Carlson, Matthew L.

Abstract Background Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

BACKGROUND AND OBJECTIVES: Vestibular schwannomas (VS) are often phenotypically benign lesions that may be technically challenging to resect because of involvement of neurovascular structures. The anterior inferior cerebellar artery (AICA) is commonly identified near VS, with variable position in relation to the tumor; however, little published literature describes anatomic and pathologic variants of AICA observed during VS resection. METHODS: A prospectively maintained cohort of surgically managed VS with available operative reports and clinical/radiographic follow-up was queried and reviewed for noted aberrations. RESULTS: We identified 66 cases with noted AICA abnormalities among 880 reviewer cases, including 20 loops extending into the internal auditory canal (2.3%), 18 arteries embedded in dura (2.0%), 15 AICA branches directly within VS (1.7%), 8 main trunk arteries coursing between cranial nerves 7 and 8 (0.9%), 3 arteries embedded in temporal bone (0.2%), 1 aneurysm (0.1%), and 1 artery bifurcating cranial nerve 6 (0.1%). The median age of AICA-variant patients was 55 years (range 19-74), and 29 were female (45%). Compared with the other AICA variants, tumors embedded with AICA tended to be larger lesions on maximal axial diameter (2.9 vs 1.6 cm; P = .006), they more commonly underwent less than total resection (73% vs 28%; P = .0001), and they had higher rates postoperative House-Brackmann scores >2 (47% vs 20%; P = .005). Two patients had radiographic and symptomatic postoperative cerebral ischemia or hemorrhage—1 from a bone-encased AICA and 1 from a dural embedded variant. CONCLUSION: Anatomic variants of AICA occur in approximately 7% of VS operations. Most aberrations do not affect surgical or clinical outcomes, and the rate of major vascular injury was low. However, certain types variably add operative time and in the case of AICA encasement in the tumor, likely indicate a more aggressive tumor phenotype with lower rates of gross total resection and high incidences of facial nerve weakness.

Abstract BACKGROUND Neurofibromatosis type 2-related schwannomatosis (NF2) is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS) as well as other nervous system tumors. Management decisions for NF2-related VS are typically predicated on tumor size, associated symptoms, patient age, and comorbidities. Observation, surgical resection, and stereotactic radiosurgery can be viable options. In patients with VS associated with NF2, vascular endothelial growth factor A (VEGF-A) inhibitor, bevacizumab, is a systemic treatment option. In this single institution study, we review our clinical experience in patients with NF2 who received bevacizumab for VS and evaluate the effect of bevacizumab treatment on VS growth and symptom progression. MATERIAL AND METHODS This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Three-dimensional volumetric data for VS were measured using manual segmentation with Visage PACS software under the direct supervision of a board-certified neuroradiologist. RESULTS Out of 76 patients with NF2 evaluated in the past 3 years, we identified 19 that received treatment with bevacizumab. Median age of NF2 diagnosis was 19 years (range 0.5-61) with a median NF2 phenotype severity score of 2 (range 1-3). Thirteen of these patients have discontinued bevacizumab, accounting for a median duration of 12.2 months (range 3.3-88 months) of bevacizumab treatment. Bevacizumab was discontinued due to hypertension (n=5), proteinuria and renal dysfunction (n=3), tumor progression (n=2), fatigue or other intolerance (n=2), or non-compliance (n=1). The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March 2023 (range 3.7-48.3 months). Fifteen patients had brain MRI data available to evaluate VS change during bevacizumab treatment, with partial response observed in 5 patients, stable disease in 8, and progression in 2. Ten of the 13 patients who stopped bevacizumab had MRI data to evaluate VS change following treatment termination. Within 6 months of bevacizumab discontinuation, 6 patients had rebound growth of their VS between 21-95% from their previous tumor volume, while 4 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. CONCLUSION Our single institution experience confirms that bevacizumab can slow progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Background: No standard schedule for cochlear implant (CI) programming has been developed, and common practices may have CI recipients seen in excess of what is necessary. The objective of this study was to review evidence for a de-escalated, evidence-based schedule for adult CI programming. Methods: Systematic review was undertaken in March 2023 of PubMed, Scopus, and CINAHL databases using the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included if (1) they evaluated an evidence-based programming/follow-up schedule in new adult CI patients or (2) they evaluated programming or outcomes in a longitudinal fashion such that they could inform CI follow-up strategies. Level of evidence was evaluated using the LEGEND evidence assessment tool. Results: Our review identified 940 studies. After screening with a priori inclusion criteria, 18 studies were ultimately included in this review. Of these, 2 demonstrated feasibility of de-escalated approaches to new adult CI programming. The remainder presented longitudinal speech and programming parameter data that demonstrated relative stability of both categories by 3 to 6 months post-activation. Conclusions: Overall, there is a paucity of literature evaluating any form of evidence-based CI programming or follow-up. Most applicable data derive from longitudinal outcomes featured in studies of other CI features, with only a handful of studies directly evaluating CI programming strategies over time. However, stability in outcomes and programming detailed in the available data supports consideration of a de-escalated programming paradigm that could primarily limit programming to the very early post-activation period (before 3 to 6 months) to enhance patient care and reduce operational strains on cochlear implant programs.

Objective Hearing loss is increasingly recognized as a chronic disease state with important health sequelae. Although considered a central component of routine audiometric testing, the degree to which various patient factors influence speech discrimination is poorly characterized to date. The primary objective of the current work was to describe associations of cognitive performance, sociodemographic factors, and pure-tone audiometry with speech discrimination in older adults. Study Design Prospective study. Setting Olmsted County, Minnesota. Patients There were 1,061 study participants 50 years or older at enrollment in the population-based Mayo Clinic Study of Aging between November 2004 and December 2019 who underwent formal audiometric and cognitive testing included in the current investigation. Main Outcome Measures The primary outcome measure was word recognition scores (WRSs; measured as <100% vs 100% as well as continuous), with pure-tone averages (PTAs; 0.5, 1, 2, and 3 kHz), age, sex, years of education, state area deprivation index (ADI) quintiles, and global cognition z scores as explanatory features. Results The mean (SD) age among the 1,061 participants was 76 (9) years with 528 (50%) males. Participant age [OR (95% CI) for a 10-year increase of 1.8 (1.4–2.3), p < 0.001], male sex [OR = 2.6 (1.9–3.7), p < 0.001], and PTA [OR for a 10-dB hearing loss increase of 2.4 (2.1–2.8), p < 0.001] were all significantly associated with <100% WRSs, with the greatest explanatory ability attributable to the PTA. Years of education (p = 0.9), state ADI quintile (p = 0.6), and global cognitive performance (p = 0.2) were not associated with WRS. The multivariable model demonstrated strong predictive ability for less than perfect WRSs, with a c index of 0.854. Similar results were seen for WRSs analyzed as continuous, with the multivariable model resulting in an R 2 value of 0.433. Conclusions Although PTA exhibited the greatest influence on speech discrimination, advancing age and male sex both independently increased the likelihood of having worse speech discrimination among older adults, even after accounting for years of education, neighborhood-level socioeconomic disadvantage, and cognitive function. These findings help identify patient factors that can be instrumental when designing screening programs for adult-onset hearing loss.

AbstractObjectiveTo evaluate the magnetic resonance (MR) image artifact and image distortion associated with the two transcutaneous bone conduction implants currently available in the United States.Study DesignCadaveric study.MethodsTwo cadaveric head specimens (1 male, 1 female) were unilaterally implanted according to manufacturer guidelines and underwent MR imaging (General Electric and Siemens 1.5 T scanners) under the following device conditions: (1) no device, (2) Cochlear Osia with magnet and headwrap, (3) Cochlear Osia without magnet, and (4) MED‐EL Bonebridge with magnet. Maximum metal mitigation techniques were employed in all conditions, and identical sequences were obtained. Blinded image scoring (diagnostic vs nondiagnostic image) was performed by experienced neuroradiologists according to anatomical subsites.ResultsAll device conditions produced artifact and image distortion. The Osia with magnet produced diagnostic T1‐ and T2‐weighted images of the ipsilateral temporal bone, however, non‐echo planar imaging diffusion‐weighted imaging (DWI) was nondiagnostic. The Osia without magnet scanned on the Siemens MR imaging demonstrated the least amount of artifact and was the only condition that allowed for diagnostic imaging of the ipsilateral temporal bone on DWI. The Bonebridge produced a large area of artifact and distortion with the involvement of the ipsilateral and contralateral temporal bones.ConclusionIn summary, of the three device conditions (Osia with magnet, Osia without magnet, and Bonebridge), Osia without magnet offered the least amount of artifact and distortion and was the only condition in which diagnostic DWI was available for the middle ear and mastoid regions on the Siemens MR imaging scanner.

Objective Compare cochlear implant (CI) performance between patients with ipsilateral sporadic vestibular schwannoma (VS) and NF2-related schwannomatosis (NF2). Compare CI performance according to VS management modality. Study Design Historical cohort. Setting Tertiary academic center. Patients Forty-nine patients (52 ears) undergoing cochlear implantation in the setting of ipsilateral sporadic (n = 21) or NF2-associated VS (n = 28). Interventions CI ipsilateral to VS. Main Outcome Measures Auditory thresholds, consonant–nucleus–consonant (CNC) word scores, and AzBio sentences in quiet scores. Results Among all patients, median post-CI pure tone average was 28 dB HL (interquartile range [IQR], 21–38), CNC word score was 39% (IQR, 6–62), and AzBio sentences in quiet score was 60% (IQR, 11–83) at a median of 12.5 months postimplantation. Despite the NF2 cohort having larger tumors, when comparing patients with sporadic versus NF2-associated VS, there were no statistically significant differences in CNC word (49% [30–70] vs. 31% [0–52]) or AzBio sentences in quiet (66% [28–80] vs. 57% [5–83]) scores. Regardless of NF2 status, all patients managed with observation, and radiosurgery achieved open-set speech. In patients who underwent microsurgery, 6 (46%) of 13 with NF2 achieved open-set speech recognition compared with 4 (67%) of 6 with sporadic disease. Conclusion Select patients with VS achieve successful hearing rehabilitation with a CI. In this cohort, tumor management strategy significantly influenced CI performance, whereas differences in NF2 status exhibited less effect. Specifically, all patients managed with observation or radiosurgery achieved open-set speech perception, whereas approximately half of people with NF2-related VS and two-thirds of people with sporadic VS achieved this outcome after tumor microsurgery. When disease permits, observation and radiosurgery should be considered in patients who may later pursue a CI.

This Viewpoint discusses how recent discoveries surrounding the natural history of sporadic vestibular schwannoma provide data to support a shift in current management paradigms.

Objective In certain cases, clinicians may consider continued observation of a vestibular schwannoma after initial growth is detected. The aim of the current work was to determine if patients with growing sporadic vestibular schwannomas could be stratified by the likelihood of subsequent growth based on initial growth behavior. Study Design Slice-by-slice volumetric tumor measurements from 3,505 serial magnetic resonance imaging studies were analyzed from 952 consecutively treated patients. Setting Three tertiary-referral centers. Patients Adults with sporadic vestibular schwannoma. Interventions Wait-and-scan. Main Outcome Measures Composite end point of subsequent growth- or treatment-free survival rates, where growth is defined as an additional increase of at least 20% in tumor volume from the volume at the time of initial growth. Results Among 405 patients who elected continued observation despite documented growth, stratification, of volumetric growth rate into less than 25% (reference: n = 107), 25 to less than 50% (hazard ratio [HR], 1.39; p = 0.06; n = 96), 50 to less than 100% (HR, 1.71; p = 0.002; n = 112), and at least 100% (HR, 2.01; p < 0.001; n = 90) change per year predicted the likelihood of future growth or treatment. Subsequent growth- or treatment-free survival rates (95% confidence interval) at year 5 after detection of initial growth were 31% (21–44%) for those with less than 25% growth per year, 18% (10–32%) for those with 25 to less than 50%, 15% (9–26%) for those with 50 to less than 100%, and 6% (2–16%) for those with at least 100%. Neither patient age (p = 0.15) nor tumor volume at diagnosis (p = 0.95) significantly differed across stratification groups. Conclusions At the time of diagnosis, clinical features cannot consistently predict which tumors will ultimately display aggressive behavior. Stratification by volumetric growth rate at the time of initial growth results in a stepwise progression of increasing likelihood of subsequent growth. When considering continued observation after initial growth detection, almost 95% of patients who have tumors that double in volume between diagnosis and the first detection of growth demonstrate further tumor growth or undergo treatment if observed to 5 years.

Objectives The current study characterizes age and incidence of cochlear implantation among qualifying children with congenital bilateral profound hearing loss in the U.S. Study Design Deidentified cochlear implantation data were acquired from prospectively collected patient registries from two cochlear implant (CI) manufacturers (Cochlear Americas and Advanced Bionics). Children <36 months old were assumed to have congenital bilateral profound sensorineural hearing loss. Setting U.S. CI centers. Patients Children <36 months old who received CIs. Interventions Cochlear implantation. Main Outcome Measures Age at implantation and incidence. Results A total of 4,236 children <36 months old underwent cochlear implantation from 2015 to 2019. The median age at implantation was 16 months (interquartile range, 12–24 mo) and did not change significantly during the 5-year study period (p = 0.09). Patients residing closer to CI centers (p = 0.03) and treated at higher-volume centers (p = 0.008) underwent implantation at a younger age. Bilateral simultaneous implantation increased from 38% to 53% of CI surgeries in 2015 and 2019, respectively. Children who received bilateral simultaneous CIs were younger compared with those receiving unilateral or bilateral sequential CIs (median, 14 versus 18 mo; p < 0.001). The incidence of cochlear implantation increased from 7,648 per 100,000 person-years in 2015 to 9,344 in 2019 (p < 0.001). Conclusion Although the incidence of pediatric CI recipients and the frequency of bilateral simultaneous implantation increased over the study period, age at implantation did not change significantly and far exceeded current Food and Drug Administration (9 mo) and American Academy of Otolaryngology and Head and Neck Surgery position statement (6–12 mo) guidelines.