Accuracy and outcomes of diffusion tensor imaging tractography in resection for vestibular schwannoma for facial nerve preservation.

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.

Intratumor injection of CCL21-coupled vault nanoparticles is associated with reduction in tumor volume in an in vivo model of glioma.

PURPOSE: Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM. METHODS: GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS. RESULTS: The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume. CONCLUSIONS: This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.

Surgery versus stereotactic radiosurgery for the treatment of multiple meningiomas in neurofibromatosis type 2: illustrative case and systematic review.

Neurofibromatosis type 2 (NF2) is a genetic neoplastic disorder that presents with hallmark bilateral vestibular schwannomas and multiple meningiomas. Though the current standard of care for meningiomas includes surgery, the multiplicity of meningiomas in NF2 patients renders complete resection of all developing lesions infeasible. Stereotactic radiosurgery (SRS) may be a viable non-invasive therapeutic alternative to surgery. We describe a particularly challenging case in a 39-year-old male with over 120 lesions who underwent more than 30 surgical procedures, and review the literature. We also searched three popular databases and compared outcomes of SRS versus surgery for the treatment of multiple meningiomas in patients with NF2. A total of 50 patients (27 radiosurgical and 23 surgical) were identified. For patients treated with SRS, local tumor control was achieved in 22 patients (81.5%) and distal control was achieved in 14 patients (51.8%). No malignant inductions were observed at an average follow-up duration of 90 months. Complications in the SRS-treated cohort were reported in 9 patients (33%). Eight patients (29.6%) died due to disease progression. Six patients experienced treatment failure and required further management. For NF2 patients treated with surgery, 11 patients (48%) showed tumor recurrence and 10 patients (43.5%) died due to neurological complications. SRS may be a safe and effective alternative for NF2-associated meningiomas. Further studies are required to identify the ideal radiosurgical candidate.

Epithelial membrane protein 2: Molecular interactions and clinical implications.

Epithelial membrane protein 2 (EMP2) is a cell surface protein that has recently emerged as an object of neuro-oncological interest due to its potential to be utilized as a biomarker and target for antibody therapies. Preclinical studies have demonstrated that EMP2 is associated with disease prognosis in a number of human cancers, including glioblastoma. The four large extracellular domains of EMP2 and its association with the extracellular matrix makes it an attractive target for future cancer therapies. Translational research suggests that EMP2 may be targeted with antibodies to improve tumor control and survival in a variety of murine models and cancer types. However, in order to translate these preclinical findings into the clinic, future research will need to focus on elucidating the role EMP2 in the normal human body by better understanding its molecular and chemical interactions. The focus of this review is to provide a comprehensive insight into current research endeavors, discuss the potential for clinically translatable applications, and predict the future directions of such research.

Outcomes of middle fossa craniotomy for the repair of superior semicircular canal dehiscence.

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<0.0001), aural fullness (p=0.0006), hearing loss (p=0.0119), disequilibrium (p=0.0002), sound- and pressure-induced vertigo (p<0.0001), and tinnitus (p<0.0001) were significantly different. Improved clinical outcomes were demonstrated in patients undergoing SSCD repair through a middle cranial fossa approach. The most common presenting symptom (autophony) was also most likely to resolve after surgery. Hearing loss is less amenable to surgical correction. Disequilibrium developed in a small number of patients after repair.

Radiosurgical Ablation of the Renal Nerve in a Porcine Model: A Minimally Invasive Therapeutic Approach to Treat Refractory Hypertension.

BACKGROUND: Hypertension is strongly associated with cardiovascular diseases such as heart failure, stroke, kidney disease, and has been correlated with an increased risk for heart attack. Current treatment regimens for hypertension are highly inadequate, with reports indicating that only 50.1% of the clinical population with the disease has their blood pressure under control. OBJECTIVE: To study the feasibility of using minimally invasive radiosurgery to ablate the renal nerves as a novel treatment for refractory hypertension, and to assess the safety and efficacy of such an approach. METHODS: A Hanford porcine (miniswine) model (N = 6) was used to investigate the feasibility of using the CyberHeart radiosurgical platform (CyberHeart Inc., Mountain View, CA, USA) to create safe renal nerve ablations. Norepinephrine (NE) levels were measured pre and post treatment. Additionally, renal nerve and arterial histology were studied to examine effect. RESULTS: Plasma norepinephrine levels showed a decrease over the six-month time point. Urea, nitrogen, and creatinine levels showed no changes post procedure. Histology documented no significant arterial injury in targeted areas. Renal nerves documented histologic change consistent with nerve ablation. CONCLUSION: CyberHeart radiosurgery of the renal nerve is feasible and resulted in norepinephrine reduction and renal nerve injury consistent with radiosurgical targeted ablation.

Utilizing virtual and augmented reality for educational and clinical enhancements in neurosurgery.

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.

Adjuvant Radiosurgery Versus Serial Surveillance Following Subtotal Resection of Atypical Meningioma: A Systematic Analysis.

BACKGROUND: Atypical meningioma (AM) is an aggressive subtype of meningioma associated with a high recurrence rates (RR) following surgical resection. Recent studies have compared outcomes of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, we systematically analyzed the current literature on AM and compared outcomes of ARS versus SS after STR. METHODS: Embase, PubMed, and Cochrane databases were queried using relevant search terms. Retrospective case series that described patients with AM treated with ARS and SS after STR were included. Tests of proportions were performed to detect significant variations in RR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) between the treatment strategies (ARS vs. SS) and among individual studies. RESULTS: A total of 619 patients (263 in the ARS group and 356 in the SS group) were identified. Mean RR, 5-year PFS, and 5-year OS were 53.5%, 50.3%, and 74.9%, respectively, for ARS versus 89.8%, 19.1%, and 89.8% for SS. RR differed between treatment strategies and ARS studies (P < 0.001), and 5-year PFS differed among treatment strategies, ARS, and SS studies (P < 0.001, P = 0.007, and P < 0.001, respectively). CONCLUSIONS: The data presented here show significant differences in RR and 5-year PFS between ARS and SS, suggesting a potential benefit of ARS. As our understanding of the clinical outcomes of various treatment strategies for AM increases, we also move closer to integrating modalities, such as radiosurgery, into management guidelines.

Cost-Effectiveness of Cardiac Radiosurgery for Atrial Fibrillation: Implications for Reducing Health Care Morbidity, Utilization, and Costs.

In the United States (U.S.), atrial fibrillation (AF) is the second-most common cardiovascular condition after hypertension, affecting four million Americans each year. Individuals with AF are three times more likely to be hospitalized over the span of a year when compared to medically matched control groups. The considerably large clinical population of individuals with AF mandates that the cost-effectiveness and efficacy of current treatment regimens for AF have egregious implications for health care spending and public health. Unfortunately, catheter ablation for AF treatment has been shown to make only modest gains in quality-adjusted life years, has yet to demonstrate cost-utility advantages over conventional therapies for AF, and has a reported rate of recurrence for AF that is notably high. Thus, there is a major unmet clinical need for a therapeutic option to treat AF that produces more consistent and efficacious results that are cost-effective. Cardiac radiosurgery as a therapy for AF has the potential to be remarkably cost-effective and produce robust patient outcomes. CyberHeart Inc. has developed the world's first-ever cardiac radiosurgery (CRS) system designed to ablate the heart non-invasively. Procedures that ablate the heart utilizing the Cyberheart CRS system are anticipated to allow higher efficacy and more consistent results than current techniques such as catheter ablation. The aim of this study is to present the current healthcare utilization and expenditures in AF treatment, report the cost-effectiveness of catheter ablation for AF, and project the potential cost-effectiveness of cardiac radiosurgery for the treatment of AF.

Incidental Meningiomas: Management in the Neuroimaging Era.

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.