miR-18a Inhibits BMP4 and HIF-1α Normalizing Brain Arteriovenous Malformations.

RATIONALE: Brain arteriovenous malformations (AVMs) are abnormal tangles of vessels where arteries and veins directly connect without intervening capillary nets, increasing the risk of intracerebral hemorrhage and stroke. Current treatments are highly invasive and often not feasible. Thus, effective noninvasive treatments are needed. We previously showed that AVM-brain endothelial cells (BECs) secreted higher VEGF (vascular endothelial growth factor) and lower TSP-1 (thrombospondin-1) levels than control BEC; and that microRNA-18a (miR-18a) normalized AVM-BEC function and phenotype, although its mechanism remained unclear. OBJECTIVE: To elucidate the mechanism of action and potential clinical application of miR-18a as an effective noninvasive treatment to selectively restore the phenotype and functionality of AVM vasculature. METHODS AND RESULTS: The molecular pathways affected by miR-18a in patient-derived BECs and AVM-BECs were determined by Western blot, RT-qPCR (quantitative reverse transcription polymerase chain reaction), ELISA, co-IP, immunostaining, knockdown and overexpression studies, flow cytometry, and luciferase reporter assays. miR-18a was shown to increase TSP-1 and decrease VEGF by reducing PAI-1 (plasminogen activator inhibitor-1/SERPINE1) levels. Furthermore, miR-18a decreased the expression of BMP4 (bone morphogenetic protein 4) and HIF-1α (hypoxia-inducible factor 1α), blocking the BMP4/ALK (activin-like kinase) 2/ALK1/ALK5 and Notch signaling pathways. As determined by Boyden chamber assays, miR-18a also reduced the abnormal AVM-BEC invasiveness, which correlated with a decrease in MMP2 (matrix metalloproteinase 2), MMP9, and ADAM10 (ADAM metallopeptidase domain 10) levels. In vivo pharmacokinetic studies showed that miR-18a reaches the brain following intravenous and intranasal administration. Intranasal co-delivery of miR-18a and NEO100, a good manufacturing practices-quality form of perillyl alcohol, improved the pharmacokinetic profile of miR-18a in the brain without affecting its pharmacological properties. Ultra-high-resolution computed tomography angiography and immunostaining studies in an Mgp-/- AVM mouse model showed that miR-18a decreased abnormal cerebral vasculature and restored the functionality of the bone marrow, lungs, spleen, and liver. CONCLUSIONS: miR-18a may have significant clinical value in preventing, reducing, and potentially reversing AVM.

Comorbid depression associated with non-routine discharge following craniotomy for low-grade gliomas and benign tumors - a nationwide readmission database analysis.

PURPOSE: Prior studies have demonstrated elevated rates of depression in patients with malignant brain tumor; however, the prevalence and effect on surgical outcomes in patients with low-grade gliomas (LGG) and benign brain tumors (BBT) remain unknown. Readmission and non-routine discharge, which includes discharge to skilled nursing, rehabilitative, and other inpatient facilities, are well-established quality of care indicators. We sought to analyze the association between comorbid depression and non-routine discharge, readmission, and other post-operative inpatient outcomes in patients with LGG and BBT. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was retrospectively queried to select for surgically treated patients with LGG and BBT. Multivariable logistic regression models adjusting for patient and hospital characteristics were used to determine the effects of comorbid depression on post-operative outcomes. Interaction of gender and depression on non-routine disposition was analyzed. RESULTS: We identified 31,654 craniotomies for resection of BBT and LGG (2010-2014). The majority of patients (64.1%) were female. The rate of depression comorbid with BBT and LGG was 11.9%. Depression was associated with non-routine discharge after surgery (OR 1.19, p 0.0002*), but was not associated with increased morbidity, mortality, or readmission at 30 or 90 days. The rate of comorbid depression was higher among female than male patients (14.0 vs. 8.0%). Depression in males was associated with a 38% increased likelihood of non-routine disposition (p = 0.0002*), while depression in females was associated with a 13% increased likelihood of non-routine disposition (p = 0.03*). CONCLUSION: Depression is prevalent in patients with LGG and BBT and is associated with increased risk of non-routine discharge following surgical intervention. The increased likelihood of non-routine disposition is greater for males than that for females. Awareness of the risk factors for depression may aid in early screening and intervention and improve overall patient outcomes.

Predictors of readmission after craniotomy for meningioma resection: a nationwide readmission database analysis.

BACKGROUND: Meningiomas are the most common benign primary brain tumors. The mainstay of treatment, surgical resection, is often curative. Given the excellent prognosis of these lesions, minimizing perioperative complications is of the utmost importance. With the establishment of the National Readmissions Database (NRD), researchers are now able to identify variables associated with postoperative complications beyond the index admission. OBJECTIVE: In this study, we sought to identify the leading causes for non-elective readmission and variables associated with increased likelihood of readmission at 30 and 90 days after discharge following a craniotomy for meningioma resection. METHODS: Adult inpatients who underwent craniotomy for meningioma resection between 2010 and 2014 were queried from the NRD. All-cause readmissions following craniotomy at 30 and 90 days were identified, and a multivariable logistic regression model was used to characterize independent risk factors. RESULTS: Among 26,034 patients who received craniotomy for meningioma resection, 2825 (10.9%) were readmitted at 30 days and 3436 (16.1%) were readmitted at 90 days. Postoperative wound infection was the most common readmission diagnosis, occurring in 9.32% and 10.2% of 30- and 90-day readmissions respectively. Patient factors associated with increased likelihood of readmission included male gender, greater illness severity, non-routine discharge, index length of hospitalization, and having Medicare or Medicaid insurance. CONCLUSIONS: Readmission following craniotomy for meningioma resection occurs at a clinically significant rate. Several patient factors were identified in association with all-cause 30- and 90-day readmissions. Further studies are required to identify means for preventing complications following discharge in these vulnerable patient populations.

A case report of two different skull base pathologies causing hearing loss in the same ear: vestibular schwannoma and superior semicircular canal dehiscence.

Vestibular schwannoma and superior semicircular canal dehiscence are both uncommon entities, especially when present in the same ear. Here we illustrate how both of these pathologies can be repaired through the same surgical exposure, of the middle cranial fossa, with complete preservation of the cochlear nerve function and relief of symptoms caused by canal dehiscence.

Recording stereoscopic 3D neurosurgery with a head-mounted 3D camera system.

Stereoscopic three-dimensional (3D) imaging can present more information to the viewer and further enhance the learning experience over traditional two-dimensional (2D) video. Most 3D surgical videos are recorded from the operating microscope and only feature the crux, or the most important part of the surgery, leaving out other crucial parts of surgery including the opening, approach, and closing of the surgical site. In addition, many other surgeries including complex spine, trauma, and intensive care unit procedures are also rarely recorded. We describe and share our experience with a commercially available head-mounted stereoscopic 3D camera system to obtain stereoscopic 3D recordings of these seldom recorded aspects of neurosurgery. The strengths and limitations of using the GoPro(®) 3D system as a head-mounted stereoscopic 3D camera system in the operating room are reviewed in detail. Over the past several years, we have recorded in stereoscopic 3D over 50 cranial and spinal surgeries and created a library for education purposes. We have found the head-mounted stereoscopic 3D camera system to be a valuable asset to supplement 3D footage from a 3D microscope. We expect that these comprehensive 3D surgical videos will become an important facet of resident education and ultimately lead to improved patient care.

MicroRNA-18a improves human cerebral arteriovenous malformation endothelial cell function.

BACKGROUND AND PURPOSE: Cerebral arteriovenous malformation (AVM) is a vascular disease that disrupts normal blood flow and leads to serious neurological impairment or death. Aberrant functions of AVM-derived brain endothelial cells (AVM-BECs) are a disease hallmark. Our aim was to use microRNA-18a (miR-18a) as a therapeutic agent to improve AVM-BEC function. METHODS: Human AVM-BECs were tested for growth factor production and proliferation under different shear flow conditions and evaluated for tubule formation. Thrombospondin-1, inhibitor of DNA-binding protein 1, and vascular endothelial growth factor (VEGF) isotype mRNA levels were quantified by quantitative real-time polymerase chain reaction. Thrombospondin-1, VEGF-A, and VEGF-D protein expression was measured using enzyme-linked immunosorbent assay. Proliferation and tubule formation were evaluated using bromodeoxyuridine incorporation and growth factor-reduced Matrigel assays, respectively. RESULTS: miR-18a increased thrombospondin-1 production but decreased inhibitor of DNA-binding protein 1, a transcriptional repressor of thrombospondin-1. miR-18a reduced VEGF-A and VEGF-D levels, both overexpressed in untreated AVM-BECs. This is the first study reporting VEGF-D overexpression in AVM. These effects were most prominent under arterial shear flow conditions. miR-18a also reduced AVM-BEC proliferation, improved tubule formation, and was effectively internalized by AVM-BECs in the absence of extraneous transfection reagents. CONCLUSIONS: We report VEGF-D overexpression in AVM and the capacity of miR-18a to induce AVM-BECs to function more normally. This highlights the clinical potential of microRNA as a treatment for AVM and other vascular diseases.

Resection of a cystic brainstem hemangioblastoma via a retrosigmoid approach.

Lesions of the brainstem pose a technical challenge due to their close proximity to critical vascular structures, neural pathways, and nuclei. Hemangioblastomas are rare lesions of the central nervous system and can cause significant neurological dysfunction, primarily due to enlargement of the cystic component. This is especially relevant when hemangioblastomas occur in eloquent brainstem regions. However, the outcomes after hemangioblastoma resection are good if complete surgical resection of the tumor of the mural nodule, can be achieved. This video demonstrates the excision of a brainstem hemangioblastoma via a left retrosigmoid craniotomy under Stealth guidance. The video can be found here: http://youtu.be/bCkuaPwMV20 .

Frailty is a Predictor of Increased Readmissions and Increased Postoperative Complications After Elective Treatment of Unruptured Aneurysms.

INTRODUCTION: Frailty is a state of decreased physiologic reserve associated with adverse treatment outcomes across surgical specialties. We sought to determine whether frailty affected patient outcomes after elective treatment (open microsurgical clipping or endovascular therapy [EVT]) of unruptured cerebral aneurysms (UCAs). METHODS: The National Readmissions Database was queried from 2010 to 2014 to identify patients who had a known UCA and underwent elective clipping or EVT. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty indicator tool. Multivariable exact logistic regression analyses were conducted to assess the associations between frailty and the primary outcome variables of 30- and 90-day readmissions, complications, length of stay (LOS), and patient disposition. RESULTS: Of 18,483 patients who underwent elective treatment for UCAs, 358 (1.9%) met the criteria for frailty. After adjusting for patient- and hospital-based factors, frailty (30-day: odds ratio [OR], 1.55; 95% confidence interval [CI], 1.11-2.17; P = 0.01; 90-day: OR, 1.47; 95% CI, 1.05-2.06; P = 0.02) and clipping versus EVT (30-day: OR, 2.12; 95% CI, 1.85-2.43; P < 0.000; 90-day: OR, 1.80; 95% CI, 1.59-2.03; P < 0.0001) were associated with increased readmission rates. Furthermore, frailty was associated with an increased rate of complications (surgical: OR, 2.91; 95% CI, 2.27-3.72; P < 0.0001; neurological: OR, 3.04; 95% CI, 2.43-3.81; P < 0.0001; major: OR, 2.75; 95% CI, 1.96-3.84; P < 0.0001), increased LOSs (incidence rate ratio, 3.08; 95% CI, 2.59-3.66; P < 0.0001), and an increased rate of nonroutine disposition (OR, 3.94; 95% CI, 2.91-5.34; P < 0.0001). CONCLUSIONS: Frailty was associated with an increased likelihood of 30- and 90-day readmissions after elective treatment of UCAs. Frailty was notably associated with several postoperative complications, longer LOSs, and nonroutine disposition in the treatment of UCAs.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

A proposed grading system for standardizing tumor consistency of intracranial meningiomas.

OBJECT: Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. METHODS: The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. RESULTS: Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency grade was 0.87 (SE 0.06, 95% CI 0.76-0.99), with 90% user agreement. Kappa analysis scores for minimum and maximum grades of tumor regions were 0.69 (agreement 72%) and 0.75 (agreement 78%), respectively. The kappa analysis score for tumor vascularity grading was 0.56 (agreement 76%). Overall consistency did not correlate with patient age, tumor location, or tumor size. A higher tumor vascularity grade was associated with a larger tumor diameter (p = 0.045) and with skull base location (p = 0.02). CONCLUSIONS: The proposed grading system provides a reliable, practical, and objective assessment of meningioma consistency and facilitates communication among providers. This system also accounts for heterogeneity in tumor consistency. With the proposed scale, meningioma consistency can be standardized as groundwork for future studies relating to surgical outcomes, predictability of consistency and vascularity using neuroimaging techniques, and effectiveness of various surgical instruments.

A review of epigenetic and gene expression alterations associated with intracranial meningiomas.

OBJECT: A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas. METHODS: The authors performed a review of the current literature to identify the epigenetic modifications associated with the formation and/or progression of meningiomas. RESULTS: Several epigenomic alterations, mainly pertaining to DNA methylation, have been associated with meningiomas. Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2 (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2, and TGF-ß epigenetic modifications allow either upregulation or downregulation of critical pathways for meningioma development, progression, and recurrence. CONCLUSIONS: Genome-wide methylation profiling demonstrated that global hypomethylation correlates with tumor grades and severity. Identification of additional epigenetic changes, such as histone modification and higher-order chromosomal structure, may allow for a more thorough understanding of tumorigenesis and enable future individualized treatment strategies for meningiomas.

Genomic and transcriptome analysis revealing an oncogenic functional module in meningiomas.

OBJECT: Meningiomas are among the most common primary adult brain tumors. Although typically benign, roughly 2%-5% display malignant pathological features. The key molecular pathways involved in malignant transformation remain to be determined. METHODS: Illumina expression microarrays were used to assess gene expression levels, and Illumina single-nucleotide polymorphism arrays were used to identify copy number variants in benign, atypical, and malignant meningiomas (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression data sets generated on Affymetrix microarrays (n = 68, including 6 malignant ones; n = 56, including 3 malignant ones). A weighted gene coexpression network approach was used to identify coexpression modules associated with malignancy. RESULTS: At the genomic level, malignant meningiomas had more chromosomal losses than atypical and benign meningiomas, with average length of 528, 203, and 34 megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one of the primary chromosomal level abnormalities in all subtypes of meningiomas. At the transcriptome level, the authors identified 23 coexpression modules from the weighted gene coexpression network. Gene functional enrichment analysis highlighted a module with 356 genes that was highly related to tumorigenesis. Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were oncogenic in other cancers such as leukemia. A putative meningioma tumor suppressor MN1 was also identified in this module with differential expression between malignant and benign meningiomas. CONCLUSIONS: The authors' genomic and transcriptome analysis of meningiomas provides novel insights into the molecular pathways involved in malignant transformation of meningiomas, with implications for molecular heterogeneity of the disease.

Surgical Outcomes Following Vestibular Schwannoma Resection in Patients over the Age of Sixty-five.

Objective Vestibular schwannoma (VS) are benign, often slow growing neoplasms. Some institutions opt for radiosurgery in symptomatic patients of advanced age versus surgical resection. The aim of the study is to analyze surgical outcomes of VS in patients over the age of 65 who were either not candidates for or refused radiosurgery. Methods This includes retrospective analysis of VS patients between 1988 and 2020. Demographics, tumor characteristics, surgical records, and clinical outcomes were recorded. Patient preference for surgery over radiosurgery was recorded in the event that patients were offered both. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor growth was defined by increase in size of >2 mm. Results In total, 64 patients were included of average age 72.4 years (65-84 years). Average maximum tumor diameter was 29 mm (13-55 mm). Forty-five patients were offered surgery or GKRS, and chose surgery commonly due to radiation aversion (48.4%). Gross total resection was achieved in 39.1% ( n = 25), near total 32.8% ( n = 21), and subtotal 28.1% ( n = 18). Average hospitalization was 5 days [2-17] with 75% ( n = 48) discharged home. Postoperative HB scores were good (HB1-2) in 43.8%, moderate (HB3-4) in 32.8%, and poor (HB5-6) in 23.4%. HB scores improved to good in 51.6%, moderate in 31.3%, and remained poor in 17.1%, marking a rate of facial nerve improvement of 10.9%. Tumor control was achieved in 95.3% of cases at an average follow-up time of 37.8 months. Conclusion VS resection can be safely performed in patients over the age of 65. Advanced age should not preclude a symptomatic VS patient from being considered for surgical resection.

Extent of resection and early postoperative outcomes following removal of cystic vestibular schwannomas: surgical experience over a decade and review of the literature.

OBJECT: Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve sheath, representing approximately 6%-8% of all newly diagnosed brain tumors, with an annual incidence of 2000-2500 cases in the US. Although most of these lesions are solid, cystic vestibular schwannomas (CVSs) compose 4%-20% of all VSs and are commonly larger at the time of presentation. The authors present their experience with the operative management of CVSs, including surgical approach, extent of resection, and postoperative facial nerve outcomes. The literature pertaining to clinical and histopathological differences between CVSs and their solid counterparts is reviewed. METHODS: The University of Southern California Department of Neurosurgery database was retrospectively reviewed to identify patients who had undergone resection of a VS between 2000 and 2010. One hundred seventy-nine patients with VS were identified. Patients with CVSs were the subject of the present analysis. Diagnosis of a CVS was made based on MRI findings. Clinical and neuroimaging data, including pre- and postoperative assessments and operative notes, were collected and reviewed. RESULTS: Twenty-three patients, 14 men (61%) and 9 women (39%), underwent 24 operations for CVSs. These patients composed 12.8% of all cases of VS. Patient ages ranged from 28 to 78 years (mean 55 years), and the mean maximal tumor diameter was 3.6 cm (range 2.0-4.0 cm). Patients most frequently presented with headache, hearing loss, vertigo, and dizziness. Preoperative facial numbness was reported in 44% of patients. Among the 24 cases, 13 were treated with retrosigmoid craniotomy and 11 via a translabyrinthine approach. Complete resection was achieved in 11 patients (48%), subtotal resection (STR) in 8 patients (35%), and near-total resection (NTR) in 4 patients (17%). Facial nerve outcomes were available in all except one case. Good facial nerve outcomes (House-Brackmann [HB] Grades I-III) were achieved in 82% of the patients who had undergone either NTR or STR, as compared with 73% of patients who had undergone gross-total resection (GTR; p > 0.05, Fisher exact test). In comparison, 83% of patients with solid VSs had a good HB grade (p = 0.38, Fisher exact test), although this finding did not reach statistical significance. Complications included wound infection (2 patients), delayed CSF leakage (1 patient), and a delayed temporal encephalocele following a translabyrinthine approach and requiring surgical repair (1 patient). CONCLUSIONS: Cystic vestibular schwannoma represents a clinical and surgical entity separate from its solid counterpart, as demonstrated by its more rapid clinical course and early surgical outcomes. Facial nerve grades may correlate with the degree of tumor resection, trending toward poorer grades with more significant resections. Although GTR is recommended whenever possible, performing an STR when facial nerve preservation is in jeopardy to improve facial nerve outcomes is the preferred strategy at the authors' institution.

Preexisting Ventricular Shunts Are Associated with Failed Evacuation of Acute Subdural Hematomas: Single-Institution Case Series of Complications and Management Strategies.

BACKGROUND: The effect of ventricular shunts on radiographic outcomes after evacuation of acute subdural hematomas (aSDHs) has not yet been established. We studied a series of patients who had undergone craniotomy for aSDH, exploring a possible relationship between the occurrence of a postoperative extra-axial collection (EAC) and the presence of a ventricular shunt. METHODS: We reviewed all craniotomies for convexity aSDH performed between July 2015 and June 2020. The medical record review included perioperative coagulation studies, platelet counts, and antiplatelet and anticoagulation agent use. Univariate and multivariate analyses were conducted to identify the factors associated with postoperative EACs and reevacuation. RESULTS: A total of 58 patients had undergone craniotomy for aSDHs, including 9 with ventricular shunts. The median age was 67 years (interquartile range, 54-78 years), and 40% of the patients were women. Of the 58 patients, 16 were taking antiplatelet agents, and 6 were taking anticoagulation agents. Ten patients had developed perioperative thrombocytopenia (platelet count, <100,000/µL). Twelve patients had perioperative coagulopathy (international normalized ratio, ≥1.5). A postoperative EAC >10 mm occurred in 17 patients (29.3%). Eight patients (13.8%) had undergone reevacuation. The presence of a shunt and an increasing preoperative aSDH size were independently associated with an EAC >10 mm (P = 0.013 and P = 0.003, respectively). Only the presence of a shunt predicted for the need for reevacuation (P = 0.001). The shunts were explanted (n = 3) or valves were adjusted (n = 3) in all but 3 cases. CONCLUSIONS: We found that a lack of brain reexpansion after aSDH evacuation worsens radiographic outcomes and was more common in patients with shunts. Increasing shunt valve resistance might help prevent the formation of large EACs after aSDH evacuation.

A Review of Medical and Surgical Options for the Treatment of Facial Pain.

Facial pain is a common medical complaint that is easily misdiagnosed. As a result, this pain often goes mistreated. Despite this, there are a variety of pharmacologic, surgical, and neuromodulatory options for the treatment of facial pain. In this review, the authors detail the forms of facial pain and their treatment options. They discuss the common medications used in the first-line treatment of facial pain and the second-line surgical and neuromodulatory options available to patients when pharmacologic options fail.

Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm is linked to increased inflammatory cell trafficking across a permeable blood-brain barrier (BBB). Elevations in serum levels of matrix metalloprotease 9 (MMP9), a BBB structural protein, have been implicated in the pathogenesis of vasospasm onset. Minocycline is a potent inhibitor of MMP9. The authors sought to detect an effect of minocycline on BBB permeability following aSAH. METHODS: Patients presenting within 24 hours of symptom onset with imaging confirmed aSAH (Fisher grade 3 or 4) were randomized to high-dose (10 mg/kg) minocycline or placebo. The primary outcome of interest was BBB permeability as quantitated by contrast signal intensity ratios in vascular regions of interest on postbleed day (PBD) 5 magnetic resonance permeability imaging. Secondary outcomes included serum MMP9 levels and radiographic and clinical evidence of vasospasm. RESULTS: A total of 11 patients were randomized to minocycline (n = 6) or control (n = 5) groups. No adverse events or complications attributable to minocycline were reported. High-dose minocycline administration was associated with significantly lower permeability indices on imaging analysis (p < 0.01). There was no significant difference with respect to serum MMP9 levels between groups, although concentrations trended upward in both cohorts. Radiographic vasospasm was noted in 6 patients (minocycline = 3, control = 3), with only 1 patient developing symptoms of clinical vasospasm in the minocycline cohort. There was no difference between cohorts with respect to Lindegaard ratios, transcranial Doppler values, or onset of vasospasm. CONCLUSIONS: Minocycline at high doses is well tolerated in the ruptured cerebral aneurysm population. Minocycline curtails breakdown of the BBB following aSAH as evidenced by lower permeability indices, though minocycline did not significantly alter serum MMP9 levels. Larger randomized clinical trials are needed to assess minocycline as a neuroprotectant against aSAH-induced vasospasm. Clinical trial registration no.: NCT04876638 (clinicaltrials.gov).

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Molecular genetics of meningiomas: a systematic review of the current literature and potential basis for future treatment paradigms.

Although a majority of meningiomas are benign neoplasms, those occurring at the cranial base may be challenging tumors to treat because of extensive tissue invasion, an inability to achieve gross-total microscopic resection, and local tumor recurrence and/or progression. A more comprehensive understanding of the genetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide novel targets for grading assessments and individualizing molecular therapies for skull base meningiomas. The authors performed a review of the current literature to identify genes that have been associated with the formation and/or progression of meningiomas. Mutations in the NF2 gene have been most commonly implicated in the formation of the majority of meningiomas. Inactivation of other tumor suppressor genes, including DAL-1 and various tissue inhibitors of matrix metalloproteinases, upregulation of several oncogenes including c-sis and STAT3, and signaling dysregulation of pathways such as the Wnt pathway, have each been found to play important, and perhaps, complementary roles in meningioma development, progression, and recurrence. Identification of these genetic factors using genome-wide association studies and high-throughput genomics may provide data for future individualized treatment strategies.

Neuroprotective effect of minocycline against acute brain injury in clinical practice: A systematic review.

Acute brain injury is a leading cause of morbidity and mortality worldwide. The term is inclusive of traumatic brain injury, cerebral ischemia, subarachnoid hemorrhage, and intracerebral hemorrhage. Current pharmacologic treatments have had minimal effect on improving neurological outcomes leading to a significant interest in the development neuroprotective agents. Minocycline is a second-generation tetracycline with high blood brain barrier penetrance due to its lipophilic properties. It functions across multiple molecular pathways involved in secondary-injury cascades following acute brain injury. Animal model studies suggest that minocycline might lead to improved neurologic outcomes, but few such trials exist in humans. Clinical investigations have been limited to small randomized trials in ischemic stroke patients which have not demonstrated a clear advantage in neurologic outcomes, but also have not been sufficiently powered to draw definitive conclusions. The potential neuroprotective effect of minocycline in the setting of traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage have all been limited to pilot studies with phase II/III investigations pending. The authors aim to synthesize what is currently known about minocycline as a neuroprotective agent against acute brain injury in humans.