Citations

Abstract Objective This study was aimed to provide a key update to the seminal works of Prof. Albert L. Rhoton Jr., MD, with particular attention to previously unpublished insights from the oral tradition of his fellows, recent technological advances including endoscopy, and high-dynamic range (HDR) photodocumentation, and, local improvements in technique, we have developed to optimize efficient neuroanatomic study. Methods Two formaldehyde-fixed cadaveric heads were injected with colored latex to demonstrate step-by-step specimen preparation for microscopic or endoscopic dissection. One formaldehyde-fixed brain was utilized to demonstrate optimal three-dimensional (3D) photodocumentation techniques. Results Key steps of specimen preparation include vessel cannulation and securing, serial tap water flushing, specimen drainage, vessel injection with optimized and color-augmented latex material, and storage in 70% ethanol. Optimizations for photodocumentation included the incorporation of dry black drop cloth and covering materials, an imaging-oriented approach to specimen positioning and illumination, and single-camera stereoscopic capture techniques, emphasizing the three-exposure-times-per-eye approach to generating images for HDR postprocessing. Recommended tools, materials, and technical nuances were emphasized throughout. Relative advantages and limitations of major 3D projection systems were comparatively assessed, with sensitivity to audience size and purpose specific recommendations. Conclusion We describe the first consolidated step-by-step approach to advanced neuroanatomy, including specimen preparation, dissection, and 3D photodocumentation, supplemented by previously unpublished insights from the Rhoton fellowship experience and lessons learned in our laboratories in the past years such that Prof. Rhoton's model can be realized, reproduced, and expanded upon in surgical neuroanatomy laboratories worldwide.

Objective: The majority of research influencing our understanding of vestibular schwannoma (VS) comes from large tertiary referral centers, and as a consequence, is inherently prone to referral bias. The objective of the current study was to characterize tertiary referral center bias in VS research. Study design: Single-institution retrospective clinical, audiometric, and radiologic review. Setting: One tertiary referral center. Patients: One hundred twenty-three patients with sporadic VS treated at our institution, consisting of a local cohort of all 41 VS patients residing in the same US county as our medical center and a referral cohort of 82 patients from outside counties matched 2:1 based on age, sex, and year of diagnosis. Intervention: Surgical resection, stereotactic radiosurgery (SRS), observation. Main outcome measures: Clinical manifestations, audiometric and radiologic findings, elected treatment modality. Results: Local patients had significantly longer follow-up after initial presentation compared to referral patients (median 4.0 vs 2.2 yr; p = 0.007). Referral patients were significantly less likely to have an incidental VS diagnosis (1% vs. 29%; p < 0.001) and presented with worse symptomatology such as hearing loss (80% vs. 54%; p = 0.002), dizziness (72% vs. 44%; p = 0.002), headache (29% vs. 15%; p = 0.075), and other cranial nerve dysfunction (11% vs. 0%; p = 0.029). Audiometrically, referral patients had significantly poorer word recognition scores at presentation (median 70% vs. 90%; p = 0.043). Local patients were more likely to have tumors confined to the IAC compared with referral patients, and had significantly smaller tumors when restricted to this region (median 4.0 vs 6.5 mm; p = 0.005). Referral patients were significantly more likely to undergo definitive management with either radiosurgery or microsurgery following primary evaluation compared to local patients (48% vs. 24%; p = 0.013). Conclusion: These data suggest that the majority of existing literature surrounding VS likely suffers from referral bias, whereby disease characteristics and management decisions are distinct from that of the general VS patient population.

Objective:To ascertain long-term hearing outcomes in patients with serviceable hearing following microsurgical resection of sporadic vestibular schwannoma (VS).Study Design:Retrospective cohort.Setting:Tertiary academic referral center.Patients:Forty-three adult subjects with unilateral sporadic VS who had serviceable hearing (American Academy of Otolaryngology–Head and Neck Surgery [AAO-HNS] class A or B) on initial postoperative audiogram following microsurgical resection between 2003 and 2016 with a minimum of two postoperative audiograms available for review.Intervention:Surgical treatment with a retrosigmoid or middle cranial fossa approach.Main Outcome Measure:Rate of maintaining serviceable hearing, as estimated using the Kaplan–Meier method, in accordance with the 1995 and 2012 AAO-HNS guidelines on reporting hearing outcomes.Results:The median immediate postoperative pure-tone average (PTA) and word recognition score (WRS) were 31 dB and 95%, respectively. At last follow-up, the median PTA was 38 dB with a median change of 5 dB from initial postoperative audiogram, and the median WRS was 90% with a median change of 0% from initial postoperative audiogram. Eight patients developed non-serviceable hearing at a median of 4.1 years following microsurgical resection (interquartile range, 2.9–7.0). The median duration of hearing follow-up for the 35 patients who maintained serviceable hearing was 3.1 years (interquartile range, 2.2–7.5). Tumor control was achieved in 41 (95%) patients. The rate of maintaining serviceable hearing at 5 years was 81%.Conclusion:Microsurgical resection provides excellent tumor control and durable long-term hearing in those with AAO-HNS class A or B hearing postoperatively. The paradigm of proactive microsurgical resection—when the tumor is small and hearing is good—hinges on the surgeon's ability to preserve residual hearing in a very high percentage of cases at or near preoperative hearing levels to maintain an advantage over conservative observation with regard to long-term hearing preservation.

Abstract Traditionally, the 50% isodose line (IDL) is used for prescription dose when vestibular schwannomas (VS) are treated with Gamma Knife radiosurgery (GKRS). To compare the effect of IDL on treatment outcomes, propensity score-matched analysis according to age at time of GKRS and tumor volume (TV) between cohorts treated at 40%IDL and 50%IDL was performed. Patients with no history of neurofibromatosis, GKRS prescribed marginal dose of 12–14 Gy and TV ≤ 10 cc were identified. Patients were excluded if follow-up time was < 2 years. Eventually, 30 and 28 patients were included in 40%IDL and 50%IDL cohorts, respectively. Mean age and TV were not significantly different between 40%IDL and 50%IDL groups; 54.5 versus 54.0 years (p=0.891) and 2148.61 versus 2031.10 mm3 (p=0.844), respectively. Median prescription dose was 12 Gy in both groups. At median follow-up times of 111 and 72 months, the 2, 5 and 10-year local control were 100%, 96.4% and 96.4% for 40%IDL and 96.4%, 86.7%, and 86.7% for 50%IDL (p=0.243), respectively. Among 40 patients with accessible follow-up MRIs (40%IDL-n=19, 50%IDL-n=21), volume reduction at last follow-up MRIs and rate of reduction per year for 40%IDL and 50%IDL were 48.1% versus 38.3% (p=0.05) and 5.5% versus 6% (p=0.749), respectively. Of 21 patients with serviceable hearing prior to GKRS and available audiograms after GKRS (40%IDL-n=8, 50%IDL-n=13), the 2, 5 and 10-year hearing preservation rate were 100%, 83.3% and 62.5% for 40%IDL versus 76.2%, 57.1% and 11.4% for 50%IDL (p=0.017). Facial paresthesia, facial palsy and ataxia/gait disturbance requiring steroid and/or shunt were lower in 40%IDL compared to the 50%IDL; 6.7% versus 17.9% (p=0.208) and 3.3% versus 7.1% (p=0.532). To summarize, VS treated at 40%IDL have slightly better local control, although not statistically significant, compared to tumors treated at 50%IDL. However, hearing preservation and safety seem to be more favorable toward 40%IDL group.

OBJECTIVEStereotactic radiosurgery (SRS) is an accepted treatment option for patients with benign parasellar tumors. Here, the authors’ objective was to determine the risk of developing new or progressive internal carotid artery (ICA) stenosis or occlusion after single-fraction SRS for cavernous sinus meningioma (CSM) or growth hormone–secreting pituitary adenoma (GHPA).METHODSThe authors queried their prospectively maintained registry for patients treated with single-fraction SRS for CSM or GHPA in the period from 1990 to 2015. Study criteria included no prior irradiation and ≥ 12 months of post-SRS radiological follow-up. Pre-SRS grading of ICA involvement was applied according to the 1993 classification schemes of Hirsch for CSM or Knosp for GHPA.RESULTSThe authors conducted a retrospective review of 283 patients, 155 with CSMs and 128 with GHPAs. Ninety-three (60%) CSMs were Hirsch category 2 and 3 tumors; 97 (76%) GHPAs were Knosp grade 2–4 tumors. Median follow-up after SRS was 6.6 years (IQR 1–24.9 years). No GHPA or category 1 CSM developed ICA stenosis or occlusion. Three (5.2%) patients with category 2 CSMs had asymptomatic ICA stenosis (n = 2) or occlusion (n = 1); 1 (1.1%) category 2 CSM patient had transient ischemic symptoms. Five (14.3%) category 3 CSMs progressed to ICA occlusion (4 asymptomatic, 1 symptomatic). The median time to stenosis/occlusion was 4.8 years (IQR 1.8–7.6). Five- and 10-year risks of ICA stenosis/occlusion in category 2 and 3 CSM patients were 7.5% and 12.4%, respectively. Five- and 10-year risks of ischemic stroke from ICA stenosis/occlusion in category 2 and 3 CSM patients were both 1.2%. Multivariate analysis showed patient age (HR 0.92, 95% CI 0.86–0.98, p = 0.01), meningioma pathology (HR and 95% CI not defined, p = 0.03), and pre-SRS carotid category (HR 4.51, 95% CI 1.77–14.61, p = 0.004) to be associated with ICA stenosis/occlusion. Internal carotid artery stenosis/occlusion was not related to post-SRS tumor growth (HR and 95% CI not defined, p = 0.41).CONCLUSIONSNew or progressive ICA stenosis/occlusion was common after SRS for CSM but was not observed after SRS for GHPA, suggesting a tumor-specific mechanism unrelated to radiation dose. Pre-SRS ICA encasement or constriction increases the risk of ICA stenosis/occlusion; however, the risk of ischemic complications is very low.

Abstract Introduction Neurosurgical anatomy is traditionally taught via anatomic and operative atlases; however, these resources present the skull base using views that emphasize three-dimensional (3D) relationships rather than operative perspectives, and are frequently written above a typical resident's understanding. Our objective is to describe, step-by-step, a retrosigmoid approach dissection, in a way that is educationally valuable for trainees at numerous levels. Methods Six sides of three formalin-fixed latex-injected specimens were dissected under microscopic magnification. A retrosigmoid was performed by each of three neurosurgery residents, under supervision by the senior authors (C.L.W.D. and M.J.L.) and a graduated skull base fellow, neurosurgeon, and neuroanatomist (M.P.C.). Dissections were supplemented with representative case applications. Results The retrosigmoid craniotomy (aka lateral suboccipital approach) affords excellent access to cranial nerve (CN) IV to XII, with corresponding applicability to numerous posterior fossa operations. Key steps include positioning and skin incision, scalp and muscle flaps, burr hole and parasigmoid trough, craniotomy flap elevation, initial durotomy and deep cistern access, completion durotomy, and final exposure. Conclusion The retrosigmoid craniotomy is a workhorse skull base exposure, particularly for lesions located predominantly in the cerebellopontine angle. Operatively oriented neuroanatomy dissections provide trainees with a critical foundation for learning this fundamental skull base technique. We outline a comprehensive approach for neurosurgery residents to develop their familiarity with the retrosigmoid craniotomy in the cadaver laboratory in a way that simultaneously informs rapid learning in the operating room, and an understanding of its potential for wide clinical application to skull base diseases.

Objective: To date, prediction models for estimating risk of acquiring non-serviceable hearing in subjects with observed vestibular schwannoma (VS) have evaluated outcomes primarily based on features at initial diagnosis. Herein, we evaluate the association of rate of hearing decline during the initial period of observation with time to non-serviceable hearing. If significant, rate of hearing decline may inform decision making after an introductory period of observation. Setting: Two tertiary care centers. Patients: VS patients with serviceable hearing who underwent at least three audiograms and two magnetic resonance imaging (MRI) studies before intervention or being lost to follow-up. The rate of change in pure-tone average (PTA) and word recognition score (WRS) was calculated as the score from the second audiogram minus the score from the first audiogram, divided by the duration in months between the two. Main Outcome Measure(s): Serviceable hearing, defined as PTA ≤50 dB HL and WRS ≥50%. Results: Among 266 patients meeting inclusion criteria, 52 developed non-serviceable hearing at last follow-up. Kaplan–Meier estimated rates of maintaining serviceable hearing (95% CI; number still at risk) at 1, 3, 5, 7, and 10 years were 97% (95–100; 206), 78% (72–85; 98), 68% (60–77; 39), 60% (50–73; 17), and 44% (29–67; 2), respectively. In a univariable setting, each 1 dB increase per month in the rate of initial PTA change was associated with a 96% increased likelihood of acquiring non-serviceable hearing (hazard ratio [HR] 1.96; 95% CI 1.44–2.68; p < 0.001). Each 1% increase per month in the rate of initial WRS change was associated with a decreased likelihood of acquiring non-serviceable hearing (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.66–0.94; p = 0.009). After multivariable adjustment, both rate of PTA change (HR 2.42; 95% CI 1.72–3.41; p < 0.001) and rate of WRS change (HR 0.81; 95% CI 0.67–0.99; p = 0.043) remained statistically significantly associated with time to non-serviceable hearing. Conclusion: Rate of early PTA and WRS decline during the initial period of observation are significantly associated with time to development of non-serviceable hearing. This information may facilitate accurate patient counseling and inform decision-making regarding prospective disease management.

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.

Objective: The etiology of sensorineural hearing loss (SNHL) in patients with jugular paraganglioma (JP) whose tumors lack inner ear fistulae or vestibulocochlear nerve involvement is unknown. Recent literature has proposed that occlusion of the inferior cochlear vein may be causative. Herein, we assess the association between radiologic involvement of the cochlear aqueduct (CA) and the development of SNHL. Study Design: Blinded, retrospective review of imaging and audiometry. Setting: Tertiary center. Patients: Adults with JP. Intervention(s): None. Main Outcome Measures: Asymmetric SNHL was assessed continuously as the difference in bone conduction pure-tone average (BCPTA) between ears and as a categorical variable (≥15 dB difference at two consecutive frequencies, or a difference in speech discrimination score of ≥15%). Involvement of the CA was considered present if there was evidence of medial T2 fluid signal loss, contrast enhancement, or bony erosion/expansion. Results: Of 30 patients meeting inclusion criteria, 15 (50%) had asymmetric SNHL. CA involvement was observed in 87% of patients with asymmetric SNHL compared with 13% in those with symmetric hearing (p = 0.0001). Univariate analysis demonstrated that age, sex, and tumor volume were not associated with asymmetric SNHL. The median difference in BCPTA between ears in patients with CA involvement was 21.3 dB HL compared to 1.2 dB HL in those without CA involvement (p < 0.0001). Regression analysis demonstrates that enhancement within the CA is associated with a BCPTA difference of 19.4 dB HL (p = 0.0006). Conclusions: Cochlear aqueduct involvement by JP is associated with SNHL in the absence of inner ear fistula, vestibulocochlear nerve involvement, or brainstem compression. Correlation with operative findings or histopathologic evidence of tumor involvement may validate this intriguing imaging finding.

Objective: Previous research has shown that tumor growth during observation of small-to-medium sized sporadic vestibular schwannomas (VSs) occurs almost exclusively within 3 to 5 years following diagnosis. This has led some to consider ending surveillance after this interval. This study seeks to characterize a cohort of patients with tumors that exhibited late growth. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Adults with sporadic VSs who initially elected observation with serial magnetic resonance imaging (MRI) surveillance. Intervention(s): None. Main Outcome Measure(s): Linear tumor growth was measured in accordance with AAO-HNS reporting guidelines. Delayed growth was defined as growth ≥2 mm in linear diameter that was first detected 5 years or more from the initial MRI. Results: From a total of 361 patients, 172 experienced tumor growth during the interval of observation. Fourteen of these 172 patients (8.1%) experienced late growth occurring at 5 years or beyond. Among patients with delayed growth, the fastest growth rate after extended quiescence was 1.33 mm/yr, and the longest delay before tumor growth detection was 11.1 years. Additional treatment was recommended for six (42.9%) of the patients with delayed growth. Of 68 tumors that remained in the IAC, 11 (16.2%) demonstrated delayed growth. Of 66 tumors that presented in the CPA, 2 (3.0%) demonstrated delayed growth. Initial size was larger for tumors demonstrating early growth compared with those with delayed growth. For tumors within the IAC, those with early growth had a significantly higher median growth rate than those with delayed growth (1.40 vs. 0.45 mm/yr, p < 0.001). Conclusions: Delayed growth encompassed 8.1% of growing VSs and 3.9% of all observed tumors. Patients with delayed growth exhibited slower growth rates compared with those who were diagnosed with growth early in their observation course. These findings support the need for lifelong surveillance of untreated VSs given the possibility of clinically significant delayed growth. Increasing the time interval between MRI studies after 5 years is a reasonable concession to balance practicalities of cost and convenience with risk of delayed of tumor growth.