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.

Initial experience with minimally invasive endoscopic evacuation of intracerebral hemorrhage in the setting of radiographic herniation.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) can rapidly result in cerebral herniation, leading to poor neurologic outcomes or mortality. To date, neither decompressive hemicraniectomy (DH) nor hematoma evacuation have been conclusively shown to improve outcomes for comatose ICH patients presenting with cerebral herniation, with these patients largely excluded from clinical trials. Here we present the outcomes of a series of patients presenting with ICH and radiographic herniation who underwent emergent minimally invasive (MIS) ICH evacuation. METHODS: We reviewed our prospectively collected registry of patients undergoing MIS ICH evacuation at a single institution from 01/01/2017 to 10/01/2021. We selected all consecutive patients with Glasgow coma scale (GCS) ≤ 8 and radiographic herniation for this case series. Clinical and radiographic variables were collected, including admission GCS score, preoperative and postoperative hematoma volumes, National Institute of Health stroke scale (NIHSS) scores, and modified Rankin scale (mRS) scores at last follow-up. RESULTS: Of 176 patients with spontaneous supratentorial ICH who underwent minimally invasive endoscopic evacuation during the study time period, a total of 9 patients presented with GCS ≤ 8 and evidence of radiographic herniation. Among these patients, the mean age was 62 ± 12 years, the median GCS at presentation was 5 [IQR 4-6], the mean preoperative hematoma volume was 94 ± 44 mL, the mean time from ictus to evacuation was 12 ± 5 h, and the mean postoperative hematoma volume was 11 ± 16 mL, for a median evacuation percentage of 97% [83-99]. Three patients (33%) died, four (44%) survived with mRS 5 and two (22%) with mRS 4. Patients had a median NIHSS improvement of 5 compared to their initial NIHSS. Age was very strongly correlate to improvements in NIHSS (r2 = 0.90). CONCLUSION: Data from this initial experience suggest emergent MIS hematoma evacuation in the setting of ICH with radiographic herniation is feasible and technically effective. Further randomized studies are required to determine if such an intervention offers overall benefits to patients and their families.

A multicenter, longitudinal survey of headaches and concussions among youth athletes in the United States from 2009 to 2019.

OBJECTIVE/ BACKGROUND: Chronic headaches and sports-related concussions are among the most common neurological morbidities in adolescents and young adults. Given that the two can overlap in presentation, studying the effects of one on another has proven difficult. In this longitudinal study, we sought to assess the relationship between chronic headaches and concussions, analyzing the role of historic concussions on chronic headaches, as well as that of premorbid headaches on future concussion incidence, severity, and recovery. METHODS: This multi-center, longitudinal cohort study followed 7,453 youth athletes who were administered demographic and clinical surveys as well as a total of 25,815 Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) assessments between 2009 and 2019. ImPACT was administered at baseline. Throughout the season concussions were examined by physicians and athletic trainers, followed by re-administration of ImPACT post-injury (PI), and at follow-up (FU), a median of 7 days post-concussion. Concussion incidence was calculated as the total number of concussions per patient years. Concussion severity and recovery were calculated as standardized deviations from baseline to PI and then FU in Symptom Score and the four neurocognitive composite ImPACT scores: Verbal Memory, Visual Memory, Processing Speed, and Reaction Time. Data were collected prospectively in a well-organized electronic format supervised by a national research-oriented organization with rigorous quality assurance. Analysis was preformed retrospectively. RESULTS: Of the eligible athletes, 1,147 reported chronic headaches (CH) at the start of the season and 6,306 reported no such history (NH). Median age of the cohort was 15.4 ± 1.6 years, and students were followed for an average of 1.3 ± 0.6 years. A history of concussions (OR 2.31, P < 0.0001) was associated with CH. Specifically, a greater number of past concussions (r2 = 0.95) as well as concussions characterized by a loss of consciousness (P < 0.0001) were associated with more severe headache burden. The CH cohort had a greater future incidence of concussion than the NH cohort (55.6 vs. 43.0 per 100 patient-years, P < 0.0001). However, multivariate analysis controlling for demographic, clinical, academic, and sports-related variables yielded no such effect (OR 0.99, P = 0.85). On multivariable analysis the CH cohort did have greater deviations from baseline to PI and FU in Symptom Score (PI OR per point 1.05, P = 0.01, FU OR per point 1.11, P = 0.04) and Processing Speed (OR per point 1.08, P = 0.04), suggesting greater concussion severity and impaired symptomatic recovery as compared to the NH cohort. CONCLUSION: A history of concussions was a significant contributor to headache burden among American adolescents and young adults. However, those with chronic headaches were not more likely to be diagnosed with a concussion, despite presenting with more severe concussions that had protracted recovery. Our findings not only suggest the need for conservative management among youth athletes with chronic headaches, they also indicate a potential health care gap in this population, in that those with chronic headaches may be referred for concussion diagnosis and management at lower rates than those with no such comorbidity.

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.

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.

Clinical and Operative Risk Factors Associated With Prolonged Length of Stay After Endoscopic Pituitary Adenoma Resection.

BACKGROUND AND OBJECTIVES: Pituitary adenomas (PAs) are the most common intrasellar tumor. Clinically relevant adenomas have a prevalence of 1 per 1000 in the general population. Transsphenoidal surgery (TSS) is the most common surgical treatment and is the first-line management for most PAs. Most patients fare well postoperatively, but a subset of patients experience a prolonged length of stay (PLOS). In this article, we aim to identify demographic and clinical factors associated with PLOS after TSS for PA. METHODS: Patients with sellar pathologies surgically treated at a single tertiary center from March 1, 2009, to May 31, 2020, were retrospectively reviewed. All patients older than 18 years receiving nonemergent endoscopic TSS for pituitary adenoma were included. Clinical and demographic characteristics were analyzed using χ 2 -tests and student t -tests. For those factors with a P -value less than .01, multivariate logistic regression and negative binomial regression models were constructed to estimate the adjusted odds of PLOS across predictive factors. RESULTS: A total of 301 patients were included in the study. This cohort had an average age of 54.65 ± 15.06 years and an average body mass index of 29.47 ± 6.69. The median length of stay was 54.9 hours [25th-75th percentiles: 43.5-72.9]. Postoperative cerebrospinal fluid leak ( P < .01), postoperative diabetes insipidus (DI) ( P < .01), increased surgery duration ( P = .01), and elevated maximal tumor dimension ( P = .01) were predictive of PLOS in logistic regression. Increased surgery duration, previous pituitary radiation, intraoperative complications, and postoperative DI (all P < .01) were associated with increased rate of PLOS in negative binomial regression. CONCLUSION: Patients undergoing endoscopic TSS for PA resection demonstrate prolonged lengths of stay if they have higher tumor burden, have lengthier surgeries with intraoperative complications, or develop postoperative complications such as cerebrospinal fluid leak or DI. Careful monitoring of these factors will allow for better resource optimization, reducing costs to both the hospital and the patient.

External Ventricular Drain Placement Teleproctoring Using a Novel Camera-Projector Navigation System: A Proof-of-Concept Study.

BACKGROUND: Teleproctoring is an emerging method of bedside clinical teaching; however, its feasibility has been limited by the available technologies. The use of novel tools that incorporate 3-dimensional environmental information and feedback might offer better bedside teaching options for neurosurgical procedures, including external ventricular drain placement. METHODS: A platform with a camera-projector system was used to proctor medical students on placing external ventricular drains on an anatomic model as a proof-of-concept study. Three-dimensional depth information of the model and surrounding environment was captured by the camera system and provided to the proctor who could provide projected annotations in a geometrically compensated manner onto the head model in real time. The medical students were randomized to identify Kocher's point on the anatomic model with or without the navigation system. The time required to identify Kocher's point and the accuracy were measured as a proxy for determining the effectiveness of the navigation proctoring system. RESULTS: Twenty students were enrolled in the present study. Those in the experimental group identified Kocher's point an average of 130 seconds faster than did the control group (P < 0.001). The mean diagonal distance from Kocher's point was 8.0 ± 4.29 mm for the experimental group compared with 23.6 ± 21.98 mm for the control group (P = 0.053). Of the 10 students randomized to the camera-projector system arm, 70% were accurate to within 1 cm of Kocher's point compared with 40% of the control arm (P > 0.05). CONCLUSIONS: Camera-projector systems for bedside procedure proctoring and navigation are a viable and valuable technology. We demonstrated its viability for external ventricular drain placement as a proof-of-concept. However, the versatility of this technology indicates that that it could be useful for a variety of even more complex neurosurgical procedures.

Bibliometric Analysis of International Medical Graduates and Professorship Promotion in Neurosurgery.

BACKGROUND: International medical graduates (IMGs) comprise ∼25% of physicians in the United States. Differences in promotion rates from assistant to associate to full professorship based on medical school location have been understudied. We aim to stratify odds of professional advancement by 3 categories: IMG with U.S. residency, IMG with international residency, and U.S. medical with U.S. residency training. METHODS: We created and queried a database after exclusions of 1334 neurosurgeons including multiple demographic factors: academic productivity and promotion rates. Stratified logistic regression modeled odds of promotion including the variables: decades out of training, Scopus h-index, gender, and training location. Odds ratios (ORs) and 95% confidence intervals (CIs) for each variable were calculated. RESULTS: Significant predictors of increased associate versus assistant professorship included decades out of training (OR = 2.519 [95% CI: 2.07-3.093], P < 0.0001) and Scopus h-index (OR = 1.085 [95% CI: 1.064-1.108], P < 0.0001) while international medical school with U.S. residency (OR = 0.471 [95% CI: 0.231-0.914], P = 0.0352) was associated with decreased promotion. Significant predictors of associate versus full professorship were decades out of training (OR = 2.781 [95% CI: 2.268-3.444], P < 0.0001) and Scopus h-index (OR = 1.064 [95% CI: 1.049-1.080], P < 0.0001). Attending medical school or residency internationally was not associated with odds of full professorship. CONCLUSIONS: Time out of residency and Scopus h-index were associated with higher academic rank regardless of career level. Attending medical school internationally with U.S. residency was associated with lower odds of associate professorship promotion over 10 years. There was no relationship between IMG and full professorship promotion. IMGs who attended residency internationally did not have lower promotion rates. These findings suggest it may be harder for IMGs to earn promotion from assistant to associate professor in neurosurgery.

Interventions to reduce repetitive ordering of low-value inpatient laboratory tests: a systematic review.

BACKGROUND: Over-ordering of daily laboratory tests adversely affects patient care through hospital-acquired anaemia, patient discomfort, burden on front-line staff and unnecessary downstream testing. This remains a prevalent issue despite the 2013 Choosing Wisely recommendation to minimise unnecessary daily labs. We conducted a systematic review of the literature to identify interventions targeting unnecessary laboratory testing. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Central and SCOPUS databases to identify interventions focused on reducing daily complete blood count, complete metabolic panel and basic metabolic panel labs. We defined interventions as 'effective' if a statistically significant reduction was attained and 'highly effective' if a reduction of ≥25% was attained. RESULTS: The search yielded 5646 studies with 41 articles that met inclusion criteria. We grouped interventions into one or more categories: audit and feedback, cost display, education, electronic medical record (EMR) change, and policy change. Most interventions lasted less than a year and used a multipronged approach. All five strategies were effective in most studies with EMR change being the most commonly used independent strategy. EMR change and policy change were the strategies most frequently reported as effective. EMR change was the strategy most frequently reported as highly effective. CONCLUSION: Our analysis identified five categories of interventions targeting daily laboratory testing. All categories were effective in most studies, with EMR change being most frequently highly effective. PROSPERO REGISTRATION NUMBER: CRD42021254076.

Characterization of length of stay after minimally invasive endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. OBJECTIVE: To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. RESULTS: Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). CONCLUSIONS: We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.

Utilization of Palliative Care Services Among Patients With Malignant Brain Tumors: An Analysis of the National Inpatient Sample (2016-2019).

BACKGROUND: Recent advances in treatment of malignant brain tumors have improved outcomes. However, patients continue to experience significant disability. Palliative care helps patients with advanced illnesses improve their quality of life. There is a paucity of clinical studies examining palliative care usage among patients with malignant brain tumors. OBJECTIVE: To assess if there were any patterns in palliative care utilization among patients hospitalized with malignant brain tumors. METHODS: A retrospective cohort representing hospitalizations for malignant brain tumors was created from The National Inpatient Sample (2016-2019). Palliative care utilization was identified by ICD-10 code. Univariable and multivariable logistic regression models, accounting for the sample design, were built to evaluate the demographic variables associated with palliative care consultation in all patients and fatal hospitalizations. RESULTS: 375 010 patients admitted with a malignant brain tumor were included in this study. Over the whole cohort, 15.0% of patients used palliative care. In fatal hospitalizations, Black and Hispanic patients had 28% lower odds of receiving a palliative care consultation compared with White patients (odds ratio for both = 0.72; P = .02). For fatal hospitalizations, patients insured privately were 34% more likely to use palliative care services compared with patients insured with Medicare (odds ratio = 1.34, P = .006). CONCLUSION: Palliative care is underutilized among all patients with malignant brain tumors. Within this population, disparities in utilization are exacerbated by sociodemographic factors. Prospective studies investigating utilization disparities across race and insurance status are necessary to improve access to palliative care services for this population.

Predictors of Prolonged Length of Stay After Pituitary Adenoma Resection: A Large Cohort Analysis Using the National Inpatient Sample (2016-2019).

OBJECTIVE: In this nationwide retrospective study, the authors aimed to identify demographic, clinical, and baseline health risk factors predictive of a prolonged length of stay (PLOS) for patients with pituitary adenomas (PAs). METHODS: The National Inpatient Sample dataset from 2016 to 2019 was utilized to identify all included hospitalizations for PA resection as identified by the appropriate diagnosis-related group code. Comorbidities were classified based on the Charlson Comorbidity Index mapping of ICD-10 codes, and PLOS was identified as any stay longer than 3 days. Univariable and multivariable logistic regression models, accounting for the sample design, were built to determine factors associated with PLOS and emergent surgery. RESULTS: Overall, 30 945 patients were included in this study with 10 535 patients having PLOS. Female patients experienced an increased odds of PLOS (odds ratio [OR]: 1.29; P < .001). Black patients (OR: 1.49; P < .001) and Hispanic patients (OR: 1.30; P = .003) had 1.49 times and 1.30 times the odds of PLOS compared to White patients, respectively. Compared to patients insured by Medicare, patients insured by Medicaid had an increased odds of PLOS (OR: 1.36; P = .007) as well as emergent surgery (OR: 5.40; P < .001). When stratified by emergent surgeries, Black patients (OR: 1.89; P < .001), Hispanic patients, (OR: 2.14; P < .001), and patients on Medicaid insurance (OR: 1.71; P < .001) were at an increased risk of emergent procedures. However, female sex (OR: 0.65; P < .001), upper third quartile (OR: 0.73; P = .017), and fourth quartile (OR: 0.69; P = .014) of patients categorized by zip code income were at decreased odds of an emergent procedure. CONCLUSIONS: Black and Hispanic patients, patients with Medicaid insurance, and patients of low socioeconomic status patients are at significantly higher risk of emergent PA resection and PLOS. Efforts to prevent emergent surgeries and shorten hospitalization after pituitary surgery may need to primarily focus on patient groups with select sociodemographic characteristics.

Early and effective intracerebral hemorrhage evacuation is associated with a lower 1-year residual cavity volume and better functional outcomes.

BACKGROUND: We explored the clinical significance of the residual hematoma cavity 1 year after minimally invasive intracerebral hemorrhage (ICH) evacuation. METHODS: Patients presenting with spontaneous supratentorial ICH were evaluated for minimally invasive surgical evacuation. Inclusion criteria included age ≥18 years, preoperative hematoma volume (Hv) ≥15 mL, presenting National Institutes of Health Stroke Scale score ≥6, and premorbid modified Rankin Scale (mRS) score ≤3. Patients with longitudinal CT scans at least 3 months after evacuation were included in the study. Remnant cavity volumes (Cv) after evacuation were computed using semi-automatic volumetric segmentation software. Relative cavity volume (rCv) was defined as the ratio of the preoperative Hv to the remnant Cv. RESULTS: 108 patients with a total of 484 head CT scans were included in the study. The median postoperative Cv was 2.4 (IQR 0.0-11) mL, or just 6% (0-33%) of the preoperative Hv. The median residual Cv on the final head CT scan a median of 13 months (range 11-27 months) after surgery had increased to 9.4 (IQR 3.1-18) mL, or 25% (10-60%) of the preoperative Hv. rCv on the final head CT scan was negatively associated with measures of operative success including evacuation percentage, postoperative Hv ≤15 mL, and decreased time from ictus to evacuation. rCv on the final head CT scan was also associated with a worse 6-month functional outcome (ß per mRS point 17.6%, P<0.0001; area under the receiver operating characteristic curve 0.91). CONCLUSION: After minimally invasive ICH evacuation the hematoma lesion decompresses significantly, with a residual Cv just 6% of the original lesion, but then gradually increases in size over time. Early and high percentage ICH evacuation may reduce the remnant Cv over time which, in turn, is associated with improved functional outcomes.

ARID1A mutation associated with recurrence and shorter progression-free survival in atypical meningiomas.

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

The Knosp Criteria Revisited: 3-Dimensional Volumetric Analysis as a Predictive Tool for Extent of Resection in Complex Endoscopic Pituitary Surgery.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Association between tumor mutations and meningioma recurrence in Grade I/II disease.

BACKGROUND: 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. MATERIALS AND METHODS: We identified 184 grade I and II meningiomas with both >90 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 a p-value of less than 0.20. Starting with that model, we performed backward selection to identify the most predictive factors. RESULTS: ATM (HR = 4.448; 95% CI: 1.517-13.046), CREBBP (HR = 2.727; 95% CI = 1.163-6.396), and POLE (HR = 0.544; HR = 0.311-0.952) were significantly associated with alterations in disease progression after adjusting for clinical and pathologic factors. In the multi-gene model, only POLE remained a significant predictor of recurrence after adjusting for the same clinical covariates. Backwards selection identified recurrence status, resection extent, and mutations in ATM (HR = 7.333; 95% CI = 2.318-23.195) and POLE (HR = 0.413; 95% CI = 0.229-0.743) as predictive of recurrence. CONCLUSIONS: Mutations 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.

Perivascular spaces as a marker of psychological trauma in depression: A 7-Tesla MRI study.

INTRODUCTION: Emerging evidence in depression suggests that blood-brain barrier (BBB) breakdown and elevated inflammatory cytokines in states of persistent stress or trauma may contribute to the development of symptoms. Signal-to-noise ratio afforded by ultra-high field MRI may aid in the detection of maladaptations of the glymphatic system related to BBB integrity that may not be visualized at lower field strengths. METHODS: We investigated the link between glymphatic neuroanatomy via perivascular spaces (PVS) and trauma experience in patients with major depressive disorder (MDD) and in healthy controls using 7-Tesla MRI and a semi-automated segmentation algorithm. RESULTS: After controlling for age and gender, the number of traumatic events was correlated with total PVS volume in MDD patients (r = 0.50, p = .028) and the overall population (r = 0.34, p = .024). The number of traumatic events eliciting horror was positively correlated with total PVS volume in MDD patients (r = 0.50, p = .030) and the overall population (r = 0.32, p = .023). Age correlated positively with PVS count, PVS total volume, and PVS density in all participants (r > 0.35, p < .01). CONCLUSIONS: These results suggest a relationship between glymphatic dysfunction related to BBB integrity and psychological trauma, and that glymphatic impairment may play a role in trauma-related symptomatology.