Letter to Our Colleagues Family Practitioners, Geriatricians, and Radiologists to Increase Awareness Regarding Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) affects elderly individuals and is characterized by a progressive deterioration of gait, urinary continence, and cognition. In most cases, it is reversible with treatment. INPH is not uncommonly an unrecognized cause of dementia. We wish to raise awareness of iNPH among primary care providers who are seeing these patients first. METHODS: We reviewed the current epidemiological data regarding iNPH as well as epidemiological data regarding Alzheimer disease. We searched for the most sensitive radiological screening test for iNPH. RESULTS: Alzheimer disease comprises 60%-70% of all dementia cases, in 2023 is affecting 6.7 million Americans, about 10.7% of people 65 and older. Epidemiological data from the Scandinavian countries confirmed that 3.7% of people older than 65 have iNPH. Surgical studies confirmed the presence of early Alzheimer's pathology in about 25% of operated patients with iNPH. Useful radiological findings of iNPH include an Evans Index greater than 0.30, and a disproportionally enlarged subarachnoid space hydrocephalus (DESH). However, the callosal angle is thought to represent the best tool to discriminate iNPH from its mimics. CONCLUSIONS: According to the available epidemiological data iNPH is underdiagnosed. We strongly encourage the primary care physicians and geriatricians to ask the radiologist to measure the callosal angle on the initial brain computed tomography (or magnetic resonance) image. If the callosal angle is ≤71°, it is appropriate to refer the patient to neurosurgery for further diagnostic work-up.

Perivascular invasion of primary human glioblastoma cells in organotypic human brain slices: human cells migrating in human brain.

INTRODUCTION: Glioblastoma (GBM) is an aggressive primary brain cancer. Lack of effective therapy is related to its highly invasive nature. GBM invasion has been studied with reductionist systems that do not fully recapitulate the cytoarchitecture of the brain. We describe a human-derived brain organotypic model to study the migratory properties of GBM IDH-wild type ex vivo. METHODS: Non-tumor brain samples were obtained from patients undergoing surgery (n = 7). Organotypic brain slices were prepared, and green fluorescent protein (GFP)-labeled primary human GBM IDH-wild type cells (GBM276, GBM612, GBM965) were placed on the organotypic slice. Migration was evaluated via microscopy and immunohistochemistry. RESULTS: After placement, cells migrated towards blood vessels; initially migrating with limited directionality, sending processes in different directions, and increasing their speed upon contact with the vessel. Once merged, migration speed decreased and continued to decrease with time (p < 0.001). After perivascular localization, migration is limited along the blood vessels in both directions. The percentage of cells that contact blood vessels and then continue to migrate along the vessel was 92.5% (- 3.9/ + 2.9)% while the percentage of cells that migrate along the blood vessel and leave was 7.5% (- 2.9/ + 3.9) (95% CI, Clopper-Pearson (exact); n = 256 cells from six organotypic cultures); these percentages are significantly different from the random (50%) null hypothesis (z = 13.6; p < 10-7). Further, cells increase their speed in response to a decrease in oxygen tension from atmospheric normoxia (20% O2) to anoxia (1% O2) (p = 0.033). CONCLUSION: Human organotypic models can accurately study cell migration ex vivo. GBM IDH-wild type cells migrate toward the perivascular space in blood vessels and their migratory parameters change once they contact vascular structures and under hypoxic conditions. This model allows the evaluation of GBM invasion, considering the human brain microenvironment when cells are removed from their native niche after surgery.

The Effect of Plating on Adjacent Segments in Anterior Cervical Discectomy and Fusions in Patients with Degenerative Spine Disease: A Retrospective Cohort Study.

Introduction: Plate distance is correlated with an increased incidence of adjacent segment pathologies (ASP). However, a correct plate-to-disk distance >5 mm is often not achieved. Therefore, this study aimed to quantify the effect of short plate-to-disk distance on the development of ASP using epidemiological measures in patients with cervical degenerative spine disease undergoing single-level anterior cervical discectomy and fusion (ACDFs). Methods: Medical records of all patients with cervical degeneration undergoing single-level ACDF with plating (between January 2015 and December 2017), and a follow-up of at least 1 year, were reviewed retrospectively. Radiologic and clinical outcomes were assessed preoperatively, postoperatively, and at last follow-up. The plate-to-adjacent disk distance was measured, and epidemiological measures were calculated to quantify the risk on adjacent-level ossification development (ALOD) and adjacent segment degeneration (ASD). Results: Thirty-eight (47.5%) of the 80 patients developed ALOD, and 12 (15.0%) developed ASD after a 2-year follow-up. The incidence of ALOD was significantly lower if the plate was >5 mm away from the adjacent disk space compared to <5 mm (cranial adjacent segment, 22.5% vs. 51.3% [P=0.010] and caudal, 21.4% vs. 47.8% [P=0.029]). A correct plate-to-disk distance resulted in a relative risk reduction of 57.2% for the cranial segment and 56.0% for the caudal segment, with a number needed to treat of 4. The ASD was only observed in the cranial adjacent segments, and a correct plate-to-disk distance resulted in a relative risk reduction of 32.1% and a number needed to treat of 18. Conclusions: Only four patients need to be treated with a correct plate-to-disk distance to avoid one case of ALOD. Therefore, it is advisable to keep the plate at a distance >5 mm away from the adjacent disk.

Current and Future Frontiers of Molecularly Defined Oligodendrogliomas.

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.

Predicting access to postoperative treatment after glioblastoma resection: an analysis of neighborhood-level disadvantage using the Area Deprivation Index (ADI).

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

OBJECTIVE: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). METHODS: Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. RESULTS: A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. CONCLUSIONS: The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

Influence of supramarginal resection on survival outcomes after gross-total resection of IDH-wild-type glioblastoma.

OBJECTIVE: The authors' goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma after gross-total resection (GTR). METHODS: The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed. RESULTS: In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01-2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13-1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27-0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52-0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98-0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35-0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45-1.21; p = 0.234). CONCLUSIONS: SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

OBJECTIVE: High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. METHODS: The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017). CONCLUSIONS: Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Intraoperative Seizure Detection During Active Resection of Glioblastoma Through a Novel Hollow Circular Electrocorticography Array.

BACKGROUND AND IMPORTANCE: Data supporting the use of electrocorticography (ECoG) monitoring during electrical stimulation in awake craniotomies for resection of supratentorial neoplasms is robust, but its applicability during active resection is often limited by the inability to keep the array in place. Given the known survival benefit of gross total resection in glioma surgery, novel approaches to surgical monitoring are warranted to maximize safe resection and optimize surgical outcomes in patients with glioblastoma. CLINICAL PRESENTATION: A 68-yr-old right-handed woman presented to the emergency department with confusion. Imaging studies revealed a bifrontal intra-axial brain lesion. She underwent a left-sided awake craniotomy procedure with cortical and subcortical mapping. During surgical resection, multiple electrographic seizures were detected on continuous ECoG monitoring with a customized 22-channel high-density hollow circular array. She remained without clinical evidence of seizures at 3 mo after surgery. CONCLUSION: We report a unique case of serial electrographic seizures detected during continuous intraoperative ECoG monitoring during active surgical resection of a glioblastoma using a novel circular hollow array during an awake craniotomy. The use of continuous ECoG monitoring during active resection may provide additional data, with potential influence in outcomes for patients undergoing resection of high-grade glial neoplasms.

Cervical chordomas: multicenter case series and meta-analysis.

BACKGROUND: En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. METHODS: MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. RESULTS: There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI 0.08-0.59; p = 0.003) and risk of death (PHR 0.31; 95%; CI 0.12-0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR 0.35; 95% CI 0.16-0.76; p = 0.009) as well as OS (PHR 0.25; 95% CI 0.08-0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR 0.06; 95% CI 0.01-0.77; p = 0.030), but not a decreased OS (PHR 0.50; 95% CI 0.19-1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95% CI 0.02-1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. CONCLUSION: This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.

Time Is Brain: Prehospital Emergency Medical Services Response Times for Suspected Stroke and Effects of Prehospital Interventions.

OBJECTIVES: To compare prehospital time for patients with suspected stroke in Florida with the American Stroke Association (ASA) time benchmarks, and to investigate the effects of dispatch notification and stroke assessment scales on prehospital time. PATIENTS AND METHODS: A retrospective analysis was performed using data from Florida's Emergency Medical Services Tracking and Reporting System database. All patients with suspected stroke transported to a treatment center from January 1, 2018, through December 31, 2018, were analyzed. Time intervals from 911 call to hospital arrival were evaluated and compared with ASA benchmarks. RESULTS: In 2018, 11,577 patients with suspected stroke were transported to a hospital (mean age, 71.5±15.7 years; 51.5% women). The median alarm-to-hospital time was 33.98 minutes (27.8 to 41.4), with a total emergency medical services (EMS) time of 32.30 minutes (26.5 to 39.478). The on-scene time was the largest time interval with a median of 13.28 minutes (10.0 to 17.4). Emergency medical services encounters met the ASA benchmarks for time in 58% to 62% of the EMS encounters in Florida (recommended 90%; P<.001). The total EMS time was reduced when a stroke notification was reported by the dispatch center (32.00 minutes vs 32.62 minutes; P=.006) or when a stroke assessment scale was used by the EMS personnel (31.88 minutes vs 32.96 minutes; P=.005). CONCLUSION: This study reveals a substantial opportunity for improvement in stroke care in Florida. Two prehospital EMS stroke interventions seem to reduce prehospital time for patients with suspected stroke. Adoption of these interventions might improve the stroke systems of care.

Treatment of posterior circulation non-saccular aneurysms with flow diversion versus stent-assisted coiling: a systematic review and meta-analysis.

Treatment of non-saccular aneurysms of the posterior circulation poses a great challenge with unpredictable outcomes due to the absence of a true aneurysm neck and the presence of perforating vessels. In this article, we aim to compare endovascular treatment of unruptured posterior circulation non-saccular aneurysms with stent-assisted coiling (SAC) and flow diversion (FD) in terms of occlusion rate and clinical outcomes. A systematic search of electronic databases from inception to August 2019 identified 484 articles for screening. After proper inclusion/exclusion criteria, 15 articles were included and data were extracted and analyzed using meta-analysis of proportions. The pooled cohort consisted of 430 aneurysms: 128 (29.7%) treated with SAC in 5 studies and 302 (70.3%) treated with FD in 11 studies. Complete/near-complete occlusion was achieved in 83% after FD (95% CI 0.75 to 0.90; I2=45%) and 84% after SAC (95% CI 0.72 to 0.91; I2=22%), with no significant difference between techniques (p=0.95). Periprocedural complications were observed in 18% after FD (95% CI 0.14 to 0.23; I2=0%) and 6% after SAC (95% CI 0.02 to 0.13; I2=0%); the subgroup analysis was statistically significant (p=0.008). Furthermore, no statistically significant difference was observed in favorable clinical outcomes between groups. These results suggest similar efficacy in occlusion rate and favorable clinical outcome for posterior circulation non-saccular aneurysms treated with SAC and FD. Stroke was the most common complication regardless of treatment modality, and a lower periprocedural complication rate was noted with SAC. Further studies are needed with the primary focus of reducing the risk of stroke with either modality.

In NPH, setting valve opening pressure close to lumbar puncture opening pressure decreases overdrainage.

BACKGROUND: The management of normal pressure hydrocephalus (NPH) can be difficult, partly because there are frequent treatment complications such as overdrainage which, when serious, may require surgical intervention. We previously reported a correlation between the difference of lumbar puncture opening pressure minus the valve opening pressure setting (LPOP-VOP) (which we refer to as the delta) and increased rates of overdrainage. This led to a modification in our practice, whereby we now set the VOP equal to, or close to, the LPOP, resulting in lower deltas. OBJECTIVE: In this new study, our aim was to compare the rate of overdrainage in our patients with higher and lower deltas and assess the significance of setting the VOP equal, or close, to the patient's LPOP. METHODS: 1. We reproduced the association between delta and overdrainage. 2. We compared the incidence of overdrainage in those whose VOP was set close to LPOP (low delta) versus those with VOP setting distant from the LPOP (higher delta). 3. We compared symptom improvement in those with a low versus higher delta. RESULTS: We confirmed the relation between high delta and an increased rate of overdrainage, lower rates of overdrainage in those whose VOP was set close to the LPOP (Delta Adjusted Practice), and better improvement of symptoms when the VOP was set closer to the LPOP. CONCLUSION: We propose that the initial VOP should be set as close as possible to the patient's LPOP to decrease overdrainage without compromising symptom improvement.

Prognostic significance of C1-C2 facet malalignment after surgical decompression in adult Chiari malformation type I: a pilot study based on the Chicago Chiari Outcome Scale.

OBJECTIVE: The authors assessed the prognostic significance of various clinical and radiographic characteristics, including C1-C2 facet malalignment, in terms of surgical outcomes after foramen magnum decompression of adult Chiari malformation type I. METHODS: The electronic medical records of 273 symptomatic patients with Chiari malformation type I who were treated with foramen magnum decompression, C1 laminectomy, and duraplasty at Mayo Clinic were retrospectively reviewed. Preoperative and postoperative Neurological Scoring System scores were compared using the Friedman test. Bivariate analysis was conducted to identify the preoperative variables that correlated with the patient Chicago Chiari Outcome Scale (CCOS) scores. Multiple linear regression analysis was subsequently performed using the variables with p < 0.05 on the bivariate analysis to check for independent associations with the outcome measures. Statistical software SPSS version 25.0 was used for the data analysis. Significance was defined as p < 0.05 for all analyses. RESULTS: Fifty-two adult patients with preoperative clinical and radiological data and a minimum follow-up of 12 months were included. Motor deficits, syrinx, and C1-C2 facet malalignment were found to have significant negative associations with the CCOS score at the 1- to 3-month follow-up (p < 0.05), while at the 9- to 12-month follow-up only swallowing function and C1-C2 facet malalignment were significantly associated with the CCOS score (p < 0.05). Multivariate analysis showed that syrinx presence and C1-C2 facet malalignment were independently associated with the CCOS score at the 1- to 3-month follow-up. Swallowing function and C1-C2 facet malalignment were found to be independently associated with the CCOS score at the 9- to 12-month follow-up. CONCLUSIONS: The observed results in this pilot study suggest a significant negative correlation between C1-C2 facet malalignment and clinical outcomes evaluated by the CCOS score at 1-3 months and 9-12 months postoperatively. Prospective studies are needed to further validate the prognostic value of C1-C2 facet malalignment and the potential role of atlantoaxial fixation as part of the treatment.

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

INTRODUCTION: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. METHODS: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. RESULTS: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001). CONCLUSION: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Intracranial Myxoid Mesenchymal Tumor/Myxoid Subtype Angiomatous Fibrous Histiocytoma: Diagnostic and Prognostic Challenges.

BACKGROUND AND IMPORTANCE: In the setting of intracranial neoplasms, EWSR1-cAMP Response Element-Binding Protein (CREB) transcription factor family fusions have been described in myxoid mesenchymal tumors, extremely rare entities with a close histopathologic and immunologic resemblance to myxoid subtype angiomatoid fibrous histiocytomas (AFH). Controversy exists on whether these central nervous system lesions are a subtype of myxoid AFH or a completely separate entity, which entitles a distinct clinical behavior and, consequently, a different approach to management. Upon review of the literature, only 14 cases of intracranial tumors harboring an EWSR1-CREB family fusion were identified, with only 3 cases presenting in middle-aged adults, none of which reported an EWSR1-CREM fusion mutation. Significant variability in reported radiographic and histopathological characteristics, as well as in clinical outcomes, was noted. Their similarity with other soft tissue tumors, added to the scarce information on its clinical behavior, represents a great diagnostic and therapeutic challenge to the treating physician. CLINICAL PRESENTATION: We present a rare case of EWSR1-CREM mutated intracranial myxoid mesenchymal tumor/myxoid subtype AFH presenting as persistent headaches in a 36-yr-old woman with radiographic evidence of rapid growth and extensive vasogenic edema, for which she underwent surgical resection. CONCLUSION: This represents a unique case of EWSR1-CREM mutated intracranial myxoid mesenchymal tumor presenting in adulthood, with evidence of aggressive behavior.

Mitotic Index and Progression-Free Survival in Atypical Meningiomas.

Extent of resection and tumor grade are considered the most important predictors of progression-free survival (PFS) in meningiomas. However, adjuvant therapy for atypical meningiomas remains controversial, with variable PFS rates of up to 40%. The current mitotic index (MI) range for atypical meningiomas is broad, comprising all tumors with >4 and <20 mitotic count per 10 high-power fields, leading to substantial within-grade variation of recurrence risk, especially in borderline histologic cases, creating discordance between the clinical course and the application of the classification criteria. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a search of electronic databases from inception to July 2019 identified 121 articles for screening. After proper exclusion criteria, 7 articles were included for data extraction and analysis using meta-analysis of proportions. The MI was the variable of interest in the multivariate regressions and analyzed as a predictor of recurrence using hazard ratios (HRs) (95% confidence intervals). Separate random effect models were used for studies reporting the MI as a continuous or categorical variable. The pooled study results in this meta-analysis demonstrate a homogeneous statistically significant correlation between the MI and the rate of local recurrence after surgical resection regardless of the reporting method (continuous: HR = 1.20; categorical: HR = 2.65). However, significant limitations were noted, including the lack of a standardized method for MI calculation and heterogeneity of MI reports. We encourage the community to report their experience with the MI with greater precision and uniformity to further assess the influence of the MI on PFS within atypical meningiomas.

Awake Craniotomy with Cortical and Subcortical Speech Mapping for Supramarginal Cavernoma Resection.

Awake craniotomy allows mapping of eloquent brain regions and monitoring neurocognitive functioning intraoperatively to maximize extent of resection and minimize cognitive morbidity.1,2 During resection of cavernous malformations in eloquent areas, intraoperative cognitive monitoring can also allow for safer maximal excision of the hemosiderin ring, which is correlated with improved seizure-free outcome.3,4 We present the case of a 33-year-old right-handed male with a new-onset seizure who presented to his local emergency department after experiencing visual hallucinations before losing consciousness. Computed tomography scan of the head revealed a calcified lesion in the left temporal/parietal area. Presurgical workup revealed left hemispheric language dominance and language activation within the overlying supramarginal gyrus representing phonologic working memory on functional magnetic resonance imaging.5 Diffusion tensor imaging identified the arcuate fasciculus and lateral portion of the superior longitudinal fasciculus to be intimately associated with the deep margin of the lesion.6 After consent was obtained, we performed an awake craniotomy and resection of the lesion through a transsulcal approach, with eloquent cortical mapping using a novel high-density circular grid,7,8 as well as subcortical stimulation/mapping and continuous intraoperative cognitive monitoring using multiple language paradigms; the patient was baselined on these paradigms preoperatively (Video 1). Several phonologic/paraphasic errors were made during resection of the hemosiderin ring, likely related to mechanical manipulation. The patient was discharged to home on postoperative day 4 with outpatient speech therapy for speech hesitancy. At 1-week postoperative testing, language skills were considered within normal limits.

Meningiomas in the elderly.

Meningiomas are benign tumors that arise from the meningo-epithelial cells of the arachnoid dura and account for approximately one-third of all adult intracranial tumors. With the evolution of diagnostic imaging and the average life span increasing, meningiomas are being detected more frequently in an older population. In the elderly population, defined by patients aged 60 years or older, meningiomas are the most incidentally detected benign primary brain tumor. As a patient ages, the rate of growth of the meningioma decreases, while comorbidities increase, making the elderly population a unique group when it comes to decision-making for treatment. Treatment options for intracranial meningiomas in the elderly include surgery, radiosurgery, or observation. Although age may have some part in treatment considerations, comorbidities, overall state of health, and tumor characteristics play a more significant role in patient outcome. This chapter will investigate the incidence, evaluation, treatment, and outcomes of intracranial meningiomas in the elderly population.

Predictors of Ventriculoperitoneal shunting following Subarachnoid Hemorrhage treated with External Ventricular Drainage.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is commonly associated with hydrocephalus due to subarachnoid hemorrhage blood products obstructing cerebrospinal fluid outflow. Hydrocephalus after aSAH is routinely managed with temporary external ventricular drainage (EVD) followed by standard EVD weaning protocols, which determine the need for ventriculoperitoneal shunting (VPS). We sought to investigate aSAH patients who initially passed EVD weaning trials and had EVD removal, but later presented with recurrent, delayed, symptomatic hydrocephalus requiring a VPS. METHODS: We conducted a retrospective review of all patients at our tertiary care medical center who presented with aSAH, requiring an EVD. We analyzed variables associated with ultimate VPS dependency during hospitalization. RESULTS: We reviewed 489 patients with aSAH over a 6-year period (2008-2014). One hundred and thirty-eight (28.2%) developed hydrocephalus requiring a temporary EVD. Forty-four (31.9%) of these patients died or had withdrawal of care during admission, and were excluded from final analysis. Of the remaining 94 patients, 29 (30.9%) failed their clamp trial and required VPS. Sixty-five (69.1%) patients passed their clamp trial and were discharged without a VPS. However, 10 (15.4%) of these patients developed delayed hydrocephalus after discharge and ultimately required VPS [mean (range) days after discharge, 97.2 (35-188)]. Compared to early VPS, the delayed VPS group had a higher incidence of symptomatic vasospasm (90.0% vs 51.7%; P = 0.03). When comparing patients discharged from the hospital without VPS, delayed VPS patients also had higher 6- and 12-month mortality (P = 0.02) and longer EVD clamp trials (P < 0.01) than patients who never required VPS but had an EVD during hospitalization. Delayed hydrocephalus occurred in only 7.8% of patients who passed the initial EVD clamp trial, compared to 14.3% who failed the initial trial and 80.0% who failed 2 or more trials. CONCLUSION: Patients who failed their initial or subsequent EVD clamp trials had a small, but increased risk of developing delayed hydrocephalus ultimately requiring VPS. Additionally, the majority of patients who presented with delayed hydrocephalus also suffered symptomatic vasospasm. These associations should be further explored and validated in a larger prospective study.