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Meningiomas are common intracranial tumors with variable prognoses not entirely captured by commonly used classification schemes. We sought to determine the relationship between meningioma mutations and oncologic outcomes using a targeted next-generation sequencing panel.We identified 184 grade I and II meningiomas with both90 days of post-surgical follow-up and linked targeted next-generation sequencing. For mutated genes in greater than 5% of the sample, we computed progression-free survival Cox-regression models stratified by gene. We then built a multi-gene model by including all gene predictors with aMutations in ATM and CREBBP were associated with accelerated meningioma recurrence, and mutations in POLE were protective of recurrence. Each mutation has potential implications for treatment. The effect of these mutations on oncologic outcomes and as potential targets for intervention warrants future study.

The Department of Neurosurgery’s residency program at The Mount Sinai Hospital was founded in 1946. The department has its origins in 1914 as a division of general surgery, with Charles Elsberg at the helm. Neurosurgery then became a separate department in 1932 under the leadership of Ira Cohen. Dr. Cohen oversaw the creation of the neurosurgery residency training program 75 years ago. Since its inception, the residency program has graduated 120 residents. For more than 100 years, The Mount Sinai Hospital has been a site of clinical excellence, groundbreaking research, and technological innovation in neurosurgery. Currently, the Department of Neurosurgery has 39 clinical faculty members, performs more than 5300 surgeries and endovascular procedures annually, and is in the top 25 neurosurgical departments for NIH funding.

Subinternships are critical experiences for medical students applying into neurosurgery to acquire knowledge of the field and network with colleagues. During the coronavirus disease 2019 pandemic, in-person rotations were suspended for 2020 and reduced for 2021. In 2020, our department developed a neurosurgical course to address this need. The course was continued in 2021, enabling assessment of student perceptions as the pandemic progresses.The virtual course consisted of weekly 1-hour seminars over a 3- to 4-month period. Prior to starting, participants were sent a comprehensive survey assessing their backgrounds, experiences, and confidences in core concepts across neurosurgical subdisciplines. Participants also completed postcourse surveys assessing the course's value and their confidence in the same topics. Responses from students completing both precourse and postcourse surveys were included, analyzed in pairwise fashion, and compared across course years.Students shared similar baseline characteristics in terms of demographics, educational background, and exposure to neurosurgery prior to the course. In the 2020 and 2021 cohorts, quality ratings for presentations were favorable for all seminars, and participants reported significantly increased confidence in core topics across all neurosurgical disciplines after the course (2020: 3.36 ± 0.26, P0.0001; 2021: 3.56 ± 0.93, P = 0.005). Most participants felt the course would remain useful following the pandemic in both the 2020 (96.9%) and 2021 (100.0%) cohorts.Survey results suggest that the course adds value for students seeking a basic didactic curriculum to supplement their education, and perhaps, an online curriculum for medical students would still be beneficial going forward as in-person rotations resume.

BACKGROUND The complexity of posterior fossa surgery can often lead to rare complications due to the anatomy involved. Vestibular schwannoma resection is a common pathology in the posterior fossa, often requiring surgical intervention. Given the proximity of this space to the brainstem, cranial nerve VII/VIII complex, and posterior inferior cerebellar artery (PICA), neurovascular complications are not infrequent. A rare vascular complication from this surgical approach is a lateral medullary infarction from injury to the lateral medullary segment of the proximal PICA, leading to central hypoventilation syndrome (CHS). OBSERVATIONS This report presents a unique case of a 51-year-old man who underwent a retrosigmoid craniectomy for resection of a vestibular schwannoma. Following surgery, the patient was unable to be weaned off the ventilator and was noted to become apneic while he slept, a clinical picture consistent with Ondine’s curse. LESSONS This report discusses the anatomical considerations of this surgical corridor leading to this complication and the management of a patient with acquired Ondine’s curse and reviews the scarce literature on this uncommon cause of acquired CHS.

OBJECTIVE High-quality neurosurgery resident training is essential to developing competent neurosurgeons. Validated formative tools to assess faculty teaching performance exist, but are not used widely among Accreditation Council for Graduate Medical Education (ACGME) residency programs in the United States. Furthermore, their longer-term impact on teaching performance improvement and educational outcomes remains unclear. The goal of this study was to assess the impact of implementing an evaluation system to provide faculty with feedback on teaching performance in a neurosurgery residency training program over a 4-year period. METHODS The authors performed a prospective cohort study in which a modified version of the System for Evaluation of Teaching Qualities (SETQ) instrument was administered to neurosurgical trainees in their department regularly every 6 months. The authors analyzed subscale score dynamics to identify the strongest correlates of faculty teaching performance improvement. ACGME program survey results and trainee performance on written board examinations were compared for the 3 years before and after SETQ implementation. RESULTS The overall response rate among trainees was 91.8%, with 1044 surveys completed for 41 faculty. Performance scores improved progressively from cycle 1 to cycle 6. The strongest correlate of overall performance was providing positive feedback to trainees. Compared to the 3 years prior, the 3 years following SETQ implementation saw significant increases in written board examination and ACGME resident survey scores compared to the national mean. CONCLUSIONS Implementation of SETQ was associated with significant improvements in faculty teaching performance as judged by trainees over a 4-year period, and guided curricular changes in the authors’ training program that resulted in improved educational outcomes.

Background Cushing disease (CD) during pregnancy is a rare but serious disease that adversely impacts maternal and fetal outcomes. As the sole use of metyrapone in the management of CD has been rarely reported, we describe our experience of using it to treat a pregnant patient with CD. Case Report A 34-year-old woman with hypertension was diagnosed with adrenocorticotropic hormone–dependent CD on the basis of a urinary free cortisol (UFC) level of 290 μg/24 h (reference range, 6-42 μg/dL) and an abnormal dexamethasone suppression test (cortisol level, 12.4 μg/dL) before becoming pregnant. She conceived naturally 12 weeks after transsphenoidal surgery and was subsequently found to have persistent disease with a UFC level of 768 μg/dL. Surgery was deemed high-risk given the proximity of the tumor to the right carotid artery and the high likelihood of residual disease. Instead, she was managed with metyrapone throughout her pregnancy and titrated to a goal UFC level of Discussion This case highlights the successful use of metyrapone throughout pregnancy to manage CD in patients in whom surgery is considered high-risk or in those with a low likelihood of cure. Although metyrapone is effective, close surveillance is required for worsening hypertension, hypokalemia, and potential adrenal insufficiency. Although no fetal adverse events have been reported, this medication crosses the placenta, and the long-term effects are unknown. Conclusion We describe a case of CD during pregnancy that was successfully treated with metyrapone.

Background Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. Methods Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. Results CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. Conclusions These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

High grade meningiomas have a prognosis characterized by elevated recurrence rates and radiation resistance. Recent work has highlighted the importance of genomics in meningioma prognostication. This study aimed to assess the relationship between the most common meningioma genomic alteration (NF2) and response to postoperative radiation therapy (RT).From an institutional tissue bank, grade 2 and 3 recurrent meningiomas with both 30 days of post-surgical follow-up and linked targeted next-generation sequencing were identified. Time to radiographic recurrence was determined with retrospective review. The adjusted hazard of recurrence was estimated using Cox-regression for patients treated with postoperative RT stratified by NF2 mutational status.Of 53 atypical and anaplastic meningiomas (29 NF2 wild-type, 24 NF2 mutant), 19 patients underwent postoperative RT. When stratified by NF2 wild-type, postoperative RT in NF2 wild-type patients was associated with a 78% reduction in the risk of recurrence (HR 0.216; 95%CI 0.068-0.682; p = 0.009). When stratified by NF2 mutation, there was a non-significant increase in the risk of recurrence for NF2 mutant patients who received postoperative RT compared to those who did not (HR 2.43; 95%CI 0.88-6.73, p = 0.087).This study demonstrated a protective effect of postoperative RT in NF2 wild-type patients with recurrent high grade meningiomas. Further, postoperative RT may be associated with no improvement and perhaps an accelerated time to recurrence in NF2 mutant tumors. These differences in recurrence rates provide evidence that NF2 may be a valuable prognostic marker in treatment decisions regarding postoperative RT. Further prospective studies are needed to validate this relationship.

The oncologic outcomes for atypical meningiomas can be poor. Generally, patients that have had a prior recurrence have a substantially elevated risk of a future recurrence. Additionally, certain tumor genomic profiles have been shown as markers of poor prognosis. We sought to characterize the genomic differences between primary and recurrent tumors as well as assess if those differences had implications on recurrence.We identified primary and recurrent gross totally resected WHO grade II meningiomas with 30 days of post-surgical follow-up at our institution. For genes with a prevalence of 5% in the cohort, we compared the mutational prevalence in primary and recurrent tumors. For a gene of interest, we assessed the time to radiographic recurrence using adjusted cox-regression.We identified 88 meningiomas (77 primary, 16 recurrent) with a median follow-up of 5.33 years. Mutations in ARID1A found in association with recurrent tumors (7/16 recurrent tumors vs 5/72 primary tumors, p 0.001). In the whole cohort, mutations in ARID1A were not associated with alterations in time to recurrence after adjusting for recurrence status (p = 0.713). When restricted to primary tumors, ARID1A is associated with a 625% increase in the hazard of recurrence (HR = 7.26 [1.42-37.0]; p = 0.017).We demonstrate mutations in ARID1A, a chromatin remodeling gene, in a higher prevalence in recurrent tumors. We further demonstrate that when mutations in ARID1A are present in primary atypical meningiomas, these tumors tend to have worse prognosis. Further prospective study may validate ARID1A as a prognostic marker.

Although many etiologies have been proposed for Chiari malformation type I (CM-I), there currently is no singular known cause of CM-I pathogenesis. Advances in imaging have greatly progressed the study of CM-I. This study reviews the literature to determine if an anatomical cause for CM-I could be proposed from morphometric studies in adult CM-I patients. After conducting a literature search using relevant search terms, two authors screened abstracts for relevance. Full-length articles of primary morphometric studies published in peer-reviewed journals were included. Detailed information regarding methodology and symptomatology, craniocervical instability, syringomyelia, operative effects, and genetics were extracted. Forty-six studies met inclusion criteria, averaging 93.2 CM-I patients and 41.4 healthy controls in size. To obtain measurements, 40 studies utilized MRI and 10 utilized CT imaging, whereas 41 analyzed parameters within the posterior fossa and 20 analyzed parameters of the craniovertebral junction. The most commonly measured parameters included clivus length (n = 30), tonsillar position or descent (n = 28), McRae line length (n = 26), and supraocciput length (n = 26). While certain structural anomalies including reduced clivus length have been implicated in CM-I, there is a lack of consensus on how several other morphometric parameters may or may not contribute to its development. Heterogeneity in presentation with respect to the extent of tonsillar descent suggests alternate methods utilizing morphometric measurements that may help to identify CM-I patients and may benefit future research to better understand underlying pathophysiology and sequelae such as syringomyelia.

While SWI/SNF chromatin remodeling complex alterations occur in approximately 20% of cancer, the frequency and potential impact on clinical outcomes in meningiomas remains to be comprehensively elucidated. A large series of 255 meningiomas from a single institution that was enriched for high grade and recurrent lesions was identified. We performed next-generation targeted sequencing of known meningioma driver genes, including NF2, AKT1, PIK3CA, PIK3R1, and SMO and SWI/SNF chromatin remodeling complex genes, including ARID1A, SMARCA4, and SMARCB1 in all samples. Clinical correlates focused on clinical presentation and patient outcomes are presented. The series included 63 grade I meningiomas and 192 high-grade meningiomas, including 173 WHO grade II and 19 WHO grade III. Samples from recurrent surgeries comprised 37.3% of the series. A total of 41.6% meningiomas were from the skull base. NF2, AKT1, PIK3CA, PIK3R1, and SMO were mutated in 40.8, 7.1, 3.5, 3.9, and 2.4% of samples, respectively. ARID1A, SMARCA4, and SMARCB1 mutations were observed in 17.3, 3.5, and 5.1% of samples, respectively. A total of 68.2% of ARID1A-mutant meningiomas harbored a p.Gln1327del in-frame deletion. ARID1A mutations were seen in 19.1% of Grade I, 16.8% of Grade II, and 15.8% of Grade III meningiomas (P = 0.9, Fisher’s exact). Median overall survival was 16.3 years (95% CI 10.9, 16.8). With multivariable analysis, the presence of an ARID1A mutation was significantly associated with a 7.421-fold increased hazard of death (P = 0.04). ARID1A mutations occur with similar frequency between low and high-grade meningiomas, but ARID1A mutations are independently prognostic of worse prognosis beyond clinical and histopathologic features.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

OBJECTIVEEndoscopic surgery is an effective treatment strategy for pituitary adenomas; however, intrinsic tumor properties such as tumor consistency can challenge or preclude gross-total resection. Preoperative characterization of tumor consistency may help to guide the surgical approach and to predict the extent of resection that is possible. Advanced radiological modalities such as 7T diffusion-weighted imaging (DWI) may be useful in probing biological tissue properties of pituitary adenomas. The objective of the present study was to examine 7T DWI as a novel method of measuring the consistency of pituitary adenomas.METHODSThirteen patients with pituitary macroadenomas underwent 7T MRI, including a DWI image acquisition. Tumor apparent diffusion coefficient (ADC) was normalized to the adjacent temporal gray matter ADC. All patients underwent resection, and a single neurosurgeon blinded to ADC values rated tumor firmness from 1 (least firm) to 5 (most firm) using objective criteria. The tumor specimens were evaluated histopathologically for cellularity, collagen content, and vascularity by a neuropathologist who was also blinded to ADC values. The tumor ADC was correlated with intraoperative consistency rating, histopathology, and extent of resection. Receiver operating characteristic (ROC) curve analyses were performed to identify thresholds to predict tumor consistency.RESULTSCorrected ADC values were significantly correlated with both tumor firmness (r = −0.60, p = 0.029) and the extent of trichrome staining (r = −0.72, p = 0.009) such that greater ADC values were associated with both decreased tumor firmness and decreased collagen staining. Correlations between ADC values and tumor vascularity were not significant (r = −0.09, p = 0.78). Corrected ADC values in totally resected tumors (1.54) were greater than those in subtotally resected tumors (0.85) (p = 0.02), and ADC values were greater with moderate tumor cellularity (1.51) than with high tumor cellularity (0.8) (p = 0.035). There was a trend-level association for partial resections to exhibit greater tumor firmness rating (3 vs 1.7; p = 0.051). Finally, the degree of trichrome staining positively correlated with tumor firmness (r = 0.60, p = 0.04). The optimal threshold for predicting intraoperative consistency rating was an ADC ratio of 0.87 (sensitivity 80%, specificity 100%, area under the curve [AUC] 0.90; p = 0.043). The optimal cutoff for distinguishing the extent of resection was 1.19 (sensitivity 85.7%, specificity 83.3% AUC 0.833; p = 0.046).CONCLUSIONSThe authors’ results suggest that a high-resolution ADC of pituitary adenomas is a sensitive measure of tumor consistency. 7T DWI may hold clinical value in the preoperative workup and surgical management of patients with pituitary macroadenomas.

OBJECTIVESpinal cord injury (SCI) is an area of key interest in military medicine but has not been studied among the US Army Special Forces (SF), the most elite group of US soldiers. SF soldiers make up a disproportionate 60% of all Special Operations casualties. The objective of this study was to better understand SCI incidence in the SF, its mechanisms of acquisition, and potential areas for intervention by addressing key issues pertaining to protective equipment and body armor use.METHODSAn electronic survey questionnaire was formulated with the close collaboration of US board-certified neurosurgeons from the Mount Sinai Hospital and Cleveland Clinic Departments of Neurosurgery, retired military personnel of the SF, and operational staff of the Green Beret Foundation. The survey was sent to approximately 6000 SF soldiers to understand SCI diagnosis and its associations with various health and military variables.RESULTSThe response rate was 8.2%. Among the 492 respondents, 94 (19.1%) self-reported an SCI diagnosis. An airborne operation was the most commonly attributed cause (54.8%). Moreover, 87.1% of SF soldiers reported wearing headgear at the time of injury, but only 36.6% reported wearing body armor, even though body armor use has significantly increased in post-9/11 SF soldiers compared with that in their pre-9/11 counterparts. SCI was significantly associated with traumatic brain injury, arthritis, low sperm count, low testosterone, erectile dysfunction, tinnitus, hyperacusis, sleep apnea, posttraumatic stress disorder, major depressive disorder, and generalized anxiety disorder. Only 16.5% of SF soldiers diagnosed with SCI had been rescued via medical evacuation (medevac) for treatment.CONCLUSIONSA high number of SF soldiers self-reported an SCI diagnosis. Airborne operations landings were the leading cause of SCI, which coincided with warfare tactics employed during the Persian Gulf War, Operation Iraqi Freedom, and other conflicts. A majority of SCIs occurred while wearing headgear and no body armor, suggesting the need for improvements in protective equipment use and design. The low rate of medevac rescue for these injuries may suggest that medical rescue was not attainable at the time or that certain SCIs were deemed minor at the time of injury.

Vision loss following surgery for pituitary adenoma is poorly described in the literature and cannot be reliably predicted with current prognostic models. Detailed characterization of this population is warranted to further understand the factors that predispose a minority of patients to post-operative vision loss.The medical records of 587 patients who underwent endoscopic transsphenoidal surgery at the Mount Sinai Medical Centre between January 2013 and August 2018 were reviewed. Patients who experienced post-operative vision deterioration, defined by reduced visual acuity, worsened VFDs, or new onset of blurry vision, were identified and analysed.Eleven out of 587 patients who received endoscopic surgery for pituitary adenoma exhibited post-operative vision deterioration. All eleven patients presented with preoperative visual impairment (average duration of 13.1 months) and pre-operative optic chiasm compression. Seven patients experienced visual deterioration within 24 h of surgery. The remaining four patients experienced delayed vision loss within one month of surgery. Six patients had complete blindness in at least one eye, one patient had complete bilateral blindness. Four patients had reduced visual acuity compared with preoperative testing, and four patients reported new-onset blurriness that was not present before surgery. High rates of graft placement (10/11 patients) and opening of the diaphragma sellae (9/11 patients) were found in this series. Four patients had hematomas and four patients had another significant post-operative complication.While most patients with pituitary adenoma experience favourable ophthalmological outcomes following endoscopic transsphenoidal surgery, a subset of patients exhibit post-operative vision deterioration. The present study reports surgical and disease features of this population to further our understanding of factors that may underlie vision loss following pituitary adenoma surgery. Graft placement and opening of the diaphragma sellae may be important risk factors in vision loss following ETS and should be an area of future investigation.

OBJECTIVEVision loss remains a debilitating complication of pituitary adenomas, although there is considerable variability in visual impairment before and after decompression surgery. Growing evidence suggests secondary damage to remote visual structures may contribute to vision loss in patients with chiasmatic compression. The present study leverages ultrahigh field 7-T MRI to study the retinotopic organization of the primary visual cortex (V1), and correlates visual defects with cortical thinning in V1 to characterize consequences of pituitary adenomas on the posterior visual system.METHODSEight patients (4 males and 4 females, mean age 44.3 years) with pituitary adenomas who exhibited chiasmatic compression and visual field defects, as well as 8 matched healthy controls (4 males and 4 females, mean age 43.3 years), were scanned at 7-T MRI for this prospective study. Whole-brain cortical thickness was calculated using an automated algorithm. A previously published surface-based algorithm was applied to associate the eccentricity and polar angle with each position in V1. Cortical thickness was calculated at each point in the retinotopic organization, and a cortical thickness ratio was generated against matched controls for each point in the visual fields. Patients with adenoma additionally underwent neuroophthalmological examination including 24–2 Humphrey automated visual field perimetry. Pattern deviation (PD) of each point in the visual field, i.e., the deviation in point detection compared with neurologically healthy controls, was correlated with cortical thickness at corresponding polar and eccentricity angles in V1.RESULTSWhole-brain cortical thickness was successfully derived for all patients and controls. The mean tumor volume was 19.4 cm3. The median global thickness of V1 did not differ between patients (mean ± SD 2.21 ± 0.12 cm), compared with controls (2.06 ± 0.13 cm, p > 0.05). Surface morphometry–based retinotopic maps revealed that all 8 patients with adenoma showed a significant positive correlation between PD and V1 thickness ratios (r values ranged from 0.31 to 0.53, p < 0.05). Mixed-procedure analysis revealed that PD = −8.0719 + 5.5873*[Median V1 Thickness Ratio].CONCLUSIONSAll 8 patients showed significant positive correlations between V1 thickness and visual defect. These findings provide retinotopic maps of localized V1 cortical neurodegeneration spatially corresponding to impairments in the visual field. These results further characterize changes in the posterior visual pathway associated with chiasmatic compression, and may prove useful in the neuroophthalmological workup for patients with pituitary macroadenoma.

Meningiomas are the most common primary central nervous system tumor. Emerging data supports that higher mutational burden portends worse clinical outcomes in meningiomas. However, there is a lack of imaging biomarkers that are associated with tumor genomics in meningiomas. We performed next-generation targeted sequencing in a cohort of 75 primary meningiomas and assessed preoperative imaging for tumor volume and peritumoral brain edema (PTBE). An Edema Index was calculated. Meningiomas that were high grade (WHO grade II or grade III) had significantly larger tumor volume and were more likely to present with PTBE. Moreover, PTBE was associated with brain invasion on histopathology and reduced overall survival. There was a direct association between Edema Index and mutational burden. For every one increase in Edema Index, the number of single nucleotide variants increased by 1.09-fold (95% CI: 1.02, 1.2) (P = 0.01). These data support that Edema Index may serve as a novel imaging biomarker that can inform underlying mutational burden in patients with meningiomas.

The tumor microenvironment is an emerging biomarker of underlying genomic heterogeneity and response to immunotherapy-based treatment regimens in solid malignancies. How tumor mutational burden influences the density, distribution, and presence of a localized immune response in meningiomas is unknown. Representative hematoxylin and eosin slides were reviewed at 40X to assess for the density of inflammatory cells. Lymphocytes and macrophages were quantified in the following ordinal manner: 0 = not present, 1 = 1–25 cells present, and 2 = greater than 26 cells present. Immune cell infiltrate grade was scored for both scattered and aggregated distributions. Next generation targeted sequencing was performed on all meningiomas included in this study. One hundred and forty-five meningiomas were evaluated in this study. Lymphocytes were observed in both scattered (95.9%) and aggregated (21.4%) distributions. A total of 115 (79.3%) meningiomas had 1–25 scattered lymphocytes, and 24 (16.6%) had > 25 scattered lymphocytes, and 6 (4.1%) had no scattered lymphocytes. Twenty (13.8%) meningiomas had 1–25 aggregated lymphocytes. Eleven (7.6%) had > 25 aggregated lymphocytes and 114 (78.6%) had no aggregated lymphocytes. Six (4.1%) meningiomas had 1–25 aggregated macrophages, 5 (3.4%) had > 25 aggregated macrophages, and 134 (92.4%) had no aggregated macrophages. Density of aggregated lymphocytes and aggregated macrophages were associated with higher tumor grade, P = 0.0071 and P = 0.0068, respectively. Scattered lymphocyte density was not associated with meningioma grade. The presence of scattered lymphocytes was associated with increased tumor mutational burden. Meningiomas that did not have scattered lymphocytes had a mean number of single mutations of 2.3 ± 2.9, compared with meningiomas that had scattered lymphocytes, 6.9 ± 20.3, P = 0.03. NF2 mutations were identified in 59 (40.7%) meningiomas and were associated with increased density of scattered lymphocytes. NF2 mutations were seen in 0 (0%) meningiomas that did not have scattered lymphocytes, 46 (40.0%) meningiomas that had 1–25 scattered lymphocytes, and 13 (54.2%) meningiomas that had > 25 scattered lymphocytes, P = 0.046. Our findings suggest that distribution of immune cell infiltration in meningiomas is associated with tumor mutational burden. NF2 mutational status was associated with an increasing density of scattered lymphocytes. As the role of immunotherapy in meningiomas continues to be elucidated with clinical trials that are currently underway, these results may serve as a novel biomarker of tumor mutational burden in meningiomas.

OBJECTIVEPredicting vision recovery following surgical decompression of the optic chiasm in pituitary adenoma patients remains a clinical challenge, as there is significant variability in postoperative visual function that remains unreliably explained by current prognostic factors. Available literature inadequately characterizes alterations in adenoma patients involving the lateral geniculate nucleus (LGN). This study examined the association of LGN degeneration with chiasmatic compression as well as with the retinal nerve fiber layer (RNFL), pattern standard deviation (PSD), mean deviation (MD), and postoperative vision recovery. PSD is the degree of difference between the measured visual field pattern and the normal pattern (“hill”) of vision, and MD is the average of the difference from the age-adjusted normal value.METHODSA prospective study of 27 pituitary adenoma patients and 27 matched healthy controls was conducted. Participants were scanned on a 7T ultra–high field MRI scanner, and 3 independent readers measured the LGN at its maximum cross-sectional area on coronal T1-weighted MPRAGE imaging. Readers were blinded to diagnosis and to each other’s measurements. Neuro-ophthalmological data, including RNFL thickness, MD, and PSD, were acquired for 12 patients, and postoperative visual function data were collected on patients who underwent surgical chiasmal decompression. LGN areas were compared using two-tailed t-tests.RESULTSThe average LGN cross-sectional area of adenoma patients was significantly smaller than that of controls (13.8 vs 19.2 mm2, p < 0.0001). The average LGN cross-sectional area correlated with MD (r = 0.67, p = 0.04), PSD (r = −0.62, p = 0.02), and RNFL thickness (r = 0.75, p = 0.02). The LGN cross-sectional area in adenoma patients with chiasm compression was 26.6% smaller than in patients without compression (p = 0.009). The average tumor volume was 7902.7 mm3. Patients with preoperative vision impairment showed 29.4% smaller LGN cross-sectional areas than patients without deficits (p = 0.003). Patients who experienced improved postoperative vision had LGN cross-sectional areas that were 40.8% larger than those of patients without postoperative improvement (p = 0.007).CONCLUSIONSThe authors demonstrate novel in vivo evidence of LGN volume loss in pituitary adenoma patients and correlate imaging results with neuro-ophthalmology findings and postoperative vision recovery. Morphometric changes to the LGN may reflect anterograde transsynaptic degeneration. These findings indicate that LGN degeneration may be a marker of optic apparatus injury from chiasm compression, and measurement of LGN volume loss may be useful in predicting vision recovery following adenoma resection.

The coronavirus disease 2019 (COVID-19) pandemic disrupted the standard management paradigms for care of patients with sinus and skull base presentations due to concern for patient and health care provider safety, given the high aerosol-generating potential of endonasal procedures.We reviewed the relevant literature complied from available sources, including PubMed, Google Scholar, and otolaryngology journals providing electronic manuscripts ahead of indexing or publication.Incorporating available evidence and the projected infection control and resource limitations at our institution, we collectively authored a dynamic set of protocols guiding (1) case stratification, (2) preoperative assessment, (3) operative setup, and (4) postoperative care of patients with sinus or skull base presentations. Due to the rapidly evolving nature of COVID-19 publications, lack of rigorous data, and urgent necessity of standardized protocols, strict inclusion and exclusion criteria were not employed.As scarce hospital resources are diverted to COVID-19 care and staff are redeployed to forward-facing roles, endonasal procedures have largely ceased, leaving patients with ongoing sinonasal and skull base complaints untreated. Skull base teams now weigh the urgency of surgery in this population with the regional availability of resources.The COVID-19 pandemic will have an enduring and unpredictable impact on hospital operations and surgical skull base practices and will require a dynamic set of management protocols responsive to new evidence and changing resources. In the current resource-limited environment, clinicians may utilize these protocols to assist with stratifying patients by acuity, performing preoperative assessment, and guiding peri- and postoperative care.

The challenges of neurosurgical patient management and surgical decision-making during the 2019-2020 COVID-19 worldwide pandemic are immense and never-before-seen in our generation of neurosurgeons. In this case-based formatted report, we present the Mount Sinai Hospital (New York, NY) Department of Neurosurgery institutional experience in the epicenter of the pandemic and the guiding principles for our current management of intracranial, skull base, and spine tumors. The detailed explanations of our surgical reasoning for each tumor case is tailored to assist neurosurgeons across the United States as they face these complex operative decisions put forth by the realities of the pandemic.

Background Seven-Tesla (7T) magnetic resonance imaging (MRI) has demonstrated value for evaluating a variety of intracranial diseases. However, its utility in trigeminal neuralgia has received limited attention. The authors of the present study applied ultra-high field multimodal MRI to two representative patients with secondary trigeminal neuralgia due to epidermoid tumors to illustrate the possible clinical and surgical advantages of 7T compared with standard clinical strength imaging. Techniques included co-registration of multiple 7T sequences to optimize the detection of potential concurrent neurovascular and neoplasm-derived compression. Methods 7T MRI studies were performed using a whole body scanner. Two- and three-dimensional renderings of potential neurovascular conflict were created by co-registering time-of-flight angiography and T2-weighted turbo spin echo images in MATLAB and GE software. Detailed comparisons of the various field strength images were provided by a collaborating neuroradiologist (B.D.). Results 7T MRI clearly illustrated minute tumor-adjacent vasculature. In contrast, conventional, low-field imaging did not consistently provide adequate details to distinguish cerebrospinal fluid pulsatility from vessels. The tumor margins, although distinct from the trigeminal nerve fibers at 7T, blended with those of the surrounding structures at 3T. Two- and three-dimensional co-registration of time-of-flight angiography with T2-weighted MRI suggested that delicate, intervening vasculature may have contributed to these illustrative patients' symptomatology. Conclusions 7T provided superior visualization of vital landmarks and subtle nerve and vessel features. Co-registration of various advanced 7T modalities may help to resolve complex disease etiologies. Future studies should explore the extent to which this dual etiology might persist across tumor types and utilize diffusion-based techniques to quantify what microstructural differences might exist between patients with trigeminal neuralgia from varying etiologies.

Emerging evidence suggests that STK11 mutations may influence clinical outcome and response to immunotherapy in cancer. Next-generation targeted sequencing of STK11 mutation status in a large cohort of 188 meningiomas. STK11 loss-of-function mutations were identified in 3.7% of meningiomas. STK11 mutations were found in both low- and high-grade lesions and samples from primary and recurrent disease. There was a 2.8-fold increased risk of death for patients whose meningioma harbored an STK11 mutation, after controlling for lesion grade and occurrence status. The median overall survival for patients with STK11-mutated meningiomas was 4.4 years compared with 16.8 years. These data identify recurrent STK11 mutations in a subset of meningiomas. Genotyping of STK11 is encouraged for meningioma patients undergoing immunotherapy-based therapy.

Objective This article aims to characterize 14 patients who underwent purely endoscopic surgical debridement of acute invasive skull base fungal rhinosinusitis, and to evaluate postoperative outcomes and risk for recurrence.Design Retrospective cohort study.Setting Tertiary single-institution neurosurgery department.Participants We performed a retrospective analysis of all patients with skull base fungal infections treated with a purely endoscopic surgical approach at Mount Sinai Hospital from 1998 to 2018.Main Outcome Measures Clinical presentation, number of recurrences, and mortality rate.Results The most common underlying medical comorbidities were hematologic malignancy in 8 (57.1%) patients and poorly controlled diabetes mellitus in 7 (50%) patients. Presenting symptoms included headache (50%), eye pain (35.7%), facial pain (28.6%), visual changes (21.4%), and nasal congestion (14.3%). The fungal organisms identified on culture were Aspergillus (42.9%), Mucorales (28.6%), Fusarium (14.3%), Penicillium (7.1%), and unspecified (7.1%). Eight (57.1%) patients developed recurrence and required multiple surgical debridements. Patients who had only a hematologic malignancy were more likely to require multiple surgical debridements compared with those who did not have a hematologic malignancy or those who had both hematologic malignancy and underlying diabetes mellitus (p = 0.03). The mortality rate from surgery was 42.9%.Conclusion Surgical endoscopic intervention is an option for definitive management of acute invasive skull base fungal rhinosinusitis; however, postoperative mortality and risk of recurrence requiring additional surgical interventions remains high. Patients with hematologic malignancy may be more susceptible to recurrent infection requiring multiple surgical debridements. We recommend early aggressive multimodal treatment. Multiple debridements may be warranted in most cases; close clinical surveillance is needed during neurosurgical intervention.

The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery.To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas.Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined.One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P.05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P.05, area under the curve 0.46).Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

OBJECTIVE Prior studies have demonstrated a relationship between underlying tumor genetics and lymphocyte infiltration in meningiomas. In this study, the authors aimed to further characterize the relationship between meningioma genomics, CD4+ and CD8+ T-cell infiltration, and oncological outcomes of meningiomas. Understanding specific characteristics of the inflammatory infiltration could have implications for treatment and prognostication. METHODS Immunohistochemically stained meningioma slides were reviewed to assess the CD4+ and CD8+ cell infiltration burden. The relationship between immune cell infiltration and tumor genomics was then assessed using an adjusted ANOVA model. For a specific gene identified by the ANOVA, the relationship between that mutation and tumor recurrence was assessed using Cox regression. RESULTS In immunohistochemically stained samples from a subcohort of 25 patients, the mean number of CD4+ cells was 42.2/400× field and the mean number of CD8+ cells was 69.8/400× field. Elevated CD8+ cell infiltration was found to be associated with the presence of a mutation in the gene encoding for DNA polymerase epsilon, POLE (51.6 cells/hpf in wild-type tumors vs 95.9 cells/hpf in mutant tumors; p = 0.0199). In a retrospective cohort of 173 patients, the presence of any mutation in POLE was found to be associated with a 46% reduction in hazard of progression (HR 0.54, 95% CI 0.311–0.952; p = 0.033). The most frequent mutation was a near–C-terminal nonsense mutation. CONCLUSIONS A potential association was found between mutant POLE and both an increase in CD8+ cell infiltration and progression-free survival. The predominant mutation was found outside of the known exonuclease hot spot; however, it was still associated with a slight increase in mutational burden, CD8+ cell infiltration, and progression-free survival. Alterations in gene expression, resulting from alterations in POLE, may yield an increased presentation of neoantigens, and, thus, greater CD8+ cell-mediated apoptosis of neoplastic cells. These findings have suggested the utility of checkpoint inhibitors in the treatment of POLE-mutant meningiomas.

In recent years, new human magnetic resonance imaging systems operating at static magnetic fields strengths of 7 Tesla or higher have become available, providing better signal sensitivity compared with lower field strengths. However, imaging human-sized objects at such high field strength and associated precession frequencies is limited due to the technical challenges associated with the wavelength effect, which substantially disturb the transmit field uniformity over the human body when conventional coils are used. Here we report a novel passive inductively-coupled radiofrequency resonator array design with a simple structure that works in conjunction with conventional coils and requires only to be tuned to the scanner’s operating frequency. We show that inductive-coupling between the resonator array and the coil improves the transmit efficiency and signal sensitivity in the targeted region. The simple structure, flexibility, and cost-efficiency make the proposed array design an attractive approach for altering the transmit field distribution specially at high field systems, where the wavelength is comparable with the tissue size.

Introduction Tolosa-Hunt syndrome (THS), a condition characterized by painful ophthalmoplegia and accompanied by cranial nerve palsies, remains as a diagnosis of exclusion. Nevertheless, the 3rd Edition of the International Classification of Headache Disorders (ICHD) has refined its diagnostic criteria to require the demonstration of granulomatous inflammation on magnetic resonance imaging or biopsy. We sought to assess the effectiveness of the new criteria in arriving at accurate diagnoses. Methods We extracted all patient charts from our institution's electronic medical record associated with ICD-9 code 378.55 (external ophthalmoplegia). We then completed the retrospective diagnostic workups to determine if subjects met ICHD-3 criteria for THS and compared our findings with their final diagnoses. Results Of 62 patients associated with ICD-9 code 378.55, 10 (16%) was identified to have presenting symptoms concerning THS. The average age at the first onset of THS-like symptoms was 58 years. Five of the 10 (50%) met ICHD-3 criteria for THS. Two of the 5 (40%) meeting ICHD-3 criteria for THS were discovered to have other diagnoses. Two of the 5 (40%) patients not meeting ICHD-3 criteria for THS nevertheless received a final diagnosis of THS. Discussion Our false-negative rate of 40% is consistent with previous case series found in the literature. Our false-positive rate of 40% is, to our knowledge, a new contribution to the literature as no other case series includes more than a single false-positive. The false-positive rate is most concerning, as a preliminary misdiagnosis of THS can delay treatment tailored to the true etiology. Furthermore, infectious etiologies can be exacerbated with steroid treatment. Conclusion Our case series suggests that ICHD-3 criteria are suboptimal for the accurate diagnosis of THS. We recommend a close follow-up for all patients with symptoms concerning THS until a definitive responsible etiology is discovered and we encourage further studies assessing ICHD-3 guidelines to optimize their sensitivity and specificity in the diagnosis of THS.

Chordomas are rare primary malignant tumors of the bones that occur along the skull base, spine, and sacrum. Long-term survival and neurological outcome continue to be challenging with continued low percentages of long-term survival. Recent studies have used genome, exome, transcriptome, and proteome sequencing to assess the mutational profile of chordomas. Most notably, Brachyury, or T-protein, has been shown to be an early mutational event in chordoma evolution. Clinically actionable mutations, including in the PI3K pathway, were identified. Preliminary evidence suggests that there may be mutational differences associated with primary tumor location. In this study, we review the therapeutic landscape of chordomas and discuss emerging targets in the genomic era.

Objective Atypical (World Health Organization grade II) meningiomas (AMs) have been associated with a substantial risk of recurrence even after complete, gross total resection (GTR). The present study evaluated the clinical and AM tumor histopathological features that might predict for the risk of recurrence and survival within this patient population. Methods The data from 72 consecutive patients who had undergone primary GTR for AM from 2007 to 2016 and corresponding tumor specimens at a single institution were reviewed. The preoperative patient and tumor characteristics were correlated with the postresection outcomes, including recurrence and 1-year survival. Cox regression models on recurrence-free survival (RFS) and Kaplan-Meier survival estimates were performed. Results The overall 1-, 3-, and 5-year RFS estimates for the AM cohort were 100.0%, 82.4%, and 78.1% after resection, respectively. A high mitotic index was an independent predictor of RFS on Cox regression analysis (hazard ratio, 1.26; P = 0.008), and the tumor volume showed a trend toward a significant association (hazard ratio, 0.93; P = 0.079). Patient age and the mitotic index were significantly associated with 1-year mortality (odds ratio, 1.11 and 1.36, respectively; P = 0.028 and P = 0.045, respectively). Conclusions AM tumors with a high proliferative index showed an increased likelihood of recurrence and short-term survival even after complete GTR. A smaller tumor volume might also have contributed to an increased risk of recurrence for patients with AM. Although other histopathological features were not linked to recurrence or mortality for patients with AM, the biopsy findings can indicate key predictive information, and further molecular analysis might reveal additional prognostic markers.

Background With the advent of extensive endoscopic approaches for pituitary tumors, there has also been an increase in surgery for larger and more complex tumors. Intraoperative manipulation during endoscopic resection of sellar tumors poses potential risk in postoperative visual function in this tumor population. This study proposes a method of accurate intraoperative monitoring of visual evoked potentials (VEPs) and its role in predicting visual function outcomes. Methods Intraoperative VEPs were monitored for 42 resections from a single surgical team, with average tumor size of 2.84 cm. Changes in VEP amplitude and latency in excess of 50% were considered significant. Preoperative and postoperative visual information was obtained from ophthalmology and hospital records, along with patient demographics, comorbidities, and tumor characteristics. Results Patients were stratified as experiencing deteriorations in VEPs that did not restore to baseline (n = 4), deteriorations in VEPs that did restore to baseline (n = 6), no change in VEPs (n = 31), and improvement in VEPs (n = 1). Correlation between VEP changes and postoperative visual fields was measured through univariate ordered logistic regression. Improved intraoperative VEP measurements were associated with odds ratio (OR) of visual field improvement of 3.15 (95% confidence interval, 1.15–8.59). Specifically, changes in VEP amplitude were positively associated with visual field improvement with OR of 4.35 (OR, 1.29–14.7). No association was observed between VEPs and other patient or tumor characteristics. Conclusion Changes in VEP amplitude during endoscopic sellar tumor resection correlate with postoperative visual function. Intraoperative VEP monitoring can serve an important role in preventing postoperative visual field loss.

Introduction Significant charge disparities exist across New York State (NYS). Race and income are associated with increased charges. To determine risk factor, we correlate hospital charges for pituitary surgery with socioeconomic factors. Additionally, we identify patients at risk for increased hospital charges and provide insight into cost-effective practices. Methods Retrospective cohort study of the Statewide Planning and Research Cooperative System (SPARCS) database from the NYS Department of Health was conducted. The SPARCS database was reviewed. Patients who underwent transsphenoidal pituitary surgery from 1995 to 2015 were identified. Income and urban status were referenced from U.S. census data. Linear regression was performed to analyze the effect of sociodemographic factors, comorbidities, and complications on hospital charges while controlling for length of stay. Results A total of 9,373 patients were identified. Black (10.8%, p Conclusion Patients incurring higher chargers were more likely to have a smoking history, hypertension, hypothyroidism, and comorbidities. The determinants of this analysis may provide insight into barriers to patient access and cost improvement strategies. In addition, this emphasizes the need for future studies to create a risk stratification model, similar to those in other fields.

Background Before the coronavirus disease 2019 (COVID-19) pandemic, medical students training in neurosurgery relied on external subinternships at institutions nationwide for immersive educational experiences and to increase their odds of matching. However, external rotations for the 2020–2021 cycle were suspended given concerns of spreading COVID-19. Our objective was to provide foundational neurosurgical knowledge expected of interns, bootcamp-style instruction in basic procedures, and preinterview networking opportunities for students in an accessible, virtual format. Methods The virtual neurosurgery course consisted of 16 biweekly 1-hour seminars over a 2-month period. Participants completed comprehensive precourse and postcourse surveys assessing their backgrounds, confidence in diverse neurosurgical concepts, and opinions of the qualities of the seminars. Responses from students completing both precourse and postcourse surveys were included. Results An average of 82 students participated live in each weekly lecture (range, 41–150). Thirty-two participants completed both surveys. On a 1–10 scale self-assessing baseline confidence in neurosurgical concepts, participants were most confident in neuroendocrinology (6.79 ± 0.31) and least confident in spine oncology (4.24 ± 0.44), with an average of 5.05 ± 0.32 across all topics. Quality ratings for all seminars were favorable. The mean postcourse confidence was 7.79 ± 0.19, representing an improvement of 3.13 ± 0.38 (P Conclusions Feedback on seminar quality and improvements in confidence in neurosurgical topics suggest that an interactive virtual course may be an effective means of improving students' foundational neurosurgical knowledge and providing networking opportunities before application cycles. Comparison with in-person rotations when these are reestablished may help define roles for these tools.