of 2 different control groups: 140 healthy bone marrow donors (group A) and 69 virtually brain tumor-free patients (group B). HLA expression was evaluated using a reverse transcriptase polymerase chain reaction-sequence-specific oligonucleotide probe. RESULTS: There was significant expression of HLA-A*11 in patients with HGGs compared with control groups A and B (P < 0.003 and P < 0.018, respectively). Significant expression of HLA genotypes in patients with HGGs was also identified for HLA-DQB1*06 (P = 0.005), HLA-DRB1*14 (P = 0.001), and HLA-DRB3*01 (P = 0.007) compared with control group B. In HGG patients, there was statistically significantly decreased expression, compared with control groups A and B, of HLA-B*07 (P = 0.002 and P = 0.03, respectively) and HLA-C*04 (P = 0.007 and P = 0.016, respectively). There was statistically significant lower expression of HLA-C*05 in the HGG group compared with group B (P < 0.03). CONCLUSION: This is the first study to describe the frequency of distribution of HLAs in a population from a restricted geographic area. The findings suggest a possible correlation between HLA allele distribution and the occurrence of newly diagnosed malignant astroglial brain tumors.

Transcranial Doppler ultrasonography in the assessment of cerebral circulation arrest: improving sensitivity by transcervical and transorbital carotid insonation and serial examinations.

INTRODUCTION: Transcranial Doppler (TCD) can detect the cerebral circulation arrest (CCA) in brain death. TCD is highly specific, but less sensitive because of false-negatives accounting for up to 10%. The aim of the study was to explore the diagnostic accuracy of TCD and to determine whether it can be augmented by strategies such as the insonation of the extracranial internal carotid artery (ICA) and sequential examinations. METHODS: Data of 184 patients, who met clinical criteria of brain death, observed from 1998 through 2006, were retrospectively reviewed. The study of cerebral arteries was performed through the transtemporal approach, suboccipital insonation of the vertebro-basilar system, transorbital insonation of the ICA and ophthalmic artery, and transcervical insonation of the extracranial ICA. Repeated exams were performed in cases of persistent diastolic flow. RESULTS: The specificity of the testing was 100%, no false-positive cases were recorded. The sensitivity of conventional TCD examination was 82.1%. The insonation of the extracranial ICA increased sensitivity to 88% allowing the detection of CCA in those patients lacking temporal windows; serial examinations further increased sensitivity to 95.6%. CONCLUSIONS: The addition of insonation of the cervical ICA and of the siphon increased sensitivity of TCD. Nevertheless, a CCA flow patterns may appear later on those segments. Serial examinations, may be needed in those cases.