Scalp incision technique for decompressive hemicraniectomy: comparative systematic review and meta-analysis of the reverse question mark versus alternative retroauricular and Kempe incision techniques.

Decompressive hemicraniectomy (DHC) is a critical procedure used to alleviate elevated intracranial pressure (ICP) in emergent situations. It is typically performed to create space for the swelling brain and to prevent dangerous and potentially fatal increases in ICP. DHC is indicated for pathologies ranging from MCA stroke to traumatic subarachnoid hemorrhage-essentially any cause of refractory brain swelling and elevated ICPs. Scalp incisions for opening and closing the soft tissues during DHC are crucial to achieve optimal outcomes by promoting proper wound healing and minimizing surgical site infections (SSIs). Though the reverse question mark (RQM) scalp incision has gained significant traction within neurosurgical practice, alternatives-including the retroauricular (RA) and Kempe incisions-have been proposed. As choice of technique can impact postoperative outcomes and complications, we sought to compare outcomes associated with different scalp incision techniques used during DHC. We queried three databases according to PRISMA guidelines in order to identify studies comparing outcomes between the RQM versus "alternative" scalp incision techniques for DHC. Our primary outcome of interest in the present study was postoperative wound infection rates according to scalp incision type. Secondary outcomes included estimated blood loss (EBL) and operative duration. We identified seven studies eligible for inclusion in the formal meta-analysis. The traditional RQM technique shortened operative times by 36.56 min, on average. Additionally, mean EBL was significantly lower when the RQM scalp incision was used. Postoperatively, there was no significant association between DHC incision type and mean intensive care unit (ICU) length of stay (LOS), nor was there a significant difference in predisposition to developing wound complications or infections between the RQM and retroauricular/Kempe incision cohorts. Superficial temporal artery (STA) preservation and reoperation rates were collected but could not be analyzed due to insufficient number of studies reporting these outcomes. Our meta-analysis suggests that there is no significant difference between scalp incision techniques as they relate to surgical site infection and wound complications. At present, it appears that outcomes following DHC can be improved by ensuring that the bone flap is large enough to enable sufficient cerebral expansion and decompression of the temporal lobe, the latter of which is of particular importance. Although previous studies have suggested that there are several advantages to performing alternative scalp incision techniques during DHC, the present study (which is to our knowledge the first to meta-analyze the literature on outcomes in DHC by scalp incision type) does not support these findings. As such, further investigations in the form of prospective trials with high statistical power are merited.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. METHOD: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007-July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. RESULTS: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4-1.2, p = 0.18). CONCLUSIONS: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms.

Localized conditional induction of brain arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia.

BACKGROUND: Longitudinal mouse models of brain arteriovenous malformations (AVMs) are crucial for developing novel therapeutics and pathobiological mechanism discovery underlying brain AVM progression and rupture. The sustainability of existing mouse models is limited by ubiquitous Cre activation, which is associated with lethal hemorrhages resulting from AVM formation in visceral organs. To overcome this condition, we developed a novel experimental mouse model of hereditary hemorrhagic telangiectasia (HHT) with CreER-mediated specific, localized induction of brain AVMs. METHODS: Hydroxytamoxifen (4-OHT) was stereotactically delivered into the striatum, parietal cortex, or cerebellum of R26CreER; Alk12f/2f (Alk1-iKO) littermates. Mice were evaluated for vascular malformations with latex dye perfusion and 3D time-of-flight magnetic resonance angiography (MRA). Immunofluorescence and Prussian blue staining were performed for vascular lesion characterization. RESULTS: Our model produced two types of brain vascular malformations, including nidal AVMs (88%, 38/43) and arteriovenous fistulas (12%, 5/43), with an overall frequency of 73% (43/59). By performing stereotaxic injection of 4-OHT targeting different brain regions, Alk1-iKO mice developed vascular malformations in the striatum (73%, 22/30), in the parietal cortex (76%, 13/17), and in the cerebellum (67%, 8/12). Identical application of the stereotaxic injection protocol in reporter mice confirmed localized Cre activity near the injection site. The 4-week mortality was 3% (2/61). Seven mice were studied longitudinally for a mean (SD; range) duration of 7.2 (3; 2.3-9.5) months and demonstrated nidal stability on sequential MRA. The brain AVMs displayed microhemorrhages and diffuse immune cell invasion. CONCLUSIONS: We present the first HHT mouse model of brain AVMs that produces localized AVMs in the brain. The mouse lesions closely resemble the human lesions for complex nidal angioarchitecture, arteriovenous shunts, microhemorrhages, and inflammation. The model's longitudinal robustness is a powerful discovery resource to advance our pathomechanistic understanding of brain AVMs and identify novel therapeutic targets.

Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury.

OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.

Assessing survival outcomes and complication profiles following surgical excision and radiotherapy as interventions for skull base chordoma: a systematic review of operative margins and surgical approaches.

INTRODUCTION: Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective. METHODS: Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant. RESULTS: Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I2 value indicated notable heterogeneity across the 55 studies [I2 = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I2 = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I2 = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I2 = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I2 = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I2 = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I2 = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I2 = 95%, (p < 0.001). CONCLUSION: Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal.

Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis.

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.

Propensity-adjusted analysis of ultra-early aneurysmal subarachnoid hemorrhage treatment and patient outcomes.

BACKGROUND: Optimal definitive treatment timing for patients with aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. We compared outcomes for aSAH patients with ultra-early treatment versus later treatment at a single large center. METHOD: Patients who received definitive open surgical or endovascular treatment for aSAH between January 1, 2014, and July 31, 2019, were included. Ultra-early treatment was defined as occurring within 24 h from aneurysm rupture. The primary outcome was poor neurologic outcome (modified Rankin Scale score > 2). Propensity adjustment was performed for age, sex, Charlson Comorbidity Index, Hunt and Hess grade, Fisher grade, aneurysm treatment type, aneurysm type, size, and anterior location. RESULTS: Of the 1013 patients (mean [SD] age, 56 [14] years; 702 [69%] women, 311 [31%] men) included, 94 (9%) had ultra-early treatment. Compared with the non-ultra-early cohort, the ultra-early treatment cohort had a significantly lower percentage of saccular aneurysms (53 of 94 [56%] vs 746 of 919 [81%], P <0 .001), greater frequency of open surgical treatment (72 of 94 [77%] vs 523 of 919 [57%], P <0 .001), and greater percentage of men (38 of 94 [40%] vs 273 of 919 [30%], P = .04). After adjustment, ultra-early treatment was not associated with neurologic outcome in those with at least 180-day follow-up (OR = 0.86), the occurrence of delayed cerebral ischemia (OR = 0.87), or length of stay (exp(ß), 0.13) (P ≥ 0.60). CONCLUSIONS: In a large, single-center cohort of aSAH patients, ultra-early treatment was not associated with better neurologic outcome, fewer cases of delayed cerebral ischemia, or shorter length of stay.

Association between external ventricular drain removal or replacement and prophylactic anticoagulation in patients with aneurysmal subarachnoid hemorrhage: a propensity-adjusted analysis.

BACKGROUND: Withholding prophylactic anticoagulation from patients with aneurysmal subarachnoid hemorrhage (aSAH) before external ventricular drain (EVD) removal or replacement remains controversial. This study analyzed whether prophylactic anticoagulation was associated with hemorrhagic complications related to EVD removal. METHOD: All aSAH patients treated from January 1, 2014, to July 31, 2019, with an EVD placed were retrospectively analyzed. Patients were compared based on the number of prophylactic anticoagulant doses withheld for EVD removal (> 1 vs. ≤ 1). The primary outcome analyzed was deep venous thrombosis (DVT) or pulmonary embolism (PE) after EVD removal. A propensity-adjusted logistic-regression analysis was performed for confounding variables. RESULTS: A total of 271 patients were analyzed. For EVD removal, > 1 dose was withheld from 116 (42.8%) patients. Six (2.2%) patients had a hemorrhage associated with EVD removal, and 17 (6.3%) patients had a DVT or PE. No significant difference in EVD-related hemorrhage after EVD removal was found between patients with > 1 versus ≤ 1 dose of anticoagulant withheld (4 of 116 [3.5%] vs. 2 of 155 [1.3%]; p = 0.41) or between those with no doses withheld compared to ≥ 1 dose withheld (1 of 100 [1.0%] vs. 5 of 171 [2.9%]; p = 0.32). After adjustment, withholding > 1 dose of anticoagulant versus ≤ 1 dose was associated with the occurrence of DVT or PE (OR 4.8; 95% CI, 1.5-15.7; p = 0.009). CONCLUSIONS: In aSAH patients with EVDs, withholding > 1 dose of prophylactic anticoagulant for EVD removal was associated with an increased risk of DVT or PE and no reduction in catheter removal-associated hemorrhage.

Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review.

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Surgical management outcomes of intracranial arteriovenous malformations after preoperative embolization: a systematic review and meta-analysis.

OBJECTIVE: Preoperative embolization for brain arteriovenous malformations (AVMs) has been shown to mitigate morbidity for high-risk AVMs, chiefly by reducing lesional blood flow before resection. However, associated risks include postembolization AVM rupture, and the effect of preoperative embolization on outcome remains uncertain. We performed a meta-analysis of the literature on preoperative embolization for microsurgically treated AVMs. METHODS: A systematic review and meta-analysis were conducted of all English-language publications reporting clinical outcomes after combined embolization and surgical resection for AVMs. Single- and 2-arm analyses were performed using random-effects modeling. RESULTS: Thirty-six studies with 2108 patients were included in this analysis. Most patients (90.6%) who underwent embolization had at least a 50% obliteration of AVMs on posttreatment preoperative angiography, with a mean rate of obliteration of approximately 80% (range 28.8-100%). Among patients who had combined treatment, 3.4% (95% confidence interval [CI] 2.1-4.6%) experienced embolization-related hemorrhagic complications before surgery. Both treatment groups achieved excellent postsurgical complete resection rates (odds ratio [OR] 1.05; 95% CI 0.60-1.85). Neither the clinical outcome (OR 1.42; 95% CI 0.84-2.40) nor the total number of hemorrhagic complications (OR 1.84; 95% CI 0.88-3.85) was significantly different between the treatment groups. CONCLUSIONS: In this meta-analysis, preoperative embolization appears to have substantially reduced the lesional volume with active AV shunting before AVM resection. Anecdotally, preoperative embolization facilitates safe and efficient resection; however, differences in outcomes were not significant. The decision to pursue preoperative embolization remains a nuanced decision based on individual lesion anatomy and treatment team experience.

Research advances in the diagnosis and treatment of moyamoya disease: a bibliometric analysis.

Moyamoya disease is a rare cerebrovascular condition involving stenotic carotid arteries and the formation of abnormal blood vessels. In this study, we aimed to characterize the key players involved in moyamoya research at the individual and institutional level and to identify the critical publications that have advanced our understanding of this disease. We performed a title-specific search of the Web of Science database using the search term "moyamoya" for publications dating from 1900 to April 2020. The 100 most frequently cited articles were obtained, screened for duplicates, and reviewed by 2 independent reviewers. These 100 articles were cited an average of 150 times each (range, 74 to 1,360 citations per article). Publication dates ranged from 1969 to 2016, with the largest number of publications (n=40) cited between 2000 and 2009. The article with the greatest number of citations (1,360 citations) was "Cerebrovascular 'moyamoya' disease: disease showing abnormal net-like vessels in base of brain," by Suzuki and Takaku, published in the Archives of Neurology, 1969. Stroke published the greatest number of the most frequently cited articles (23 of 100). The institution that contributed the most articles was Tohoku University (16%); the majority of the most frequently cited articles originated in Japan (62%). We identified the 100 most cited articles on moyamoya disease over the past 51 years to recognize significant and impactful works. These results can be used as a guide to evaluate our current understanding of moyamoya disease and to direct future efforts.

Emerging pathogenic mechanisms in human brain arteriovenous malformations: a contemporary review in the multiomics era.

A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture of brain arteriovenous malformations (bAVMs). While the understanding of bAVMs has largely been formulated based on animal models of rare hereditary diseases in which AVMs form, a new era of "omics" has permitted large-scale examinations of contributory genetic variations in human sporadic bAVMs. New findings regarding the pathogenesis of bAVMs implicate changes to endothelial and mural cells that result in increased angiogenesis, proinflammatory recruitment, and breakdown of vascular barrier properties that may result in hemorrhage; a greater diversity of cell populations that compose the bAVM microenvironment may also be implicated and complicate traditional models. Genomic sequencing of human bAVMs has uncovered inherited, de novo, and somatic activating mutations, such as KRAS, which contribute to the pathogenesis of bAVMs. New droplet-based, single-cell sequencing technologies have generated atlases of cell-specific molecular derangements. Herein, the authors review emerging genomic and transcriptomic findings underlying pathologic cell transformations in bAVMs derived from human tissues. The application of multiple sequencing modalities to bAVM tissues is a natural next step for researchers, although the potential therapeutic benefits or clinical applications remain unknown.

Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review.

OBJECTIVE: Good functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH) are often dependent on early detection and treatment of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI). There is growing evidence that continuous monitoring with cranial electroencephalography (cEEG) can predict CVS and DCI. Therefore, the authors sought to assess the value of continuous cEEG monitoring for the detection of CVS and DCI in aSAH. METHODS: The cerebrovascular database of a quaternary center was reviewed for patients with aSAH and cEEG monitoring between January 1, 2017, and July 31, 2019. Demographic data, cardiovascular risk factors, Glasgow Coma Scale score at admission, aneurysm characteristics, and outcomes were abstracted from the medical record. Patient data were retrospectively analyzed for DCI and angiographically assessed CVS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and odds ratio for cEEG, transcranial Doppler ultrasonography (TCDS), CTA, and DSA in detecting DCI and angiographic CVS were calculated. A systematic literature review was conducted in accordance with PRISMA guidelines querying the PubMed, Cochrane Controlled Trials Register, Web of Science, and Embase databases. RESULTS: A total of 77 patients (mean age 60 years [SD 15 years]; female sex, n = 54) were included in the study. Continuous cEEG monitoring detected DCI and angiographically assessed CVS with specificities of 82.9% (95% CI 66.4%-93.4%) and 94.4% (95% CI 72.7%-99.9%), respectively. The sensitivities were 11.1% (95% CI 3.1%-26.1%) for DCI (n = 71) and 18.8% (95% CI 7.2%-36.4%) for angiographically assessed CVS (n = 50). Furthermore, TCDS detected angiographically determined CVS with a sensitivity of 87.5% (95% CI 71.0%-96.5%) and specificity of 25.0% (95% CI 7.3%-52.4%). In patients with DCI, TCDS detected vasospasm with a sensitivity of 85.7% (95% CI 69.7%-95.2%) and a specificity of 18.8% (95% CI 7.2%-36.4%). DSA detected vasospasm with a sensitivity of 73.9% (95% CI 51.6%-89.8%) and a specificity of 47.8% (95% CI 26.8%-69.4%). CONCLUSIONS: The study results suggest that continuous cEEG monitoring is highly specific in detecting DCI as well as angiographically assessed CVS. More prospective studies with predetermined thresholds and endpoints are needed to assess the predictive role of cEEG in aSAH.

Microsurgical treatment of ruptured aneurysms beyond 72 hours after rupture: implications for advanced management.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to primary stroke centers are often transferred to neurosurgical and endovascular services at tertiary centers. The effect on microsurgical outcomes of the resultant delay in treatment is unknown. We evaluated microsurgical aSAH treatment > 72 h after the ictus. METHODS: All aSAH patients treated at a single tertiary center between August 1, 2007, and July 31, 2019, were retrospectively reviewed. The additional inclusion criterion was the availability of treatment data relative to time of bleed. Patients were grouped based on bleed-to-treatment time as having acute treatment (on or before postbleed day [PBD] 3) or delayed treatment (on or after PBD 4). Propensity adjustments were used to correct for statistically significant confounding covariables. RESULTS: Among 956 aSAH patients, 92 (10%) received delayed surgical treatment (delayed group), and 864 (90%) received acute endovascular or surgical treatment (acute group). Reruptures occurred in 3% (26/864) of the acute group and 1% (1/92) of the delayed group (p = 0.51). After propensity adjustments, the odds of residual aneurysm (OR = 0.09; 95% CI = 0.04-0.17; p < 0.001) or retreatment (OR = 0.14; 95% CI = 0.06-0.29; p < 0.001) was significantly lower among the delayed group. The OR was 0.50 for rerupture, after propensity adjustments, in the delayed setting (p = 0.03). Mean Glasgow Coma Scale scores at admission in the acute and delayed groups were 11.5 and 13.2, respectively (p < 0.001). CONCLUSIONS: Delayed microsurgical management of aSAH, if required for definitive treatment, appeared to be noninferior with respect to retreatment, residual, and rerupture events in our cohort after adjusting for initial disease severity and significant confounding variables.

A two-stage combined anterolateral and endoscopic endonasal approach to the petroclival region: an anatomical study and clinical application.

OBJECT: The pretemporal transcavernous anterior petrosal (PTAP) approach and the combined petrosal (CP) approach have been used to resect petroclival meningiomas (PCMs). In this cadaveric anatomical study, a two-stage combined PTAP and endoscopic endonasal far medial (EEFM) approach (the PTAPE approach) was compared morphometrically to the CP approach. A case study provides a clinical example of using the PTAPE approach to treat a patient with a PCM. The key elements of the approach selection process are outlined. METHODS: Five cadaveric specimens underwent a CP approach and 5 underwent a PTAPE approach. The area of drilled clivus, length of multiple cranial nerves (CNs), and the area of brain stem exposure were measured, reported as means (standard deviations) by group, and compared. RESULTS: The total area of the clivus drilled in the PTAPE group (695.3 [121.7] mm2) was greater than in the CP group (88.7 [17.06] mm2, P < 0.01). Longer segments of CN VI were exposed via the PTAPE than the CP approach (35.6 [9.07] vs. 16.3 [6.02] mm, P < 0.01). CN XII (8.8 [1.06] mm) was exposed only in the PTAPE group. Above the pontomedullary sulcus, the total area of brain stem exposed was greater with the PTAPE than the CP approach (1003.4 [219.5] mm2 vs. 437.6 [83.7] mm2, P < 0.01). Similarly, the total exposure of the medulla was greater after the PTAPE than the CP exposure (240.2 [57.06] mm2 vs. 48.1 [19.9] mm2, P < 0.01). CONCLUSION: A combined open-endoscopic paradigm is proposed for managing large PCMs. This approach incorporates the EEFM approach to address the limitations of the PTAP and the CP approach in a systematic fashion. Understanding the anatomical findings of this study will aid in tailoring surgical approaches to patients with these complex lesions.

Pediatric intracranial arterial injuries by penetrating gunshot wounds: an institutional experience.

PURPOSE: Pediatric intracranial injuries due to penetrating gunshot wounds are a rare entity that is often fatal. A subset of patients may experience an intracerebral arterial injury; however, literature on the pediatric population is limited. This study analyzes a large institution's experience with pediatric head gunshot wounds and intracranial arterial injuries. METHODS: All pediatric patients ≤ 18 years of age who presented to our institution with a penetrating gunshot wound from 2008 to 2018 were retrospectively analyzed. RESULTS: Thirty-seven patients presented with an intracerebral penetrating gunshot injury. There were 18 deaths (49%) in the cohort. A total of 20 patients (54%) had vascular imaging. Of the remaining 17 patients with no vascular imaging, 13 (35%) died before any vascular studies were obtained. Four (20%) of the 20 patients with vascular imaging experienced an intracerebral arterial injury. Three of these 4 patients died before treatment could be administered. One patient with a firearm injury underwent embolization of a distal middle cerebral artery pseudoaneurysm and was discharged home with a Glasgow Outcome Scale score of 5 on follow-up. CONCLUSION: Pediatric patients with penetrating intracranial gunshot wounds often die before vascular imaging can be obtained.

Delays in presentation and mortality among Black patients with mechanical thrombectomy after large-vessel stroke at a US hospital.

OBJECTIVE: The incidence and severity of stroke are disproportionately greater among Black patients. In this study, the authors sought to examine clinical outcomes among Black versus White patients after mechanical thrombectomy for stroke at a single US institution. METHODS: All patients who underwent mechanical thrombectomy at a single center from January 1, 2014, through March 31, 2020, were retrospectively analyzed. Patients were grouped based on race, and demographic characteristics, preexisting conditions, clinical presentation, treatment, and stroke outcomes were compared. The association of race with mortality was analyzed in multivariable logistic regression analysis adjusted for potential confounders. RESULTS: In total, 401 patients (233 males) with a reported race of Black (n = 28) or White (n = 373) underwent mechanical thrombectomy during the study period. Tobacco use was more prevalent among Black patients (43% vs 24%, p = 0.04), but there were no significant differences between the groups with respect to insurance, coronary artery disease, diabetes, illicit drug use, hypertension, or hyperlipidemia. The mean time from stroke onset to hospital presentation was significantly greater among Black patients (604.6 vs 333.4 minutes) (p = 0.007). There were no differences in fluoroscopy time, procedural success (Thrombolysis in Cerebral Infarction grade 2b or 3), hospital length of stay, or prevalence of hemicraniectomy. In multivariable analysis, Black race was strongly associated with higher mortality (32.1% vs 14.5%, p = 0.01). The disparity in mortality rates resolved after adjusting for the average time from stroke onset to presentation (p = 0.14). CONCLUSIONS: Black race was associated with an increased risk of death after mechanical thrombectomy for stroke. The increased risk may be associated with access-related factors, including delayed presentation to stroke centers.

Small intracranial aneurysms in the Barrow Ruptured Aneurysm Trial (BRAT).

BACKGROUND: Treatment of small ruptured aneurysms (SRAs) remains controversial, with literature reporting difficulty with endovascular versus microsurgical approaches. This paper analyzes outcomes after endovascular coiling and microsurgical clipping among patients with SRAs prospectively enrolled in the Barrow Ruptured Aneurysm Trial (BRAT). METHOD: All BRAT patients were included in this study. Patient demographics, aneurysm size, aneurysm characteristics, procedure-related complications, and outcomes at discharge and at 1-year and 6-year follow-up were evaluated. A modified Rankin scale (mRS) score > 2 was considered a poor outcome. RESULTS: Of 73 patients with SRAs, 40 were initially randomly assigned to endovascular coiling and 33 to microsurgical clipping. The rate of treatment crossover was significantly different between coiling and clipping; 25 patients who were assigned to coiling crossed over to clipping, and no clipping patients crossed over to coiling (P < 0.001). Among SRA patients, 15 underwent coiling and 58 underwent clipping; groups did not differ significantly in demographic characteristics or aneurysm type (P ≥ 0.11). Mean aneurysm diameter was significantly greater in the endovascular group (3.0 ± 0.3 vs 2.6 ± 0.6; P = 0.02). The incidence of procedure-related complications was similar for endovascular and microsurgical treatments (odds ratio [95% confidence interval], 1.0 [0.1-10.0], P = 0.98). Both groups had comparable overall outcome (mRS score > 2) at discharge and 1-year and 6-year follow-up (P = 0.48 and 0.73, respectively). CONCLUSIONS: Most SRA patients in the BRAT underwent surgical clipping, with a high rate of crossover from endovascular approaches. Endovascular treatment was equivalent to surgical clipping with regard to procedure-related complications and neurologic outcomes.