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Background Traditional endoscopic anterior cranial base resection involves the total removal of the ethmoidal cells, including the middle and superior turbinates. This is associated with increased volume of the nasal cavity postoperatively, with increased crusting and permanent change of the nasal airflow. Here we provide a step-by-step description of the technique and evaluate the feasibility of the superior ethmoidal approach for anterior cranial base resection with maximum exposure of the anterior cranial base while keeping the middle turbinates, uncinate processes, and ostiomeatal complexes intact. Methods Three fresh cadaveric heads were used for dissections. This technique was successfully performed in 2 consecutive cases of large olfactory groove meningiomas. Results In all anatomic dissections, satisfactory exposure of the cranial base was achieved while keeping the middle turbinate, uncinate process, ethmoid bulla, and middle meatus intact bilaterally. Successful resection of 2 consecutive cases of olfactory groove meningioma was performed using this approach. Conclusions The endoscopic superior ethmoidal approach for anterior cranial base resection is a feasible and safe approach that maximizes preservation of the nasal structures while providing optimal access to the anterior skull base. It can be used in pathologies that involve the anterior cranial base and do not involve the nasal structures.

// Noemi Garcia-Romero 1, 2, * , Josefa Carrion-Navarro 1, 3, * , Susana Esteban-Rubio 1, 3, * , Elisa Lazaro-Ibanez 4 , Maria Peris-Celda 5 , Marta M. Alonso 6 , Juan Guzman-De-Villoria 7 , Carlos Fernandez-Carballal 8 , Ana Ortiz de Mendivil 1 , Sara Garcia-Duque 1 , Carmen Escobedo-Lucea 4 , Ricardo Prat-Acin 9 , Cristobal Belda-Iniesta 1, 3 , Angel Ayuso-Sacido 1, 2, 3 1 Fundacion de Investigacion HM Hospitales, HM Hospitales, Madrid, Spain 2 IMDEA Nanoscience, Madrid, Spain 3 Facultad de Medicina (IMMA), Universidad San Pablo-CEU, Madrid, Spain 4 Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland 5 Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 6 Clinica Universidad de Navarra, CIMA, Pamplona, Spain 7 Servicio de Radiodiagnostico, Hospital General Universitario Gregorio Maranon, Madrid, Spain 8 Servicio de Neurocirugia, Hospital General Universitario Gregorio Maranon, Madrid, Spain 9 Departamento de Neurocirugia, Hospital Universitario la Fe, Valencia, Spain * These authors have contributed equally to this work Correspondence to: Angel Ayuso-Sacido, email: ayusosacido@gmail.com Keywords: extracellular vesicles, brain tumors, blood-brain barrier, biomarkers Received: September 20, 2016 Accepted: November 07, 2016 Published: November 26, 2016 ABSTRACT Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs−apoptotic bodies, shedding microvesicles and exosomes−cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1 G395A , an essential biomarker in the current management of human glioma

Objectives/Hypothesis To conceive and critically evaluate an adaptation of the split calvarial osteopericranial flap for reconstruction following endoscopic endonasal resection of the anterior skull base. Study Design Cadaveric anatomic study. Methods Five cadavers were embalmed with methanol, and vasculature was injected with latex. Endoscopic endonasal resection of the anterior skull base was performed, followed by reconstruction with a unilateral osteopericranial flap and a contralateral conventional pericranial flap. Results Rigid reconstruction was achieved in all specimens. Osteoplastic flap harvest was made more reliable by drilling the diploe below the graft with a curved bur. Dimensions of the bony flap were ideally shorter and wider than the defect, allowing for flap inset and rigid support by the orbits without compromise of the flap vascular supply. Endoscopic inset of the flap is feasible via nasion-frontal osteotomy and inlay technique. Conclusion Rigid anterior skull base reconstruction via split calvarial osteopericranial flap is adaptable to current endoscopic techniques. This provides more anatomic reconstruction than current methods and may lead to decreased complication rates following anterior skull base resection. Level of Evidence N/A. Laryngoscope, 125:826–830, 2015

Object The object of this paper was to describe the surgical anatomy and technical nuances of the endonasal transcavernous posterior clinoidectomy approach with interdural pituitary transposition and to report the clinical outcome of this technical modification. Methods The surgical anatomy of the proposed approach was studied in 10 colored silicon-injected anatomical specimens. The medical records of 12 patients that underwent removal of the posterior clinoid(s) with this technique were reviewed. Results The natural anatomical corridor provided by the cavernous sinus is used to get access to the posterior clinoid by mobilizing the pituitary gland in an interdural fashion. The medial wall of the cavernous sinus is preserved intact and attached to the gland during its medial and superior mobilization. This provides protection to the gland, allowing for preservation of its venous drainage pathways. The inferior hypophyseal artery is transected to facilitate the manipulation of the medial wall of the cavernous sinus and pituitary gland. This approach was successfully performed in all patients, including 6 with chordomas, 5 with petroclival meningiomas, and 1 with an epidermoid tumor. No patient in this series had neurovascular injury related to the posterior clinoidectomy. There were no instances of permanent hypopituitarism or diabetes insipidus. Conclusions The authors introduce a surgical variant of the endoscopic endonasal posterior clinoidectomy approach that does not require intradural pituitary transposition and is more effective than the purely extradural approach. The endoscopic endonasal transcavernous approach facilitates the removal of prominent posterior clinoids increasing the working space at the lateral recess of the interpeduncular cistern, while preserving the pituitary function.

BACKGROUND The endoscope is being introduced as an adjuvant to improve visualization of certain areas in open cranial surgery. OBJECTIVE To describe the endoscopic anatomy of common aneurysm sites and to compare it with the microsurgical anatomy. METHODS Pterional, anterior interhemispheric, and subtemporal approaches to the most common aneurysm sites were examined in cadaveric heads under the surgical microscope and with the endoscope. RESULTS The endoscopic view, particularly with the angled endoscopes, provides a significant improvement compared with the microscopic view, especially for poorly visualized sites such as the medial aspect of the supraclinoid carotid artery and its branches, the area below the anterior perforated substance and optic tract, and the carotid and basilar bifurcations. The endoscope aided in the early visualization of perforating branches at each aneurysm site except the middle cerebral artery. Small-diameter optics (2.7 mm) provided greater space for dissection and less potential for tissue damage in narrow places, whereas the larger 4-mm diameter optics provided better visualization and less panoramic distortion. The positioning of the endoscope for each aneurysm site is reviewed. CONCLUSION The endoscope provides views that complement or improve the microscopic view at each aneurysm site except the middle cerebral artery. Endoscopy training and a thorough knowledge of endoscopic vascular anatomy are essential to safely introduce endoscopic assistance in vascular surgery.

Introduction Large and even moderate sized, extra-axial cerebellopontine angle (CPA) tumors may fill this restricted space and distort the regional anatomy. It may be difficult to determine even with high resolution magnetic resonance imaging (MRI) if the tumor is dural-based, or what the nerve of origin is if a schwannoma. While clinical history and exam are helpful, they are not unequivocal, particularly since many patients present with a myriad of symptoms, or conversely an incidental finding. We present an atypical appearing, asymptomatic CPA tumor, ultimately identified at surgery to be a trigeminal schwannoma. Case History A 40-year-old man presented with new-onset seizure. MRI identified an incidental heterogeneously contrast-enhancing CPA lesion (Fig. 1A–D). The tumor was centered on the internal auditory canal (IAC) with no tumor extension into Meckel's cave, IAC or jugular foramen. Audiometry demonstrated 10db of relative left-sided hearing loss with 100% word recognition. Physical examination was negative for focal neurologic deficits. A retrosigmoid craniotomy was performed and an extra-axial, yellow-hued mass was encountered and resected, which was ultimately confirmed to originate from the trigeminal nerve (Video 1). Gross total resection was achieved, and the patient recovered from surgery with partial ipsilateral trigeminal sensory loss and no other new neurologic deficits. Conclusion Pure CPA trigeminal schwannomas are rare, but should be considered in the differential for enhancing CPA lesions. Although, Meckel's cave involvement is frequently observed, it is not universal, and pure CPA schwannomas of all cranial nerves IV–XII have been reported in the literature.The link to the video can be found at: https://youtu.be/AlodYCu70F8.

A 52-yr-old woman was referred to a tertiary medical center for evaluation of 2 yr of progressive visual symptoms and 1 yr of retro-orbital pressure. Her ophthalmologic exam was unrevealing except for mild asymmetrical impairment in color perception. A gadolinium contrast-enhanced magnetic resonance image of the head showed a left extraconal orbital apex lesion consistent with cavernous hemangioma. Computed tomography reveled bony remodeling of the medial-inferior orbital walls with superior orbital fissure expansion. The lesion was endoscopically resected and confirmed by pathological analysis. The endoscopic approach is demonstrated in detail, including correlation with cadaveric anatomic specimens‡. During the approach, a rescue nasoseptal flap was raised in case the orbit required further support after tumor resection, but was replaced as this was not needed. This patient had a brief period of postoperative diplopia, which resolved 1 wk after surgery. Her subjective visual deficits and pressure have also resolved. Advantages of the endoscopic approach include improved direct visualization of the lesion, lack of external skin incisions, avoidance of significant neurovascular retraction, and shorter hospital stays than alternative orbitotomy or craniotomy approaches. This 4-handed approach demands endoscopic expertise of 2 surgeons, and is often performed by rhinology-neurosurgery or rhinology-ophthalmology surgical teams. The risk of postoperative diplopia should be discussed with the patient during informed consent. ‡ Anatomic specimen photography courtesy Dr Peris-Celda.

Objectives This video was aimed to describe the relevant anatomy and key surgical steps of retrosigmoid approach for gross total resection of a medium-sized vestibular schwannoma (VS). Design The procedure is described in a surgical instructional video. Setting The surgery took place at a tertiary skull base referral center. Participant Patient is a 63-year-old woman who reported with nonserviceable hearing (Pure Tone Average 60 dB Hearing level, Word Recognition Score 45%), occasional tinnitus, and a VS in the left cerebellopontine angle (CPA), extending into internal auditory canal (IAC), measuring 1.7 cm parallel to the petrous temporal bone. Main Outcome Measures The VS was resected by retrosigmoid approach. Results The surgery results gross total resection of the VS with postoperative House–Brackmann grade 1 facial nerve function and no postoperative complications. Conclusion The retrosigmoid approach is a good strategy to remove VS involving the CPA and the IAC.The link to the video can be found at: https://youtu.be/B6K_UkrKitg.

Objectives This video was aimed to describe the surgical indications, relevant anatomy, and surgical steps of retrosigmoid approach for resection of a large cystic vestibular schwannoma (VS). Design The operative steps are described in a surgical instructional video. Setting The surgery took place at a tertiary skull base referral center. Participant Patient is a 62-year-old man who reported with right sided profound hearing loss with no word recognition, progressive dizziness and tinnitus, excruciating burning pain in the V2 distribution of right trigeminal nerve, wide-based gait, and a right cerebellopontine angle (CPA) cystic VS measuring 3.3 cm. Main Outcome Measures The large cystic VS was resected through retrosigmoid approach. Results The surgery resulted in removal of the large cystic VS with initial delayed facial weakness that completely resolved (House Brackmann grade 1) by 3 month follow-up. The patient had no other postoperative complications and is convalescing well from the procedure. Conclusion Cystic VS presents some unique challenges compared with their solid counterparts. The cystic tumor capsule may be very adherent to the adjacent structures, and distinguishing thin cyst walls from the arachnoid of the CPA, can be quite challenging. The retrosigmoid approach provides adequate surgical exposure for VS tumor resection.The link to the video can be found at: https://youtu.be/sFNvRWG465Q.

Background Carefully tailoring the transclival approach to the involved parts of the upper, middle, or lower clivus requires a precise understanding of the focal relationships of the clivus. Objective To develop an optimal classification of the upper, middle, and lower clivus and to define the extra and intracranial relationships of each clival level. Methods Ten cadaveric heads and 10 dry skulls were dissected using the surgical microscope and endoscope. Results The clivus is divided into upper, middle, and lower thirds by 2 endocranial landmarks: the dural pori of the abducens nerves and the dural meati of the glossopharyngeal nerves. Useful surgical landmarks exposed in the transnasal approach that aid in locating the junction of the clival divisions are the lower limit of the paraclival segment of the internal carotid artery, which is located 4.9 mm above the posterior opening of the vidian canal, and the pharyngeal tubercle. The upper, middle, and lower clival approaches provide access to the anterior midline parts of the previously described upper, middle, and lower neurovascular complexes in the posterior fossa. The nasal and nasopharyngeal relationships important in expanding the transnasal approach to the borders of the clivus are reviewed. Conclusion The transclival approach can be carefully tailored to expose focal lesions in the anterior part of the posterior fossa.

Object Foramen ovale (FO) puncture allows for trigeminal neuralgia treatment, FO electrode placement, and selected biopsy studies. The goals of this study were to demonstrate the anatomical basis of complications related to FO puncture, and provide anatomical landmarks for improvement of safety, selective lesioning of the trigeminal nerve (TN), and optimal placement of electrodes. Methods Both sides of 50 dry skulls were studied to obtain the distances from the FO to relevant cranial base references. A total of 36 sides from 18 formalin-fixed specimens were dissected for Meckel cave and TN measurements. The best radiographic projection for FO visualization was assessed in 40 skulls, and the optimal trajectory angles, insertion depths, and topographies of the lesions were evaluated in 17 specimens. In addition, the differences in postoperative pain relief after the radiofrequency procedure among different branches of the TN were statistically assessed in 49 patients to determine if there was any TN branch less efficiently targeted. Results Most severe complications during FO puncture are related to incorrect needle placement intracranially or extracranially. The needle should be inserted 25 mm lateral to the oral commissure, forming an approximately 45° angle with the hard palate in the lateral radiographic view, directed 20° medially in the anteroposterior view. Once the needle reaches the FO, it can be advanced by 20 mm, on average, up to the petrous ridge. If the needle/radiofrequency electrode tip remains more than 18 mm away from the midline, injury to the cavernous carotid artery is minimized. Anatomically there is less potential for complications when the needle/radiofrequency electrode is advanced no more than 2 mm away from the clival line in the lateral view, when the needle pierces the medial part of the FO toward the medial part of the trigeminal impression in the petrous ridge, and no more than 4 mm in the lateral part. The 40°/45° inferior transfacial–20° oblique radiographic projection visualized 96.2% of the FOs in dry skulls, and the remainder were not visualized in any other projection of the radiograph. Patients with V1 involvement experienced postoperative pain more frequently than did patients with V2 or V3 involvement. Anatomical targeting of V1 in specimens was more efficiently achieved by inserting the needle in the medial third of the FO; for V2 targeting, in the middle of the FO; and for V3 targeting, in the lateral third of the FO. Conclusions Knowledge of the extracranial and intracranial anatomical relationships of the FO is essential to understanding and avoiding complications during FO puncture. These data suggest that better radiographic visualization of the FO can improve lesioning accuracy depending on the part of the FO to be punctured. The angles and safety distances obtained may help the neurosurgeon minimize complications during FO puncture and TN lesioning.

Objective Reconstruction of large clival defects after an endoscopic endonasal procedure is challenging. The objective is to analyze the morphology, indications, and limitations of the extended nasoseptal flap, which adds the nasal floor and inferior meatus mucosa, compared with the standard nasoseptal flap, for clival reconstruction. Design Twenty-seven sides of formalin-fixed anatomical specimens and 13 computed tomography (CT) scans were used. Under 0-degree endoscopic visualization, a standard flap on one side and an extended flap on the other side were performed, as well as exposure of the sella, cavernous sinus, and clival dura mater. Coverage of both flaps was assessed, and they were incised and extracted for measurements. Results The extended flap has two parts: septal and inferior meatal. The extended flaps are 20 mm longer and add 774 mm 2 of mucosal area. They cover a clival defect from tuberculum to foramen magnum in 66.6% cases and from below the sella in 91.6%. They cover both parasellar and paraclival segments of the internal carotid arteries. The lateral inferior limits are the medial aspect of the hypoglossal canals and Eustachian tubes. CT scans can predict the need or limitation of an extended nasoseptal flap. Conclusions The nasal floor and inferior meatus mucosa adds a significant area for reconstruction of the clivus. A defect laterally beyond the hypoglossal canals is not likely covered with this variation of the flap. Preoperative CT scans are useful to guide the reconstruction techniques.

Objectives Infraorbital nerve (ION) decompression, excision to remove intrinsic tumors, and resection with oncological margins in malignancies with perineural invasion or dissemination are usually accomplished with an open approach. The objective is to describe the surgical anatomy, technique, and indications of the endonasal endoscopic approach (EEA) to the ION with nasolacrimal duct preservation. Design Eleven sides of formalin-fixed specimens were dissected. An anterior maxillary antrostomy was performed. The length of the ION prominence within the sinus and anatomic features of the covering bone were studied. A 45-degree endoscope visualized the infraorbital prominence endonasally. An angled dissector and dural blade allowed for dissection and resection of the ION ipsilaterally and contralaterally. Results The bone features of the ION prominence allowed for ipsilateral dissection in 10 out of 11 sides. In one case with the ION surrounded by thick cortical bone, the dissection could only be started by drilling contralaterally. The 45-degree endoscope visualized 92.2% and 100% of the length of the nerve using the ipsilateral and contralateral nostrils, respectively. Ipsilaterally, 83% of its length was resected, and 96.3% was resected contralaterally. Conclusion The ION can be approached using an ipsilateral EEA with nasolacrimal duct preservation in most cases. The contralateral approach provides a wider angle to access the ION. This technique is primarily indicated in cases where the EEA can be used for tumor resection and oncological margins within the ION.

Background Postoperative cerebrospinal fluid leak after endoscopic pituitary surgery ranges from 1.9% to 10% in different series. Vascularized flaps have reduced the incidence of leak; however, this carries nasal morbidity. This study presents a technique for sellar reconstruction with free mucosal graft from the nasal cavity floor including inferior meatus mucosa. This technique aims to standardize sellar reconstruction without the use of the nasoseptal flap and to keep the advantage of mucosal coverage of the defect in all cases. Methods Fifty consecutive patients who had endoscopic surgery for pituitary tumors and reconstruction with nasal cavity floor free mucosal graft were retrospectively reviewed. There were a total of 50 patients with postoperative follow-up from 3 to 16 months. Collagen dural graft was used inlay and free mucosal graft overlay to cover the sellar defect. No fat grafts or lumbar drains were used. A Sinonasal Outcome Test-22 (SNOT-22) was performed before, 1 and 3 months after surgery. Results There were 40% detected intraoperative leaks and no postoperative leaks. Nasal endoscopy performed at 1 month follow-up showed complete healing of the graft to the skull base and near total or complete mucosalization of the donor site. No significant difference was found in the SNOT-22 comparing the total preoperative and 1-month scores. Conclusions The nasal cavity floor free mucosal graft is an easy and safe technique, with minimal nasal morbidity. There were no postoperative cerebrospinal fluid leaks, despite aggressive tumor resection. No lumbar drains or fat graft were used. The harvest of mucosal graft does not worsen the quality of life measured with the SNOT-22 test.

Background Spinal cord stimulation (SCS) has been a valuable resource for the treatment of chronic, nonmalignant pain that persists in the face of maximal medical management. A recent study demonstrated efficacy of cervical SCS in a multicenter registry. Here, in our single center study, we are able to delve into patient specifics, explore outcomes with percutaneous vs. paddle implants, and examine impact of patient symptomatology. Methods We prospectively collected data on subjects who underwent cervical SCS via numeric rating scale (NRS), McGill Pain Questionnaire, Oswestry Disability Index (ODI), and Beck Depression Inventory. Subjects completed this battery pre-operatively, at six months and at one year. Data were analyzed via repeated measures ANOVA, bivariate correlation analysis, and paired t-tests. Results In 30 consecutive subjects, 24 had a complete data set. The diagnosis was failed neck surgery syndrome (13%), Complex regional pain syndrome (29%), and neuropathic pain (58%). Compared with baseline, NRS score significantly improved at six months (p = 0.021) and one year (p = 0.047). ODI score also improved at one year (p = 0.009). At both six months and one year, subjects with percutaneous implants reported significantly less disability on ODI (p = 0.016 and 0.034, respectively), as compared with those who received paddle implants. There was no difference in NRS score or any other outcome measure based on type of implant. Diagnosis or region of pain did not correlate with any measure of outcome. Discussion We demonstrate that neck and arm pain can be improved with cervical SCS at six month and one-year follow-ups. Both percutaneous and paddle implants have benefit. We tend to place percutaneous implants for radicular pain and retrograde C1-2 paddles for axial pain that is ineffectively treated during the trial.

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas., We are grateful for the financial support from PI10/01069, PI14/00077, and the ‘Miguel Servet Program’ CP11/00147 (AAS), PI-01495 (RP), and PI12/00775) (PSG) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain, supported by FEDER funds, and Ministerio de Economía y Competitividad, Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD12/0036/0027) (PSG).

Objectives/Hypothesis: The aim of this study was to investigate and compare the surgical anatomy of two different routes to access and drain petrous apex (PA) cholesterol granulomas: the expanded endonasal approach (EEA) and the transcanal infracochlear approach (TICA). Study Design: Anatomic and radiologic study. Methods: The EEA and TICA to the PA were performed in 11 anatomic specimens with the assistance of imaging guidance. The PA was categorized into three zones: superior PA, anterior-inferior PA, and posterior-inferior PA. The maximum drainage window achieved by each approach was calculated using the imaging studies of each anatomic specimen. Results: The EEA was able to reach superior PA and anterior-inferior PA in all specimens and posterior-inferior PA in 90%. The TICA did not provide access to superior PA in any case. The TICA was suitable to reach anterior-inferior PA in 80% of specimens and posterior-inferior PA in 60%. Based on the radiologic study, the EEA provided a drainage window three times larger than the TICA. Conclusions: The transnasal approach provides reliable access to the PA when combined with internal carotid artery exposure and allows for large drainage window. The transcanal approach is less versatile and more limited than the transnasal approach but provides access to the most posterior and inferior portion of the PA without Eustachian tube transection. Here we propose a new surgical classification that may help to decide the most suitable approach to the PA according to the location and extension of the lesion. Laryngoscope, 2012

Object Iatrogenic injury of the V2 segment of the vertebral artery (VA) is a rare but serious complication and can be catastrophic. The purpose of this study was to characterize the relationship of the V2 segment of the VA to the surrounding anatomical structures and to highlight the potential site and mechanisms of injury that can occur during common neurosurgical procedures involving the subaxial cervical spine. Methods Ten adult cadaveric specimens (20 sides) were included in this study. Quantitative anatomical measurements between selected landmarks and the VA were obtained. In addition, lateral mass screws were placed bilaterally, from C-3 to C-7, reproducing either the Magerl technique or a modified technique. The safety angle, defined as the axial deviation from the screw trajectory needed to injure the VA, and the distance from the entry point to the VA were measured at each level for both techniques. Results The VA coursed closer to the midline at C3–4 and C4–5 (mean distance [SD] 14.9 ± 1.1 mm) than at C2–3 or C5–6. Within the intertransverse space it coursed closer to the uncinate processes of the vertebral bodies (1.8 ± 1.1 mm) than to the anterior tubercle of the transverse processes (3.4 ± 1.6 mm). The distance between the VA and the uncinate process was less at C3–6 (1.3 ± 0.7 mm) than at C2–3 (3.3 ± 0.8 mm). The VA coursed on average at a distance of 11.9 ± 1.7 mm from the anterior and 4.2 ± 2.6 mm from the posterior aspect of the intervertebral disc space. Lateral mass screw angles were 25° lateral and 39.1° cranial for the Magerl technique, and 36.6° lateral and 46.1° cranial for the modified technique. The safety angle was greater and screw length longer when using this modified technique. Conclusions The relation of the V2 segment of the VA to anterior procedures and lateral mass instrumentation at the subaxial cervical spine was reviewed in this study. A detailed anatomical knowledge of the V2 segment of the VA combined with careful preoperative imaging is mandatory for safe cervical spine surgery.

Objectives/Hypothesis: Measure the dimensions of the nasoseptal (NS) flap and the anterior skull base (ASB) defect. Verify whether the flap is sufficient to cover the defect. Study the anatomy of the septal artery (SA). Study Design: Anatomical and radiological study. Methods: After endoscopic craniofacial resection, sufficiency of the flap to cover the ASB defect was assessed. The SA was dissected. The number of branches in the pedicle and the distance between the artery and the sphenoid ostium were noted. Radiologic study analyzing CT scans of 30 patients for comparison among measurements of the NS flap and the ASB defect was performed. Results: In all cases the flap was sufficient to cover the ASB. Two branches of the SA were found in the pedicle in 71.4%. The distance between the SA and the sphenoid ostium was 9.3 mm. The reconstruction area of the flap (17.12 cm2) was larger than the defect area (8.64 cm2) (P < .001). The difference between the superior length of the flap and the anterior-posterior distance of the defect was ≤5 mm in 26.7%. Comparison between the anterior flap width and the anterior defect width revealed that in 33% the difference was ≤5 mm. Conclusions: The dimensions of NS flap are sufficient to cover completely the ASB defect. The anterior edge of the defect presents increased risk for failure in coverage. Additional width adding the nasal floor mucosa to the flap is important to decrease the risk of gap in the anterior orbit-orbit defect. It is more common to find two branches of the SA in the pedicle. Laryngoscope, 121:2514–2520, 2011

Craniopharyngiomas tend to arise from the anterior superior margin of the pituitary gland and they may grow in the sellar and parasellar areas involving the pituitary gland and infundibulum, hypothalamus, optic nerves and chiasm, and ventricles. The tumor is usually supplied by perforating arteries arising from the internal carotid, anterior and posterior communicating, and anterior cerebral arteries. Surgical classifications of craniopharyngiomas are based on their relation to the chiasm, diaphragma sellae, third ventricle, and/or infundibulum. This classification is important in planning surgical strategies. This chapter focuses on the sellar, suprasellar, and parasellar anatomy basic to craniotomies or expanded endoscopic endonasal approaches.

To conceive and critically evaluate an adaptation of the split calvarial osteopericranial flap for reconstruction following endoscopic endonasal resection of the anterior skull base.Cadaveric anatomic study.Five cadavers were embalmed with methanol, and vasculature was injected with latex. Endoscopic endonasal resection of the anterior skull base was performed, followed by reconstruction with a unilateral osteopericranial flap and a contralateral conventional pericranial flap.Rigid reconstruction was achieved in all specimens. Osteoplastic flap harvest was made more reliable by drilling the diploe below the graft with a curved bur. Dimensions of the bony flap were ideally shorter and wider than the defect, allowing for flap inset and rigid support by the orbits without compromise of the flap vascular supply. Endoscopic inset of the flap is feasible via nasion-frontal osteotomy and inlay technique.Rigid anterior skull base reconstruction via split calvarial osteopericranial flap is adaptable to current endoscopic techniques. This provides more anatomic reconstruction than current methods and may lead to decreased complication rates following anterior skull base resection.

BACKGROUND: Neurosurgical management of cerebellar lesions remains challenging. Thus, it is important to have sound knowledge of the microsurgical anatomy of the cerebellum and dentate nucleus (DN) and to define different types of exposure in a variety of surgical interventions. OBJECTIVE: To examine the anatomy of the DN from a neurosurgical viewpoint using fiber tracking techniques. METHODS: Ten formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under 6 to 40 magnification. Anatomic images were created with 3-dimensional diffusion tensor imaging. The relationships of the DN to tentorium and suboccipital and lateral surfaces of the cerebellum and its spatial positioning relative to different surgical approaches in the cerebellum and fourth ventricle were examined. The fiber tracts terminating at and surrounding the DN were defined. RESULTS: The DN is at greater risk of being injured in the transvermian and supratonsillar approaches to the cerebellum and fourth ventricle, with lesser risk in the telovelar and subtonsillar approaches. Superior approaches are safer compared with other approaches. CONCLUSION: The DN represents an important anatomic structure in surgical interventions involving the posterior fossa, particularly in the elderly because of the common occurrence of atrophy-related problems in this age group. Functionally and anatomically, the DN is closely related to the superior and middle cerebellar peduncles. The inferior cerebellar peduncle poses positional risks because it follows an anterior and superior course relative to the DN. The telovelar approach is a safer procedure for interventions involving the pathological lesions of the fourth ventricle floor.

Background Olfactory schwannomas of the anterior cranial base (ACB) are rare tumors, and their association with hereditary hemorrhagic telangiectasia (HHT) has not previously been described. The majority of ACB schwannomas arise from the sinonasal tracts and may demonstrate intracranial extension. We report a case of an olfactory schwannoma-dense adherence to the basal frontal lobe. Complete tumor resection was performed through a unilateral extended endonasal endoscopic approach with preservation of the contralateral olfactory bulb. Anterior cranial base repair was achieved with the use of a mucoperichondrial vascularized pedicled nasoseptal flap. Clinical Presentation A 25-year-old woman with a history of migraines presented with unilateral epistaxis and progressive worsening of her headache symptoms. The patient had a history of HHT. Nasal endoscopy showed mild telangiectasias, but no clear evidence of a mass. A computerized tomographic scan showed a large left-sided expansile lesion in the left ethmoid region with expansion and remodeling of the anterior cranial base and medial left orbit. Magnetic resonance imaging with contrast showed the mass to be avidly enhancing. Angiography was performed and demonstrated a mild vascular blush. Conclusions We report a rare case of HTT and olfactory schwannoma completely resected with a unilateral extended endoscopic endonasal approach. Reconstruction was performed with the use of nasoseptal flap. This is the first reported single-stage fully endoscopic endonasal unilateral approach for resection of an olfactory schwannoma with preservation of the contralateral olfactory cleft. The patient's sense of smell and taste was maintained after surgery.

Glioblastoma multiforme (GBM) is the most lethal type of brain tumour in the adult humans. The cancer-initiating cell (CIC) hypothesis supports the notion that failures in current approaches to GBM treatment might be attributed to the survival of the CIC subpopulation. Recent evidence shows the idea that using CIC-enriched cell lines derived from human GBM as new targets for drug discovery programs, may improve the chance of successfully translating the basic research findings into clinical trials. Although this approach appears promising, many important biological and technical issues (characterization of functional CIC markers, inter- and intra-tumoral CIC heterogeneity, and isolation and maintenance inconsistency) need to be resolved.

Measure the dimensions of the nasoseptal (NS) flap and the anterior skull base (ASB) defect. Verify whether the flap is sufficient to cover the defect. Study the anatomy of the septal artery (SA).Anatomical and radiological study.After endoscopic craniofacial resection, sufficiency of the flap to cover the ASB defect was assessed. The SA was dissected. The number of branches in the pedicle and the distance between the artery and the sphenoid ostium were noted. Radiologic study analyzing CT scans of 30 patients for comparison among measurements of the NS flap and the ASB defect was performed.In all cases the flap was sufficient to cover the ASB. Two branches of the SA were found in the pedicle in 71.4%. The distance between the SA and the sphenoid ostium was 9.3 mm. The reconstruction area of the flap (17.12 cm(2) ) was larger than the defect area (8.64 cm(2) ) (P.001). The difference between the superior length of the flap and the anterior-posterior distance of the defect was ≤ 5 mm in 26.7%. Comparison between the anterior flap width and the anterior defect width revealed that in 33% the difference was ≤ 5 mm.The dimensions of NS flap are sufficient to cover completely the ASB defect. The anterior edge of the defect presents increased risk for failure in coverage. Additional width adding the nasal floor mucosa to the flap is important to decrease the risk of gap in the anterior orbit-orbit defect. It is more common to find two branches of the SA in the pedicle.

e22118 Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults accounting for -75% of astrocytic tumors. It corresponds to WHO grade IV glioma. Hedgehog (Hh)-Gli p...

The sellar wall of the sphenoid sinus and its recesses have been previously studied, but their intracranial relationships to the diaphragma sellae, tuberculum, clinoid segment of the internal carotid artery, chiasmatic sulcus, and middle clinoid process need further definition.To describe these intra- and extracranial relationships of the recesses in the anterior sellar wall.The middle clinoid was studied in 132 parasellar areas of dry crania. Thirty-eight parasellar areas of formalin-fixed/silicone-colored specimens were dissected. After transsphenoidal endoscopic exposure, the optic, carotid, and sellar prominences; lateral opticocarotid and tuberculum recesses; and caroticosellar and medial opticocarotid points were identified. High-speed drills opened 1-mm perforations at these points to allow study of intracranial relationships.Two recesses and 2 junction points can be recognized in the sphenoid sinus: lateral opticocarotid and tuberculum recesses and medial opticocarotid and caroticosellar points. The lateral opticocarotid recess corresponds to the optic strut base, and the clinoid segment of the internal carotid artery is located medially. The diaphragma sellae attachment is at the level of the tuberculum recess, which in 50% of cases corresponds to the tuberculum. A middle clinoid in base or height greater than 1.5 mm is present in 21.1% and a caroticoclinoid ring in 3%. The middle clinoid is 1 mm inferior and lateral to the caroticosellar point and 4.7 mm inferior to the medial opticocarotid point.An understanding of the intra- and extracranial relationships of the recesses of the sphenoid sinus will aid in accurately directing transsphenoidal approaches.

Introduction: Glioblastoma (GB) is the most common primary malignant brain tumor in adults accounting for 12% to 15% of all intracranial neoplasms and 60% to 75% of astrocytic tumors. It corresponds to WHO grade IV glioma, typically affects subcortical white matter of cerebral hemispheres and less than a half of patients survive more than 1 year. Since the isolation of tumor stem cells (TSC) from GB, numerous works have been focusing on this subpopulation of cells instead of the tumor bulk. It has been demonstrated that TSC derived from glioblastomas are closer to the genotype and phenotype of tumors they come from than serum-cultured cell lines since serum causes irreversible differentiation of traditional GB cell lines. Moreover, TSC bear remarkable similarity to normal neural stem cells (NSC). NSC renewal and progenitor differentiation are regulated by the niche or microenvironment surrounding them. Certain signals involved classically in embryonic development like Notch, BMP, Noggin, Eph/ephrins and Hedgehog-Gli (Hh-Gli) seem to be important in maintaining these neurogenic niches and might play an important role in brain tumors. Gli1, the final effector of Hh-Gli pathway, was originally isolated from a human glioma cell line. A number of groups have some doubts regarding the role of Gli in glioma biology. This assumption may arise from the use of cerebellum samples (with high Gli expression) as control in cDNA amplification experiments. Recent works, however, have confirmed the general presence of an active Hh-Gli pathway in GB by different means. GB-derived neurospheres of GB expressing activation of Hh-Gli, treated with cyclopamine (Hh-Gli inhibitor) showed 40% to 60% reduction in growth and no new neurospheres formation when the inhibitor was retired. The aim of the present study is to analyze the expression of Hh-Gli intermediates in a series of human GB and TSC derived from some of them. We have compared the levels of transcript with controls of white and grey matter and found important correlations with clinical characteristics of the patients. Materials and Methods: We studied 43 astrocytomas (39 high-grade and 4 low-grade) and 12 controls: 4 white matter, 4 grey matter and 4 hippocampus (from adult epileptic patients with mesial temporal sclerosis), one culture of NSC from white matter and NSC from hippocampus. After the histological diagnosis, TSC were cultured. We designed primers of the intermediates of the Hh-Gli pathway: Patch1, Smoothened (Smo), Gli1, Gli2, Sufu, and the stem cell marker CD133. The transcription of these genes in tumours, TSC and controls was quantified with real-time PCR. We demonstrated the multipotentiality of the TSC with differentiation assays in vitro and oncogenicity in athymic mice. Demographic, clinical and radiologic characteristics were obtained from the patient's clinical history. All the data were statistically analyzed with SPSS software. Results: 26 of 43 tumors showed disregulation of some of the intermediates of Hh-Gli. Some of the intermediates: Gli1, Gli2 and Smo were significantly upregulated in tumors compared to controls. The analysis of 3 lineages of TSC showed an increase of effectors of Hh-Gli with serial passages in vitro. Furthermore, several important clinical characteristics were related to Hh-Gli: Sufu, a tumor suppressor, was upregulated in disseminated tumors across white matter fibers at diagnosis and Smo with an increased tumor size, both factors involved in patient's prognosis. Conclusions: This study demonstrates that most glial neoplasms show disregulation of Hh-Gli in tumors and TSC and opens an important investigation line towards drug discovery with Hh-Gli inhibitors. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B9.

O conhecimento do sistema de drenagem sanguínea intracraniano é indispensável para intervenções cirúrgicas. Permanece confusa e negligenciada a descrição do canal vascular entre o seio cavernoso e o plexo pterigóideo, alguns autores definindo-o como uma veia, plexo ou seio da dura-máter. Dessa forma, esta pesquisa teve como objetivo descrever seus aspectos anatômicos, topográficos e microscópicos. Considerando as análises macroscópicas, foram usados 50 blocos anatômicos da base do crânio de humanos adultos, 170 crânios secos e 1.000 imagens de tomografia computadorizada (TC). Somado a isso, a fossa média do crânio de três espécimes fixadas em álcool 70% foram dissecadas e documentadas seguindo a metodologia e técnica de dissecção propostas pelo Dr. Albert L. Rhoton Jr. Os componentes microscópicos e ultraestruturais do canal venoso foram avaliados pelas colorações histológicas de Hematoxilina e Eosina, Picrosirius, Weigert e Tricrômio de Masson, assim como por Microscopia Eletrônica de Varredura. O Seio Emissário do Forame Oval (SEFO) esteve sempre presente entre o seio cavernoso e o plexo pterigóideo em ambos antímeros, com trajeto inferior passando internamente pelos forames oval e/ou venoso (de Vesalius), anteriormente ao ramo mandibular do nervo trigêmeo e sua raiz motora. O forame venoso (FV) foi encontrado como rota alternativa de uma pequena projeção do SEFO. Durante as análises o FV foi observado em 46,8% das TCs (25,4% bilateral e 21,4% unilateral) e em 45,2% dos crânios secos (18,8% bilateral e 26,4% unilateral). Em 9,5% das tomografias e 21,1% dos crânios foi observado uma abertura na face externa da fossa média do crânio sem comunicação com sua face interna, portanto não sendo considerada como forames verdadeiros. A organização histológica do SEFO e de seu ramo em direção ao FV foi semelhante ao encontrado no seio transverso, com fibras colágenas dispostas em sentido transversal e longitudinal, não sendo observadas as camadas média e externa, características de veias. Sua camada elástica se limitava a uma fina e discreta marcação próxima ao lúmen do canal. Assim como observado no seio transverso, ambos canais apresentaram células em formato losangular e com núcleos centrais arredondados. A injeção dos espécimes com látex colorido, fotodocumentação 3D e High Dynamic Range (HDR) conforme descrito por Dr. Rhoton é primordial para o ensino anatômico e neurocirúrgico. Para tanto, foi importante respeitar todas as etapas de canulação, lavagem, injeção do látex, dissecção e fotodocumentação macroscópica de modo a garantir a eficiência e qualidade das imagens ao final do processo. A técnica HDR contribuiu melhorando a nitidez, brilho e contraste das imagens finais que podem ser utilizadas para os diferentes tipos de projeções 3D as quais devem ser escolhidas considerando o objetivo da apresentação e quantidade do público alvo. Em síntese, o SEFO foi uma estrutura constante sempre comunicando o seio cavernoso com o plexo pterigóideo, sua presença não foi dependente do conteúdo do FV e ambos canais apresentaram estrutura microscópica e ultraestrutural semelhante aos seios da duramáter. Ambos canais devem ser considerados durante procedimentos cirúrgicos na fossa média do crânio e como rotas de disseminação de infecções do meio extracraniano para a cavidade do crânio. The knowledge of intracranial blood drainage system is indispensable during surgical interventions.The description of the vascular system located between the cavernous and pterygoid plexus remains confused and neglected. Some researchers define it as a vein, a plexus or as a dural sinus. Therefore, this work aimed to describe its anatomy, topographic and microscopic aspects. Concerning the macroscopic aspects, the study included the analysis of fifty anatomic blocks of the skulls base from adult humans, 170 dry skulls and 1.000 computed tomography (CT) images. In addition, the middle cranial fossa of three specimens were dissected and documented accordingly to the metodology proposed by Dr. Albert L. Rhoton Jr. Microscopic and ultraestrucutral features of the aforementioned venous channel were evaluated using histological samples stained using Hematoxylin and Eosin, Picrosirius red, Weigert and Masson`s trichrome. Besides that, scanning electron microscopy was performed. The Emissary Sinus of Foramen Ovale (ESFO) was always present between the cavernous sinus and the pterygoid plexus on both sides, with its inferio path passing through the foramen ovale and/or sphenoidal emissary foramen (of Vesalius), cranially to the mandibular nerve and the motor root of the trigeminal nerve. The sphenoidal emissary foramen (SEF) was found as an alternative pathway to a small projection of the ESFO. During our analysis, the SEF was observed in 46,8% CTs (25,4% bilateral and 21,4% unilateral), and in 45,2% dry skulls (18,8% bilateral e 26,4% unilateral). In 9,5% CTs and 21,1% dry skulls it was observed an opening on the external surface of the skulls base without communication with the inner surface, therefore not being considered as a truly foramina. The histological arrangement of the ESFO and its branches towards the SEF ressembled the ones found in the transverse sinus with the layers of collagen fibers organized on both transversal and longitudinal directions. It was not possible to identify the middle and adventitial layers, features characteristic of veins; the elastic layer was very thin, near the lumen. Also as found on transverse sinus, ESFO was composed with rhombus shape cells with rounded cell nuclei. Specimens injection with latex, 3D and HDR photodocumentation as described by Dr. Rhoton are of paramount importance to anatomy and neurosurgery teaching. So, it was important to respect all steps of the process: cannulation, flushing, latex injection, dissection and macroscopic photodocumentation to garantee the good quality of all images at the end of the process. HDR technique improved the shapeness, brightness, and contrast of the images final version, which can be used on different 3D presentations accordingly to their goals and target-audience. In summary, the ESFO was a frequent observed structure, always communicating the cavernous sinus with the pterygoid plexus. Its presence does not depend on SEF`s content, both channels presented microscopically and the ultrastructure ressembled those of a dural sinus. Thus, both channels should be considered during surgial approaches in the middle cranial fossa and, it works as a route for infectious to spread from extracranial sites to cranial cavity.