Faculty Bibliography

Background: The transcochlear approach extends the anterior exposure afforded by the translabyrinthine technique. Although this wider exposure allows improved access to cranial nerves and the brainstem with less retraction on the cerebellum, the classical description involving facial nerve transposition often results in permanent facial paresis. This study discusses the role of the transcochlear approach in resection of cerebellopontine angle tumors including patient selection, surgical technique, and outcomes. Study Design: Retrospective review. Methods: This is a retrospective review conducted at a single academic institution. Cases performed by our skull base team (neurotologist and neurosurgeon) between 2000 and 2015 were reviewed. All cases utilizing the transcochlear approach were included. Factors including tumor size, completeness of resection, facial nerve function, post-operative complications, and length of stay were analyzed. Results: Fourteen cases were included. All of these patients had pre-operative severe hearing loss except for two in which surgery was performed urgently in the setting of hydrocephalus and brainstem compression. Eight out of 14 patients had pre-operative facial paresis. Tumor size ranged from 2.2-7 cm in greatest dimension (mean = 4.56 cm). All patients underwent a transcochlear approach to and removal of tumor with blind sac of the external auditory canal. In addition, 3 patients underwent an immediate facial nerve to hypoglossal anastomosis. Post-operatively, patients remained in the hospital for 3-5 days (mean = 4). Of the patients who started out with normal facial nerve function (n = 6), 3 recovered to House-Brackmann scores II or greater. There were no reported CSF leaks requiring hospitalization and 1 abdominal hematoma from fat graft harvest. There was a single mortality reported in the peri-operative period; however, on autopsy the cause of death was unrelated to the surgery itself or any subsequent intracranial event. Conclusions: As in other surgical approaches destructive to the labyrinth, patients were selected with consideration of their pre-operative hearing status and/or their candidacy for hearing preservation surgery. Patients with pre-operative facial nerve paralysis and hearing loss were deemed particularly appropriate candidates for the transcochlear technique given the additional exposure and the lack of added morbidity. In these cases the surgeon also has the option to perform dynamic facial nerve reanimation at the time of tumor resection

Background: Salvage surgery for progressive symptoms or recurrent growth of vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is uncommon. It has been reported to be more difficult, the same or easier than expected compared with microsurgical resection (MS) of treatment-naive VS, with variable facial nerve outcomes. We conducted a matched cohort analysis to evaluate facial nerve outcomes for patients undergoing MS for progressive symptoms or recurrent growth of VS after SRS compared with MS for treatment-naive VS. Methods: We evaluated the records of 365 non-NF2 VS patients treated with MS from 2001 to 2014. All patients who had postoperative notes were considered to have "adequate follow-up" and included in the study. Nine patients underwent resection for VS after prior SRS (MS-POST SRS) with no prior intervention, 7 of which had adequate follow-up, and 331 patients that underwent MS for treatment naive VS (MS-NO SRS), 317 of which had adequate follow-up. From this dataset, we created propensity score matched cohorts to retrospectively compare facial nerve preservation and clinical outcomes. The propensity score model incorporated age at surgery, tumor size, and pre-operative HB grade, and cases were matched at a ratio of 4:1 MS-NO SRS to MS-POST SRS cases. Results: The MS-POST SRS (n = 7) and MS-NO SRS (n = 28) groups differed only in preoperative hearing status (p < 0.01). Preoperative HB grades were similar between MS-POST SRS and MS-NO SRS groups (p>0.3). The average time-to-intervention after SRS in the MS-POST SRS group was 44.4 months. The indication for MS after SRS was symptom progression with tumor growth in 4 cases, and only tumor growth in the remaining 3. Postoperatively, 3 cases in the MS-POST SRS group demonstrated improvement in HB grade and none became worse whereas 3 of 28 cases in the MS-NO SRS group demonstrated improvement and 12 cases had decrement in HB grade relative to baseline (p < 0.05). There was no significant difference in the extent of resection with both cohorts (MS-POST SRS and MS-NO SRS) attaining gross total resection in 85.7% of cases. Subsequent intervention was not required for any case in the MS-POST SRS group and 2 cases in the MS-NO SRS group, although this difference was not significant. Both cases requiring subsequent intervention in the MS-POST SRS group were gross total resections via the translabyrinthine approach, with subsequent intervention required at 62 and 48 months. There were no significant differences in the complication rate for individual complications or the overall complication rate between cohorts. Conclusions: At a center with high clinical volume, microsurgical resection of VS after prior SRS was associated with good postoperative facial nerve preservation and low morbidity, comparable to those observed in resection of treatment-naive VS. In addition there were similar outcomes in terms of extent of resection between the two groups. The good outcomes reported here may reflect a confluence of factors which include patient selection, the experience of the attending surgeons, the use of more contemporary SRS dosing protocols during initial treatment for these patients, and divergent goals of therapy between cohorts

Objective: Cerebral venous sinus thrombosis (CVST) is a rare but potentially dangerous complication following craniotomies involving the posterior fossa, the skull base, and craniotomies involving the superior sagittal sinus. Surgical manipulation of the sinuses has been shown to cause sinus thromboses of varying degrees. This phenomenon is often clinically silent, with only a small number of patients becoming symptomatic. Recent advances in neuroimaging provide higher resolution evaluation of cerebral sinuses pre and postoperatively, often revealing clinically silent filling defects. Although sinus thrombosis can be a major cause of morbidity and mortality, its incidence and factors that contribute to its formation in the postoperative population remain unclear. In addition, current guidelines advise to anticoagulate with Heparin upon diagnosis, which can be contraindicated for immediate post craniotomy patients. The goal of this study is to evaluate retrospective data of patient outcomes and factors that might contribute to sinus thrombus formation. Methods: A retrospective chart review was conducted at NYU Langone Medical Center. Ninety-seven patients were included who underwent either a retrosigmoid/translabrynthine/suboccipital resection of a posterior fossa tumor or a supratentorial craniotomy for resection of parasagittal/falcine tumor between July 1, 2014 and July 1, 2015. Pre operative Magnetic Resonance Venography (MRV) was obtained per the attending surgeon's discretion. Based on intraoperative findings, clinical symptoms, and surgeon's preference, a postoperative MRV was obtained. Decision to treat a thrombosis was made based on the results of the MRV and clinical symptoms. Treatments included observation, intravenous fluids (IVF) alone, anti-platelet therapy with Aspirin alone, or a combination of the two. Results: A total of 7 of 97 patients (7.22%) had postoperative sinus thrombosis. Of those patients, 5 had occlusion of the venous sinuses. In the occlusion group, 4 had preoperative imaging documenting patency of the sinuses. An additional 2 patients had postoperative MRVs revealing partial thrombosis of the sinus, 1 that was new and 1 that did not have a preoperative MRV for comparison. Compared with the cohort of patients without postoperative thromboses, there was no significant difference in age, BMI, length of surgery, or surgical approach. Of the 5 patients with postoperative thrombotic occlusion, 4 underwent intervention (1 with IVF alone, 2 with IVF and aspirin, and 1 with aspirin alone). Two patients with thromboses also developed CSF leaks requiring lumbar drainage and operative repair. One patient had a persistent CSF leak requiring a shunt. Of the 2 patients with partial thrombosis, 1 was placed on IVF and aspirin. At 3 months follow up, 1 out of 5 patients in the occlusion group had recanalization of the previously thrombosed sinus. Conclusions: MRV is a non-invasive method to evaluate the caliber and patency of dural venous sinuses in post craniotomy patients. Symptomatic thrombosis is rare and can be managed either conservatively or with IVF and/or anti platelet therapy, both which are safer than anticoagulation with heparin in post craniotomy patients. A larger prospective trial is necessary to further characterize the incidence of postoperative venous sinus thrombosis, identify risk factors, and to devise recommendations for therapy

OBJECTIVE: Dose-response relationships for meningioma radiosurgery are poorly characterized. We evaluated determinants of local recurrence for meningiomas treated with Gamma Knife radiosurgery (GKRS), to guide future treatment approaches to optimize tumor control. MATERIALS AND METHODS: A total of 101 consecutive patients (108 tumors) who underwent GKRS for benign, atypical, or malignant meningiomas between 1998 and 2011 were studied. Local recurrence was assessed. Cox proportional hazards and logistic regression analyses were used to determine the association of patient-related, tumor-related, and treatment-related characteristics with local recurrence. Acute and late toxicity was evaluated. RESULTS: World Health Organization (2007 classification) tumor grade was I (82%), II (11%), or III (7%). Median dose was 14 Gy (range, 10 to 18 Gy) for grade I tumors and 16 Gy (range, 12 to 20 Gy) for grade II and III tumors. Median follow-up was 25 months (maximum, 17 y). Two- /5-year actuarial local control rates were 100%/98% for grade I tumors and 76%/56% for grade II/III tumors. Higher tumor grade and lower GKRS dose were associated with local failure. In this cohort, there was a 42% relative reduction in local recurrence for each 1 Gy of dose escalation. CONCLUSIONS: Treatment was well tolerated with no moderate or severe toxicity. Tumor control was excellent in benign tumors and suboptimal in higher grade tumors. Because the main determinant of local recurrence was GKRS dose, we recommend dose escalation for atypical or malignant tumors to doses between 16 and 20 Gy where critical structures allow.

BACKGROUND: Median overall survival (OS) of patients with melanoma brain metastases (MBM) is usually 6 months or less. There are rare reports of patients with treated MBM who survived for years. These outlier cases represent valuable opportunities to study the somatic and germline factors that may have influenced patient outcome and led to extended survival. CASE PRESENTATION: Here we report the clinical scenario of a 67 year old man with a recurrent brain metastasis from melanoma who has survived over 12 years post-resection. We review the literature relating to clinical and molecular variables associated with long term survival post-brain metastasis. We present the somatic characteristics of this individual patient's tumor as well as an analysis of inherited genetic variants related to immune function. The patient's resected brain tumor is BRAF V600E mutated, NRAS wild type (WT), and TERT C250T mutated. The patient is a carrier of germline variants in immunomodulatory loci associated with prolonged survival. CONCLUSIONS: Our data suggest that genetic variants in immunomodulatory loci may partially contribute to this patient's unusually favorable outcome and should not be overlooked. With further and future investigation, knowledge of inherited single nucleotide polymorphisms (SNPs) may provide clinicians with more individualized prognostic information for melanoma patients, with potential implications for surveillance strategies and therapeutic interventions.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate imaging correlates to the changes occurring during angiogenesis in gliomas. This was accomplished through in vivo assessment of vascular parameters (relative CBV and permeability surface-area product) and their changing relationship with increasing glioma grade. MATERIALS AND METHODS: Seventy-six patients with gliomas underwent preoperative perfusion CT and assessment of relative CBV and permeability surface-area product. Regression analyses were performed to assess the rate of change between relative CBV and permeability surface-area product and to test whether these differed for distinct glioma grades. The ratio of relative CBV to permeability surface-area product was also computed and compared among glioma grades by using analysis of variance methods. RESULTS: The rate of change in relative CBV with respect to permeability surface-area product was highest for grade II gliomas followed by grade III and then grade IV (1.64 versus 0.91 versus 0.27, respectively). The difference in the rate of change was significant between grade III and IV (P = .003) and showed a trend for grades II and IV (P = .098). Relative CBV/permeability surface-area product ratios were the highest for grade II and lowest for grade IV. The pair-wise difference among all 3 groups was significant (P < .001). CONCLUSIONS: There is an increase in relative CBV more than permeability surface-area product in lower grade gliomas, whereas in grade III and especially grade IV gliomas, permeability surface-area product increases much more than relative CBV. The rate of change of relative CBV with respect to permeability surface-area product and relative CBV/permeability surface-area product ratio can serve as an imaging correlate to changes occurring at the tumor microvasculature level.

A major impeding factor in designing effective therapies against glioblastoma (GBM) is its extensive molecular heterogeneity and the diversity of microenvironmental conditions within any given tumor. To test whether heterogeneity with the GBM stem cell (GSC) population is required to ensure tumor growth in such diverse microenvironments, we used human GBM biospecimens to examine the identity of cells marked by two established GSC markers: CD133 and activation of the Notch pathway. Using primary GBM cultures engineered to express GFP upon activation of Notch signaling, we observed only partial overlap between cells expressing cell surface CD133 and cells with Notch activation (n = 3 specimens), contrary to expectations based on prior literature. To further investigate this finding, we FACS-isolated these cell populations and characterized them. While both CD133+ (CD133 + /Notch-) and Notch+(CD133-/Notch+) cells fulfill GSC criteria, they differ vastly in their transcriptome, metabolic preferences and differentiation capacity, thus giving rise to histologically distinct tumors. CD133+ GSCs have increased expression of hypoxia-regulated and glycolytic genes, and are able to expand under hypoxia by activating anaerobic glycolysis. In contrast, Notch+ GSCs are unable to utilize anaerobic glycolysis under hypoxia, leading to decreased tumorsphere formation ability. While CD133+ GSCs give rise to histologically homogeneous tumors devoid of large tumor vessels, tumors initiated by Notch+ GSCs are marked by large perfusing vessels enveloped by pericytes. Using a lineage tracing system, we showed that pericytes are derived from Notch+ GSCs. In addition, Notch+ cells are able to give rise to all tumor lineages in vitro and in vivo, including CD133 + /Notch- cells, as opposed to Notch- populations, which have restricted differentiation capacity and do not generate Notch+ lineages. Our findings demonstrate that GSC heterogeneity is a mechanism used by tumors to sustain growth in diverse microenvironmental conditions

OBJECTIVE: The aim of this study was to develop a multidimensional metric for assessing quality of life (QoL) in patients with neurofibromatosis type 2 (NF2). STUDY DESIGN: Electronically distributed questionnaire. SETTING: University tertiary care hospital, NF2 support groups. SUBJECTS AND METHODS: Structured interviews with NF2 providers and patients identified relevant domains. Items in each domain were extracted from validated QoL modules, then combined with items unique to NF2 and pretested on NF2 providers and patients. The final 61-item questionnaire was administered electronically to patients with NF2 (N = 118). The form assessed overall QoL and 11 additional domains, including hearing, balance, facial function, vision, oral intake, future uncertainty, psychosocial, cognition, sexual activity, pain, and vocal communication. Responses were compared with reference values for the general population, patients with head and neck cancer, and patients with brain cancer. RESULTS: Overall, QoL in patients with NF2 was lower than that of the general population (P < .01) and similar to that of patients with cancer. Patients with more facial weakness, hearing loss, and imbalance reported significantly lower QoL. However, domains most predictive of overall QoL were psychosocial, future uncertainty, and pain. Compared with patients with head and neck and brain cancer, patients with NF2 demonstrated significantly higher levels of psychosocial stressors, including disease-related anxiety, personal and financial stress, and lack of social support (P < .01). CONCLUSION: Psychosocial stress and pain significantly affect QoL in NF2, indicating that mental health, pain management, and financial counseling could have an important impact on QoL in this population.