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Background and Objectives: Women represent ∼20% of the national neurosurgical resident cohort but only ∼10% of academic neurosurgeons in the United States. Recognizing that the publication of scientific literature contributes to academic advancement, we measured authorship trends of academic neurosurgeons to query publication differences as an explanation for the discrepancy of female representation in academic positions., Methods: Physician data were obtained from program and individual physician webpages. Annual total, first author, and senior author publications were recorded for each neurosurgeon from 1980 to 2020. Mean publication number as a function of the year relative to residency graduation was calculated for all, first author, and senior author publications for all timepoints with >50 individuals. The mean first years of publication were compared using unpaired 2-tailed t-tests. The slope of publication for the senior author and all publications was calculated using individual best-fit lines from years 0 to 10 relative to residency graduation., Results: Overall, 1601 faculty members were evaluated (female = 167 [10.4%], male = 1434 [89.6%]). First-author publication for female members peaked at 0.60 publications/year, and for male members at 0.80 publications/year, both at -1 year from graduation (P = .038). Female first publication occurred earlier (-2.4 vs 1.45 years; P < .00001). The mean increase in all publications/year from years 0 to 10 was 0.25 for women and 0.28 for men (P = .68). The increase in senior publications/year was 0.11 for women and 0.13 for men (P = .39). The ratio of total publications to the Scopus h-index was 3.08 for women and 3.62 for men (P = .07)., Conclusion: These data suggest that women publish earlier but have fewer first-author publications at -1 year, the timepoint of peak publication for both genders. There was no significant gender difference in rates of the first author and all publications over the years 0 to 10. The ratio of publications to the h-index did not differ significantly but showed a trend suggesting that women produce higher-impact articles and may need fewer publications to achieve the same change in the h-index., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT., Methods: This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures., Results: Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04)., Conclusions: Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To systematically review the reported outcomes and complications of different treatment options for choroid plexus arteriovenous malformations (AVMs), specifically focusing on surgical resection and endovascular embolization. A systematic literature review was performed using a PubMed query for studies published between January 1975 and July 2021. All studies describing the clinical presentation, management, and outcome of confirmed choroid plexus AVM cases were included. A total of 20 studies were included in the final analysis. Of these, 18 were singlepatient case reports, one article contained two patients, and a single study was a cohort of 24 patients. Patient age ranged from one day to 61 years, with a mean of 31.8±20.4 years. Most choroid plexus AVMs were located in the lateral ventricles (14 patients, 70.0%), while there were four (20.0%) located in the third ventricle, and two in the fourth ventricle (10.0%). Almost all patients were treated with surgical resection (18 patients, 90%). In 14 patients (77.8%), complete resection of the AVM was achieved. A residual AVM was reported in one case (5.6%). Most patients were reported to have improved from their presentation status over time (14 patients, 70.0%). Presence or absence of long-term sequelae (e.g., neurologic deficits) were reported for 14 patients (70%). Eleven of these patients (78.6%) were reported to have no neurological sequelae. While data on choroid plexus AVMs remains limited, the available evidence suggests gross total resection of lesions in this location can be safely achieved with subsequent reduction in preoperative symptoms.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a precise, incisionless approach to cerebral lesioning and an alternative to neuromodulation in movement disorders. Despite rigorous clinical trials, long-term patient-centered outcome data after MRgFUS for tremor-predominant Parkinson's Disease (TPPD) are relatively lacking., Objective: To report long-term data on patient satisfaction and quality of life after MRgFUS thalamotomy for TPPD., Methods: In a retrospective study of patients who underwent MRgFUS thalamotomy for TPPD at our institution between 2015 and 2022, a patient survey was administered to collect self-reported measures of tremor improvement, recurrence, Patients' Global Impression of Change (PGIC), and side effects. Patient demographics, FUS parameters, and lesion characteristics were analyzed., Results: A total of 29 patients were included with a median follow-up of 16 months. Immediate tremor improvement was achieved in 96% of patients. Sustained improvement was achieved in 63% of patients at last follow-up. Complete tremor recurrence to baseline occurred for 17% of patients. Life quality improvement denoted by a PGIC of 1 to 2 was reported by 69% of patients. Long-term side effects were reported by 38% of patients and were mostly mild. Performing a secondary anteromedial lesion to target the ventralis oralis anterior/posterior nucleus was associated with higher rates of speech-related side effects (56% vs 12%), without significant improvement in tremor outcomes., Conclusion: Patient satisfaction with FUS thalamotomy for tremor-predominant PD was very high, even at longer term. Extended lesioning to target the motor thalamus did not improve tremor control and may contribute to greater frequency of postoperative motor- and speech-related side effects., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Though women now comprise approximately 21.5% of all neurosurgery residents in the United States, women only represent 10% of practicing neurosurgeons nationally. Serving as a journal editor is 1 measure of academic success. We investigated characteristics of editorial boards for top neurosurgical journals to identify factors influencing membership on editorial boards. We sought to identify gender differences to explain the paucity of women on editorial boards., Methods: This is a cross-sectional study of editorial boards for the top 10 English-language neurosurgical journals. Data were obtained from journal websites, program faculty lists, or physician online profiles. Gender differences were compared using Student t test and χ 2 analysis., Results: Seven hundred twenty-two editorial board members were examined (female n = 65; male n = 650; unidentified n = 7). Overall, women had fewer years in practice (P = 0.002) and more often had additional advanced degrees (P = 0.009) while men had higher h-indices (P < 0.0001). Within the boards of Neurosurgery and Acta Neurochirurgica, men had been in practice longer (P = 0.014; P = 0.023) and had higher h-indices (P = 0.003; P = 0.025). Male editors for Journal of Neurosurgery: Spine and World Neurosurgery had higher h-indices (P = 0.007; P = 0.018)., Conclusions: Women constitute ∼9% of editorial boards for top neurosurgical journals, a percentage comparable to the amount of practicing female academic neurosurgeons. This finding is encouraging as in that there appears to be no readily identifiable bias in the selection of editorial board members. The differences in years in practice and h-index suggest that gender distribution may equalize with time as more women enter practice and produce scientific literature. Efforts to recruit and retain women in neurosurgery should be pursued to rectify this discrepancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a "gold standard" in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sokolowski, Soldozy, Sharifi, Norat, Kearns, Liu, Williams, Yağmurlu, Mastorakos, Miller, Kalani, Park, Kellogg and Tvrdik.)

Background: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety., Objective: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS., Methods: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male., Results: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort., Conclusion: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method., Methods/design: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method., Discussion: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Background: Although complete nidal obliteration of brain arteriovenous malformations (AVM) is generally presumed to represent durable cure, postobliteration hemorrhage, and AVM recurrence have become increasingly recognized phenomena. The goal of the study was to define hemorrhage and nidal recurrence risks of obliterated AVMs treated with stereotactic radiosurgery (SRS)., Methods: This is a retrospective cohort study from the International Radiosurgery Research Foundation comprising AVM patients treated between 1987 and 2020. Patients with AVM obliteration on digital subtraction angiography (DSA) were included. Outcomes were (1) hemorrhage and (2) AVM recurrence. Follow-up duration began at the time of AVM obliteration and was censored at subsequent hemorrhage, AVM recurrence, additional AVM treatment, or loss to follow-up. Annualized risk and survival analyses were performed. A sensitivity analysis comprising patients with AVM obliteration on magnetic resonance imaging or DSA was also performed for postobliteration hemorrhage., Results: The study cohort comprised 1632 SRS-treated patients with AVM obliteration on DSA. Pediatric patients comprised 15% of the cohort, and 42% of AVMs were previously ruptured. The mean imaging follow-up after AVM obliteration was 22 months. Among 1607 patients with DSA-confirmed AVM obliteration, 16 hemorrhages (1.0%) occurred over 2223 patient-years of follow-up (0.72%/y). Of the 1543 patients with DSA-confirmed AVM obliteration, 5 AVM recurrences (0.32%) occurred over 2071 patient-years of follow-up (0.24%/y). Of the 16 patients with postobliteration hemorrhage, AVM recurrence was identified in 2 (12.5%). In the sensitivity analysis comprising 1939 patients with post-SRS AVM obliteration on magnetic resonance imaging or DSA, 16 hemorrhages (0.83%) occurred over 2560 patient-years of follow-up (0.63%/y)., Conclusions: Intracranial hemorrhage and recurrent arteriovenous shunting after complete nidal obliteration are rare in AVM patients treated with SRS, and each phenomenon harbors an annual risk of <1%. Although routine postobliteration DSA cannot be recommended to SRS-treated AVM patients, long-term neuroimaging may be advisable in these patients.

Cortical spreading depolarizations (CSDs) are characterized by waves of diminished electroencephalography activity that propagate across the cortex with subsequent loss of ionic homeostasis. CSDs have been found in many pathological conditions, including migraine, traumatic brain injury, and ischemic stroke. Because of CSD-associated ionic and metabolic disturbances at the peri-infarct area after ischemic stroke, it is thought that CSDs exacerbate tissue infarction and worsen clinical outcomes. Microglia, the main innate immune cells in the brain, are among the first responders to brain tissue damage. Recent studies demonstrated that microglia play a critical role in CSD initiation and propagation. In this article, we discuss the significance of CSD in the setting of ischemic stroke and how microglia may modulate peri-infarct CSDs, also known as iso-electric depolarizations. Finally, we discuss the significance of microglial Ca 2+ and how it might be used as a potential therapeutic target for patients with ischemic stroke., (© 2022. The Author(s).)

Background: Women have historically been underrepresented in academic medicine, particularly in surgical subspecialties. This study investigated potential associations between gender and promoting practices in academic neurosurgery., Methods: Faculty data, including time from residency, professorship, specialty, and h-index, were obtained from websites of the institutions listed in the American Association of Neurological Surgeons Neurosurgical Residency Training Program Directory. Demographics, training, and appointments were compared between male and female neurosurgeons. Predictors of professorship, chair, directorship, and division leadership were identified using multivariable models., Results: The study examined 1629 faculty members. Women were more likely to be assistant professors (P < 0.0001), while men were more likely to be full professors (P < 0.0001), hold chair positions (P = 0.007), lead subspecialty divisions (P = 0.008), and have a higher Scopus h-index (P < 0.0001). In a multivariable analysis, years from training (P < 0.001), fellowship (P = 0.009), h-index (P < 0.001), and chair/program director/division leadership position (P < 0.001) were significant positive predictors of full professorship. Holding additional advanced degrees (P = 0.010), leading a subspecialty division (P = 0.005), and having a higher h-index (P = 0.002) positively predicted chair position. However, when accounting for all other factors, gender was not a significant predictor of full professorship, division leadership, chair, or program directorship., Conclusions: While significantly more men hold leadership positions in U.S. academic institutions, after controlling for contributing variables, there did not appear to be an association between gender and full professorship, division leadership, chair, or program directorship in academic neurosurgery. While the field still has significant work to do to achieve gender equity, these results may serve as encouragement to women who are looking to advance their careers in academic neurosurgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients who survive the initial ictus of spontaneous intracerebral hemorrhage (ICH) remain vulnerable to subsequent injury of the perilesional parenchyma by molecular and cellular responses to the hematoma. Secondary brain injury after ICH, which contributes to long-term functional impairment and mortality, has emerged as an attractive therapeutic target. This review summarizes preclinical and clinical evidence for neuroprotective therapies targeting secondary injury pathways following ICH. A focus on therapies with pleiotropic antiinflammatory effects that target thrombin-mediated chemotaxis and inflammatory cell migration has led to studies investigating statins, anticholinergics, sphingosine-1-phosphate receptor modulators, peroxisome proliferator activated receptor gamma agonists, and magnesium. Attempts to modulate ICH-induced blood-brain barrier breakdown and perihematomal edema formation has prompted studies of nonsteroidal antiinflammatory agents, matrix metalloproteinase inhibitors, and complement inhibitors. Iron chelators, such as deferoxamine and albumin, have been used to reduce the free radical injury that ensues from erythrocyte lysis. Stem cell transplantation has been assessed for its potential to enhance subacute neurogenesis and functional recovery. Despite promising preclinical results of numerous agents, their outcomes have not yet translated into positive clinical trials in patients with ICH. Further studies are necessary to improve our understanding of the molecular events that promote damage and inflammation of the perihematomal parenchyma after ICH. Elucidating the temporal and pathophysiologic features of this secondary brain injury could enhance the clinical efficacy of neuroprotective therapies for ICH., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood., Objective: To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs., Methods: We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC)., Results: The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013)., Conclusion: Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role., (© Congress of Neurological Surgeons 2021.)

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging., Competing Interests: Conflict of interest disclosure All authors certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes., Objective: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features., Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation., Results: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts., Conclusion: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates., Objective: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study., Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes., Results: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar., Conclusion: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background and Purpose: Ischemic injury triggers multiple pathological responses in the brain tissue, including spreading depolarizations across the cerebral cortex (cortical spreading depolarizations [CSD]). Microglia have been recently shown to play a significant role in the propagation of CSD. However, the intracellular responses of myeloid cells during ischemic stroke have not been investigated., Methods: We have studied intracellular calcium activity in cortical microglia in the stroke model of the middle cerebral artery occlusion, using the murine Polr2a-based and Cre-dependent GCaMP5 and tdTomato reporter (PC::G5-tdT). High-speed 2-photon microscopy through cranial windows was employed to record signals from genetically encoded indicators of calcium. Inflammatory stimuli and pharmacological inhibition were used to modulate microglial calcium responses in the somatosensory cortex., Results: In vivo imaging revealed periodical calcium activity in microglia during the hyperacute phase of ischemic stroke. This activity was more frequent during the first 6 hours after occlusion, but the amplitudes of calcium transients became larger at later time points. Consistent with CSD nature of these events, we reproducibly triggered comparable calcium transients with microinjections of potassium chloride (KCl) into adjacent cortical areas. Furthermore, lipopolysaccharide-induced peripheral inflammation, mimicking sterile inflammation during ischemic stroke, produced significantly greater microglial calcium transients during CSD. Finally, in vivo pharmacological analysis with CRAC (calcium release-activated channel) inhibitor CM-EX-137 demonstrated that CSD-associated microglial calcium transients after KCl microinjections are mediated at least in part by the CRAC mechanism., Conclusions: Our findings demonstrate that microglia participate in ischemic brain injury via previously undetected mechanisms, which may provide new avenues for therapeutic interventions.

Objective: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus., Methods: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death., Results: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively., Conclusions: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Background: Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined., Objective: To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs., Methods: To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes., Results: The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively., Conclusion: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: The caudate nucleus is a C-shaped structure that is located in the center of the brain and is divided into 3 parts: the head, body, and tail., Methods: We detail the anatomic connections, relationships with other basal ganglia structures, and clinical implications of injury to the caudate nucleus., Results: Anatomically, the most inferior transcapsular gray matter is the lentiform peduncle, which is the connection between the lentiform nucleus and caudate nucleus as well as the amygdala. The border between the tail and body of the caudate nucleus is the posterior insular point. The tail of the caudate nucleus is extraependymal in some parts and intraependymal in some parts of the roof of the temporal horn of the lateral ventricle. The tail of the caudate nucleus crosses the inferior limiting sulcus (temporal stem), and section of the tail during approaches to lesions involving the temporal stem may cause motor apraxia. The mean distance from the temporal limen point, which is the junction of the limen insula and inferior limiting sulcus, to the tail of the caudate nucleus in the temporal stem is 15.87 ± 3.10 mm., Conclusions: Understanding of the functional anatomy and connections of the distinct parts of the caudate nucleus is essential for deciding the extent of resection of lesions involving the caudate nucleus and the types of deficits that may be found postoperatively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs., Methods: The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared., Results: The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation., Conclusions: Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.

Background Compensation has historically been unequal for men versus women in medical fields, particularly in surgical subspecialties.  Objective We analyzed associations between gender and compensation and identified factors associated with compensation among male and female academic neurosurgeons in the United States (US) public institutions. Methods This is a cross-sectional study of available data for the 2016-2017 fiscal years associated with male and female neurosurgical faculty from public, academic institutions within the US. The data used for analysis included total annual salary, which consisted of the base salary and additional compensation. Other gleaned data included faculty demographics, training, and academic appointments. The male and female neurosurgeons' data were separated into two respective gender groups and then were compared. Predictors of compensation were identified using univariable and non-imputed and multiply-imputed multivariable statistical models. Results The cohort was comprised of 460 neurosurgery faculty members (female n=34; male n=426). Total annual salaries were comparable between the genders. Females were more likely to be younger (p=0.001), to have completed neurosurgery training recently (p=0.003), to have had fellowship training (p=0.011), and to have lower h--indices (p=0.003) compared to males. Males and females differed in academic ranks (p=0.035) and neurosurgical subspecialties (p=0.038). Midwest (a[Formula: see text])=-US$337,516.7, p=0.002), South (a[Formula: see text]=-US$302,500.5, p=0.003), and West (a[Formula: see text]=-US$276,848.8, p=0.005) practices were independent predictors of lower annual compensation. Chair position (a[Formula: see text]=US$174,180.3, p=0.019) and associate professorship (a[Formula: see text]=US$126,633.4, p=0.037) were independent predictors of higher annual compensation. Gender was not a significant predictor of total annual compensation. Conclusions Total salaries were not different between male and female neurosurgeons in public, academic institutions in the US. Gender was not a significant predictor of total annual compensation. This study is applicable to public institutions in states with Freedom of Information Act reporting requirements., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Kearns et al.)

Background: Dural arteriovenous fistulas (DAVFs) can be categorized based on location., Objective: To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors., Methods: This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage)., Results: The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041)., Conclusion: After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors., Methods: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated., Results: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022)., Conclusions: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

Surgical resection of basal ganglia (BG) and thalamic cavernous malformations (CMs) has not yet become standardized in the field of neurosurgery due to the eloquent location of these lesions and the relative paucity of literature on the subject. This review presents a consolidation of the available literature on outcomes and complication rates after surgical resection of these lesions. A systematic literature review was performed via PubMed database for articles published between 1985 and 2019. Studies comprising ≥2 patients receiving surgery for BG or thalamic CMs with available follow-up data were included. Pooled data included patient demographics, CM preoperative characteristics, and surgical outcomes Twenty studies comprising 227 patients were included for analysis. Complete resection was achieved in 94.7% (fixed-effects pooled estimate [FE]: 94.9%[91.0%-97.8%]; random-effects pooled estimate [RE]: 90.0%[79.8%-96.9%]), and hemorrhage of incompletely resected CMs occurred in 50% (FE: 55.9%[25.9%-83.6%]; RE: 55.9%[25.9%-83.6%]) of patients. Early morbidity was observed in 24.0% (FE: 24.9%[17.8%-32.6%]; RE: 24.9%[17.8%-32.6%]). At final follow-up, 67.3% (FE: 67.7%[58.8%-76.0%]; RE: 67.8%[52.2%-81.6%]) and 20.6% (FE: 20.6%[13.6%-28.6%]; RE: 20.9%[9.8%-34.9%]) had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.3% (FE: 2.3%[0.6%-5.1%]; RE: 2.3%[0.6%-5.1%]). Therefore, high cure rates with low rates of postoperative morbidity can be achieved in BG or thalamic CM surgery. Most patients had improved neurological function at final follow-up. Complete resection should be attempted to reduce rates of repeat hemorrhage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years)., Methods: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated., Results: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years., Conclusions: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

Objective: Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects., Methods: The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome., Results: The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044)., Conclusions: SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

Contrast-enhanced ultrasound (CEUS) is a relatively new imaging modality in the realm of neurosurgical disease. CEUS permits the examination of blood flow through arteries, veins, and capillaries via intravascular contrast agents and allows vascular architectural mapping with extreme sensitivity and specificity. While it has established utility in other organ systems such as the liver and kidneys, CEUS has not been studied extensively in the brain. This report presents a review of the literature on the neurosurgical applications of CEUS and provides an outline of the imaging modality's role in the diagnosis, evaluation, and treatment of neurosurgical disease.

Objective: Predicting future hemorrhage risk may allow better selection of patients with cerebral cavernous malformations (CCMs) who will likely benefit from treatment. In this study, we sought to identify predictors of CCM hemorrhage, and to compare subsequent symptomatic hemorrhage risks between patients with and without previous hemorrhage., Methods: We performed a retrospective review of consecutive CCM patients at our institution between 1982 and 2017. Patients with diffuse or familial CCM syndromes, and those without follow-up data were excluded. The primary endpoint was acute symptomatic hemorrhage causing transient or permanent neurological symptoms. Primary endpoint incidences were compared between patients with and without previous hemorrhage., Results: The study cohort comprised 84 patients with 90 CCMs. Previous hemorrhage was the only significant predictor for the primary endpoint (P = 0.003). CCMs with previous hemorrhage had a higher risk of symptomatic hemorrhage in follow-up than those without previous hemorrhage (26.9 vs. 1.5 symptomatic hemorrhages per 1000 CCM-months, P < 0.001). CCMs with and without previous hemorrhage had annual hemorrhage rates of 2.7% and 0.15%, respectively. Symptomatic hemorrhage-free survival rates were significantly lower in CCMs with previous hemorrhage (log-rank test, P < 0.001). Actuarial hemorrhage-free survival rates for CCMs with previous hemorrhage were 75%, 60%, 60%, and 60% at 1, 2, 3, and 4 years, respectively, compared with rates of 95%, 95%, 95%, and 84% for CCMs without previous hemorrhage., Conclusions: Previous hemorrhage is a predictor of subsequent symptomatic hemorrhage in CCMs. Compared with CCMs without previous hemorrhage, those with prior hemorrhage have a significantly higher risk of future symptomatic hemorrhage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- The goal of this study was to systematically review the outcomes and complications after surgical resection of brain stem cavernous malformations (BCMs). Methods- A systematic literature review was performed using the PubMed database for studies published between 1986 and 2018. All studies comprising ≥2 patients with surgically resected BCMs and available follow-up data were included. Data extracted from studies included patient demographics, BCM location, and surgical outcomes. Results- Eighty-six studies comprising 2493 patients (adult and pediatric) were included for final analysis. Complete resection was achieved in 92.3% (fixed-effects pooled estimate [FE], 92.9% [91.7%-94.0%]; random-effects pooled estimate [RE], 89.4% [86.5%-92.0%]) of patients, and rehemorrhage of residual BCMs occurred in 58.6% (FE, 58.8% [49.7%-67.6%]; RE, 57.2% [43.5%-70.2%]). Postoperative morbidity occurred in 34.8% (FE, 30.9% [29.0%-32.8%]; RE, 31.1% [25.8%-36.6%]) of patients. Postoperative morbidities included motor deficit in 11.0% (FE, 9.9% [8.1%-11.7%]; RE, 11.1% [7.0%-16.0%]), sensory deficit in 6.7% (FE, 6.3% [4.8%-7.9%]; RE, 7.6% [4.5%-11.5%]), tracheostomy/gastrostomy in 6.0% (FE, 5.2% [4.3%-6.1%]; RE, 3.8% [2.6%-5.3%]), and other cranial nerve deficits in 29.4% (FE, 27.6% [25.3%-29.9%]; RE, 33.9% [25.7%-42.6%]) of patients. At final follow-up, 57.9% (FE, 57.6% [55.6%-59.6%]; RE, 57.2% [52.1%-62.3%]) and 25.9% (FE, 24.1% [22.4%-25.9%]; RE, 18.5% [14.6%-22.8%]) of patients had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.6% (FE, 1.9% [1.4%-2.5%]; RE, 1.8% [1.4%-2.5%]). Conclusions- High cure rates and low rates of postoperative morbidity can be achieved with surgery in patients with BCMs. Most patients had improved preoperative symptoms at final follow-up. To avoid rehemorrhage, complete resection should be the goal of surgery.

Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; P =0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; P =0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; P =0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; P =0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; P =0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; P =0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; P =0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.

Objective: The benefits and risks of pre-stereotactic radiosurgery (SRS) embolization have been reported in different studies. The goal of this study was to compare the long-term outcome of arteriovenous malformations (AVMs) treated with and without pre-SRS embolization., Methods: A database including 1159 patients with AVMs who underwent SRS was reviewed. The embolized group was selected by including AVMs with pre-SRS embolization, maximal diameter > 30 mm, and estimated volume > 8 ml. The nonembolized group was defined as AVMs treated by SRS alone with matched de novo nidus volume. Outcomes including incidences of favorable clinical outcome (obliteration without hemorrhage, cyst formation, worsening, or new seizures), obliteration, adverse effects, and angioarchitectural complexity were evaluated., Results: The study cohort comprised 17 patients in the embolized group (median AVM volume 17.0 ml) and 35 patients in the nonembolized group (median AVM volume 13.1 ml). The rates of obliteration (embolized cohort: 33%, 44%, and 56%; nonembolized cohort: 32%, 47%, and 47% at 4, 6, and 10 years, respectively) and favorable outcome were comparable between the 2 groups. However, the embolized group had a significantly higher incidence of repeat SRS (41% vs 23%, p = 0.012) and total procedures (median number of procedures 4 vs 1, p < 0.001), even with a significantly higher margin dose delivered at the first SRS (23 Gy vs 17 Gy, p < 0.001). The median angioarchitectural complexity score was reduced from 7 to 5 after embolization. Collateral flow and neovascularization were more frequently observed in the embolized nonobliterated AVMs., Conclusions: Both embolization plus SRS and SRS alone were effective therapies for moderately large (8-39 ml) AVMs. Even with a significantly higher prescription dose at the time of initial SRS, the embolized group still required more procedures to reach final obliteration. The presence of collateral flow and neovascularization could be risk factors for a failure to obliterate following treatment.

Objective: The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas., Methods: This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients' clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications., Results: The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087)., Conclusions: In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.

Calcium signaling plays a significant role in microglial activation. Genetically encoded calcium indicators (GECI) have been widely used for calcium imaging studies in many brain cell types, including neurons, astrocytes, and oligodendrocytes. However, microglial calcium imaging approaches have been hampered by idiosyncrasies of their gene expression and malleable cell properties. The generation of PC::G5-tdT, a Polr2a locus-based conditional mouse reporter of calcium, facilitated the deployment of GECI in microglia. When crossed with the Iba1(Aif1)-IRES-Cre line, all brain microglia of the progeny are labeled with the calcium indicator variant GCaMP5G and the red fluorescent protein tdTomato. This reporter system has enabled in vivo studies of intracellular calcium in large microglial cell populations in cerebral pathologies such as ischemic stroke. In this chapter, we outline specific guidelines for genetic, surgical, imaging, and data analysis aspects of microglial calcium monitoring of the ischemic cortex following middle cerebral artery occlusion.