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Background Impairment of facial nerve (FN) function is a common postoperative complication in surgical resections of Vestibular Schwannomas (VS). Diffusion tensor imaging (DTI) tractography creates in vivo imaging of the anatomical location of white matter tracts that can be preoperatively used to visualize the displaced FN. We present an analysis of patients who underwent DTI tractography imaging prior to VS resection. Methods Patient charts were reviewed from March 2012 to April 2015 who underwent DTI tractography prior to surgical resection for VS. Reliability of this measure was compared to the intraoperative FN location as determined by the surgeon. House Brackmann (HB) score was used to assess facial nerve function. Results A total of 11 patients were included with a mean age of 43 years (range: 19–64) and mean follow-up length of 11.9 months (range: 3.1–34.2). The average maximum tumor diameter was 2.82 cm (range: 1.7–4.2). DTI tractography was accurate in 90.9% (10/11) of patients. Postoperatively, 72.7% (8/11) had a HB score of I or II, 18.2% (2/11) had a HB score of III, and 9.1% (1/11) had a HB score of IV. Conclusions Facial nerve visualization for VS resection can be accurately visualized using DTI tractography. This modality may lead to reduction of postoperative FN damage.

Objective The objective of this study was to examine the effect of cochlear dose on hearing preservation in stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) for vestibular schwannoma (VS). Design This is a retrospective case–control study. Setting This study was completed at the Ronald Reagan UCLA Medical Center, a university-affiliated tertiary care center. Participants Patients who underwent SRS (marginal dose of 12 Gy) or fSRT (marginal dose of 50.4 Gy) procedures for VS were included in the study. Main Outcome Measures The main outcome measure was hearing preservation. Audiometric data, when available, were used to determine the level of hearing according to the Gardner Robertson scale. Results A total of 38 patients (14 SRS and 24 fSRT) were analyzed. SRS patients with decreased hearing received a significantly higher minimum cochlear dose (7.41 vs. 4.24 Gy, p = 0.02) as compared with those with stable hearing. In fSRT patients, there were no significant differences in cochlear dose for patients with decreased hearing as compared with those with stable hearing. For SRS patients, who received a minimum cochlear dose above 6 Gy, there was a significant risk of decreased hearing preservation (odds ratio: 32, p = 0.02). Conclusion Higher minimum cochlear dose was predictive of decreased hearing preservation following SRS. Though the study is low powered, the radiation dose to the cochlea should be a parameter that is considered when planning SRS or fSRT therapies for patients with VS.

Superior semicircular canal dehiscence (SSCD) is a rare defect of the arcuate eminence that causes an abnormal connection between the superior semicircular canal and middle cranial fossa. Patients often present with a variety of auditory and vestibular symptoms. Trigger avoidance is the initial strategy, but surgery may be necessary in debilitating cases. We retrospectively reviewed SSCD patients undergoing repair via a middle fossa craniotomy between March 2011 and September 2015. Forty-nine patients undergoing 58 surgeries were identified. Autophony was the most common symptom at presentation (n=44; 90%). Mean follow-up was 10.9months, with 100% of patients reporting resolution of at least one symptom. Aural fullness was the most commonly resolved symptom following surgical repair (n=19/22; 86%). Hearing loss (n=11/25; 44%) and tinnitus (n=11/38; 29%) were the most common symptoms to persist following surgery. The most common symptom to develop after surgery was disequilibrium (n=4/18; 22%). Upon comparing the overall pre-operative and post-operative groups, the number of patients with autophony (p

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel minimally invasive modality that uses heat from laser probes to destroy tissue. Advances in probe design, cooling mechanisms, and real-time MR thermography have increased laser utilization in neurosurgery. The authors perform a systematic analysis of two commercially available MRgLITT systems used in neurosurgery: the Visualase® thermal therapy and NeuroBlate® Systems. Data extraction was performed in a blinded fashion. Twenty-two articles were included in the quantitative synthesis. A total of 223 patients were identified with the majority having undergone treatment with Visualase (n=154, 69%). Epilepsy was the most common indication for Visualase therapy (n=8 studies, 47%). Brain mass was the most common indication for NeuroBlate therapy (n=3 studies, 60%). There were no significant differences, except in age, wherein the NeuroBlate group was nearly twice as old as the Visualase group (p

Neurosurgery has undergone a technological revolution over the past several decades, from trephination to image-guided navigation. Advancements in virtual reality (VR) and augmented reality (AR) represent some of the newest modalities being integrated into neurosurgical practice and resident education. In this review, we present a historical perspective of the development of VR and AR technologies, analyze its current uses, and discuss its emerging applications in the field of neurosurgery.

OBJECTIVE Superior semicircular canal dehiscence (SSCD) is a rare disorder characterized by the formation of a third opening in the inner ear between the superior semicircular canal and the middle cranial fossa. Aberrant communication through this opening causes a syndrome of hearing loss, pulsatile tinnitus, disequilibrium, and autophony. This study analyzed the clinical outcomes of a single-institution series of patients with SSCD undergoing surgical repair by the same otolaryngologist and neurosurgeon. METHODS All patients who underwent SSCD repair at the University of California, Los Angeles, between March 2011 and November 2014 were included. All patients had their SSCD repaired via middle fossa craniotomy by the same otolaryngologist and neurosurgeon. Outcomes were analyzed with Fisher's exact test. RESULTS A total of 18 patients with a mean age of 56.2 years (range 27–84 years) and an average follow-up of 5.0 months (range 0.2–21.8 months) underwent 21 cases of SSCD repair. Following treatment, all patients (100%) reported resolution in ≥ 1 symptom associated with SSCD. Autophony (p = 0.0005), tinnitus (p = 0.0059), and sound- and/or pressure-induced dizziness (p = 0.0437) showed significant symptomatic resolution. Following treatment, 29% (2/7) of patients developed imbalance, 20% (1/5) of patients developed sound- and/or pressure-induced dizziness, and 18% (2/11) of patients developed aural fullness. Among patients with improved symptoms following surgical repair, none reported recurrence of symptoms at subsequent follow-up visits. CONCLUSIONS SSCD remains an underdiagnosed and undertreated condition. Surgical repair of SSCD using a middle fossa craniotomy is associated with a high rate of symptom resolution. Continued investigation using a larger patient cohort and longer-term follow-up could further demonstrate the effectiveness of using middle fossa craniotomy for SSCD repair.

The number of patient imaging studies has increased because of precautious physicians ordering scans when a vague symptom is presented; subsequently, the number of incidental meningiomas detected has increased as well. These brain tumors do not present with related symptoms and are usually small. MRI and computed tomographic scans most frequently capture incidental meningiomas. Incidental meningiomas are managed with observation, radiation, and surgical resection. Ultimately, a conservative approach is recommended, such as observing an incidental meningioma and then only radiating if the tumor displays growth, whereas a surgical approach is to be used only when proven necessary.

Surgeons need to visualize the facial nerve reliably in relation to the vestibular schwannoma (VS) in surgical planning. Diffusion tensor imaging (DTI) tractography has enabled unprecedented in vivo preoperative visualization. We collected data to measure the accuracy of DTI for an accurate location of the nerve in preoperative VS resection planning. A PubMed search for relevant studies was conducted. Inclusion criteria were gross total resection of VS, preoperative DTI identification of the facial nerve, and intraoperative cranial nerve localization by the surgeon. Exclusion criteria were tumors other than VS and unsuccessful preoperative location of the cranial nerve. Accuracy rate was calculated by comparing the intraoperative and preoperative locations detailed by DTI. The query identified 38 cases of VS that fit our inclusion criteria. Overall, 89% had surgical findings that agreed with the DTI location of the facial nerve. Of these cases, 32 patients had a postoperative House-Brackmann grade I or II. Our findings suggest that DTI is a reliable method for facial nerve imaging. Implementation of this technique may help decrease facial nerve injury during surgery. Limitations and further studies are needed to better understand what factors correlate with successful location of the facial nerve and DTI in patients with VS.

Management of intracranial chordomas remains challenging, despite improvements in microsurgical techniques and radiotherapy. Here, we analyzed the prognostic factors associated with improved rates of tumor control in patients with intracranial chordomas, who received either gross (GTR) or subtotal resections (STR). A retrospective review was performed to identify all patients who were undergoing resection of their intracranial chordomas at the Ronald Reagan University of California Los Angeles Medical Center from 1990 to 2011. In total, 57 patients undergoing 81 resections were included. There were 24 females and 33 males with a mean age of 44.6 years, and the mean tumor diameter was 3.36 cm. The extent of resection was not associated with recurrence. For all 81 operations, the 1 and 5 year progression free survival (PFS) was 87.5 and 40.4%, and 88.0 and 33.6% for STR and GTR, respectively (p=0.90). Adjuvant radiotherapy was associated with improved rates of PFS (hazard ratio [HR] 0.20; p=0.009). Additionally, age >45 years (HR 5.88; p=0.01) and the presence of visual deficits (HR 7.59; p=0.03) were associated with worse rates of tumor control. Tumor size, sex, tumor histology, and recurrent tumors were not predictors of recurrence. Younger age, lack of visual symptoms on presentation and adjuvant radiotherapy were associated with improved rates of tumor control following surgery. However, GTR and STR produced comparable rates of tumor control. The surgical management of intracranial chordomas should take a conservative approach, with the aim of maximal but safe cytoreductive resection with adjuvant radiation therapy, and a major focus on quality of life.

Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control ( p = 0.28). Higher dose SRT (> 6,000 cGy) ( p = 0.013) and younger age ( p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control.

The current standard treatment for glioblastoma multiforme (GBM) is surgery followed by chemotherapy and external radiation. Even with the standard treatment, the 2 year survival rate for GBM is less than 20%, making research for alternative treatments necessary. Transferrin receptor 1 (TfR1) controls the rate of cellular iron uptake by tuning the amount of iron delivered to the cells to meet metabolic needs. Kawabata et al. (J Biol Chem 1999;274:20826–32) cloned a second TfR molecule known as transferrin receptor 2 (TfR2) in 1999. Multiple experimental studies have documented increased expression of TfR1 on both proliferating cells and cells that have undergone malignant transformation. Calzolari et al. concluded that TfR2 is frequently expressed in human cell lines in 2007 (Blood Cells Mol Dis 2007;39:82–91) and in GBM in particular in 2010 (Transl Oncol 2010;3:123–34). In GBM, a highly significant correlation (p < 0.0001) was found between the expression level of TfR2 and overall survival, showing that higher levels of TfR2 expression were associated with an overall longer survival. The data on which of the two transferrin receptors is the better target is also unclear and should be studied. The transferrin pathway may be a promising target, but more research should be completed on the antigenicity to discern the viability of it as an immunotherapy target.

Glioblastoma multiforme (GBM) is characterized as one of the most common and most deadly malignant primary brain tumors. Current treatment modalities include the use of surgical resection and adjuvant chemotherapy and radiation therapy, though survival is still limited. Because of this, new treatment strategies are needed to improve overall survival. Immunotherapy has emerged as a potential treatment, but still possesses certain limitations to have a substantial clinical effect. In addition, nanotechnology has emerged as potent treatment effectors that have been shown to augment the effects of therapies including chemotherapy, gene therapy, and more. Nanoparticles possess a novel approach due to the myriad of functional groups that can create targeted treatments, though further optimization is still required. In this review, the authors will present the current uses and abilities of nanotechnology and its implication for use with immunotherapy in the treatment of GBM.

The US health care system is fragmented in terms of quality care, costs, and patient satisfaction. With the passage of the Affordable Care Act, national attention has been placed on the health care system, but effective change has yet to be observed. Unnecessary costs, medical errors, and uncoordinated efforts contribute to patient morbidity, mortality, and decreased patient satisfaction. In addition to national efforts, local initiatives within individual departments must be implemented to improve overall satisfaction without the sacrifice of costs. In this article, the current issues with the health care system and potential initiatives for neurosurgery are reviewed.

Background Superior semicircular canal dehiscence (SSCD) presents with varying degrees of auditory and vestibular dysfunction. The condition is confirmed on high-resolution computed tomography (CT) imaging, and symptoms are often improved by surgical repair. Although a classic middle fossa craniotomy has been used with good results, recent advances in technique have allowed for modification of the traditional approach into a smaller skin incision and a minimally invasive middle fossa keyhole craniectomy roughly 1.7 cm in diameter. Objective To delineate this novel approach and describe the technique for accurate localization of the dehiscence using preoperative measurements and intraoperative image guidance, thereby minimizing the need for a larger skin incision and craniotomy. Methods Patients were independently diagnosed with SSCD by the senior authors. Once relevant imaging was acquired, the novel keyhole technique was performed. Patients' vestibular and auditory symptoms before and after the procedure were assessed. Outcomes from a series of patients treated with this keyhole approach were tabulated and reported. Results Twelve cases from 11 patients were included in this series. Auditory symptoms had high rates of resolution with pulsatile tinnitus, internal amplification of sounds, and autophony being resolved in a majority of cases. Only 2 cases reported hearing decline. Sound/pressure induced vertigo and disequilibrium also demonstrated high rates of resolution. No complications were reported. Conclusion The minimally invasive middle fossa keyhole craniectomy is a novel approach for the repair of SSCD. This approach may contribute to resolved auditory and vestibular symptoms with low morbidity and quick recovery.

The objective of this study was to evaluate the characteristic symptoms of and treatments for lateral semicircular canal dehiscence (LSCD) and posterior semicircular canal dehiscence (PSCD) and its proposed mechanism. A dehiscence acquired in any of the semicircular canals may evoke various auditory symptoms (autophony and inner ear conductive hearing loss) or vestibular symptoms (vertigo, the Tullio phenomenon, and Hennebert sign) by creating a “third mobile window” in the bone that enables aberrant communication between the inner ear and nearby structures. A PubMed search was performed using the keywords lateral, posterior, and semicircular canal dehiscence to identify all relevant cases. Our data suggest that PSCD, although clinically rare, is most likely associated with a high-riding jugular bulb and fibrous dysplasia. Patients may experience auditory manifestations that range from mild conductive to extensive sensorineural hearing loss. LSCD is usually associated with chronic otitis media with cholesteatoma.

INTRODUCTION: Glioblastoma multiforme (GBM) is a deadly disease with a survival of approximately 15 months. Epithelial membrane protein 2 (EMP2) is correlated with advanced disease and adverse outcomes in several cancers and has recently been found to be expressed on the surface of GBM cells. Its expression in GBM increases integrin surface expression resulting in activation of focal adhesion kinase and Src and promoting increased tumor growth, cell migration, and invasion. METHODS: Subcutaneous and orthotopic mouse models were utilized for this study. In the subcutaneous model, n = 4 BALB/c mice were inoculated with U373 cells and treated with weekly systemic treatments of either anti-EMP2 or control IgG1. Tumor size was measured weekly. In the intracranial model, n = 6 BALB/c nude mice were inoculated with U87 cells overexpressing EMP2 and treated with weekly systemic injections of either anti-EMP2 or control IgG1. Tumor size was followed with bioluminescence imaging. RESULTS: In the subcutaneous model, tumor growth was significantly reduced at 50 days when treated with anti-EMP2 antibody (19 mm3 vs. 45 mm3, p < 0.05), and the residual tumors displayed significant necrosis compared to the control group. In the intracranial model, the treatment group showed a trend toward reduced tumor growth compared to the control group. The mean fold change in average tumor radiance in the treatment group was 402 compared to 543 in the control group. CONCLUSION: Our data present an extremely novel biomarker and therapeutic target for GBM. These findings suggest that targeting EMP2 may be an effective treatment modality for GBM. Further studies are needed to fully elucidate the role of targeting EMP2 in the treatment of GBM.

Microscopy of plant cells has evolved greatly within the past 50 years. Advances in live cell imaging, automation, optics, video microscopy, and the need for high content studies has stimulated the development of computational tools for manipulating, managing, and interpreting quantitative data. These tools automatically and semiautomatically determine, sizes, signal intensities, velocities, classes, and many other features of cells and subcellular structures. Quantitative methods provide data that is a basis for mathematical models and statistical analyses that lead the way to a quantitative systems outlook to cell biology. Four-dimensional video analysis provides vital data concerning the often ignored temporal dynamics within a cell. Here, we will review studies employing technology to detect regions of interest using segmentation, classify data using machine learning and track dynamics in living cells using video analysis. Many of the live cell studies presented would have been impractical without these advanced computational techniques. These examples illustrate the utility and potential for video bioinformatics to augment our knowledge of the dynamics of cells and cellular components in plants.

Central neurocytomas (CNs) are rare central nervous system tumors that occur in the lateral ventricles. They are prevalent in young adults and are typically benign with excellent prognosis following surgical resection. Because of the rarity of the disease and its similar features with more common tumors, misdiagnosis becomes an issue. Optimal treatment is achieved only when the correct tumor types are distinguished. Typical clinical manifestations include symptoms of increased intracranial pressure, although no clinical feature is pathognomonic to CN. Radiologic imaging, histology, magnetic resonance spectroscopy, and immunohistochemistry must be used to elucidate tumor characteristics and properly diagnose CN.

Benign osteoblastoma is a rare, vascular, osteoid-forming bone tumor that occurs even less frequently in the cranial bones. Benign osteoblastoma of the cranium affects women slightly more often than men and typically presents in the first three decades of life. Although clinical presentation can vary depending on location, cranial osteoblastoma usually presents as a painful, non-mobile, subcutaneous mass or swelling. On CT scan, it generally presents as a well-demarcated, mixed lytic and sclerotic lesion, with enlarged diploe, thinning outer and/or inner tables, and varying degrees of calcification. It is hypo to isointense on T1-weighted MRI and has variable presentation on T2-weighted MRI. Gross total resection is the definitive treatment, while subtotal resection is utilized when it is necessary to preserve critical adjacent neurovascular structures.

Despite recent advances in treatment, the prognosis for glioblastoma multiforme (GBM) remains poor. The lack of response to treatment in GBM patients may be attributed to the immunosuppressed microenvironment that is characteristic of invasive glioma. Regulatory T-cells (Tregs) are immunosuppressive T-cells that normally prevent autoimmunity when the human immune response is evoked; however, there have been strong correlations between glioma-induced immunosuppression and Tregs. In fact, induction of Treg activity has been correlated with glioma development in both murine models and patients. While the exact mechanisms by which regulatory T-cells function require further elucidation, various cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TFG-β) have been implicated in these processes and are currently under investigation. In addition, hypoxia is characteristic of tumor development and is also correlated with downstream induction of Tregs. Due to the poor prognosis associated with immunosuppression in glioma patients, Tregs remain a promising area for immunotherapeutic research.

BACKGROUND: Glioblastoma multiforme (GBM) is a deadly disease with a survival of approximately 15 months. Epithelial membrane protein 2 (EMP2) is correlated with advanced disease and adverse outcomes in several cancers and has recently been found to be expressed in GBM. Mechanistically, EMP2 promotes αvβ3 integrin surface expression, resulting in an activation of focal adhesion kinase and Src. The consequences of this activation are an increase in tumor growth, cell migration, and invasion. Our preliminary studies suggest that targeting EMP2 with anti-EMP2 antibody results in GBM cell death. METHODS: A custom large tissue microarray (TMA) containing glioma tumor samples from 184 consecutive patients at UCLA was stained for EMP2 expression using human EMP2 antisera. Staining intensity was quantified by an independent pathologist on a 0-3 histological score scale. EMP2 expression level for each sample was correlated with patients' clinical data and outcomes. RESULTS: In the large-scale glioma TMA, EMP2 was expressed strongly in over 90% of GBM samples. EMP2 expression level correlated with increasing grade of glioma, with GBM expressing the highest levels. Furthermore, EMP2 overexpression was significantly associated with increased tumor malignancy and statistically worse patient outcomes. CONCLUSION: Our data presents an extremely novel biomarker and therapeutic target for GBM. These finding suggest that EMP2 expression can be utilized with high validity to determine prognosis in patients with GBM and represents a highly attractive target for anti-glioblastoma therapies. Future prospective, multicenter studies are needed to further validate this large-scale UCLA tissue microarray analysis.