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William R. Copeland, Grant W. Mallory, Brian A. Neff, Colin L. W. Driscoll and Michael J. Link

OBJECT

The following study was conducted to identify risk factors for a postoperative CSF leak after vestibular schwannoma (VS) surgery.

METHODS

The authors reviewed a prospectively maintained database of all patients who had undergone resection of a VS at the Mayo Clinic between September 1999 and May 2013. Patients who developed a postoperative CSF leak within 30 days of surgery were compared with those who did not. Data collected included patient age, sex, body mass index (BMI), tumor size, tumor side, history of prior tumor treatment, operative time, surgical approach, and extent of resection. Both univariate and multivariate regression analyses were performed to evaluate all variables as risk factors of a postoperative CSF leak.

RESULTS

A total of 457 patients were included in the study, with 45 patients (9.8%) developing a postoperative CSF leak. A significant association existed between increasing BMI and a CSF leak, with those classified as overweight (BMI 25–29.9), obese (BMI 30–39.9), or morbidly obese (BMI ≥ 40) having a 2.5-, 3-, and 6-fold increased risk, respectively. Patients undergoing a translabyrinthine (TL) approach experienced a higher rate of CSF leaks (OR 2.5, 95% CI 1.3–4.6; p = 0.005), as did those who had longer operative times (OR 1.04, 95% CI 1.02–1.07; p = 0.0006). The BMI, a TL approach, and operative time remained independent risk factors on multivariate modeling.

CONCLUSIONS

Elevated BMI is a risk factor for the development of a postoperative CSF leak following VS surgery. Recognizing this preoperatively can allow surgeons to better counsel patients regarding the risks of surgery as well as perhaps to alter perioperative management in an attempt to decrease the likelihood of a leak. Patients undergoing a TL approach or having longer operative times are also at increased risk of developing a postoperative CSF leak.

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Kathryn M. Van Abel, Matthew L. Carlson, Colin L. Driscoll, Brian A. Neff and Michael J. Link

Object

The authors' objective was 2-fold: 1) to compare outcomes of microsurgical resection for vestibular schwannoma (VS) between patients aged 70 years or older and patients younger than 70 years and 2) to test the hypothesis that symptomatic tumors in elderly patients represent a more aggressive variant of VS than those in younger adults, resulting in increased morbidity and a higher rate of recurrence after subtotal resection (STR).

Methods

A retrospective matched cohort study was conducted. Patients aged 70 years or older who had undergone microsurgical resection of VS were matched to adult patients younger than 70 years; the matching was performed on the basis of surgical approach, completeness of resection, and tumor size. Associations between clinical, radiographic, and surgical data and postoperative outcome were analyzed using conditional logistic regression.

Results

Twenty patients aged 70 years or older (mean age ± SD 75.9 ± 5.3, range 70–86 years) were identified and matched to a cohort of younger adult patients (mean age ± SD 55.7 ± 13.8, range 25–69 years). The mean tumor size in both groups was approximately 3 cm. Overall, the elderly patients had a poorer preoperative American Society of Anesthesiology physical status score (p = 0.038), were more likely to report imbalance (OR 9.61, p = 0.016), and more commonly exhibited compromised balance and coordination (OR 9.61, p = 0.016) than patients in the younger cohort.

There were no differences between the 2 cohorts in perioperative complications (p = 0.26) or facial nerve function (p > 0.5) at any time. The elderly patients were 13 times more likely to have long-term postoperative imbalance (OR 13.00, p = 0.013) than the younger patients. Overall, 9 tumors recurred among 32 patients undergoing STR; 6 of these patients underwent additional interventions (stereotactic radiosurgery in 5 patients and microsurgery in 1) and showed no evidence of tumor progression at the last follow-up. The median growth rate of the recurrent tumor in the 6 elderly patients was 4.8 mm/year (range 2.1–14.9 mm/year) and, in the 3 control patients, 2.2 mm/year (range 1.9–4.0 mm/year). Overall, the mortality data showed a trend toward statistical significance (p = 0.068) with a higher risk of death in the elderly.

Conclusions

As the number of elderly patients with VS increases, microsurgical resection will remain an important management option for these patients. Despite a poorer preoperative physical status in elderly patients, their morbidity profiles are similar to those in adult patients younger than 70 years. However, elderly patients may require longer convalescence due to prolonged postoperative imbalance. Not surprisingly, overall diminished functional reserve and advanced comorbidities may increase the mortality risk associated with surgical intervention in the elderly patients. Finally, there was a high risk of further tumor growth following STR in the elderly patients (6 [37.5%] of 16), underscoring the need for close postoperative radiological surveillance and consideration of early stereotactic radiosurgery for the tumor remnant following the STR.

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Matthew L. Carlson, Jeffrey T. Jacob, Bruce E. Pollock, Brian A. Neff, Nicole M. Tombers, Colin L. W. Driscoll and Michael J. Link

Object

The goals of this retrospective cohort study were as follows: 1) to describe the long-term prevalence and timing of hearing deterioration following low-dose (12- to 13-Gy marginal dose) stereotactic radiosurgery (SRS) for vestibular schwannoma (VS); and 2) to identify clinical variables associated with long-term preservation of useful hearing following treatment.

Methods

Patients with serviceable hearing who underwent SRS for VS between 1997 and 2002 were studied. Data including radiosurgery treatment plans, tumor characteristics, pre- and posttreatment pure tone average, speech discrimination scores, and American Academy of Otolaryngology–Head and Neck Surgery hearing class were collected. Time to nonserviceable hearing was estimated using the Kaplan-Meier method. Univariate and multivariate associations with time to nonserviceable hearing were evaluated using Cox proportional hazards regression models.

Results

Forty-four patients met the study criteria and were included. The median duration of audiometric follow-up was 9.3 years. Thirty-six patients developed nonserviceable hearing at a mean of 4.2 years following SRS. The Kaplan-Meier estimated rates of serviceable hearing at 1, 3, 5, 7, and 10 years following SRS were 80%, 55%, 48%, 38%, and 23%, respectively. Multivariate analysis revealed that pretreatment ipsilateral pure tone average (p < 0.001) and tumor size (p = 0.009) were statistically significantly associated with time to nonserviceable hearing.

Conclusions

Durable hearing preservation a decade after low-dose SRS for VS occurs in less than one-fourth of patients. Variables including preoperative hearing capacity and tumor size may be used to predict hearing outcomes following treatment. These findings may assist in pretreatment risk disclosure. Furthermore, these data demonstrate the importance of long-term follow-up when reporting audiometric outcomes following SRS for VS.

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Brian A. Neff, Matthew L. Carlson, Megan M. O'Byrne, Jamie J. Van Gompel, Colin L. W. Driscoll and Michael J. Link

OBJECTIVE

The aim of this study was to evaluate the incidence, presentation, and treatment outcomes of trigeminal nerve–mediated symptoms secondary to large vestibular schwannomas (VSs) with trigeminal nerve contact. Specifically, the symptomatic results of pain, paresthesias, and numbness after microsurgical resection or stereotactic radiosurgery (SRS) were examined.

METHODS

The authors conducted a retrospective review of a database for concomitant diagnosis of trigeminal neuralgia (TN) or trigeminal neuropathy and VS between 1994 and 2014 at a tertiary academic center. All patients with VS with TN or neuropathy were included, with the exception of those patients with neurofibromatosis Type 2 and patients who elected observation. Patient demographic data, symptom evolution, and treatment outcomes were collected. Population data were summarized, and outcome comparisons between microsurgery and SRS were analyzed at last follow-up.

RESULTS

Sixty (2.2%) of 2771 total patients who had large VSs and either TN or neuropathy symptoms met inclusion criteria. The average age of trigeminal symptom onset was 53.6 years (range 24–79 years), the average age at VS diagnosis was 54.4 years (range 25–79 years), and the average follow-up for the microsurgery and SRS groups was 30 and 59 months, respectively (range 3–132 months). Of these patients, 50 (83%) had facial numbness, 16 (27%) had TN pain, and 13 (22%) had paresthesias (i.e., burning or tingling). Subsequently, 50 (83%) patients underwent resection and 10 (17%) patients received SRS.

Treatment of VS with SRS did not improve trigeminal symptoms in any patient. This included 2 subjects with unimproved facial numbness and 4 patients with worsened numbness. Similarly, SRS worsened TN pain and paresthesias in 5 patients and failed to improve pain in 2 additional patients. The Barrow Neurological Institute neuralgia and hypesthesia scale scores were significantly worse for patients undergoing SRS compared with microsurgery.

Resection alleviated facial numbness in 22 (50%) patients, paresthesias in 5 (42%) patients, and TN in 7 (70%) patients. In several patients, surgery was not successful in relieving facial numbness, which failed to improve in 17 (39%) cases and became worse in 5 (11%) cases. Also, surgery did not change the intensity of facial paresthesias or neuralgia in 6 (50%) and 3 (25%) patients, respectively. Microsurgery exacerbated facial paresthesias in 1 (8%) patient but, notably, did not aggravate TN in any patient.

CONCLUSIONS

Overall, resection of large VSs provided improved outcomes for patients with concomitant TN, facial paresthesia, and numbness compared with SRS. However, caution should be used when counseling surgical candidates because a number of patients did not experience improvement. This was especially true in patients with preoperative facial numbness and paresthesias, who frequently reported that these symptoms were unchanged following surgery.

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Neil S. Patel, Matthew L. Carlson, Michael J. Link, Brian A. Neff, Jamie J. Van Gompel and Colin L. W. Driscoll

OBJECTIVE

The object of this study was to ascertain outcomes of cochlear implantation (CI) following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS).

METHODS

The authors conducted a retrospective chart review of adult patients with VS treated with SRS who underwent CI between 1990 and 2019 at a single tertiary care referral center. Patient demographics, tumor features, treatment parameters, and pre- and postimplantation audiometric and clinical outcomes are presented.

RESULTS

Seventeen patients (18 ears) underwent SRS and ipsilateral CI during the study period. Thirteen patients (76%) had neurofibromatosis type 2 (NF2). Median age at SRS and CI were 44 and 48 years, respectively. Median time from SRS to CI was 60 days, but notably, 4 patients underwent SRS and CI within 1 day and 5 patients underwent CI more than 7 years after SRS. Median marginal dose was 13 Gy. Median treatment volume at the time of SRS was 1400 mm3 (range 84–6080 mm3, n = 15 patients). Median post-CI PTA was 28 dB HL, improved from 101 dB HL preoperatively (p < 0.001). Overall, 11 patients (12 ears) exhibited open-set speech understanding. Sentence testing was performed at a median of 10 months (range 1–143 months) post-CI. The median AzBio sentence score for patients with open-set speech understanding was 76% (range 19%–95%, n = 10 ears). Two ears exhibited Hearing in Noise Test (HINT) sentence scores of 49% and 95%, respectively. Four patients achieved environmental sound awareness without open-set speech recognition. Two had no detectable auditory percepts.

CONCLUSIONS

Most patients who underwent CI following SRS for VS enjoyed access to sound at near-normal levels, with the majority achieving good open-set speech understanding. Implantation can be performed immediately following SRS or in a delayed fashion, depending on hearing status as well as other factors. This strategy may be applied to cases of sporadic or NF2-associated VS.

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Matthew L. Carlson, Kathryn M. Van Abel, William R. Schmitt, Colin L. W. Driscoll, Brian A. Neff, John I. Lane and Michael J. Link

Object

The authors describe the unique occurrence of nodular enhancement within the fundus of the internal auditory canal (IAC) lateral to the preoperative radiological tumor margin following gross-total vestibular schwannoma (VS) resection.

Methods

The nature of the study was a retrospective chart review of records. The authors reviewed the cases of all patients who underwent microsurgical resection of a VS between January 2000 and January 2010 at a single tertiary referral center. Patients with incomplete resection, neurofibromatosis Type 2, and those with fewer than 2 postoperative MR images available for review were excluded.

Postsurgical patients with IAC enhancement located lateral to the preoperative imaging–delineated tumor margin were identified. Lesion morphology was characterized on serial MR imaging studies. Clinical follow-up and outcomes were recorded.

Results

Over the past decade, 350 patients underwent microsurgical VS resection. Of these, 16 patients met study criteria and were found to have postsurgical enhancement in the distal aspect of the IAC lateral to the imaging limits of the preoperative tumor margin on the first postoperative MR imaging study (37.5% women, median age 45 years). Initial MR imaging was performed at a mean of 3.1 months following surgery, and the mean radiological follow-up duration was 39.8 months (range 16.4–101.9 months). None of the 16 patients developed recurrence during the follow-up course.

Conclusions

In contrast to previous publications that have reported a high rate of recurrence in cases involving nodular enhancement within the original tumor bed, postoperative enhancement in the IAC lateral to the original tumor margin appears to carry much less risk for tumor recurrence. These findings may be helpful when counseling patients on the recommended frequency of postoperative follow-up imaging.

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Matthew L. Carlson, Dusica Babovic-Vuksanovic, Ludwine Messiaen, Bernd W. Scheithauer, Brian A. Neff and Michael J. Link

Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of benign tumors of the peripheral nervous system and the CNS, including schwannomas, meningiomas, and ependymomas. The gene responsible for the development of NF2 acts as a tumor suppressor gene. Stereotactic radiotherapy (SRT) or single-fraction stereotactic radiosurgery has been increasingly used in the past decades to treat benign tumors in patients with NF2. These radiotherapy methods are less invasive and can be potentially used to treat multiple tumors in a single session. The risk of inducing malignancy is unclear. Few reports exist of malignant peripheral nerve sheath tumors, meningiomas, or ependymomas occurring after SRT or stereotactic radiosurgery in patients with NF2. The authors present the first documented case of rhabdomyosarcoma following SRT for multiple NF2-associated schwannomas. Compared with patients with sporadic tumors, NF2 patients having a germline tumor suppressor gene defect may be more prone to secondary malignancies after treatment involving radiation therapy.

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William R. Schmitt, Jasper R. Daube, Matthew L. Carlson, Jayawant N. Mandrekar, Charles W. Beatty, Brian A. Neff, Colin L. Driscoll and Michael J. Link

Object

The goal of vestibular schwannoma surgery is tumor removal and preservation of neural function. Intraoperative facial nerve (FN) monitoring has emerged as the standard of care, but its role in predicting long-term facial function remains a matter of debate. The present report seeks to describe and critically assess the value of applying current at supramaximal levels in an effort to identify patients destined for permanent facial paralysis.

Methods

Over more than a decade, the protocol for stimulating and assessing the FN during vestibular schwannoma surgery at the authors' institution has consisted of applying pulsed constant-current stimulation at supramaximal levels proximally and distally following tumor resection to generate an amplitude ratio, which subtracted from 100% yields the degree to which the functional integrity of the FN “dropped off” intraoperatively. These data were prospectively collected and additional variables that might impact postoperative FN function were retrospectively reviewed from the medical record. Only patients with anatomically intact FNs and > 12 months of follow-up data were analyzed.

Results

There were 267 patients available for review. The average posterior fossa tumor diameter was 24 mm and the rate of long-term good (House-Brackmann Grade I–II) FN function was 84%. Univariate logistic regression analysis revealed that prior treatment, neurofibromatosis Type 2 status, tumor size, cerebellopontine angle extension, subjectively thinned FN at the time of operation, minimal stimulation threshold, percent dropoff by supramaximal stimulation (SMS), and postoperative FN function all correlated statistically (p < 0.05) with long-term FN function. When evaluating patients with significant FN weakness at the time of hospital discharge, only the percent dropoff by SMS remained a significant predictor of long-term FN function. However, the positive predictive value of SMS for long-term weakness is low, at 46%.

Conclusions

In a large cohort of patients, the authors found that interrogating intraoperative FN function with SMS is safe and technically simple. It is useful for predicting which patients will ultimately have good facial function, but is very limited in identifying patients destined for long-term facial weakness. This test may prove helpful in the future in tailoring less than gross-total tumor removal to limit postoperative facial weakness.

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Neil S. Patel, Matthew L. Carlson, Bruce E. Pollock, Colin L. W. Driscoll, Brian A. Neff, Robert L. Foote, Christine M. Lohse and Michael J. Link

OBJECTIVE

The morbidity of gross-total resection of jugular paraganglioma (JP) is often unacceptable due to the potential for irreversible lower cranial neuropathy. Stereotactic radiosurgery (SRS) has been used at the authors’ institution since 1990 for the treatment of JP and other benign intracranial tumors. Conventional means of assessing tumor progression using linear measurements or elliptical approximations are imprecise due to the irregular shape and insinuating growth pattern of JP. The objective of this study was to assess long-term tumor control in these patients by using slice-by-slice 3D volumetric segmentation of serial MRI data.

METHODS

Radiographic data and clinical records were reviewed retrospectively at a single, tertiary-care academic referral center for patients treated from 1990 to 2017. Volumetric analyses by integration of consecutive tumor cross-sectional areas (tumor segmentation) of serial MRI data were performed. Tumor progression was defined as volumetric growth of 15% or greater over the imaging interval. Primary outcomes analyzed included survival free of radiographic and clinical progression. Secondary outcomes included new or worsened cranial neuropathy.

RESULTS

A total of 85 patients were treated with Gamma Knife radiosurgery (GKRS) for JP at the authors’ institution over the last 27 years. Sixty patients had pretreatment and serial posttreatment contrast-enhanced MRI follow-up suitable for volumetric analysis. A total of 214 MR images were analyzed to segment tumor images in a slice-by-slice fashion to calculate integral tumor volume. The median follow-up duration was 66 months (range 7–202 months). At 5 years the tumor progression-free survival rate was 98%. Three tumors exhibited progression more than 10 years after GKRS. Estimated survival free of radiographic progression rates (95% confidence interval [CI]; n = number still at risk) at 5, 10, and 15 years following radiosurgery were 98% (95% CI 94%–100%; n = 34), 94% (95% CI 85%–100%; n = 16), and 74% (95% CI 56%–98%; n = 6), respectively. One patient with tumor progression required treatment intervention using external beam radiation therapy, constituting the only case of clinical progression. Two patients (3%) without preexisting lower cranial nerve dysfunction developed new ipsilateral vocal fold paralysis following radiosurgery.

CONCLUSIONS

SRS achieves excellent long-term tumor control for JP without a high risk for new or worsened cranial neuropathy when used in primary, combined modality, or recurrent settings. Long-term follow-up is critical due to the potential for late radiographic progression (i.e., more than 10 years after SRS). As none of the patients with late progression have required salvage therapy, the clinical implications of this degree of tumor growth have yet to be determined.

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Avital Perry, Christopher S. Graffeo, Lucas P. Carlstrom, Aditya Raghunathan, Colin L. W. Driscoll, Brian A. Neff, Matthew L. Carlson, Ian F. Parney, Michael J. Link and Jamie J. Van Gompel

OBJECTIVE

Tumor-associated macrophages (TAMs) have been implicated as pathologic actors in phenotypically aggressive vestibular schwannoma (VS), potentially mediated via programmed death-ligand 1 (PD-L1). The authors hypothesized that PD-L1 is a key regulator of the VS immune microenvironment.

METHODS

Forty-six consecutive, radiation-naïve, sporadic VSs that were subtotally resected at primary surgery were assessed via immunohistochemical analysis, including analysis of CD163 and PD-L1 expression. Pathologic data were correlated with clinical endpoints, including tumor control, facial nerve function, and complications.

RESULTS

Baseline parameters were equivalent between stable and progressive post–subtotal resection (STR) VS. CD163 percent positivity and M2 index were significantly increased among tumors that remained stable (34% vs 21%, p = 0.02; 1.13 vs 0.99, p = 0.0008), as well as patients with favorable House-Brackmann grade I or II facial nerve function (31% vs 13%, p = 0.04; 1.11 vs 0.97, p = 0.05). PD-L1 percent positivity was significantly associated with tumor progression (1% vs 11%, p = 0.01) and unfavorable House-Brackmann grade III–VI facial nerve function (1% vs 38%, p = 0.02). On multivariate analysis, PD-L1 was independently significant in all models (likelihood ratio 4.4, p = 0.04), while CD163 was dependent in all iterations.

CONCLUSIONS

In contrast to prior reports, in this study, the authors observed significantly increased levels of M1, CD163+ TAMs in association with VS that progressed after STR. Progressive tumors are characterized by increased PD-L1, potentially highlighting a mechanism of immune evasion that results in TAM deactivation, tumor growth, and further infiltration of anti-tumor immune cells. Targeting PD-1/PD-L1 may offer therapeutic promise, particularly in the setting of disease control after STR.