Khandalavala, Karl R.

Abstract Background Evaluation of middle ear prostheses requires high-resolution imaging to assess position and structural integrity. Purpose To assess the diagnostic performance of photon-counting-detector (PCD)-CT for middle ear prosthesis imaging in cadaveric specimens. Materials and Methods Nine different middle ear prostheses were implanted in five fresh-frozen whole-head specimens, both in correct anatomic position and displaced to mimic malposition. Specimens were scanned on PCD-CT (NAEOTOM Alpha, Siemens) and energy-integrating-detector (EID)-CT (SOMATOM Force, Siemens), reconstructed at 0.2mm and 0.4mm, respectively. Eighteen cases (9 prostheses, 2 positions) per scanner were evaluated by two neuroradiologists (36 readings), blinded to scanner and position, who scored prosthesis position, reader confidence, and overall image quality. Agreement with the reference standard and between readers was compared. Results PCD-CT showed higher diagnostic confidence compared with EID-CT, while accuracy and inter-reader agreement did not demonstrate significant differences between scanners. Correct readings, PCD-CT versus EID-CT: lateral contact, 31/36 (86.1%; 95% CI: 58.3%-94.4%) vs. 29/36 (80.6%; 55.6%-91.7%), p = 0.500; medial contact, 30/36 (83.3%; 55.6%-94.4%) vs. 26/36 (72.2%; 50.0%-83.3%), p = 0.250. PCD-CT identified all cases of complete contact loss (score 3), while EID-CT missed one reading per contact. Inter-reader agreement may be higher with PCD-CT vs EID-CT (lateral: κw: 0.804 [0.578-0.941] vs. 0.571 [0.302-0.778], p = 0.250; medial: 0.684 [0.191-0.934] vs. 0.481 [0.024-0.835], p = 0.250). Reader confidence was significantly higher with PCD-CT; mean paired differences for Readers 1 and 2 were 9.4 (1.8-17.1; Holm-adjusted p = 0.019) and 23.1 points (13.4-32.7; p < 0.001) for lateral contact, and 16.4 (10.0-22.8; p < 0.001) and 17.8 points (6.8-28.8; p = 0.007) for medial contact. Readers preferred PCD-CT image quality in 16/18 (88.9%; 65.3%-98.6%) and 17/18 cases (94.4%; 72.7%-99.9%), respectively. Conclusion PCD-CT was associated with significantly higher reader confidence and preferred image quality, without significant differences in diagnostic accuracy or inter-reader agreement. These findings suggest PCD-CT is a promising modality for postoperative middle ear evaluations that warrants further investigations.

Objective: To describe cochlear implant outcomes in a patient with bilateral rapidly progressive hearing loss secondary to Kelch-like protein–11 (KLHL11) IgG rhombencephalitis. Patient: A 26-year-old male presenting to neurotology clinic at a tertiary care center for evaluation of bilateral rapidly progressive sensorineural hearing loss, unresponsive to systemic corticosteroid therapy. Interventions: Bilateral simultaneous cochlear implantation. Main Outcome Measures: Postimplant speech testing (CNC word, AzBio sentence scoring), and changes to hearing function with fluctuations in systemic disease symptomatology. Results: Preoperative testing demonstrated poor speech perception (bilateral AzBio sentence in quiet: 43%, right-sided CNCw score: 38%, and left-sided CNCw score: 0%). Despite systemic disease progression of KLHL11-IgG rhombencephalitis, including worsening cerebellar ataxia and dysarthria, cochlear implant performance did not decrease at the time of last follow-up. At 1-year, binaural and monaural speech testing were both significantly improved compared with the 1-month testing (bilateral AzBio sentence in quiet: 91%, right-sided CNCw score: 70%, and left-sided CNCw score: 32%). Conclusions: Cochlear implantation may offer meaningful auditory rehabilitation in patients with KLHL11-IgG associated rhombencephalitis with relative auditory nerve sparing, despite ongoing disease progression. Further studies are required to evaluate the durability and generalizability of cochlear implantation across the spectrum of disease-related hearing loss.

Objective: To synthesize the available evidence on medical therapies investigated for the management of NF2-related vestibular schwannomas (VS). Study design: Systematic review. Setting: Not applicable. Patients: NF2-related VS patients. Interventions: Systemic medical therapies. Main outcome measures: Tumor control and hearing outcomes. Results: Thirty studies met inclusion criteria: 18 investigated bevacizumab, 5 mTOR inhibitors, 5 tyrosine kinase inhibitors (TKIs), and 2 the vascular endothelial growth factor receptor (VEGFR) vaccine. Bevacizumab demonstrated the most consistent activity, with hearing improvement in up to 61% of patients, stable hearing in up to 84%, and tumor response in up to 60% (Level 4 evidence). Outcomes for mTOR inhibitors were variable, with 1 study stopped for futility, while others reported up to 100% hearing and tumor stability (Level 4 evidence). Five different TKIs showed hearing improvement rates ranging from 17 to 60% and tumor responses of 10 to 23.5% (Level 4 evidence). The VEGFR vaccine appeared safe and immunologically active, with radiologic and hearing improvement in one-third of patients (Level 4 evidence). Conclusions: Bevacizumab remains the most studied and clinically active systemic therapy for NF2-related VS, although evidence is largely nonrandomized. Other systemic therapies have demonstrated variable results in terms of hearing outcomes or tumor control. High-quality prospective and randomized controlled trials are needed to clarify efficacy, durability, and comparative effectiveness.

ABSTRACT Objective Management of vestibular schwannoma (VS) remains controversial. Very small VSs represent a pivotal group: on one hand, they pose the least risk to the patient from the perspective of being small; yet, not recommending treatment may result in missing a critical window for achieving the best outcome. This debate fundamentally hinges on whether treatment improves upon the natural history of the disease. There is an unproven assumption that very small tumors behave similarly to the broader observed population. To address this central question, we conducted a multicenter retrospective review to compare the natural history of tumor growth and hearing for patients with very small VS (1–3 mm) with a referent cohort with larger tumors. Methods All patients diagnosed with sporadic VS 1–3 mm were reviewed at 3 large skull base referral centers and compared with a referent cohort of patients with tumors > 3 mm. Tumor growth‐free survival rates, treatment‐free survival rates, and rates of maintenance of class A, B, or C hearing were estimated using the Kaplan–Meier method. Results In total, 123 patients with very small VS and a referent cohort of 326 patients were studied. Seventeen patients with very small VS experienced tumor growth at a median of 3.2 years after diagnosis (IQR 2.6–5.1), demonstrating a median growth rate of 1.0 mm per year (IQR 0.9–1.8). In comparison, 167 of the patients in the referent cohort experienced tumor growth at a median of 1.7 years after diagnosis (IQR 0.8–3.1). Tumor growth‐free survival rates (95% CI, number still at risk) at 5 years after diagnosis for the 2 cohorts were 84% (75–93, 39) and 45% (40–52, 100), respectively ( p < 0.001). Six patients with very small VS underwent treatment after tumor growth at a median of 3.2 years after diagnosis (IQR 3.2–3.8), compared with 138 patients in the referent cohort at a median of 2.2 years after diagnosis (IQR 1.4–3.6). Treatment‐free survival rates (95% CI, number still at risk) at 5 years after diagnosis for the 2 cohorts were 92% (86–98, 55) and 54% (49–61, 125), respectively ( p < 0.001). Among the 105 patients with very small VS and class A, B, or C hearing at diagnosis, 3 progressed to class D. Comparatively, among the 225 patients in the referent cohort with class A, B, or C hearing at diagnosis, 70 progressed to class D at a median of 2.6 years after diagnosis (IQR 1.0–4.8). Rates of maintenance of class A, B, or C hearing (95% CI, number still at risk) at 5 years after diagnosis were 96% (92–100, 28) for patients with very small VS and 65% (57–73, 70) for the referent cohort ( p < 0.001). Conclusions The natural history of tumor growth and hearing for very small VS diverges favorably from the cumulative natural history data and provides a more appropriate benchmark to compare clinical outcomes of upfront surgery or radiosurgery for this population. At 5 years after diagnosis, 96% of very small VS maintained class A, B, or C hearing and only 8% received treatment for growth within this multicenter cohort. Cumulatively, these data substantiate initial wait‐and‐scan management via size threshold surveillance in this population. Level of Evidence 3.

Objective: To systematically review studies evaluating systemic medical therapies for sporadic vestibular schwannoma (VS) and perform meta-analyses to assess associations with tumor control. Study design: Systematic review and meta-analysis. Setting: Not applicable. Patients: Sporadic VS patients. Interventions: Systemic medical therapies. Main outcome measures: Tumor growth. Results: Nine retrospective studies met criteria: 5 on nonsteroidal anti-inflammatory drugs (NSAIDs), 3 on metformin, and 1 on losartan (all level 3 evidence). A meta-analysis of ORs from 5 studies demonstrated no significant association between aspirin use and tumor growth (pooled OR: 0.77; 95% CI: 0.48-1.23; I²: 76%). Conversely, a meta-analysis of ORs from 3 studies on metformin showed significantly lower odds of tumor growth (pooled OR: 0.46; 95% CI: 0.30-0.72; I²: 0%). The study on losartan did not identify a statistically significant association of losartan with tumor growth. Less than half of the studies reported HRs to appropriately reflect the inherently time-dependent nature of tumor growth. Conclusions: Evidence for systemic therapies in sporadic VS remains preliminary. Our meta-analysis of ORs demonstrates that NSAID use is not significantly associated with tumor growth, metformin users had lower odds of tumor growth, and evidence for losartan remains limited; however, all available studies provide only level 3 evidence. At present, there is insufficient data to recommend routine use of aspirin, metformin, or losartan with the intent of mitigating VS tumor growth during wait-and-scan management. High-quality prospective studies with appropriate time-to-event methodology to assess tumor growth are required to establish the clinical utility of systemic therapies in the management of patients with sporadic VS.

Objective: To explore the existing evidence on novel imaging modalities that may aid in prognostication of vestibular schwannoma (VS) clinical outcomes across various management approaches. Study design: Scoping review. Setting: Not applicable. Patients: Individuals diagnosed with VS. Interventions: Novel imaging techniques. Main outcome measures: Tumor growth and response to medical therapy. Results: A total of 18 articles were included in this review. Of these, 7 focused on pretreatment prognosis, 6 evaluated radiosurgery outcomes, 4 examined microsurgery outcomes, and 1 assessed response to bevacizumab. The imaging modalities investigated included radiomics (n = 10), positron emission tomography (PET; n = 2), dynamic contrast-enhanced MRI (DCE-MRI; n = 2), both PET and DCE-MRI (n = 1), magnetic resonance elastography (MRE; n = 1), contrast-enhanced CT (CE-CT; n = 1), and slip interface imaging (SII; n = 1). Radiomic studies yielded encouraging results in predicting tumor growth after wait-and-scan and radiosurgery, with reported accuracies ranging from 52% to 88%, sensitivities from 13% to 95%, specificities from 50% to 94%, and area under the curves from 0.65 to 0.99. PET studies identified several promising ligands associated with tumor growth during wait-and-scan, suggesting a potential role in prognostication. DCE-MRI also demonstrated associations with tumor growth and treatment response to bevacizumab. Studies on MRE, CE-CT, and SII identified novel imaging parameters associated with tumor stiffness and adhesion. Conclusions: Several emerging imaging modalities hold potential for improving clinical outcome prognostication in VS. Techniques such as radiomics, PET, and DCE-MRI have shown promising results; however, the supporting evidence is still limited and heterogeneous. Further research is necessary to validate and refine these approaches to enhance their clinical utility.

Objective: Cochlear implantation (CI) under local anesthesia facilitates intraoperative behavioral patient feedback to potentially improve acoustic hearing preservation and limit intracochlear trauma. Patient feedback during electrode insertion is potentially confounded by loudness adaptation, a perception of tone decrease despite stable presentation, or insufficient intensity discrimination, a failure to detect a change in hearing despite one actually occurring. Both loudness adaptation and intensity discrimination are critical factors for awake CI and have not been systematically studied in the CI candidate population. Patients: Adult candidates for CI. Interventions: Under routine audiometric testing conditions in a soundproof booth, a standard behavioral audiogram, audiogram obtained in recorded ambient operating room (OR) noise, loudness adaptation to sustained suprathreshold (+10 and +20 dB) pure tones at 500, 1000, 2000, and 4000 Hz in both quiet and in ambient OR noise, and intensity discrimination to sustained suprathreshold (+10 and +20 dB) pure tones at 500, 1000, 2000, and 4000 Hz were performed. Main outcome measures: Pure tone average (PTA) in quiet and in ambient OR noise, proportion of patients reporting loudness adaptation at different suprathreshold levels and frequencies, and reliability of intensity discrimination. Results: In total, 20 ears were included for study. The median PTA was similar between testing in quiet (68 dB, IQR: 63 to 73) and in ambient OR noise (68 dB, IQR: 62 to 73). Most participants (n = 11, 55%) reported loudness adaptation when testing at +10 dB suprathreshold intensity, with a decreased proportion (n = 8, 40%) demonstrating adaptation at the higher tone intensity (+20 dB suprathreshold). Loudness adaptation varied among frequencies, with a trend toward increasing adaptation at higher frequencies at both testing intensities. Participants demonstrated excellent intensity discrimination, detecting a 5 dB difference when testing at +10 dB both in quiet and with background OR noise in 82 of the 85 (96%) tests performed across the frequency range, although with lower intensity discrimination at +20 dB, particularly in background OR noise. Conclusions: For CI candidates, pure tone audiometric performance did not significantly differ in background OR noise, confirming the reliability of intraoperative audiometric testing. For optimal tone presentation, there is decreasing loudness adaptation with increased tone presentation (+20 dB suprathreshold) and in lower frequencies of tone presentation. Intensity discrimination was reliable at a 5 dB increment across a range of testing parameters.

Objective: To evaluate hearing outcomes after treatment with stereotactic radiosurgery (SRS) for sporadic vestibular schwannoma (VS) among patients with baseline 100% word recognition scores (WRS). Study design: Historical cohort. Setting: Tertiary academic medical center. Patients: Patients with 100% WRS on audiometric testing at initial treatment with SRS. Interventions: Gamma Knife SRS. Main outcome measures: Rate of maintaining serviceable hearing (SH), defined as American Academy of Otolaryngology-Head and Neck Surgery hearing class A or B. Results: In total, 125 patients had 100% WRS at SRS for sporadic VS. Median age at SRS was 56 years (IQR: 51 to 62) and median pure tone average (PTA) at SRS was 20 dB HL (IQR: 13 to 31). Sixty-eight patients progressed to non-SH at a median of 3.4 years after SRS (IQR: 1.0 to 8.6); the median duration of follow-up for the 57 patients who maintained SH was 5.1 years (IQR: 2.8 to 9.6). Rates of maintaining SH (95% CI, number still at risk) at 1, 3, 5, 7, and 10 years after SRS were 88% (82 to 94, 101), 75% (68 to 84, 81), 61% (53 to 71, 55), 58% (49 to 68, 43), and 44% (35 to 56, 26), respectively. Each 10-dB HL increase in PTA at SRS was associated with a 52% increased risk of progression to non-SH (hazard ratio: 1.52, 95% CI: 1.24-1.87, P <0.001). Conclusions: Despite having 100% pretreatment WRS, most patients with sporadic VS treated with SRS experienced clinically significant hearing decline over time. Even among this cohort of patients with excellent baseline hearing, at 10 years after treatment, only 44% of patients maintained SH.

OBJECTIVE The objective of this study was to describe the long-term efficacy of single-fraction stereotactic radiosurgery (SRS) for the primary treatment of sporadic vestibular schwannoma. METHODS Adult (≥ 18 years of age) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients met inclusion criteria, the majority (n = 566, 76%) of whom had tumors extending into the cerebellopontine angle at SRS. The median patient age at SRS was 62 years, half (50%) of the patients were women, and 744 (99%) exhibited House-Brackmann grade I facial nerve function at SRS. A total of 42 patients experienced radiosurgical failure and underwent salvage treatment; the median duration of follow-up for the patients who did not undergo salvage treatment was 7.0 years. Overall tumor control rates (95% CI, number still at risk) at 1, 3, 5, 10, and 15 years after SRS were 100% (100%–100%, 718), 98% (97%–99%, 589), 96% (94%–97%, 464), 92% (90%–95%, 258), and 91% (89%–94%, 125), respectively. Patient age (hazard ratio [HR] for a 10-year increase of 0.92, 95% CI 0.71–1.19; p = 0.5), presence of a macrocystic tumor (HR 0.59, 95% CI 0.14–2.46; p = 0.5), and treated tumor volume (HR for a 1-cm 3 increase of 1.02, 95% CI 0.88–1.18; p = 0.8) were not significantly associated with the risk of salvage. Three distinct post-SRS tumor behavior patterns were observed, with 13% of patients demonstrating tumor pseudoprogression, all but 4 of whom demonstrated pseudoprogression by year 5 post-SRS. CONCLUSIONS SRS demonstrates durable tumor control through 15 years of follow-up in most patients (91%); however, a minority are found to still experience SRS failure even beyond 10 years of surveillance. Although occurring in only a minority of patients, tumor pseudoprogression can be evident out to 5 years or longer post-SRS.

OBJECTIVE Wait-and-scan surveillance is now commonly employed for initial management of small- and medium-sized vestibular schwannomas. Although small differences in tumor size are unlikely to impact outcomes significantly, treatment with either radiosurgery or microsurgery is usually recommended following radiological detection of tumor growth. The objective of the current study was to identify potential inflection points in vestibular schwannoma tumor size, where the risks of treatment with single-fraction stereotactic radiosurgery (SRS) accelerate to inform timing of intervention. METHODS Adult (≥ 18 years old) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients with a median age at SRS of 62 years were studied, the majority (n = 566 [76%]) of whom had tumors extending into the cerebellopontine angle (CPA) at SRS. The optimal tumor size cut point to predict SRS failure and need for salvage treatment was 4 mm or more of CPA extension (c-index 0.59, HR 3.60, p = 0.01). The optimal tumor size cut point to predict the outcome of facial nerve paresis was 13 mm or more of CPA extension, resulting in a c-index of 0.63 (HR 2.88, p = 0.01). Among patients with at least 3 months of surveillance before SRS, those with a tumor growth rate ≥ 2.5 mm/year were more likely to undergo salvage treatment than those with a growth rate < 2.5 mm/year, although this difference did not achieve statistical significance (HR 1.82, p = 0.18). CONCLUSIONS The risk of SRS failure requiring salvage treatment and the risk of post-SRS facial nerve paralysis increase at sizes of approximately 4 and 13 mm extension into the CPA, respectively, providing a size threshold anchor to help guide treatment decision-making regarding timing of SRS. Furthermore, rapid tumor growth during the initial wait-and-scan period may be associated with an increased risk of radiosurgical failure, which may influence choice of treatment.