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OBJECTIVE Although younger adults have been shown to have better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the significance of this relationship in the adolescent and young adult (AYA) population is not well defined given its undefined rarity. Correspondingly, the goal of this study was to determine the prognostic significance of age in this specific demographic following MT for large-vessel occlusions. METHODS A prospectively maintained international multi-institutional database, STAR (Stroke Thrombectomy and Aneurysm Registry), was reviewed for all patients aged 12–18 (adolescent) and 19–25 (young adult) years. Parameters were compared using chi-square and t-test analyses, and associations were interrogated using regression analyses. RESULTS Of 7192 patients in the registry, 41 (0.6%) satisfied all criteria, with a mean age of 19.7 ± 3.3 years. The majority were male (59%) and young adults (61%) versus adolescents (39%). The median prestroke modified Rankin Scale (mRS) score was 0 (range 0–2). Strokes were most common in the anterior circulation (88%), with the middle cerebral artery being the most common vessel (59%). The mean onset-to–groin puncture and groin puncture–to-reperfusion times were 327 ± 229 and 52 ± 42 minutes, respectively. The mean number of passes was 2.2 ± 1.2, with 61% of the cohort achieving successful reperfusion. There were only 3 (7%) cases of reocclusion. The median mRS score at 90 days was 2 (range 0–6). Between the adolescent and young adult subgroups, the median mRS score at last follow-up was statistically lower in the adolescent subgroup (1 vs 2, p = 0.03), and older age was significantly associated with a higher mRS at 90 days (coefficient 0.33, p < 0.01). CONCLUSIONS Although rare, MT for AIS in the AYA demographic is both safe and effective. Even within this relatively young demographic, age remains significantly associated with improved functional outcomes. The implication of age-dependent stroke outcomes after MT within the AYA demographic needs greater validation to develop effective age-specific protocols for long-term care across both pediatric and adult centers.

Civilian cranial gunshot wounds are common injuries associated with significant morbidity and mortality. Simple wound closure has been previously proposed as an alternative treatment option for a small subset of patients, but the exact outcomes of this strategy are not well-defined. The objective of this paper was to describe the scientific literature reporting simple wound closure of civilian cranial gunshot wounds, its effect on short-term and long-term neurologic outcomes, and rates of seizures and infections. A systematic literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The strength of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. Seventeen studies were found that met inclusion criteria. There was very low strength of evidence that patients treated with simple wound closure can achieve good short and long-term neurologic outcomes. There was very low strength of evidence that simple wound closure has a higher incidence of mortality compared to operative intervention, especially in patients with initial low Glasgow Coma Scale (GCS) scores. There was very low strength of evidence that patients treated with simple wound closure have a small risk of subsequently developing infections or seizures. In conclusion, under most circumstances, neurosurgical operative intervention should be viewed as the optimal treatment for salvageable civilian cranial gunshot wound patients. However, our literature review showed that simple wound closure is safe and viable. More data are needed to determine the appropriate clinical scenario for using this alternative option.

Introduction: Infantile endodermal oculomotor nerve cyst (EONC) is an extremely rare entity. There are very few pediatric cases reported in the literature, and as expected, oculomotor palsy is the most common presenting symptom. To date however, the risk of recurrence of these lesions following surgical intervention is unclear due to a lack of long-term radiological follow-up. Case Presentation: We present a case of a 13-month-old male patient with an EONC and detail his surgical fenestration and postoperative course. Somewhat surprisingly, re-expansion occurred within 6 months and remained stable 2 years later. Discussion: A surgical approach to fenestration of an EONC in an infant is possible and should be performed by an expert neurosurgeon. Early recurrence is underreported in the current literature, and we encourage longer term radiological surveillance of these lesions after surgery to optimize primary and recurrent management in the future.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0–1 years in group 1, 1–2 years in group 2, and 2–3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.

OBJECTIVEGlioblastoma (GBM) during infancy is rare, and the clinical outcomes of congenital GBM are not well understood. Correspondingly, the aim of this study was to present a long-term survivor case from the authors’ institution, and establish an integrated cohort of cases across the published literature to better understand the clinical course of this disease in this setting.METHODSThe authors report the outcomes of an institutional case of congenital GBM diagnosed within the first 3 months of life, and performed a comprehensive literature search for published cases from 2000 onward for an integrated survival analysis. All cases were integrated into 1 cohort, and Kaplan-Meier estimations, Fisher’s exact test, and logistic regression were used to interrogate the data.RESULTSThe integrated cohort of 40 congenital GBM cases consisted of 23 (58%) females and 17 (42%) males born at a median gestational age of 38 weeks (range 22–40 weeks). Estimates of overall survival (OS) at 1 month was 67%, at 1 year it was 59%, and at 10 years it was 45%, with statistically superior outcomes for subgroups in which patients survived to be treated by resection and chemotherapy. In the overall cohort, multivariable analysis confirmed resection (p < 0.01) and chemotherapy (p < 0.01) as independent predictors of superior OS. Gestational age > 38 weeks (p < 0.01), Apgar scores ≥ 7 at 5 minutes (p < 0.01), absence of prenatal hydrocephalus (p < 0.01), and vaginal delivery (p < 0.01) were associated with greater odds of surgical diagnosis versus autopsy diagnosis.CONCLUSIONSCongenital GBM can deviate from the expected poor prognosis of adult GBM in terms of OS. Both resection and chemotherapy confer statistically superior prognostic advantages in those patients who survive within the immediate postnatal period, and should be first-line considerations in the initial management of this rare disease.

Aim: To determine the biodistribution of lanthanum (III) oxide (La2O3) nanoparticle (NP) therapy to the brain and its biocompatibility with radiation therapy (RT) and chemotherapy (CT). Materials & methods: Healthy balb/c nude mice were administered 4 weekly doses of La2O3 NP therapy via tail vein injection. Organ weights and lanthanum concentrations were evaluated. Results: La2O3 NP penetrated the brain. Concentrations were found to peak in the brain at 24 h after injection and persisted at 8 weeks after injection. Neither RT nor CT affected biodistribution. No adverse events or safety concerns in other organs were noted. Conclusion: La2O3 NP can reach the brain to target neurological disease and is biocompatible with RT and CT in a biological system.

Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the central nervous system (CNS) that occurs predominantly in children. More is being discovered about this disease to improve understanding and outcomes. The aim of this analysis was to evaluate citation and other bibliometric characteristics of the 50 most cited articles in the contemporary literature in order to better model the trajectory of our current efforts. Elsevier’s Scopus database was searched for the 50 most cited articles about ATRT. To look for trends, earliest 25 articles were separated from the latest 25 articles and then were compared. Various bibliometric parameters were summarized and compared using Pearson’s chi-square and Mann–Whitney U tests. The 50 most cited articles were published between 1990 and 2016, from 5 unique countries in 29 unique journals, with genetic and retrospective observational cohort studies the most common design (n = 11 each). Overall median values were as follows: citation count, 145.4 citations (range, 67–626); citation rate per year, 11.7 (range, 3.5–51.4); number of authors 12 (range, 1–95); with 32 (64%) originating from the USA. Compared with older articles, newer articles had statistically lower citation counts (101.8 vs 189.0; P < 0.01), higher number of authors (17.3 vs 6.6; P < 0.01), and were less likely published from the USA (40% vs 88%; P < 0.01) The 50 most cited articles about ATRT were characterized in this analysis. There was a distinct focus in these studies on the genetic composition and consequences of these tumors. Trends over time suggest greater impact will be had in highly collaborative efforts worldwide. Moving forward, it will be of great interest to see how the findings of these basic science finding will translate into future clinical studies.

Although recurrent anaplastic ependymoma in pediatric patients is not uncommon, recurrent disease leading to widespread metastases to the peritoneum is extremely rare. We present a case of an 18-month old male who initially presented with posterior fossa anaplastic ependymoma, who then proceeded to present 1 year later with spinal recurrence, and then 2 years after that with widespread disease involving the intracranial ventricular system and peritoneum. We posit that surgical interventions to treat primary and recurrent presentations in combination with a conduit to the peritoneum via a ventriculoperitoneal shunt contributed to the mechanisms of this complex case.

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.

Departments of neurosurgery in the United States have had a long history of hosting international visitors for the advancement of their neurosurgical education. The goal of the present study was to determine the existence of a geographic profile of international visitors for education purposes, both students and graduates, to the United States through the anecdotal experience of 1 department to explore the reach and worth of hosting such opportunities.Administrative records were retrospectively reviewed for international visitors over the preceding 10 years, 2009-2019, were surveyed at 1 institution. Visitors were grouped as either medical students or graduates, visiting for clinical or research purposes. Geographic trends were compared using the Pearson chi-squared test.We identified 128 visitors from 33 countries during the study period. The most common home countries were Italy (10%), China (9%), and India (7%). The cohort involved 62 (48%) students and 66 (52%) graduates, and 59 (46%) and 69 (54%) visited for clinical and research purposes, respectively. The geographic distribution of student versus graduate visitors was statistically significant by region (P0.01). However, the geographic distribution of clinical versus research visitors was not statistically different by region (P = 0.62).There appears to be international appeal worldwide to participate in neurosurgical education in the United States. At our institution, every geographic region was represented in our most recent decade of experience. International visitor profiles appear to be associated with particular geographic patterns depending on their status as either a medical student or graduate.

The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from Kaplan–Meier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.

Access to treatment for glioblastoma (GBM) can be impacted by multiple demographic parameters. Barriers specific to the Hispanic population of the United States (US) are not fully understood. Therefore, the aim of this study was to elucidate geographic disparities for access to GBM treatment in the US Hispanic population. All GBM patients with known Hispanic ethnicity status (and Caucasian race) in the US National Cancer Database (NCDB) between the years 2005–2016 were retrospectively reviewed. Treatment statuses of surgical resection, chemotherapy, radiation therapy and triple therapy (resection, chemotherapy and radiation) were summarized, and analyzed by comparison and regression analyses over US Census regions. A total cohort size of 40,232 Caucasian GBM patients were included, with 3,111 (8%) identifying as Hispanic. The odds of treatment by chemotherapy (OR 0.78, P

Systematic reviews and meta-analyses in the neurosurgical literature have surged in popularity over the last decade. It is our concern that, without a renewed effort to critically interpret and appraise these studies as high or low quality, we run the risk of the quality and value of evidence-based medicine in neurosurgery being misinterpreted. Correspondingly, we have outlined 4 major domains to target in interpreting neurosurgical systematic reviews and meta-analyses based on the lessons learned by a collaboration of clinicians and academics summarized as 4 pearls. The domains of (1) heterogeneity, (2) modeling, (3) certainty, and (4) bias in neurosurgical systematic reviews and meta-analyses were identified as aspects in which the authors' approaches have changed over time to improve robustness and transparency. Examples of how and why these pearls were adapted were provided in areas of cranial neuralgia, spine, pediatric, and neuro-oncology to demonstrate how neurosurgical readers and writers may improve their interpretation of these domains. The incorporation of these pearls into practice will empower neurosurgical academics to effectively interpret systematic reviews and meta-analyses, enhancing the quality of our evidence-based medicine literature while maintaining a critical focus on the needs of the individual patients in neurosurgery.

STUDY DESIGN Review. OBJECTIVE To provide practicing spine surgeons a primer with key insights for reading, interpreting, and clinically integrating systematic reviews and meta-analyses. SUMMARY OF BACKGROUND DATA Evidence-based medicine (EBM) refers to a family of standardized techniques for critical appraisal of clinical research. Within the contemporary spine literature, EBM is most commonly encountered in the form of systematic reviews and meta-analyses. Although these analytic techniques are potentially useful when appropriately applied to well-formulated questions with adequate primary data in the literature, the rapid and somewhat indiscriminate increase in volume of systematic reviews and meta-analyses published may be associated with an overall dilution in their quality, as well as misperceptions regarding the applicability of particular EBM studies to spine surgery in general. METHODS The collective experience of spine specialists with vested interests in advancing EBM and its utility was summarized into a primer. RESULTS We emphasize components that are pertinent methodologically (search strategy, study number, meta-analysis, bias, and certainty), and pertinent clinically (outcomes) to interpreting, and clinically integrating systematic reviews and meta-analyses into spine surgery practice. CONCLUSIONS Armed with these insights into these five perspectives, we anticipate that practicing spine surgeons will be better equipped to interpret systematic reviews and meta-analyses in a fashion that will meaningfully impact their patient care. LEVEL OF EVIDENCE 2.

Individual evidence suggests that multiple modalities can be used to treat entrapment pathology by Morton’s neuroma, including injection, neurolysis, and neurectomy. However, their impacts on patient pain and satisfaction have yet to be fully defined or elucidated. Correspondingly, our aim was to pool systematically identified metadata and substantiate the impact of these different modalities in treating Morton’s neuroma with respect to these outcomes. Searches of 7 electronic databases from inception to October 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidences of outcomes were extracted and pooled by random-effects meta-analysis of proportions. A total of 35 articles satisfied all criteria, reporting a total of 2998 patients with Morton’s neuroma managed by one of the three modalities. Incidence of complete pain relief after injection (43%; 95% CI, 23–64%) was significantly lower than neurolysis (68%; 95% CI, 51–84%) and neurectomy (74%; 95% CI, 66–82%) (P = 0.02). Incidence of complete satisfaction after injection (35%; 95% CI, 21–50%) was significantly lower than neurolysis (63%; 95% CI, 50–74%) and neurectomy (57%; 95% CI, 47–67%) (P

BackgroundRecently, there has been a shift in management of unruptured cerebral arteriovenous malformations (AVMs) following studies suggesting that medical management alone was superior to interventional therapy.ObjectiveTo evaluate the influence of contemporary AVM management on AVM rupture patterns in the United States.Methods154 297 AVM admissions were identified between 2003 and 2017 in the National Inpatient Sample. Annual AVM intervention and rupture rates were computed and multivariable logistic regression assessed the likelihood of AVM intervention pre- and post-2014. Segmented regression identified significant change points and fitted segmented linear models for annual intervention and rupture rates. Correlation coefficients assessed the relationship between annual AVM intervention and rupture rates.ResultsFor unruptured AVMs, intervention likelihood and proportion decreased after 2014 (28.1% to 22.3%, pConclusionsAfter 2014, the likelihood of intervention for unruptured AVMs decreased while the incidence of ruptured AVMs increased. These findings suggest that fewer unruptured AVM treatments may lead to increases in AVM rupture incidence.

Background H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking. Methods We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome. Results were validated for clinical relevance and mechanistic importance using patient specimens from biopsy and autopsy, patient-derived cell lines, inhibition by gene knockdown and small molecule inhibitors, and patient-derived xenografts. Results Kinase inhibitors were highly toxic to H3K27M-mutant DMG cells. Within this class, STAT3 inhibitors demonstrated robust cytotoxic activity in vitro. Mechanistic analyses revealed one form of activated STAT3, phospho-tyrosine- 705 STAT3 (pSTAT3), was selectively upregulated in H3K27M-mutant cell lines and clinical specimens. STAT3 inhibition by CRISPR/Cas9 knockout, shRNA or small molecule inhibition reduced cell viability in vitro, and partially restored expression of the polycomb repressive mark H3K27me3, which is classically lost in H3K27M-mutant DMG. Putative STAT3-regulated genes were enriched in an H3K27M-knockout DMG cell line, indicating relative gain of STAT3 signaling in K27M-mutant cells. Treatment of patient-derived intracranial xenografts with WP1066, a STAT3 pathway inhibitor currently in clinical use for pediatric brain tumors, resulted in stasis of tumor growth, and increased overall survival. Finally, pSTAT3(Y705) was detected in circulating plasma extracellular vesicles of patients with H3K27M-mutant DMG. Conclusions STAT3 is a biologically relevant therapeutic target in H3K27M-mutant DMG. STAT3 inhibition should be considered in future clinical trials.

Diffuse leptomeningeal glioneuronal tumor (DLGNT), also known as oligodendrogliomatosis, is a rare neuro-oncologic condition along the neuraxis that remains poorly understood in children. We sought to describe our institutional experience and quantitively summarize the clinical survival and prognostic features of DLGNT in the pediatric population across the contemporary literature.We report four institutional cases of pediatric DLGNT diagnosed between 2000 and 2020 based on retrospective review of our records, and performed a comprehensive literature search for published cases from 2000 onwards to create an integrated cohort for analysis. Kaplan-Meier estimations, Fisher's exact test, and logistic regression were utilized to interrogate the data.Of our four cases, three females aged 2-, 3- and 13-years old at diagnosis survived 6-years, 3-years and 14-months respectively, and one male aged 5-years old at diagnosis was still alive 5 years later. Our overall integrated cohort consisted of 54 pediatric DLGNT patients, with 19 (35%) female and 35 (65%) male patients diagnosed at an average age of 6.4 years (range, 1.3-17 years) by means of surgical biopsy. Chemotherapy was used in 45 cases (83%), and mean follow-up time of 54 months (range, 3-204). Across the entire cohort, overall survival 1 month after diagnosis was 96% (95% CI 86-99%), and by 10 years was 69% (95% CI 49-82%). On multivariate analysis of complete data, chemotherapy treatment (HR=0.23, P = 0.04) was statistically predictive of longer overall survival.More than 2-out-of-3 pediatric DLGNT patients survive beyond one decade. Chemotherapy is statistically associated with longer survival in DLGNT pediatric patients and should form the core of any treatment regimen in this setting. Early detection by means of judicious imaging and surgical biopsy for tissue diagnosis can lead to earlier treatment and likely superior outcomes.

OBJECTIVE MRI is increasingly employed to assess intrauterine fetal anomalies. Central nervous system (CNS) anomalies are common structural conditions that warrant evaluation with fetal MRI and subsequent prenatal consultation with a pediatric neurosurgeon. As the use of fetal MRI increases, there is greater impetus to understand the most common CNS structural anomalies diagnosed in utero, as well as their natural histories. METHODS The authors performed a single-center retrospective review of fetal MRI evaluations performed between January 2012 and December 2020. Children who underwent both prenatal and postnatal neurosurgical evaluations of CNS anomalies were included. Specific CNS anomalies on fetal MRI, associated extra-CNS findings, and suspicion for genetic abnormality or syndromes were noted. Postnatal clinical status and interventions were assessed. RESULTS Between January 2012 and December 2020, a total of 469 fetal MRI evaluations were performed; of these, 114 maternal-fetal pairs had CNS anomalies that warranted prenatal consultation and postnatal pediatric neurosurgical follow-up. This cohort included 67 male infants (59%), with a mean ± SD follow-up of 29.8 ± 25.0 months after birth. Fetal MRI was performed at 27.3 ± 5.8 weeks of gestational age. The most frequently reported CNS abnormalities were ventriculomegaly (57%), agenesis or thinning of the corpus callosum (33%), Dandy-Walker complex (DWC) (21%), neuronal migration disorders (18%), and abnormalities of the septum pellucidum (17%). Twenty-one children (18%) required neurosurgical intervention at a mean age of 2.4 ± 3.7 months. The most common surgical conditions included myelomeningocele, moderate to severe ventriculomegaly, encephalocele, and arachnoid cyst. Corpus callosum agenesis or thinning was associated with developmental delay (p = 0.02) and systemic anomalies (p = 0.05). The majority of prenatal patients referred for DWC had Dandy-Walker variants that did not require surgical intervention. CONCLUSIONS The most common conditions for prenatal neurosurgical assessment were ventriculomegaly, corpus callosum anomaly, and DWC, whereas the most common surgical conditions were myelomeningocele, hydrocephalus, and arachnoid cyst. Only 18% of prenatal neurosurgical consultations resulted in surgical intervention during infancy. The majority of referrals for prenatal mild ventriculomegaly and DWC were not associated with developmental or surgical sequelae. Patients with corpus callosum abnormalities should be concurrently referred to a neurologist for developmental assessments.

Falcine meningiomas present significant surgical challenges because they often involve the falx bilaterally, are concealed by a significant amount of normal brain parenchyma and are frequently deep in location and in close proximity to the anterior cerebral arteries. Many prefer the interhemispheric approach for these lesions, but this operative corridor is not without risk as venous infarctions and cortical injury can occur.We present an alternative technique utilizing a transcortical approach to resect a giant, bilobed falcine meningioma in a 68-year-old female who presented with progressive abulia, urinary incontinence, and bilateral lower extremity weakness over 2 years. A unilateral right frontal craniotomy and a corticectomy through the right superior frontal gyrus was used to safely resect the entire tumor. The patient tolerated the procedure well and was discharged home without issue. Pathology demonstrated that the lesion was an atypical meningioma and she subsequently received adjuvant fractionated radiotherapy. At 2-year follow-up, she has no neurologic deficits, never developed any postoperative seizures and has not had any evidence of tumor recurrence.The transcortical approach can be used as a safe alternative for resecting falcine meningiomas without adding significant undue risk to the patient.

Outpatient brain surgery has many advantages for the psychological and physical wellbeing of patients, as well as reduced costs to the health care system. Compared with inpatient admissions, same day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. We aim to establish a prospectively collected quality outcomes database to examine the outcomes of patients that undergo brain tumor resection and are discharged home the same day as surgery.We have established a prospectively collected quality outcomes database to examine the outcomes of all patients that underwent brain tumor resection by a single neurosurgeon (R.J.K) at our institution from August 2020 to August 2021 and were discharged home the same day as surgery.Over the one-year period this study was conducted, 37 of 334 patients met inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after an overnight observation. No postoperative complications were noted at two-week postoperative follow-up.In select patients undergoing brain tumor surgery, same day discharge should be considered. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history. Once discharged, open communication with the patient and their family is critical to detect complications that should trigger rehospitalization and intervention.

INTRODUCTION: Current trends in surgical neuro-oncology have shown that early discharges are both safe and feasible with shorter lengths of stay (LOS) associated with fewer thromboembolic complications, less hospital-acquired infections, reduced costs, and greater patient satisfaction. Traditionally, infratentorial tumor resections have been associated with longer LOS and limited data exists evaluating predictors of early discharge in these patients. The objective was to assess patients undergoing posterior fossa craniotomies for tumor resection and identify variables associated with a postoperative day 1 (POD1) discharge and determine any differences in outcomes and readmission rates. METHODS: A retrospective review of posterior fossa craniotomies for tumor resection at our institution was performed from 2011 to 2020. Laser ablations, craniotomies for non-tumoral pathologies, and biopsies were excluded. Complete demographic, clinical, surgical and postoperative data was collected for each patient. RESULTS: 173 patients were identified and 25 (14.5%) were discharged on POD1. Median length of stay was 6 days. The POD1 discharges had significantly better preoperative Karnofsky performance scores (p

Background Large-scale brain networks and higher cognitive functions are frequently altered in neuro-oncology patients, but comprehensive non-invasive brain mapping is difficult to achieve in the clinical setting. The objective of our study is to evaluate traditional and non-traditional eloquent areas in brain tumor patients using a machine-learning platform. Methods We retrospectively included patients who underwent surgery for brain tumor resection at our Institution. Preoperative MRI with T1-weighted and DTI sequences were uploaded into the Quicktome platform. We categorized the integrity of nine large-scale brain networks: language, sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention, salience and limbic. Network integrity was correlated with preoperative clinical data. Results One-hundred patients were included in the study. The most affected network was the central executive network (49%), followed by the default mode network (43%) and dorsal attention network (32%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (3.42 vs 2.19, P < .001), compared to patients without deficits. Furthermore, we found that patients without neurologic deficits had an average 2.19 networks affected and 1.51 networks at-risk, with most of them being related to non-traditional eloquent areas (P < .001). Conclusion Our results show that large-scale brain networks are frequently affected in patients with brain tumors, even when presenting without evident neurologic deficits. In our study, the most commonly affected brain networks were related to non-traditional eloquent areas. Integrating non-invasive brain mapping machine-learning techniques into the clinical setting may help elucidate how to preserve higher-order cognitive functions associated with those networks.

Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastoma at both the molecular and cellular level necessitates developing novel individualized treatment modalities via genomics-driven approaches. Methods This study leverages numerous pharmacogenomic and tissue databases to examine drug repositioning for glioblastoma. RNA-seq of glioblastoma tumor samples from The Cancer Genome Atlas (TCGA, n = 117) were compared to “normal” frontal lobe samples from Genotype-Tissue Expression Portal (GTEX, n = 120) to find differentially expressed genes (DEGs). Using compound gene expression data and drug activity data from the Library of Integrated Network-Based Cellular Signatures (LINCS, n = 66,512 compounds) CCLE (71 glioma cell lines), and Chemical European Molecular Biology Laboratory (ChEMBL) platforms, we employed a summarized reversal gene expression metric (sRGES) to “reverse” the resultant disease signature for GBM and its subtypes. A multiparametric strategy was employed to stratify compounds capable of blood-brain barrier penetrance with a favorable pharmacokinetic profile (CNS-MPO). Results Significant correlations were identified between sRGES and drug efficacy in GBM cell lines in both ChEMBL(r = 0.37, P < .001) and Cancer Therapeutic Response Portal (CTRP) databases (r = 0.35, P < 0.001). Our multiparametric algorithm identified two classes of drugs with highest sRGES and CNS-MPO: HDAC inhibitors (vorinostat and entinostat) and topoisomerase inhibitors suitable for drug repurposing. Conclusions Our studies suggest that reversal of glioblastoma disease signature correlates with drug potency for various GBM subtypes. This multiparametric approach may set the foundation for an early-phase personalized -omics clinical trial for glioblastoma by effectively identifying drugs that are capable of reversing the disease signature and have favorable pharmacokinetic and safety profiles.

OBJECTIVE The effect of congenital cardiac status on endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) failure in hydrocephalic infants is unknown. Because cardiac status in infants can impact central venous pressure (CVP), it is possible that congenital heart disease (CHD) and congenital cardiac anomalies may render these cerebrospinal fluid diversion interventions more susceptible to failure. Correspondingly, the aim of this study was to determine how CHD and congenital cardiac anomalies may impact the failure of these initial interventions. METHODS A retrospective review of the Nationwide Inpatient Sample (NIS) database was conducted. Infants (aged < 1 year) with known congenital cardiac status managed with either ETV or VPS were included. Quantitative data were compared using either parametric or nonparametric methods, and failure rates were modeled using univariable and multivariable regression analyses. RESULTS A total of 18,763 infants treated with ETV or VPS for hydrocephalus were identified in our search, with ETV used to treat 7657 (41%) patients and VPS used to treat 11,106 (59%). There were 6722 (36%) patients who presented with CHD at admission, and a total of 25 unique congenital cardiac anomalies were detected across the cohort. Overall, the most common anomaly was patent ductus arteriosus (PDA) in 4990 (27%) patients, followed by atrial septal defect (ASD) in 2437 (13%) patients and pulmonary hypertension in 810 (4%) patients. With respect to initial intervention failure, 3869 (21%) patients required repeat surgical intervention during admission. This was significantly more common in the ETV group than the VPS group (36% vs 10%, p < 0.01). In both the ETV and VPS groups, CHD (p < 0.01), including all congenital cardiac anomalies, was an independent and significant predictor of failure. ASD (p < 0.01) and PDA (p < 0.01) both significantly predicted ETV failure, and PDA (p < 0.01) and pulmonary hypertension (p = 0.02) both significantly predicted VPS failure. CONCLUSIONS These results indicate that congenital cardiac status predicts ETV and VPS failure in patients with infantile hydrocephalus. The authors hypothesized that this finding was primarily due to changes in CVP; however, this may not be completely universal across both interventions and all congenital cardiac anomalies. Future studies about optimization of congenital cardiac status with ETV and VPS are required to understand the practical significance of these findings.

BACKGROUND Developing mapping tools that allow identification of traditional or non-traditional eloquent areas is necessary to minimize the risk of postoperative neurologic deficits. The objective of our study is to evaluate the use of a novel cloud-based platform that uses machine learning to identify cerebral networks in patients with brain tumors. METHODS We retrospectively included all adult patients who underwent surgery for brain tumor resection or thermal ablation at our Institution between the 16th of February and the 15th of May of 2021. Pre and postoperative contrast-enhanced MRI with T1-weighted and high-resolution Diffusion Tensor Imaging (DTI) sequences were uploaded into the Quicktome platform. After processing the data, we categorized the integrity of seven large-scale brain networks: sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention and limbic. Affected networks were correlated with pre and postoperative clinical data, including neurologic deficits. RESULTS Thirty-five (35) patients were included in the study. The average age of the sample was 63.2 years, and 51.4% (n=18) were females. The most affected network was the central executive network (40%), followed by the dorsal attention and default mode networks (31.4%), while the least affected were the visual (11%) and ventral attention networks (17%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (p=0.021), compared to patients without deficits. In addition, we found that patients without neurologic deficits had an average of 2.06 large-scale networks affected, with 75% of them not being related to traditional eloquent areas as the sensorimotor, language or visual circuits. CONCLUSIONS The Quicktome platform is a practical tool that allows automatic visualization of large-scale brain networks in patients with brain tumors. Although further studies are needed, it may assist in the surgical management of traditional and non-traditional eloquent areas.

BACKGROUND Malignant peripheral nerve sheath tumors (MPNST) are rare tumors found throughout the body, with their clinical course in children still to be completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this demographic from a large national database. METHODS All MPNST patients aged ≤18 year in the U.S. National Cancer Database (NCDB) between 2005-2016 were retrospectively reviewed. Data were summarized and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 251 pediatric MPNST cases were identified. Overall, mean age at diagnosis was 13.1 years (range, 1-18) with there being 132 (53%) females and 119 (47%) males. There were 84 (33%) MPNSTs located in extremities, 127 (51%) less than 1cm in size, and 22 (9%) have metastasis at diagnosis. In terms of treatment, surgery was pursued in 187 (74%) patients, chemotherapy in 116 (46%) patients, and radiation therapy in 129 (61%) patients. Five-year overall survival was estimated to be 52% (95% CI, 45-59%), and with median survival of 64 months (range, 36-136). Multivariate regression revealed older age (HR 1.10, P< 0.01), with metastases at time of diagnosis (HR 2.14, P=0.01), and biopsy only (HR 2.98, P< 0.01) all significantly and independently predicted shorter overall survival. Chemotherapy and radiation therapy were not statistically significant. CONCLUSIONS Pediatric MPNSTs are rare malignant entities, and only approximately half of patients will survive to five years. There remains a clear survival benefit in pursuing maximal safe resection in these patients. As such, judicious workup with meticulous surgical resection by an expert team should then be considered the standard of care for these tumors in children.

One potentially fatal complication of spine surgery is myocardial infarction (MI). There is still uncertainty of the true incidence of MI within subsets of spine surgeries. The aim of this study was to survey the contemporary spine literature and ascertain the true incidence of MI after lumbar spine surgery, as well as to provide commentary on the inherent assumptions made when interpreting cohort versus database studies on this topic.A systematic search of 4 electronic databases from inception to November 2020 was conducted following PRISMA guidelines. Articles were screened against prespecified criteria. MI incidence was then estimated by random-effects meta-analyses of proportions based on cohort versus database studies.A total of 34 cohort studies and 32 database studies describing 767,326 lumbar procedures satisfied all criteria for selection. There were 12,170 (2%) cases from cohort studies and 755,156 (98%) cases from database studies. Cohort studies reported a significantly older patient cohort (P0.01) and longer follow-up period than did database studies (P0.03). Using cohort studies only, the incidence of MI was 0.44% (P heterogeneity0.01), whereas using database studies only, the incidence of MI was 0.41% (P heterogeneity0.01). These 2 incidences were statistically different (P interaction = 0.01). Bias analysis indicated that cohort studies were more vulnerable to small-study biases than were database studies.Although infrequent, the incidence of MI after lumbar spine surgery is unequivocally nonzero. Furthermore, the literature on this topic remains skewed based on study type, and translation of academic findings into practice should be wary of this.

Pediatric brainstem lesions are diagnoses that require tissue sampling to advance our understanding of them and their management. Frameless, robot-assisted biopsy of these lesions has emerged as a novel, viable biopsy approach. Correspondingly, the aim of this study was to quantitively and qualitatively summarize the contemporary literature regarding the likelihood of achieving tumor diagnosis and experiencing any postoperative complications.Searches of 7 electronic databases from inception to September 2022 were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were screened against prespecified criteria. Outcomes were pooled by random-effects meta-analyses of proportions where possible.A total of 8 cohort studies satisfied all criteria. They described 99 pediatric patients with brainstem lesions in whom frameless, robot-assisted biopsy was involved in their work-up. There were 62 (63%) male and 37 (37%) female patients with a median age of 9 years at time of biopsy. Overall, all patients had sufficient tissue obtained by initial biopsy for evaluation. Pooled estimate of achieving tumor diagnosis was 100% (95% confidence interval [CI] 97%-100%) across all studies with a high degree of certainty. Across all studies, there were no cases of procedure-related mortality. The pooled estimates of transient and permanent complications after biopsy were 10% (95% CI 4%-19%) and 0% (95% CI 0%-2%), respectively, of very low and low degrees of certainty each.The contemporary metadata demonstrates the frameless, robot-assisted biopsy of pediatric brainstem lesions is both effective and safe when performed in an experienced setting. Further research is needed to augment robot and automated technologies into workup algorithms.

OBJECTIVE Spinal and peripheral nerve tumors are a heterogeneous group of neoplasms that can be associated with significant morbidity and mortality despite the current standard of care. Immunotherapy is an emerging therapeutic option to improve the prognoses of these tumors. Therefore, the authors sought to present an updated and unifying review on the use of immunotherapy in treating tumors of the spinal cord and peripheral nerves, including a discussion on mechanism of action, drug delivery, current treatment techniques, and preclinical and clinical studies. METHODS Current data in the literature regarding immunotherapy were collated and summarized. Targeted tumors included primary and secondary spinal tumors, as well as peripheral nerve tumors. RESULTS Four primary modalities of immunotherapy (CAR T cell, monoclonal antibody, viral, and cytokine) have been reported to target spine and peripheral nerve tumors. Of the primary spinal tumors, spinal cord astrocytomas had the most preclinical evidence supporting immunotherapy success with CAR T-cell therapy targeting the H3K27M mutation, whereas spinal schwannomas and ependymomas had the most evidence reported for monoclonal antibody therapy preclinically. Of the secondary spinal tumors, primary CNS lymphomas demonstrated some clinical response to immunotherapy, whereas multiple myeloma and bone tumor experiences with immunotherapy were largely limited to concept only. Within peripheral nerve tumors, the use of immunotherapy to treat neurofibromas in the setting of syndromes has been suggested in theory, and possible immunotherapeutic targets have been identified in malignant peripheral nerve tumors. To date, there have been 2 clinical trials involving spine tumors and 2 clinical trials involving peripheral nerve tumors that have reported results, all of which are promising but require validation. CONCLUSIONS Immunotherapy to treat spinal and peripheral nerve tumors has become an emerging area of research and interest. A large amount of preclinical data supporting the translation of this therapy into practice, aimed at ameliorating the poor prognoses of specific tumors, have been reported. Future clinical studies for translation will focus on the optimal therapy type and administration route to best target these tumors, which often preclude total surgical resection given their proximity to the neural and vascular elements of the spine.

ImportanceHigh-grade gliomas (HGG) are the most aggressive and common malignant brain tumors in adults. They have a dismally fatal prognosis. Even if gross total resection of the enhancing tumor is achieved, inevitably, invading tumor cells that are indistinguishable to the un-aided eye are left behind, which eventually leads to tumor recurrence. 5-aminolevulinic acid (5-ALA) is an increasingly utilized intraoperative fluorescent imaging agent for patients with HGG. It enhances visualization of HGG tissue. Despite early promising randomized clinical trial data suggesting a survival benefit for 5-ALA-guided surgery, the growing body of literature must be analyzed to confirm efficacy on patient outcomes.Objective To perform a systematic review of the literature to evaluate whether there is a beneficial effect upon survival and extent of resection due to the utilization of 5-ALA in HGG surgery. Evidence ReviewLiterature regarding 5-ALA usage in HGG surgery was reviewed according to the PRISMA guidelines. One database, PubMed, was searched for assorted combinations of the keywords “5-ALA,” “high-grade glioma,” “5-aminolevulinic acid,” and “resection” in July 2020 for case reports and retrospective, prospective, and randomized clinical trials assessing and analyzing 5-ALA intraoperative use in patients with HGG. Entailed studies on PubMed and SCOPUS were found for screening using a snowball search technique upon the initially searched PubMed papers. Systematic reviews and meta-analyses were excluded from our PRISMA table. Findings1,951 previously published studies were screened, 536 of which were further evaluated, and ultimately 45 were included in our systematic review. There were no date restrictions on the screened publications. Our literature search was finalized on July 16, 2020. We found an observed increase in the overall survival (OS) and progression-free survival (PFS) of the 5-ALA group compared to the white light group, as well as an observed increase in the OS and PFS of complete resections compared to incomplete resections. Of the studies that directly compared the use of 5-ALA to white light (13 of the total analyzed 45, or 28.9%), 5-ALA lead to a better PFS and OS in 88.4% and 67.5% of patients, respectively. When the studies that reported postoperative neurologic outcomes of surgeries using 5-ALA vs. white light were analyzed, 42.2% of subjects demonstrated 5-ALA use was associated with less post-op neurological deficits, whereas 34.5% demonstrated no statistically significant difference between 5-ALA and without. 23.3% of studies showed that intraoperative 5-ALA guided surgeries lead to more post-op neurological deficits. Conclusions and RelevanceUtilization of 5-ALA was found to be associated with a greater extent of resection in HGG surgeries, as well as longer OS and PFS. Postop neurologic deficit rates were mixed and inconclusive when comparing 5-ALA groups to white light groups. 5-ALA is a useful surgical adjunct for resection of HGG when patient safety is preserved.

Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health Organization (WHO) Grades 2 or 3. The rarity of these tumors in adults has left a number of clinical management questions open. Correspondingly, the aim of this study was to aggregate a large PPTID cohort with sufficient statistical power from a large national cancer database to analyze prognostic parameters.All PPTID patients aged over 18 years in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized and survival was modeled using Kaplan-Meier and Cox regression analyses.A total of 103 adult PPTID patients were identified in the NCDB with 63 (61%) WHO Grade 2 and 40 (39%) WHO Grade 3 tumors. Overall, mean age was 53 ± 18 years with even gender distribution. A total of 75 (73%) patients underwent surgical resection for diagnosis, with gross total resection (GTR) was the most common resection outcome in 50/75 (67%). Chemotherapy was utilized in 18 (17%) patients, and radiation therapy in 37 (36%) patients. Overall, 5-year survival rate was estimated to be 54% (95% CI 42-64%), with mean survival was 84 (95% CI 69-99) months. Patients with Grade 2 tumors survived statistically longer than Grade 3 tumor counterparts (P 0.01). Overall, older age (HR 1.09, P 0.01) was associated with shorter survival, whereas GTR (HR 0.43, P = 0.02) was associated with longer survival. Both these parameters were significant within Grade 2 and Grade 3 subgroup analyses as well.PPTID are rare tumors with expected mean survival more than 5 years, although Grade 2 tumors are expected to survive longer than Grade 3 tumors. Age and gross total resection are significant independent predictors of survival in PPTID overall, as well as within Grade 2 and Grade 3 subgroups separately. The prognostic role and benefit of adjuvant therapy is yet to be elucidated, mandating more molecular and biologic research be done to further optimize clinical management in the future.

Surgical resection of high-grade brainstem gliomas is challenging and treatment mostly involves radiation and chemotherapy. In this study, we utilized registry data to determine prognostic features and impact of chemotherapy and radiation on overall survival. The National Cancer Database was queried from 2006 to 2015 for adult cases with histologically confirmed high-grade brainstem glioma. Covariates including patient demographics, comorbidities, tumor characteristics and treatment parameters were captured. Multivariable Cox proportional hazards regression was performed to identify predictors of survival. A total of 422 patients were analyzed. Most patients (66.6%) underwent postoperative radiation with chemotherapy, 9.2% underwent radiation alone, while the remaining had no postoperative treatment (24.2%). Overall median survival was 9.8 months (95% CI 8.8–12). Survival was longer (p

Post-traumatic hydrocephalus (PTH) is a potentially morbid sequela of decompressive craniectomy for traumatic brain injury (TBI). Subdural hygromas are commonly identified following decompressive craniectomy, but the clinical relevance and predictive relationship with PTH in this patient cohort is not completely understood. Survey of seven electronic databases from inception to June 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Multivariate hazard ratios (HRs) for PTH by the presence of subdural hygroma were extracted and pooled by meta-analysis of proportions with random effects modeling. We systematically identified nine pertinent studies describing outcomes of 1010 TBI patients managed by decompressive craniectomy. Of the overall cohort, there were 211 (21%) females and median age was 37.5 years (range 33–53). On presentation, median Glasgow Coma Scale was 7 (range, 5–8). In sum, PTH was reported in 228/840 (27%) cases, and subdural hygroma was reported in 449/1010 (44%) cases across all studies. Pooling multivariate-derived HRs indicated that subdural hygroma was a significant, independent predictor of PTH (HR, 7.1; 95% CI, 3.3–15.1). The certainty of this association was deemed low due to heterogeneity concerns. The presence of subdural hygroma is associated with increased risk of PTH after decompressive craniectomy among TBI patients based on the current literature and may mandate closer clinical surveillance when detected. Prospective studies, including those of intracranial hydrodynamics following decompressive craniectomy in the setting of TBI, will better validate the certainty of these findings.

Background Aneurysm rerupture and bilateral fixed and dilated pupils (bFDPs) typically have a poor prognosis across all age groups. The synchronous occurrence of both features in the infantile demographic has not been previously reported. Case Description We describe the near-fatal clinical course of a 7-month-old infant who experienced an acute giant aneurysm rerupture with signs of bFDPs. The patient was rapidly managed with neurosurgical intervention and has achieved a favorable outcome 1 year later. Conclusions This case highlights that survival of infants who present with intracranial aneurysmal rerupture and bFDPs is amenable to rapid neurosurgical intervention and should be remembered in clinical practice.

Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs). However, the diagnostic potential of this finding in MPNSTs remains yet to be fully substantiated. Correspondingly, our aim was to pool systematically-identified metadata in the literature and substantiate the incidence of H3K27me3 loss in this setting. Searches of 7 electronic databases from inception to May 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of loss was then pooled by random-effects meta-analysis of proportions. Nine pertinent studies described a total of 823 high-grade MPNST samples. When pooled, incidence (sensitivity) of complete H3K27me3 loss was estimated to be 53% (95% CI 42–64%). For MPNST subtypes, estimated incidences of complete loss in NF1 subtype was 52% (95% CI 41–62), in sporadic subtype was 53% (95% CI 36–70%), in the epithelioid subtype was 0% (95% CI 0–7%), and radiation-associated subtype was 98% (95% CI 86–100%). Finally, incidence of incomplete loss (specificity) in 1231 MPNST-mimic samples was estimated to be 96% (95% CI 90–99%). Certainty of these outcomes ranged from very low to high. The incidence of complete H3K27me3 loss is substantial in high-grade MPNSTs and is low in MPNST-mimics. Greater cohort study and biological investigation will validate the certainty of these findings as well as elucidate their true molecular and clinical significances.

Objective Traditionally, extent of resection (EOR) has been seen as a surgical parameter that can predict survival outcomes of surgically managed WHO grade II gliomas. The aim of this study was to evaluate if such an influence was potentially affected by 1p/19q codeletion status based on a national cancer registry. Patient and methods All adults diagnosed with grade II gliomas between the years 2004 to 2014 were queried from the National Cancer Database (NCDB). The population was then divided based on 1p/19q codeletion status, and then Kaplan-Meier, univariate and multivariate Cox regression analyses were utilized to evaluate the prognostic effect of EOR. Results In total, 1,498 grade II gliomas satisfied inclusion for analysis, with the 1p/19q non-codeleted in 705 (47%) cases, and codeletion in 793 (53%) cases. When the cohort was divided based on codeletion status, Kaplan-Meier modelling and univariate regression analyses indicated that gross total resection (GTR) was significantly associated with greater 5-overall survival (OS) in both 1p/19q non-codeleted and codeletion groups. Upon multivariate analysis which incorporated adjuvant therapy status, the significance of GTR was only retained in the 1p/19q non-codeletion group after post-hoc adjustment. Conclusion Our findings indicate that the survival impact of GTR in grade II gliomas may be affected by 1p/19q codeletion status within the first five years after surgery based on overall survival. Therefore, molecular diagnostics have potential clinical application in surgery outcomes, and validation of the reported findings will assist in surgical planning if such an association can be thoroughly established.

Although the dismal clinical prognosis of diffuse intrinsic pontine glioma (DIPG) has not changed, there has been significant progress in the academic literature made in the biological understanding of this brainstem tumor. The aim of this analysis was to evaluate citation and other bibliometric characteristics of the 100 most-cited DIPG articles in the current literature in order to better understand the current state of our academic efforts in this area. Elsevier’s Scopus database was searched for the 100 most-cited articles that focussed on DIPG. Articles were dichotomized as either primarily basic science (BSc) or clinical (CL) articles. Various bibliometric parameters were summarized and comparison between BSc and CL articles was performed using Pearson’s chi-square and Mann–Whitney U tests. Of the 100 most-cited articles, 36 (36%) were BSc and 64 (64%) were CL articles. Overall median values were as follows: citation count, 52 (range, 27–261); citation rate per year, 8.6 (range, 1.7–104); number of authors, 9 (range, 1–63); and publication year, 2011 (range, 1997–2017). Articles were published in a total of 43 different journals and predominately originated in the USA (n = 67, 67%). When compared with CL articles, BSc articles reported significantly greater citation count (P = 0.03), citations rate per year (P

Idarucizumab is the first Food and Drugs Administration (FDA) approved reversal agent for anticoagulant dabigatran, a direct thrombin inhibitor. Emerging evidence suggests idarucizumab can improve clinical outcome following dabigatran-associated hemorrhage, however, its specific use in intracranial hemorrhage has been poorly described. The aim of this study was to systematically review the available literature of idarucizumab in the setting of dabigatran-associated ICH to evaluate its efficacy in the stabilizing/resolving of the primary hemorrhage. A systematic search of 7 electronic databases from their earliest records to August 2018 was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. There were 864 articles identified for screening against selection criteria. The search identified 9 articles to be included in our analysis, describing hemorrhage outcomes in 23 dabigatran-associated cases of ICH managed by idarucizumab. Mean overall age was 76.2 years, with 43% females, and bleeding was subdural, subarachnoid and intracerebral in 43%, 13% and 43% cases respectively. Surgical intervention was pursued in 48% of cases. During the course of the hospitalization, the hemorrhages stabilized/resolved in 87% of patients, and worsened in 13%. In-hospital complications occurred in 4% of cases, and mortality occurred in 4% of cases as well. The available literature suggests that idarucizumab can be applied in the setting of ICH, for its therapeutic effect in patients presenting with dabigatran-associated ICH appears acceptable with no compromise to clinical safety. However, currently there is a paucity of data about various aspects that are involved in other aspects of ICH treatment, including recovery, that limits the significance of the current literature. As more evidence is published relating specifically to long-term ICH outcomes that have been treated by idarucizumab, we will be better placed to establish the optimal role of idarucizumab in the setting of dabigatran-associated ICH.

Objective Achieving optimal intraoperative surgical field visibility and minimizing blood loss are two important parameters in endoscopic sinus surgery (ESS). The aim of this meta-analysis was to compare two total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) to determine if either conferred superior outcomes of these and other parameters based on randomized control trials (RCTs) only. Methods The recommended Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and searches of electronic databases from inception to September 2018 identified 157 articles for screening. Data were extracted and analyzed using meta-analysis of proportions. Results In total, we identified 15 RCTs that satisfied our selection criteria. There were 828 ESS cases described, with 391 (47%) and 437 (53%) being managed by TIVA and IA, respectively. Pooled analysis demonstrated significantly superior visibility scores for TIVA compared to IA based on 10-point grading scores (P = 0.049, visual analog scale; P = 0.009, Wormald scale) and 5-point grading scores (P = 0.002, Boezaart scale). Blood loss was significantly less following TIVA (P = 0.003), with no significant difference in intraoperative heart rate (P = 0.70) or mean arterial pressure (P = 0.96). Additionally, duration of surgery (P = 0.16) and anesthesia (P = 0.39) were comparable between the two approaches. Conclusion This meta-analysis indicates that TIVA has the potential to confer superior surgical field visibility and reduce intraoperative blood loss compared to IA in ESS. Currently, there are significant heterogeneity concerns in this meta-analysis, which temper any expectations that either approach is absolutely superior to the other. Caution should be exercised when interpreting these results until further validation can be achieved. Level of evidence 1A Laryngoscope, 130:575-583, 2020.

Rathke's cleft cysts (RCCs) are benign growths of the embryological Rathke's pouch. Surgical decompression provides effective symptomatic relief in most cases; however, the effect of gross total resection (GTR) of the cyst wall on recurrence, as well as pituitary function, is unclear. The aim of this meta-analysis was to pool the current literature and ascertain the recurrence control afforded by GTR of the cyst wall compared with subtotal resection (STR). Searches of seven electronic databases from inception to January 2019 were conducted following PRISMA guidelines, resulting in 476 articles to be screened. Outcomes were analyzed using meta-analysis of proportions. A total of 10 retrospective cohort studies satisfied selection criteria, describing 655 surgically managed RCC cases, with 254 (39%) and 401 (61%) achieving GTR and STR of the cyst wall, respectively. GTR was associated with significantly reduced overall RCC recurrence by fixed-effects (FE) modeling (RR, 0.66; 95% CI, 0.45-0.96), but not by random effects (RE) modeling (RR, 0.75; 95% CI, 0.51-1.12). Based on both models, GTR was associated with significantly reduced symptomatic recurrence (RE model, RR, 0.37, 95% CI, 0.14-0.95) and significantly increased postoperative diabetes insipidus (RE model, RR, 2.60; 95% CI, 1.34-5.03). There was insufficient data to evaluate other pituitary axes in this context. The current evidence indicates that GTR of the RCC cyst wall has the potential to affect the incidence of overall and symptomatic RCC recurrences, as well as drive postoperative DI incidence. However, expectations of clinical and pragmatic benefit following cyst wall resection should be titrated carefully against the potential for postoperative and pituitary morbidities which currently remain poorly defined. Greater granularity is required to understand all factors that can influence recurrence and quality of life when evaluating resection of RCC.

Subtotal resection (STR) of vestibular schwannoma (VS) tumors remains controversial and little is known regarding post-operative volume changes. Authors retrospective reviewed the medical records from January 1st 2002 to January 1st 2018, for all patients who had undergone primary STR of large VS at a single tertiary academic institution. Our series consists of 34 patients with a mean age of 53.9 (median 53; range 21–87) years that had STR of their VS tumor. The mean pre-operative tumor diameter and volume was 3.9 cm (median 3.0 cm; range 1.6–6.0 cm) and 11.7 cm3 (median 9.6 cm3; range 2.8–44.3 cm3), respectively, with a mean extent of resection of 86% (median 90%; range 53–99%). The mean radiographic and clinical follow-up was 40 months (range 6–120 months) and 51 months (range 7–141 months), respectively. 85% of patients had optimal House–Brackmann (HB) scores (Grade 1 & 2) immediately post-operatively, and 91% at 1 year; 94% of patients had normal (HB 1) at last follow-up. There was significant regression of residual tumor volume at 1 year (p = 0.006) and 2 years (p = 0.02), but not at 3 years (p = 0.08), when compared to the prior year. There was significant regression of size over time, with a mean slope estimate of − 0.70 units per year (p

Systematic review and meta-analysis of randomised controlled trials. The purpose of this study is to perform a systematic review and meta-analysis of antifibrinolytic agents for paediatric spine surgery. Bleeding is an important consideration in paediatric scoliosis surgery; blood loss leads directly to higher morbidity and mortality. Antifibrinolytics are an attractive non-invasive method of reducing bleeding as evidenced in arthroplasty, cardiac surgery and adult scoliosis surgery. A thorough database search of Medline, PubMed, EMBASE and Cochrane was performed according to PRISMA guidelines, and a systematic review was performed. Five randomised controlled trials were identified in this meta-analysis, consisting of a total of 285 spine surgery patients with subgroups of tranexamic acid (n = 101), epsilon aminocaproic acid (n = 61) and control (n = 123). This meta-analysis found that antifibrinolytics lead to statistically significant reductions in peri-operative blood loss (MD − 379.16, 95% CI [− 579.76, − 178.57], p

The resection of insular gliomas remains a neurosurgical challenge due to the close proximity of functionally-important cortical, white matter tracts, and vasculature structures. More recently, the feasibility of resection has gained traction, however, there is a lack of consolidated neurological deficit metrics. Thus, the aim of this study was to determine the incidences of neurological deficits following insular glioma resection to better guide selection algorithms and resource allocations. Searches of seven electronic databases from inception to August 2018 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and pooled using meta-analysis of proportions. Meta-regression was used to identify potential sources of heterogeneity. Nineteen observational studies reported the neurological outcomes of 890 insular glioma patients. The pooled incidences of new temporary and permanent motor deficits were 11% (95% CI, 6-17%) and 4% (95% CI, 2-7%) respectively, and new temporary and permanent language deficits were 11% (95% CI, 6-17%) and 2% (95% CI, 0-4%) respectively. Single-surgeon series reported significantly lower incidences of both permanent motor (2% vs 7%; P 0.001) and language (1% vs 3%; P = 0.03) deficits. The incidences of motor and language neurological deficits following insular glioma resection have been quantified, and will assist in determining the suitability and appropriateness of pursuing surgical resection for insular glioma. We note that permanent neurological deficits are lowest when reported by series describing outcomes of a single surgeon, indicating most optimal outcomes may be best achieved after intense training and/or greater experience.