Citations

Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68+ macrophages to S100+ macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68+ cells were present at significantly higher concentrations in tumors that progressed (p = 0.03). Higher macrophage density was significantly associated with both tumor progression (p = 0.02) and unfavorable facial nerve function (p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint (p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.

Objective: To report the presentation, diagnosis, management, and convalescence of labyrinthine sequestrum (LS) and summarize all previously published cases. Patient(s): Eleven-year-old female with LS. Intervention(s): Multidisciplinary diagnostic evaluation and treatment. Main Outcome Measures: Imaging and laboratory findings, medical and surgical treatment. Results: We describe a case of LS secondary to medically recalcitrant suppurative otitis media in an 11-year-old female and review all eight previously reported cases. The index patient presented after 6 months of otitis media, profound unilateral hearing loss, with symptoms suggesting meningitis. Temporal bone CT demonstrated marked bony destruction of the left otic capsule. Gadolinium-enhanced MRI showed an enhancing process with evidence of meningitis and subdural empyema. The patient was treated with surgical debridement and culture directed antibiotic therapy. Posttreatment imaging showed resolution of intracranial infection with fibrous bony healing of the otic capsule resembling fibrous dysplasia. Conclusion: LS is a rare form of labyrinthitis characterized by centrifugal destruction of the otic capsule. The current index case highlights the importance of combined medical and surgical treatment and describes for the first time in the literature the fibrous ossification of the otic capsule following disease resolution.

Objective: To describe audiometric outcomes following stereotactic radiosurgery (SRS) for jugular paraganglioma (JP). Study Design: Retrospective review. Setting: Tertiary referral center. Patients: Patients with pretreatment serviceable hearing (American Academy of Otolaryngology—Head and Neck Surgery [AAO-HNS] Class A or B) and serial post-SRS audiometric follow-up who underwent Gamma Knife SRS for JP between 1990 and 2017. Intervention(s): Gamma Knife SRS. Main Outcome Measures: Progression to nonserviceable hearing; correlation between baseline hearing and treatment parameters with audiometric outcomes. Results: Of 85 patients with JP who underwent SRS during the study period, 35 (66% female, median age 53) had pretreatment serviceable hearing and serial post-treatment audiometry available for review. Median tumor volume at the time of treatment was 7,080 mm3, median cochlear point dose was 5.8 Gy (interquartile range [IQR] 4.1 to 7.3 Gy), and median marginal and maximum tumor doses were 16 and 32 Gy, respectively. After a median follow-up of 37 months (IQR 16 to 77 mo), the median change in pure-tone average and speech discrimination score in the treated ear was −1.2 dB HL/yr (IQR −4.5 to 0.3) and 0%/yr (IQR 0–3.5%), compared with 0.07 dB HL/yr (IQR −0.03 to 0.12) and 0 %/yr (IQR 0 to 0%) in the contralateral untreated ear. Seven patients developed nonserviceable hearing (AAO-HNS Class C or D) at a median of 13.2 months following SRS (IQR 4.8 to 24 mo). Among those who maintained serviceable hearing, median audiometric follow-up was 42 months (IQR 18 to 77 mo). The Kaplan–Meier estimated rates of serviceable hearing at 1, 3, and 5 years following SRS were 91%, 80%, and 80%, respectively. Sixty percent of patients with pulsatile tinnitus who underwent SRS experienced varying levels of symptomatic improvement following treatment. Conclusion: The short- and intermediate-term risk of progression to nonserviceable hearing following SRS for JP is low. Data regarding the impact of cochlear dose from the vestibular schwannoma literature should not be freely applied to JP, since the impact of SRS parameters on hearing preservation seems to be less significant.

Objective: To examine practice variance of cochlear implant candidacy assessment and off-label indications across centers in the United States. Methods: Cross-sectional survey of the American Neurotology Society (ANS). Results: A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting ACGME accreditation in neurotology and employment at an academic center. The annual volume of cochlear implant surgeries varied considerably across centers. Seventy-eight percent of respondents performed cochlear implantation for at least one of the following indications within the last 2 years: profound hearing loss in children less than 12 months of age (35, 43%), children with asymmetrical hearing loss where at least one ear was better than performance cutoff for age (25, 31%), adults with asymmetrical hearing where at least one ear was better than the performance cutoff for adult criteria (49, 61%), single-sided deafness (37, 46%), and ipsilateral vestibular schwannoma (28, 35%). Centers with a higher annual implant volume more frequently performed off-label implantation in all queried populations (all, p≤0.001), and performed surgery on infants with congenital deafness at a younger age (p = 0.013), compared with centers with lower surgical volume. When surveyed regarding speech perception testing practices for adult candidacy assessment, 75 (100%) respondents who answered this question reported routine use of AzBio sentences, 42 (56%) CNC word scores, and 26 (35%) HINT testing; only 7 (9%) reported using BKB-SIN testing and 6 (8%) reported using CUNY scores. Fifty-one (68%) reported routine use of speech-in-noise testing to determine adult cochlear implant candidacy, 21 (28%) reported selective use only when patient scores were borderline in quiet, and 3 (4%) reported that their center does not currently use testing in noise for candidacy determination. Nineteen (26%) solely used +10 dB signal-to-noise ratio (SNR), 12 (16%) solely used +5 dB SNR, and 41 (55%) used both +10 and +5 dB SNR. Overall, 19% (N = 14) only perform unilateral implantation in the Medicare population, while 81% (N = 58) consider bilateral implantation. Conclusion: Significant variation in cochlear implant candidacy assessment and off-label implantation exists across centers and providers in the United States resulting in healthcare inequities. The high percentage of surgeons performing implantations for off-label or nontraditional indications reflects the overly restrictive and dated status of current implant guidelines. With greater adoption of more difficult speech perception testing in noise, careful clinical judgment is needed to maintain a favorable risk–benefit balance for prospective implant candidates.

Objective: To examine surgical and device-related cochlear implant practice patterns across centers in the United States. Methods: Cross-sectional survey of the American Neurotology Society (ANS). Results: A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting Accreditation Council for Graduate Medical Education (ACGME) accreditation in neurotology and employment at an academic center. The annual volume of cochlear implant surgeries varied considerably across centers. Eighty percent of respondents report to offer all three Food and Drug Administration (FDA) approved device brands at their center. In cases where hearing preservation is not a goal, 56% of respondents prefer a perimodiolar electrode design, while 44% prefer a lateral wall electrode. With regard to insertion technique for scala tympani access, 64% prefer inserting through the round window (RW) membrane, 26% prefer an extended round window (ERW) approach, while only 10% prefer a cochleostomy. In cases where hearing preservation is a goal of surgery, 86% of respondents prefer a lateral wall electrode design, while only 14% prefer a perimodiolar electrode design. With regard to insertion technique, 86% prefer RW insertion, while only 9% prefer an ERW approach, and only 5% prefer a cochleostomy. Respondents who prefer RW electrode insertion more commonly use a lateral wall electrode, whereas those who prefer an ERW or cochleostomy approach more commonly use a periomodiolar electrode (p < 0.001). There was a statistically significant greater number of surgeons that prefer lateral wall electrodes (p < 0.001) and RW insertion (p < 0.001) for hearing preservation cases compared with non-hearing preservation cases. For implantation of a hypothetical patient with significant residual hearing, within the range of hybrid device candidacy, the great majority of surgeons prefer a conventional length electrode and only 29% prefer to implant a hybrid device. In cases where hearing preservation is a goal, the overwhelming majority of respondents (96%, n = 74) reported using at least one form of steroid application. Ninety-two percent (n = 71) used intraoperative intravenous steroids, 55% (n = 42) prescribed postoperative oral steroids, 44% (n = 34) bathed the middle ear with steroids during surgery, and 30% (n = 23) prescribed preoperative oral steroids. Together, 65% of respondents use a variation of the tight subperiosteal pocket technique for internal device fixation, 19% prefer a bony well and trough with tie-downs, 10% prefer a bony well and trough without tie-downs, and 5% prefer a screw fixation system. Of the 50 who prefer utilizing a subperiosteal pocket, 31 (62%) incorporate a bony trough and 19 (38%) perform a subperiosteal pocket alone without a bony trough. Conclusion: The results of this survey reflect the evolution in surgical and device-related preferences for cochlear implantation in the United States. An increasing number of surgeons prefer the RW approach for electrode insertion. When hearing preservation is not a goal, there is a near even preference for lateral wall and perimodiolar electrode designs; however, the great majority of surgeons prefer a lateral wall design when attempting to preserve residual acoustic hearing. Even in cases where substantial residual hearing exists, many surgeons prefer conventional length electrodes to hybrid designs. These changes reflect the prioritization of atraumatic surgery and parallel the development of thinner and more atraumatic electrodes.

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

OBJECTIVE Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients. METHODS Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression. RESULTS Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097–0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01–0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9). CONCLUSIONS The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.