Phase 0 Clinical Trial of Everolimus in Patients with Vestibular Schwannoma or Meningioma
Inhibition of mTORC1 signaling has been shown to diminish growth of meningiomas and schwannomas in preclinical studies, and clinical data suggest that everolimus, an orally administered mTORC1 inhibitor, may slow tumor progression in a subset of NF2 patients with vestibular schwannoma (VS). To assess the pharmacokinetics, pharmacodynamics and potential mechanisms of treatment resistance, we performed a pre-surgical (phase 0) clinical trial of everolimus in patients undergoing elective surgery for VS or meningiomas. Eligible patients with meningioma or VS requiring tumor resection enrolled on study received everolimus 10 mg daily for 10 days immediately prior to surgery. Everolimus blood levels were determined immediately prior to and after surgery. Tumor samples were collected intraoperatively. Ten patients completed protocol therapy. Median pre- and post-operative blood levels of everolimus were found to be in a high therapeutic range (17.4 ng/ml and 9.4 ng/ml, respectively). Median tumor tissue drug concentration determined by mass spectrometry was 24.3 pg/mg (range 9.2-169.2). We observed only partial inhibition of phospho-S6 in the treated tumors, indicating incomplete target inhibition compared to control tissues from untreated patients (p=0.025). Everolimus led to incomplete inhibition of mTORC1 and downstream signaling. These data may explain the limited anti-tumor effect of everolimus observed in clinical studies for NF2 patients and will inform the design of future pre-clinical and clinical studies targeting mTORC1 in meningiomas and schwannomas.
Awake cochlear implantation
An increasing number of elderly patients are seeking hearing rehabilitation strategies, including cochlear implantation. Elderly patient who are frail or those with significant pre-existing comorbidities have a higher risk of perioperative morbidity after undergoing surgery with general anesthesia. Additionally, there is a growing concern that general anesthesia could increase the risk of dementia or postoperative cognitive decline. In patients who wish to avoid the perceived medical and cognitive risks attributed to general anesthesia or for those who are deemed medically unfit for general anesthesia, surgery under local anesthesia with conscious sedation may be offered. This article details the surgical technique of local anesthesia with conscious sedation and describes the modifications and technical nuances which may be employed for executing a successful surgery.
The importance of intraoperative plain radiographs during cochlear implant surgery in patients with normal anatomy
Although malpositioning of the cochlear implant (CI) electrode array is rare in patients with normal anatomy, when occurring it may result in reduced hearing outcome. In addition to intraoperative electrophysiologic tests, imaging is an important modality to assess correct electrode array placement. The purpose of this report was to assess the incidence and describe cases in which intraoperative plain radiographs detected a malpositioned array. Intraoperative anti-Stenver"™s view plain X-rays are conducted routinely in all CI surgeries in our tertiary center before awakening the patient and breaking the sterile field. Data of patients undergoing 399 CI surgeries were retrospectively analyzed. A total of 355 had normal inner ear and temporal bone anatomy. Patients with intra or extracochlear malpositioned electrode arrays demonstrated in the intraoperative X-ray were described. There were four cases of electrode array malposition out of 355 implantations with normal anatomy (1.1%): two tip fold-overs, one extracochlear placement and one partial insertion. All electrodes were reinserted immediately; repeated radiographs were normal and the patients achieved good hearing function. Intraoperative plain anti-Stenver"™s view X-rays are valuable to confirm electrode array location, allowing correction before the conclusion of surgery. These radiographs are cheaper, faster, and emit much less radiation than other imaging options, making them a viable cost-effective tool in patients with normal anatomy.
Tracking Spontaneous Vestibular Schwannoma Regression with Volumetric Measurements
OBJECTIVE:To characterize a series of patients with MRI evidence of spontaneous vestibular schwannoma (VS) regression. STUDY DESIGN/METHODS:Retrospective case series. METHODS:Retrospective review between 2012 and 2020 from a single, tertiary-care center of all patients with an untreated, sporadic VS and spontaneous regression in volumetric tumor size over the course of observation. The main outcome measures included VS size and location, presenting symptoms, medication use, changes in pure-tone averages and word recognition scores. RESULTS:/yr). Five patients were classified as having major regression, defined by a relative decrease in volume of >40%, while eight patients had minor regression (<40% relative volume reduction). No significant differences in initial tumor size, rate of regression, or audiometric changes were observed between the major and minor regression cohorts. CONCLUSIONS:Patients with evidence of a spontaneously shrinking VS have a heterogeneous presentation. Due to the scarcity of this phenomenon, predicting which tumors will eventually undergo regression remains unclear. Employing volumetric measurements to compare serial MRI scans may improve the accuracy of detecting shrinking tumors. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2020.
Cochlear Implant Outcomes in Neurofibromatosis Type 2: Implications for Management
OBJECTIVE:To describe our institutional experience with cochlear implantation (CI) for rehabilitation of hearing loss in Neurofibromatosis type 2 (NF2) patients. STUDY DESIGN/METHODS:Retrospective review between 1989 and 2019. SETTING/METHODS:Tertiary-care center. PATIENTS/METHODS:Twenty-four patients (67% female, mean age 45.6years) with NF2. Management of their ipsilateral vestibular schwannoma included microsurgery (n=12), stereotactic radiation (n=5), and observation (n=7). INTERVENTIONS/METHODS:Cochlear implantation. MAIN OUTCOME MEASURES/METHODS:Ability to obtain open-set speech, daily device usage and long-term device benefit. RESULTS:All patients achieved some degree of sound awareness with CI. Nineteen patients (79%) achieved open-set speech understanding with a mean word-recognition score of 43% (range 0-88%). Patients with tumors 1.5 cm or less demonstrated the better speech understanding, without significant differences among treatment modalities. For tumors greater than 1.5 cm, patients who underwent microsurgery had a lower rate of open-set speech understanding compared to those treated with radiation or observation. Regular daily device use in 83% of patients was found. Long-term use (>10years) was observed in several patients, though some ultimately required reimplantation with an auditory brainstem implant due to progressive tumor growth. Mean follow-up duration was 4.1 years (range 0.4-15). CONCLUSIONS:Cochlear implantation can be an effective treatment for hearing loss in NF2 patients provided the cochlear nerve is intact, regardless of prior management for the ipsilateral tumor. The degree of benefit varies and is influenced by tumor size. Management strategies that preserve the cochlear nerve maximize the interval during which a CI could be of benefit to NF2 patients.
Cochlear Implantation in Sporadic Vestibular Schwannoma and Other Retrocochlear Pathology: A Case Series
OBJECTIVE:To describe outcomes with cochlear implantation (CI) for rehabilitation of hearing loss in patients with sporadic vestibular schwannomas (VS) and other retrocochlear pathologies. STUDY DESIGN/METHODS:Retrospective review. SETTING/METHODS:Tertiary-care center. PATIENTS/METHODS:Twenty three cases in 19 patients (53% men, mean age 55.8 yr) with non-neurofibromatosis type 2 related retrocochlear pathology. INTERVENTIONS/METHODS:Unilateral or bilateral CI. MAIN OUTCOME MEASURES/METHODS:Word recognition score, device usage. RESULTS:Etiology of deafness included sporadic VS (nâ€Š=â€Š9, 39%), radiation after head and neck or central nervous system (CNS) malignancy (nâ€Š=â€Š8, 35%), superficial siderosis (nâ€Š=â€Š3, 13%), neurosarcoidosis (nâ€Š=â€Š2, 9%), and pontine stroke (nâ€Š=â€Š1, 4%). Mean follow-up duration was 2.3 years (standard deviation [SD] 3.0; range, 0.2-9.4). Auditory perception was achieved in 20 out of 22 patients (91%) who have been activated. Mean WRS in patients with sporadic VS was 18% (SD 20; range, 0-44). Mean WRS in patients with non-VS retrocochlear pathology was 55% (SD 30; range, 0-94). Data logs showed 7.0â€Šh/d of average use (SD 4.3; range, 0-13). CONCLUSIONS:Appropriately selected patients with retrocochlear pathology may benefit from CI so long as the patient has a cochlear fluid signal and an intact cochlear nerve. Patients with sporadic VS patients and normal contralateral hearing exhibited guarded outcomes with CI, whereas most patients with non-VS retrocochlear pathologies demonstrated open-set speech understanding scores comparable to or slightly worse than conventional CI candidates. Since variable performance benefit is observed with CI in patients with retrocochlear pathology, counseling is imperative to align patient expectations with realistic outcomes.
Cochlear Implantation in Adults With Single-sided Deafness: Outcomes and Device Use
OBJECTIVE:To describe our experience with adults undergoing cochlear implantation (CI) for treatment of single-sided deafness (SSD). STUDY DESIGN/METHODS:Retrospective case review. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Fifty-three adults with SSD. INTERVENTIONS/METHODS:Unilateral CI. MAIN OUTCOME MEASURES/METHODS:Speech perception testing in quiet and noise, tinnitus suppression, and device usage from datalogs. RESULTS:The mean age at CI was 53.2 years (SD 11.9). The mean duration of deafness was 4.0 years (SD 7.8). The most common etiology was idiopathic sudden SNHL (50%). Word recognition improved from 8.7% (SD 15) preoperatively to 61.8% (SD 20) at a mean follow-up of 3.3 years (SD 1.8) (pâ€Š<â€Š0.0001). Adaptive speech recognition testing in the "binaural with CI" condition (speech directed toward the front and noise toward the normal hearing ear) revealed a significant improvement by 2.6-dB SNR compared to the preoperative unaided condition (pâ€Š=â€Š0.0002) and by 3.6-dB SNR compared to when a device to route sound to the contralateral side was used (pâ€Š<â€Š0.0001). Tinnitus suppression was reported to be complete in 23 patients (43%) and improved in 20 patients (38%) while the device was on. The addition of the CI did not lead to a decrement in hearing performance in any spatial configuration. Device usage averaged 8.7 (SD 3.7) hours/day. CONCLUSIONS:Cochlear implantation in adult SSD patients can suppress tinnitus and achieve speech perception outcomes comparable with CI in conventional candidates. Modest improvements in spatial hearing were also observed and primarily attributable to the head shadow effect. Careful patient selection and counseling regarding potential benefits are important to optimize outcomes.
Cochlear Implantation Under Local Anesthesia With Conscious Sedation in the Elderly: First 100 Cases
OBJECTIVE:To report the outcomes on a large series of elderly patients who underwent cochlear implantation (CI) surgery under local anesthesia with conscious sedation (LA-CS). METHODS:Retrospective chart review on 100 consecutive elderly patients (>â€‰65â€‰years) who underwent CI with LA-CS at a tertiary care center between August 2013 and January 2020. An age-matched control group of 50 patients who underwent CI with general anesthesia (GA) are used for comparison. Outcomes measured included time in the operating room, time in the postanesthesia care unit (PACU), and rate of adverse events. RESULTS:Cochlear implant surgery under LA-CS was successfully performed in 99 (99%) patients. One patient requiring conversion to GA intraoperatively. No patients in the LA-CS group experienced cardiopulmonary adverse events; however, three patients (6%) in the GA group experienced minor events including atrial fibrillation and/or demand ischemia. Overnight observation in the hospital due to postoperative medical concerns or prolonged wake-up from anesthesia was required in one patient (1%) from the LA-CS cohort and 12 patients (24%) from the GA cohort. Perioperative adverse events exclusive to the LA-CS group included severe intraoperative vertigo (8%), temporary facial nerve paresis (3%), and wound infection (1%). The average amount of time spent in the operating room was 37â€‰minutes less for procedures performed under LA-CS compared to GA (P <â€‰.05). The average amount of time in recovery was similar for both groups (P >â€‰.05). CONCLUSION/CONCLUSIONS:Cochlear implant surgery under LA-CS offers many benefits and is a safe, feasible, and cost-effective alternative to GA when performed by experienced CI surgeons. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2020.
Assessing temporal responsiveness of primary stimulated neurons in auditory brainstem and cochlear implant users
The reasons why clinical outcomes with auditory brainstem implants (ABIs) are generally poorer than with cochlear implants (CIs) are still somewhat elusive. Prior work has focused on differences in processing of spectral information due to possibly poorer tonotopic representation and higher channel interaction with ABIs than with CIs. In contrast, this study examines the hypothesis that a potential contributing reason for poor speech perception in ABI users may be the relative lack of temporal responsiveness of the primary neurons that are stimulated by the ABI. The cochlear nucleus, the site of ABI stimulation, consists of different neuron types, most of which have much more complex responses than the auditory nerve neurons stimulated by a CI. Temporal responsiveness of primary stimulated neurons was assessed in a group of ABI and CI users by measuring recovery of electrically evoked compound action potentials (ECAPs) from single-pulse forward masking. Slower ECAP recovery tended to be associated with poorer hearing outcomes in both groups. ABI subjects with the longest recovery time had no speech understanding or even no hearing sensation with their ABI device; speech perception for the one CI outlier with long ECAP recovery time was well below average. To the extent that ECAP recovery measures reveal temporal properties of the primary neurons that receive direct stimulation form neural prosthesis devices, they may provide a physiological underpinning for clinical outcomes of auditory implants. ECAP recovery measures may be used to determine which portions of the cochlear nucleus to stimulate, and possibly allow us to enhance the stimulation paradigms.
Skull Base Aerosol Generating Cases Amidst the COVID-19 Pandemic: An Experience from the Epicenter
Soon after the World Health Organization declared the severe acute respiratory syndrome coronavirus 2 a global health emergency on January 30, 2020, New York City was plagued by the virus and its health system and economy pushed to their limits. The majority of the limited neurosurgical data in relation to COVID-19 is anecdotal and the higher theoretical risk of transmission of the virus among skull base aerosol generating (SBAG) cases has not been investigated or discussed in a neurosurgical population. We discuss a series of 13 patients who underwent 15 SBAG surgical procedures during the peak of COVID-19 in our hospital system and the protocols use perioperatively for their procedures. Our data support that with proper preoperative testing, a well-delineated surgical algorithm, and appropriate personal protective equipment, emergent/urgent cases can be done safely in hospitals that are currently experiencing high volumes of COVID-19 cases as we did in March to May of 2020.