Complications of Implanted Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

INTRODUCTION: Vagus Nerve Stimulation (VNS) has emerged as a promising tool in ischemic stroke rehabilitation. However, there has been no systematic review summarizing its adverse effects, critical information for patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis reports the adverse effects of VNS. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify common complications after VNS therapy. The search was executed in: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. RESULTS: After title-and-abstract screening of 4933 studies, 21 were selected for final inclusion. Across these studies, 1474 patients received VNS implantation. VNS was used as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). CONCLUSIONS: Complications from VNS are mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. In prior studies, VNS has served as treatment option in several instances of treatment-resistant conditions, such as epilepsy and psychiatric conditions, and its use in stroke recovery and rehabilitation should continue to be explored.

NF2 mutations are associated with resistance to radiation therapy for grade 2 and grade 3 recurrent meningiomas.

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

NF2 mutation associated with accelerated time to recurrence for older patients with atypical meningiomas.

PURPOSE: Meningiomas occur more frequently in older adults, with the incidence rates increasing from 5.8/100,000 for adults 35-44 years old to 55.2/100,000 for those 85+. Due to the increased risk of surgical management in older adults, there is a need to characterize the risk factors for aggressive disease course to inform management decisions in this population. We therefore sought to determine age-stratified relationships between tumour genomics and recurrence after resection of atypical meningiomas. METHODS: We identified 137 primary and recurrent Grade 2 meningiomas from our existing meningioma genomic sequencing database. We examined the differential distribution of genomic alterations in those older than 65 compared to younger. We then performed an age stratified survival analysis to model recurrence for a mutation identified as differentially present. RESULTS: In our cohort of 137 patients with grade 2 meningiomas, alterations in NF2 were present at a higher rate in older adults compared to younger (37.8% in < 65 vs. 55.3% in > 65; recurrence adjusted p-value =0.04). There was no association between the presence of NF2 and recurrence in the whole cohort. In the age-stratified model for those less than 65 years old, there was again no relationship. For patients in the older age stratum, there is a relationship between NF2 and worsened recurrence outcomes (HR = 3.64 (1.125 - 11.811); p = 0.031). CONCLUSIONS: We found that mutations in NF2 were more common in older adults. Further, the presence of mutant NF2 was associated with an increased risk of recurrence in older adults.

Association of mutations in DNA polymerase epsilon with increased CD8+ cell infiltration and prolonged progression-free survival in patients with meningiomas.

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.

Virtual reality surgical planning for endoscopic endonasal approaches to the craniovertebral junction.

PURPOSE: To demonstrate the utility of virtual reality (VR) for preoperative surgical planning of endoscopic endonasal craniovertebral junction (CVJ) surgery. MATERIALS AND METHODS: Five patients who had undergone endoscopic endonasal surgery of the craniovertebral junction with preoperative virtual reality surgical planning were identified and described. RESULTS: The anterior approach to the CVJ has been traditionally accomplished transorally. However, recently the transnasal endoscopic approach to this location has been described. Multiple anatomical studies have been conducted using the nasopalatine, nasoaxial, and rhinopalatine lines (NPL, NAxL, RPL) in an attempt to preoperatively delineate the inferior limits of endoscopic dissection. The use of advanced surgical simulation using immersive virtual reality is an innovative approach for analyzing CVJ anatomy and developing a surgical plan. VR simulation through the use of interactive and highly accurate patient specific models allows for the creation of three-dimensional (3D) digital reconstructions via the fusion of CT and MRI studies. Incorporation of simulation technology has been shown to increase surgeon proficiency while simultaneously decreasing complication rates. The described case series demonstrates the novel utility of VR planning for designing the endoscopic surgical approach to the CVJ. CONCLUSIONS: VR technology allows for the creation of anatomically accurate 3D models that can be used for preoperative planning of endoscopic endonasal surgery. Such models help in the development of safe surgical plans by predicting inferior and lateral planes of dissection and assisting in the identification of critical structures.

Post-operative vision loss: analysis of 587 patients undergoing endoscopic surgery for pituitary macroadenoma.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Surgical outcomes in patients with endoscopic versus transcranial approach for skull base malignancies: a 10-year institutional experience.

OBJECT: The authors performed an extensive comparison between patients treated with open versus an endoscopic approach for skull base malignancy with emphasis on surgical outcomes. METHODS: A single-institution retrospective review of 60 patients who underwent surgery for skull base malignancy between 2009 and 2018 was performed. Disease features, surgical resection, post-operative morbidities, adjuvant treatment, recurrence, and survival rates were compared between 30 patients who received purely open surgery and 30 patients who underwent purely endoscopic resection for a skull base malignancy. RESULTS: Of the 60 patients with skull base malignancy, 30 underwent open resection and 30 underwent endoscopic resection. The most common hisotype for endoscopic resection was squamous cell carcinoma (26.7%), olfactory neuroblastoma (16.7%), and sarcoma (10.0%), and 43.3%, 13.3%, and 10.0% for the open resection cohort, respectively. There were no statistical differences in gross total resection, surgical-associated cranial neuropathy, or ability to achieve negative margins between the groups (p > 0.1, all comparisons). Patients who underwent endoscopic resection had shorter surgeries (320.3 ± 158.5 minutes vs. 495.3 ± 187.6 minutes (p = 0.0003), less intraoperative blood loss (282.2 ± 333.6 ml vs. 696.7 ± 500.2 ml (p < 0.0001), and shorter length of stay (3.5 ± 3.7 days vs. 8.8 ± 6.0 days (p < 0.0001). Additionally, patients treated endoscopically initiated adjuvant radiation treatment more quickly (48.0 ± 20.3 days vs. 72.0 ± 20.5 days (p = 0.01). CONCLUSIONS: An endoscopic endonasal approach facilitates a clinically meaningful improvement in surgical outcomes for skull base malignancies.

Accuracy of artificial intelligence for the detection of intracranial hemorrhage and chronic cerebral microbleeds: a systematic review and pooled analysis.

BACKGROUND: Artificial intelligence (AI)-driven software has been developed and become commercially available within the past few years for the detection of intracranial hemorrhage (ICH) and chronic cerebral microbleeds (CMBs). However, there is currently no systematic review that summarizes all of these tools or provides pooled estimates of their performance. METHODS: In this PROSPERO-registered, PRISMA compliant systematic review, we sought to compile and review all MEDLINE and EMBASE published studies that have developed and/or tested AI algorithms for ICH detection on non-contrast CT scans (NCCTs) or MRI scans and CMBs detection on MRI scans. RESULTS: In total, 40 studies described AI algorithms for ICH detection in NCCTs/MRIs and 19 for CMBs detection in MRIs. The overall sensitivity, specificity, and accuracy were 92.06%, 93.54%, and 93.46%, respectively, for ICH detection and 91.6%, 93.9%, and 92.7% for CMBs detection. Some of the challenges encountered in the development of these algorithms include the laborious work of creating large, labeled and balanced datasets, the volumetric nature of the imaging examinations, the fine tuning of the algorithms, and the reduction in false positives. CONCLUSIONS: Numerous AI-driven software tools have been developed over the last decade. On average, they are characterized by high performance and expert-level accuracy for the diagnosis of ICH and CMBs. As a result, implementing these tools in clinical practice may improve workflow and act as a failsafe for the detection of such lesions. REGISTRATION-URL: https://www.crd.york.ac.uk/prospero/ Unique Identifier: CRD42021246848.

Time to Evacuation and Functional Outcome After Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation.

BACKGROUND AND PURPOSE: We present a retrospective analysis of patients who underwent minimally invasive endoscopic intracerebral hemorrhage (ICH) evacuation to identify variables that were associated with long-term outcome. METHODS: Minimally invasive endoscopic ICH evacuation was performed on patients with supratentorial ICH who fit prespecified clinical inclusion and exclusion criteria. Demographic, clinical, and radiographic factors previously demonstrated to impact functional outcome in ICH were included in a univariate analysis to identify factors associated with favorable outcome (modified Rankin Scale score, 0-3) at 6 months. Factors associated with a favorable outcome in the univariate analysis (P≤0.20) were included in a multivariate logistic regression analysis with the same dependent variable. RESULTS: Ninety patients underwent MIS endoscopic ICH evacuation within 72 hours of ictus. In a multivariate analysis, factors associated with good long-term functional outcome included time to evacuation (per hour; OR, 0.95 [95% CI, 0.92-0.98], P=0.004), age (per decade, odds ratio [OR], 0.49 [95% CI, 0.28-0.77], P=0.005), presence of intraventricular hemorrhage (OR, 0.15 [95% CI, 0.04-0.47], P=0.002), and lobar location (OR, 18.5 [95% CI, 4.5-103], P=0.0005). Early evacuation was not associated with an increased risk of rebleeding. CONCLUSIONS: Young age, lack of intraventricular hemorrhage, lobar location, and time to evacuation were independently associated with good long-term functional outcome in patients undergoing minimally invasive endoscopic ICH evacuation. The OR for time to evacuation suggests that for each additional hour, there was a 5% reduction in the odds of achieving a favorable outcome.

NF2 mutation status and tumor mutational burden correlate with immune cell infiltration in meningiomas.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Peritumoral edema correlates with mutational burden in meningiomas.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: These data support that Edema Index may serve as a novel imaging biomarker that can inform underlying mutational burden in patients with meningiomas.

The utility of augmented reality in lateral skull base surgery: A preliminary report.

OBJECTIVE: To discuss the utility of augmented reality in lateral skull base surgery. PATIENTS: Those undergoing lateral skull base surgery at our institution. INTERVENTION(S): Cerebellopontine angle tumor resection using an augmented reality interface. MAIN OUTCOME MEASURE(S): Ease of use, utility of, and future directions of augmented reality in lateral skull base surgery. RESULTS: Anecdotally we have found an augmented reality interface helpful in simulating cerebellopontine angle tumor resection as well as assisting in planning the incision and craniotomy. CONCLUSIONS: Augmented reality has the potential to be a useful adjunct in lateral skull base surgery, but more study is needed with large series.

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia.

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.

Mobile Interventional Stroke Team Model Improves Early Outcomes in Large Vessel Occlusion Stroke: The NYC MIST Trial.

BACKGROUND AND PURPOSE: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. METHODS: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months. RESULTS: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes (P<0.01). MIST and mothership had similar median door-to-recanalization times of 192 minutes and 179 minutes, respectively (P=0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%; P<0.01). MIST had 52.8% of patients with modified Rankin Scale of ≤2 at 3 months compared with 38.9% in DS (P=0.10). CONCLUSIONS: MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03048292.

COVID-19 and Decompressive Hemicraniectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Young patients with malignant cerebral edema have been shown to benefit from early decompressive hemicraniectomy. The impact of concomitant infection with coronavirus disease 2019 (COVID-19) and how this should weigh in on the decision for surgery is unclear. METHODS: We retrospectively reviewed all COVID-19-positive patients admitted to the neuroscience intensive care unit for malignant edema monitoring. Patients with >50% of middle cerebral artery involvement on computed tomography imaging were considered at risk for malignant edema. RESULTS: Seven patients were admitted for monitoring of whom 4 died. Cause of death was related to COVID-19 complications, and these were either seen both very early and several days into the intensive care unit course after the typical window of malignant cerebral swelling. Three cases underwent surgery, and 1 patient died postoperatively from cardiac failure. A good outcome was attained in the other 2 cases. CONCLUSIONS: COVID-19-positive patients with large hemispheric stroke can have a good outcome with decompressive hemicraniectomy. A positive test for COVID-19 should not be used in isolation to exclude patients from a potentially lifesaving procedure.

Brain Metastases from Biliary Tract Cancers: A Case Series and Review of the Literature in the Genomic Era.

BACKGROUND: Biliary tract cancers (BTCs) are highly fatal malignancies that make up less than 1% of all cancers. BTC is often diagnosed at an unresectable stage; surgical resection remains the only definitive treatment. Brain metastases (BMs) from BTC are extremely rare, and few studies on patients with BMs from BTC exist. The aim of this study was to identify clinical characteristics associated with poor prognosis for patients with BMs from BTC. MATERIALS AND METHODS: We performed a retrospective review of electronic medical records for patients with BMs from BTC managed at Mount Sinai Hospital from 2000 to 2017. Data on patient characteristics, magnetic resonance imaging findings, treatment regimens, and clinical outcomes were analyzed. RESULTS: We identified 1,910 patients with BTC. Nine patients developed BMs, with an incidence of 0.47%. Of these nine patients, six had intrahepatic cholangiocarcinoma, two had extrahepatic cholangiocarcinoma, and one had gallbladder cancer. Six (66.7%) patients had one BM, one (11.1%) patient had two BMs, and two (22.2%) patients had three or more BMs. Four (44.4%) patients underwent BM resection, and seven (77.8%) received BM radiation. Median overall survival from time of BM diagnosis was 3.8 months (95% confidence interval 0.1-16.9). CONCLUSION: Development of BMs from BTC is rare; however, prognosis is less than 4 months. BM diagnosis can occur within 2 years of primary diagnosis. As targeted therapeutics emerge, future studies ought to focus on identifying genomic BM markers associated with BTC subtypes. IMPLICATIONS FOR PRACTICE: In the largest retrospective study of biliary tract cancer brain metastases, the clinical presentation and outcomes are reported of nine patients with an extremely rare clinical entity. The genomic literature and potential therapeutic targets for these patients with limited treatment options is comprehensively and exhaustively discussed.

Neurosurgical management of brain and spine tumors in the COVID-19 era: an institutional experience from the epicenter of the pandemic.

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.

Reappraising the Tolosa-Hunt Syndrome Diagnostic Criteria: A Case Series.

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.

STK11 mutation status is associated with decreased survival in meningiomas.

BACKGROUND: Emerging evidence suggests that STK11 mutations may influence clinical outcome and response to immunotherapy in cancer. MATERIALS AND METHODS: Next-generation targeted sequencing of STK11 mutation status in a large cohort of 188 meningiomas. RESULTS: 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. CONCLUSION: These data identify recurrent STK11 mutations in a subset of meningiomas. Genotyping of STK11 is encouraged for meningioma patients undergoing immunotherapy-based therapy.

Systematic Review of Malpractice Litigation in the Diagnosis and Treatment of Acute Stroke.

Background and Purpose- The emergency management of stroke is complex and highly time-sensitive. Recent landmark trials demonstrating the strong benefit of thrombectomy have led to rapid change in stroke management. This article reviews a large number of medical malpractice lawsuits related to the emergency management of stroke to characterize factors involved in these lawsuits. Methods- Three large legal databases were used to search for jury verdicts and settlements in cases related to the acute care of stroke patients in the United States. Search terms included "stroke" and "medical malpractice." Cases were screened to include only cases in which the allegation involved negligence in the acute care of a patient suffering a stroke. Results- We found 246 medical malpractice cases related to the acute management of ischemic stroke and 26 related to intracranial hemorrhage. Seventy-one cases specifically alleged a failure to treat with tPA (tissue-type plasminogen activator) and 7 cases alleged a failure to treat, or to timely treat, with thrombectomy. Overall there were 151 cases (56%) which ended with no payout, 74 cases (27%) were settled out of court, and 47 cases (17%) went to court and resulted in a verdict for the plaintiff. The average payout in settlements was $1 802 693, and the average payout in plaintiff verdicts was $9 705 099. Conclusions- Malpractice litigation is a risk in acute stroke care and can lead to significant financial consequences. The majority of malpractice lawsuits related to the emergency management of stroke allege a failure to diagnose and failure to treat. Allegations of a failure to treat acute ischemic stroke with tPA were frequently found and are common in lawsuits. Allegations of a failure to treat a large vessel occlusion with thrombectomy were less frequently found. Given recent changes in practice guidelines and the demonstrated strong treatment effect of thrombectomy, it is likely that such litigation will increase in the coming years.