Transcortical endoportal subchoroidal endoscope-assisted approach to the third ventricle: from virtual reality to anatomical laboratory.

BACKGROUND: Surgical approaches to the third ventricle (TV) have always represented a technical challenge in neurosurgery. Virtual reality (VR) is attaining increasing relevance in training programs and preoperative planning. The aim of this study is to demonstrate the worthwhile mutual contribution of VR simulations and specimen dissections to develop a new surgical approach to the TV. METHODS: The transcortical endoportal subchoroidal endoscope assisted (TEPSEA) approach was planned and simulated thanks to VR (Surgical Theater©, LLC, Cleveland, OH, USA), and then implemented on cadaver specimens by using the VBAS portal system (Viewsite™ Brain Access System TC Model, Vycor Medical™ Inc., Boca Raton, FL, USA). We assessed anthropometric measurements during VR planning and evaluated surgical operability during anatomical dissections. RESULTS: Surgical field depths measured between 75.6 and 85.3 mm to mammillary bodies and habenular commissure, which were in mean 20.2 mm away. An 18-mm movement was estimated for 15°-posterior tilting of a 70-mm long VBAS. Excellent exposure and maneuverability were achieved within the TV through a 2.47 cm2 portal working area. The 30°-endoscope assistance expanded the access towards the anterior and posterior walls of the TV particularly to the infundibular recess, mammillary bodies, habenular commissure and pineal recess. CONCLUSIONS: We documented the utility of a step-by-step VR planning and simulation followed by anatomical dissections to study surgical approaches to deep brain areas. The TEPSEA exploits the portal system and endoscopic assistance to access the entire TV minimizing cortical and white matter manipulation.

Beyond Antoni: A Surgeon's Guide to the Vestibular Schwannoma Microenvironment.

Introduction Vestibular schwannomas (VS) are histologically benign tumors arising from cranial nerve VIII. Far from a homogenous proliferation of Schwann cells, mounting evidence has highlighted the complex nature of the inflammatory microenvironment in these tumors. Methods A review of the literature pertaining to inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in VS was performed. Relevant studies published up to June 2020 were identified based on a literature search in the PubMed and MEDLINE databases and the findings were synthesized into a concise narrative review of the topic. Results The VS microenvironment is characterized by a dense infiltrate of inflammatory cells, particularly macrophages. Significantly higher levels of immune cell infiltration are observed in growing versus static tumors, and there is a demonstrable interplay between inflammation and angiogenesis in growing VS. While further mechanistic studies are required to ascertain the exact role of inflammation in angiogenesis, tumor growth, and Schwann cell control, we are beginning to understand the key molecular pathways driving this inflammatory microenvironment, and how these processes can be monitored and targeted in vivo . Conclusion Observational research has revealed a complex and heterogeneous tumor microenvironment in VS. The functional landscape and roles of macrophages and other immune cells in the VS inflammatory infiltrate are, however, yet to be established. The antiangiogenic drug bevacizumab has shown the efficacy of targeted molecular therapies in VS and there is hope that agents targeting another major component of the VS microenvironment, inflammation, will also find a place in their future management.

The inflammatory microenvironment in vestibular schwannoma.

Vestibular schwannomas are tumors arising from the vestibulocochlear nerve at the cerebellopontine angle. Their proximity to eloquent brainstem structures means that the pathology itself and the treatment thereof can be associated with significant morbidity. The vast majority of these tumors are sporadic, with the remainder arising as a result of the genetic syndrome Neurofibromatosis Type 2 or, more rarely, LZTR1-related schwannomatosis. The natural history of these tumors is extremely variable, with some tumors not displaying any evidence of growth, others demonstrating early, persistent growth and a small number growing following an extended period of indolence. Emerging evidence now suggests that far from representing Schwann cell proliferation only, the tumor microenvironment is complex, with inflammation proposed to play a key role in their growth. In this review, we provide an overview of this new evidence, including the role played by immune cell infiltration, the underlying molecular pathways involved, and biomarkers for detecting this inflammation in vivo. Given the limitations of current treatments, there is a pressing need for novel therapies to aid in the management of this condition, and we conclude by proposing areas for future research that could lead to the development of therapies targeted toward inflammation in vestibular schwannoma.

The microenvironment in sporadic and neurofibromatosis type II-related vestibular schwannoma: the same tumor or different? A comparative imaging and neuropathology study.

OBJECTIVE: Inflammation and angiogenesis may play a role in the growth of sporadic and neurofibromatosis type 2 (NF2)-related vestibular schwannoma (VS). The similarities in microvascular and inflammatory microenvironment have not been investigated. The authors sought to compare the tumor microenvironment (TME) in sporadic and NF2-related VSs using a combined imaging and tissue analysis approach. METHODS: Diffusion MRI and high-temporal-resolution dynamic contrast-enhanced (DCE) MRI data sets were prospectively acquired in 20 NF2-related and 24 size-matched sporadic VSs. Diffusion metrics (mean diffusivity, fractional anisotropy) and DCE-MRI-derived microvascular biomarkers (transfer constant [Ktrans], fractional plasma volume, tissue extravascular-extracellular space [ve], longitudinal relaxation rate, tumoral blood flow) were compared across both VS groups, and regression analysis was used to evaluate the effect of tumor size, pretreatment tumor growth rate, and tumor NF2 status (sporadic vs NF2-related) on each imaging parameter. Tissues from 17 imaged sporadic VSs and a separate cohort of 12 NF2-related VSs were examined with immunohistochemistry markers for vessels (CD31), vessel permeability (fibrinogen), and macrophage density (Iba1). The expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 was evaluated using immunohistochemistry, Western blotting, and double immunofluorescence. RESULTS: Imaging data demonstrated that DCE-MRI-derived microvascular characteristics were similar in sporadic and NF2-related VSs. Ktrans (p < 0.001), ve (p ≤ 0.004), and tumoral free water content (p ≤ 0.003) increased with increasing tumor size and pretreatment tumor growth rate. Regression analysis demonstrated that with the exception of mean diffusivity (p < 0.001), NF2 status had no statistically significant effect on any of the imaging parameters or the observed relationship between the imaging parameters and tumor size (p > 0.05). Tissue analysis confirmed the imaging metrics among resected sporadic VSs and demonstrated that across all VSs studied, there was a close association between vascularity and Iba1+ macrophage density (r = 0.55, p = 0.002). VEGF was expressed by Iba1+ macrophages. CONCLUSIONS: The authors present the first in vivo comparative study of microvascular and inflammatory characteristics in sporadic and NF2-related VSs. The imaging and tissue analysis results indicate that inflammation is a key contributor to TME and should be viewed as a therapeutic target in both VS groups.

Primary epithelial-myoepithelial carcinoma of the pituitary gland.

Primary salivary gland-like tumors of the sella are rare and often challenging to diagnose. They reportedly derive from serous and mucinous glands that remain trapped in the infundibulum during embryogenesis. We report a 68-year-old man who presented with partial left third cranial nerve palsy, visual loss in the left eye without visual field defects, headache, weight loss and reduced muscle bulk. Neuroimaging studies demonstrated a solid and cystic, avidly enhancing lesion expanding the pituitary fossa and extending to the left cavernous sinus. The patient underwent craniotomy and the tissue removed showed features of epithelial-myoepithelial carcinoma similar to the salivary gland, skin and breast counterpart. No primary tumor was found outside the sella. The lesion behaved aggressively despite radio-chemotherapy and the patient died 22 months from the onset. The tumor showed a novel TP53 in-frame deletion (Gly154del) while no variants were found in H-RAS hotspot regions (codons 12, 13 and 61). Our report expands the spectrum of salivary gland-like tumors primarily occurring in the sella and emphasizes the need for specialist review of rare, non-neuroendocrine tumors of the pituitary and sella regions.

Anatomic Study on Neuroendoportal Transcortical Approach to Lateral Ventricles.

BACKGROUND: Resection of intraventricular lesions remains a challenge for modern neurosurgery. Endoscopy has provided great advantages in ventricular surgery, even if limited in terms of operability, due to the restricted working channel and impossibility for bimanual surgical manipulation. Tubular approaches have been considered as an option, enabling the use of microsurgical techniques, minimizing violation of brain tissue. The aim of our study was to describe and critically evaluate the use of portal surgery to access lateral ventricles in terms of surgical exposure and operability. METHODS: A microanatomic laboratory cadaver study was conducted with a stepwise description of the surgical technique. The operability score was applied for quantitative analysis of surgical operability, and an illustrative case is reported. RESULTS: Through the anterior approach, the neuroport provides maximal operability at the foramen of Monro and the posterior aspect of the frontal horn, while through the posterior approach maximal operability is achieved in the paratrigonal area. Endoscopic assistance does not affect operability but provides adjunctive exposure in blind spots, as the roof of the frontal horn, the most anterior aspect of the temporal and occipital horn. CONCLUSIONS: Ventricular tubular systems provide adequate visualization, with minimal brain retraction, improving operability as compared with endoscopy. Endoscopic assistance critically widens surgical exposure in blind spots without providing concomitant significant advantage in terms of surgical operability.

Bilateral Temporal Myofascial Flap for the Reconstruction of Frontal Sinus Defects.

BACKGROUND: A frontal sinus infection, following a transsinus skull base procedure, portends potentially life-threatening complications, making surgical revision mandatory in refractory infections. The authors describe the application of the bilateral temporal myofascial flap (BTMF) as a valuable option for frontal sinus reconstruction, when pericranial or galeal-frontalis myofascial flap (GFMF) is no longer available. METHODS: A microanatomic laboratory cadaver investigation was conducted to obtain anthropometric measurements. Surgical technique is described, and intraoperative images are provided. RESULTS: The surgical steps of this technique and the related intraoperative images are reported. One case illustration regarding frontal sinus reconstruction following a postoperative infection, as a complication after a transsinus procedure, is reported. CONCLUSION: The BTMF should be considered as a valuable option for frontal sinus reconstruction after transsinus skull base procedures when GFMF is not available.

Gamma Knife Radiosurgery for Low-Grade Gliomas: Clinical Results at Long-Term Follow-Up of Tumor Control and Patients' Quality of Life.

OBJECTIVE: First-line therapy for low-grade gliomas (LGGs) is surgery, in some cases followed by radiotherapy and chemotherapy. Gamma Knife radiosurgery (GKRS) has gained more relevance in the management of these tumors. The aim of this study was to assess efficacy and safety of GKRS for treatment of LGGs. METHODS: Between 2001 and 2014, 42 treatments were performed on 39 patients harboring LGGs; 48% of patients underwent previous surgery, and 20.5% underwent previous radiotherapy. Mean tumor volume was 2.7 cm3, and median margin dose was 15 Gy. RESULTS: Mean follow-up was 60.5 months (range, 6-164 months). Actuarial progression-free survival was 74.9%, 52.8%, and 39.1% at 1 year, 5 years, and 10 years; actuarial overall survival was 97.4%, 94.6%, and 91.8% at 9 months, 1 year, and 5 years. Solid tumor control was achieved in 69.2% of patients, whereas cystic enlargement was recorded in 12.9% of cases. At last follow-up, volume reduction was recorded in 57.7% of cases, and median volume decreased by 33.3%. Clinical improvement was observed in 52.4% of patients. Karnofsky performance scale score was improved in 15 patients (45.5%), unchanged in 17 patients (51.5%), and worsened in 1 patient (3%). Mean posttreatment scores of 36-item short form health survey domains did not significantly differ from scores in a healthy Italian population. CONCLUSIONS: This study confirms safety and effectiveness of GKRS for LGGs in controlling tumor growth, relevantly improving patients' overall and progression-free survival. GKRS improved patients' functional performance and quality of life, optimizing social functioning and minimizing disease-related psychological impact.

Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm.

OBJECTIVE There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs. METHODS Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm3. Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm3 (range 10.1-34.3 cm3). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18-25 Gy). RESULTS Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19-87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I-II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0.024). CONCLUSIONS According to the results of this study, volume-staged GKRS is an effective and safe treatment strategy for large, complex, cerebral AVMs for which microsurgery or endovascular approaches could carry substantially higher risks to the patient. Radiation doses up to 20 Gy can be safely administered. The time interval between stages should be shorter than 11.7 months to increase the chance of obliteration. High nidal flow and a patient age younger than 44 years were factors associated with nidus obliteration and significant nidus reduction, respectively.

Endoscope-Assisted Transmaxillosphenoidal Approach to the Sellar and Parasellar Regions: An Anatomic Study.

BACKGROUND: Anterolateral skull base surgery in the sellar and parasellar regions has always represented a technical challenge for neurosurgeons. The microscopic endoscope-assisted transmaxillosphenoidal approach (MEMSA) affords a direct surgical corridor free from critical skull base structures. Here we describe and critically evaluate the use of MEMSA to access the sellar and parasellar areas, in terms of surgical exposure and operability. METHODS: Six cadaveric heads were examined. A stepwise dissection using MEMSA was performed. Relevant anatomy and surgical technique were critically described and comparatively reviewed. The operability score was applied for quantitative analysis of surgical operability. RESULTS: MEMSA provides wide bilateral surgical exposure and vascular control of the sellar, suprasellar, and parasellar regions, achieving the highest operability on the midline and in the parasellar region. The approach can be tailored to the lesion, with the surgical corridor easily widened toward the contralateral pterygopalatine fossa. Anatomic knowledge of maxillary sinus landmarks is key to the use of this approach. Favorable sphenoidal anatomy is the main limiting factor, making MEMSA a surgical alternative to endoscopic endonasal routes in situations where those routes are not feasible, and the approach of choice in selected cases of primarily sellar lesions widely extending contralaterally to the approached maxillary sinus. CONCLUSIONS: MEMSA is a safe and effective technique that provides access to the sellar, suprasellar, and contralateral parasellar areas via a direct, minimally disruptive surgical corridor. The preservation of nasal anatomy ensures the availability of mucosal flaps for use in further reconstruction.

The current role of Gamma Knife radiosurgery in the management of intracranial haemangiopericytoma.

BACKGROUND: Haemangiopericytomas (HPCs) are rare tumours characterised by aggressive behaviour with tendency to local recurrence and to metastasise. WHO grade II and grade III tumours show different progression-free survival and overall survival rates. Gross total tumour resection is still considered the treatment of choice. Adjuvant radiation therapies represent an option in the treatment strategy regardless the extent of resection. Based on this consideration, Gamma Knife radiosurgery has been introduced either as a primary treatment or as an adjuvant treatment for residual or recurrent tumours. METHOD: A systematic search was performed on PubMed, Web of Science and Google Scholar for clinical series reporting Gamma Knife radiosurgery, Cyberknife and Linear Accelerator (LINAC) for the management of intracranial HPCs. RESULTS: Fourteen studies focusing on the effects of Gamma Knife radiosurgery for intracranial HPCs were included. Four studies reported data on Cyberknife radiosurgery and LINAC. A total of 208 patients harbouring 366 tumours have been reported. Patient's features, radiosurgical treatment characteristics and follow-up data of the pertinent literature have been critically revised. CONCLUSIONS: Gamma Knife radiosurgery and the other radiosurgical techniques represent a feasible and effective therapy in the management of HPCs. Tumour control and survival rate are comparable to those reported for radiotherapy. Further studies should be focused to define the exact role of Gamma Knife radiosurgery in the management of HPCs.

Sudden onset of Chiari malformation type 1 in a young child after trauma.

INTRODUCTION: Chiari 1 malformation is a rare craniovertebral junction malformation accounting up to 1 case in every 1000 newborns per year. It is characterized by herniation of cerebellar tonsils below the foramen magnum sometimes with syringomyelia. Usually, patients have a long history of slowly progressive neurological symptoms. Uncommonly, Chiari 1 malformation could present with a sudden onset, also after trauma. Few cases are reported about young children. METHODS: The authors report a case of a 6-month child with symptoms at onset after a mild trauma. The pertinent literature is reviewed. CONCLUSIONS: Symptoms of Chiari 1 malformation are usually slowly progressive. Few cases have been reported of the sudden onset of symptoms, some of these after trauma. In young children, the clinical setting could be insidious and potentially lethal. A sudden onset of Chiari 1 malformation must be considered as a consequence of trauma, usually after performing a brain MRI. Management of these cases is still controversial, and surgery may be indicated in managing symptoms; however, it seems to not affect clinical outcome.

Presentation and surgical results of incidentally discovered nonfunctioning pituitary adenomas: evidence for a better outcome independently of other patients' characteristics.

OBJECTIVE: Few data are available on the surgical results in patients with incidentally discovered nonfunctioning pituitary adenoma (NFPA). We investigated the efficacy and safety of surgery in patients with incidentally discovered NFPA. DESIGN: Retrospective analysis of prospectively recorded outcomes. METHODS: From 1990 to 2011, of 804 consecutive patients undergoing surgery for NFPA, 212 cases had an incidentally discovered tumor (26.4%). Among them, 117 patients were asymptomatic, while 95 had some visual and/or hormonal deficit. The main outcome of the study was to evaluate the frequency of radical resection as judged on the first postoperative neuroimaging study and detection of recurring disease during long-term follow-up. RESULTS: Postoperative residual tumor was detected in 8.9% of patients with asymptomatic incidentalomas as compared with 31.2% of patients with symptomatic incidentalomas (P<0.001) and 41.2% of patients in the control group (P<0.001). Multivariate analysis confirmed that having an asymptomatic incidentaloma was independently associated with a better outcome. The 5-year recurrence-free survival in patients with incidentaloma was 86.8% (95% CI 80.2-92.4%) as compared with 77.9% (95% CI 73.6-82.2%; P<0.01) in the control group. This difference was almost completely due to a lower frequency of relapse in asymptomatic patients. Multivariate analysis confirmed the independent lower risk of tumor recurrence in asymptomatic NFPA. CONCLUSION: Our study shows for the first time that surgically treated patients with asymptomatic NFPA have a better early and long-term outcome that is independent from all the other demographic, clinical, and morphologic characteristics of the patients.