A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Arteriovenous malformations in the cerebellopontine angle: assessment of the "backdoor resection" technique and microsurgical results in 38 patients.

OBJECTIVE: Posterior fossa arteriovenous malformations (AVMs) represent 7% to 15% of all intracranial AVMs and are associated with an increased risk of hemorrhage, morbidity, and mortality compared with supratentorial AVMs, thus prompting urgent and definitive treatment. Cerebellopontine angle (CPA) AVMs are a unique group of posterior fossa AVMs incorporating characteristics of brainstem and cerebellar lesions, which are particularly amenable to microsurgical resection. This study reports the clinical, radiological, operative, and outcome features of patients with CPA AVMs in a large cohort. METHODS: The authors conducted a single-surgeon, 2-institution retrospective cohort study of all consecutive patients with CPA AVMs treated with microsurgical resection during a 25-year period. RESULTS: CPA AVMs represented 22% (38 of 176) of all infratentorial AVMs resected by the senior author. Overall, 38 patients (22 [58%] male and 16 [42%] female) met the study inclusion criteria and were analyzed. Most patients presented with hemorrhage (n = 29, 76%). The median age at surgery was 56 (range 6-82) years. Subtypes included 22 (58%) petrosal cerebellar AVMs, 11 (29%) lateral pontine AVMs, and 5 (13%) AVMs involving both the brainstem and cerebellum. Most AVM niduses were small (< 3 cm; n = 35, 92%) and compact (n = 31, 82%). Fourteen (37%) patients harbored flow-related aneurysms. Twenty (53%) patients underwent preoperative embolization. Complete angiographic obliteration was achieved with microsurgery in 35 (92%) patients. Five (13%) patients with poor neurological conditions at presentation died before hospital discharge. Of the 7 (18%) patients with new postoperative neurological deficits, 5 had transient deficits. The median (interquartile range) follow-up was 1.7 (0.5-3.2) years; 32 (84%) patients were alive at last follow-up, and 30 (79%) had achieved a favorable neurological outcome (modified Rankin Scale [mRS] score 0-2). The only independent predictor of unfavorable postoperative outcome (mRS score 3-6) was the preoperative mRS score (p = 0.002). CONCLUSIONS: CPA AVMs are unique posterior fossa lesions, including petrosal cerebellar and lateral pontine AVMs. The "backdoor resection" technique provides a safe and efficient strategy with high obliteration rates and a low risk of treatment-related morbidity. Microsurgical resection should be considered the frontline treatment for most CPA AVMs, except for those with a significant diffuse brainstem component.

Transcirculation retrograde placement of a Pipeline embolization device for treatment of a vertebrobasilar junction aneurysm.

Transcirculation catheterization, also known as the retrograde approach, involves the navigation of a catheter or other endovascular device from one arterial circulation to the other (right to left, or anterior to posterior).1-4 We present a case of a complex vertebrobasilar junction aneurysm previously treated by bilateral vertebral artery deconstruction, precluding antegrade access (video 1). Following the creation of a protective occipital artery to posterior inferior cerebellar artery (PICA) bypass, the patient was treated with transcirculation placement of a Pipeline embolization device (PED).5-9 The right internal carotid artery was accessed with a guide catheter using a transradial approach. The microwire-microcatheter combination was then tracked through the right posterior communicating artery, down the basilar trunk, and to the left PICA. The PED was successfully deployed from the left vertebral artery to the mid-basilar artery. At 3-month follow-up, the aneurysm was completely obliterated. The nuances of transcirculation technique, especially for flow diversion, are discussed. (Used with permission from Barrow Neurological Institute, Phoenix, Arizona, USA.)neurintsurg;jnis-2023-021363v1/V1F1V1Video 1Transcirculation retrograde placement of a Pipeline embolization device for treatment of a vertebrobasilar junction aneurysm previously treated by bilateral vertebral artery deconstruction, precluding antegrade access.

Sex-dependent characteristics and outcomes after clipping of unruptured intracranial aneurysms: a multicenter propensity score-matched study.

OBJECTIVE: Disparities in the epidemiology and growth rates of aneurysms between the sexes are known. However, little is known about sex-dependent outcomes after microsurgical clipping of unruptured intracranial aneurysms (UIAs). The aim of this study was to examine sex differences in characteristics and outcomes after microsurgical clipping of UIAs and to perform a propensity score-matched analysis using an international multicenter cohort. METHODS: This retrospective cohort study involved the participation of 15 centers spanning four continents. It included adult patients who underwent clipping of UIAs between January 2016 and December 2020. Patients were stratified according to their sex and analyzed for differences in morbidities and aneurysm characteristics. Based on this stratification, female patients were matched to male patients in a 1:1 ratio with a caliper width of 0.1 using propensity score matching. Endpoints included postoperative complications, neurological performance, and aneurysm occlusion at discharge and 24 months after clip placement. RESULTS: A total of 2245 patients with a mean age of 57.3 (range 20-87) years were included. Of these patients, 1675 (74.6%) were female. Female patients were significantly older (mean 57.6 vs 56.4 years, p = 0.03) but had fewer comorbidities. Aneurysms of the internal carotid artery (7.1% vs 4.2%), posterior communicating artery (6.9% vs 1.9%), and ophthalmic artery (6.0% vs 2.8%) were more commonly treated surgically in females, while clipping of aneurysms of the anterior communicating artery was more frequent in males (17.0% vs 25.3%; all p < 0.001). After propensity score matching, female patients were found to have had significantly fewer pulmonary complications (1.4% vs 4.2%, p = 0.01). However, general morbidity (24.5% vs 25.2%, p = 0.72) and mortality (0.5% vs 1.1%, p = 0.34), as well as neurological performance (p = 0.58), were comparable at discharge in both sexes. Lastly, rates of aneurysm occlusion at the time of discharge (95.5% vs 94.9%, p = 0.71) and 24 months after surgery (93.8% vs 96.1%, p = 0.22) did not significantly differ between male and female patients. CONCLUSIONS: Despite overall differences between male and female patients in demographics, comorbidities, and treated aneurysm location, sex did not relevantly affect surgical performance or perioperative complication rates.

Assessing the Relationship between Surgical Timing and Postoperative Seizure Outcomes in Cavernoma-Related Epilepsy: A Single-Institution Retrospective Analysis of 63 Patients with a Review of the Literature.

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010-31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Posterior Interhemispheric-Transtentorial Approach for Resection of an Arteriovenous Malformation of the Superior Medullary Velum and Fourth Ventricle: 2-Dimensional Operative Video.

Brain arteriovenous malformations (AVMs) of the fourth ventricle represent a rare subtype associated with an aggressive natural course.1,2 In this case, a woman in her early 50s presented with dizziness. An AVM was diagnosed in the left superior cerebellar peduncle extending into the fourth ventricle. The AVM was supplied by superior cerebellar artery branches and classified as a Spetzler-Martin grade III and a Lawton-Young grade III, with a supplemented grade of 6.3,4 Being a single case report, institutional review board approval was not needed. Patient consent was obtained. The lesion was accessed through a torcular craniotomy and posterior interhemispheric-transtentorial approach, employing gravity to naturally retract the parietooccipital lobe.5-7 Dissection continued into the quadrigeminal and ambient cisterns, where the tentorium was incised parallelling the straight sinus to reach the superior vermis. Partial resection of the lingual and central lobules of the vermis facilitated access to the superior medullary velum. The superior cerebellar artery feeders were divided and followed to the superior cerebellar peduncle and through the superior medullary vellum. A vertical incision in the superior medullary velum facilitated entry into the fourth ventricle, where the AVM nidus was dissected circumferentially and resected en bloc. Intraoperative indocyanine green videoangiography and postoperative digital subtraction angiography confirmed complete obliteration of the AVM. After surgery, the patient experienced mild ataxia, but motor symptoms greatly improved during 3-month follow-up. This video illustrates resection of a complex fourth ventricular AVM through a posterior interhemispheric-transtentorial approach, highlighting pivotal considerations of patient positioning and approach selection to optimize treatment outcome for complex posterior fossa AVM resection.

Dolichoectatic Posterior Inferior Cerebellar Artery Aneurysm Treated With Excision and Posterior Inferior Cerebellar Artery Double Reimplantation Bypass: 2-Dimensional Operative Video.

Posterior inferior cerebellar artery (PICA) aneurysms account for 0.3% of all intracranial aneurysms, and they commonly present with a complex fusiform morphology that necessitates unique bypass strategies.1-5 An adolescent boy with a familial predisposition to aneurysmal subarachnoid hemorrhage was identified as harboring a fusiform aneurysm of the right distal PICA, characterized by 2 outflow branches. Our recommended treatment strategy involved a right far lateral craniotomy, followed by P1 PICA reanastomosis and P2 PICA reimplantation. Informed written consent was obtained. On exposure, the aneurysm was trapped, and the inflow and 2 outflow PICA branches were excised. Revascularization was established through a P1 PICA end-to-end reanastomosis using running continuous suturing techniques, followed by P2 PICA end-to-side reimplantation into a more distal portion of PICA. Subsequent indocyanine green videoangiography confirmed patency of the P2 PICA reimplantation; however, the initial P1 PICA reanastomosis was noted to be thrombosed. After several unsuccessful attempts to dissolve the thrombus, the decision was made to proceed with a P2 PICA side-to-side in situ reimplantation into the V4 segment of the vertebral artery. Indocyanine green videoangiography and postoperative digital subtraction angiography confirmed patency of the PICA double reimplantation bypass. The patient tolerated the procedure well and was discharged home at his neurological baseline. This video showcases the microsurgical treatment of a complex dolichoectatic, distal PICA aneurysm using a double reimplantation technique, in addition to highlighting bypass decision-making processes for managing complex PICA aneurysms.

External Validation of the Modified Southwestern Aneurysm Severity Index in the Barrow Ruptured Aneurysm Trial Surgical Cohort.

BACKGROUND AND OBJECTIVES: Predicting functional outcomes after surgical management of ruptured aneurysms is essential. This study sought to validate the modified Southwestern Aneurysm Severity Index (mSASI), which predicts functional outcomes 1 year after treatment. METHODS: The surgical arm of a randomized controlled trial, the Barrow Ruptured Aneurysm Trial, was used to validate the mSASI model. mSASI scores incorporating the Hunt and Hess scale, Non-Neurological American Society of Anesthesiologists Physical Classification Status, imaging findings, and other modifiers were assigned and evaluated against the Glasgow Outcome Scale (GOS) score at 1 year. The model's performance was assessed for discrimination and calibration. Similar evaluations were constructed using the modified Rankin Scale (mRS) as the 1-year functional outcome measurement. Long-term outcomes (3, 6, 10 years) were also evaluated. RESULTS: Of 280 clinical trial patients treated surgically, 242 met the inclusion criteria. The mean age was 54.1 ± 12.9 years; 31% were men. Favorable GOS score (4-5) and mRS score (0-2) at 1 year were observed in 73.6% and 66.1% of patients, respectively. The mSASI model predicted unfavorable GOS score at 1 year with fair to good discrimination (area under the curve = 0.75, 95% CI = 0.68-0.82) and accurate calibration (R2 = 0.98). Similar results were obtained when mRS was used as the outcome measure (area under the curve = 0.75, 95% CI = 0.68-0.82; R2 = 0.95). CONCLUSION: The mSASI model was externally validated in our cohort to predict functional outcomes using the GOS or mRS scores 1 year after surgery. This index may be used for prognosticating outcomes of patients undergoing surgery for ruptured aneurysms at short-term and long-term intervals.

Racial and Socioeconomic Status among a Patient Population Presenting with Aneurysmal Subarachnoid Hemorrhage versus Unruptured Intracranial Aneurysm: A Single-Center Study.

Racial and socioeconomic health disparities are well documented in the literature. This study examined patient demographics, including socioeconomic status (SES), among individuals presenting with aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (UIA) to identify factors associated with aSAH presentation. A retrospective assessment was conducted of all patients with aSAH and UIA who presented to a large-volume cerebrovascular center and underwent microsurgical treatment from January 2014 through July 2019. Race and ethnicity, insurance type, and SES data were collected for each patient. Comparative analysis of the aSAH and UIA groups was conducted. Logistic regression models were also employed to predict the likelihood of aSAH presentation based on demographic and socioeconomic factors. A total of 640 patients were included (aSAH group, 251; UIA group, 389). Significant associations were observed between race and ethnicity, SES, insurance type, and aneurysm rupture. Non-White race or ethnicity, lower SES, and having public or no insurance were associated with increased odds of aSAH presentation. The aSAH group had poorer functional outcomes and higher mortality rates than the UIA group. Patients who are non-White, have low SES, and have public or no insurance were disproportionately affected by aSAH, which is historically associated with poorer functional outcomes.

Posterior Interhemispheric Approach for Occlusion of a Galenic (Type 1) Tentorial Dural Arteriovenous Fistula: 2-Dimensional Operative Video.

Galenic dural arteriovenous fistulas account for 1 of the 6 types of tentorial dural arteriovenous fistulas (type I). These fistulas are located around the great cerebral vein of Galen, with dural arterial supply through the tentorial arteries of Bernasconi and Cassinari or other posterior fossa branches, such as the posterior meningeal artery. In this case, a man in his 60s presented with a headache and was found to have this high-risk lesion, which was Borden grade III and Cognard grade IV. The lesion persisted despite embolization through the middle meningeal artery. This video discusses the microsurgical management of this lesion through a torcular craniotomy and a posterior interhemispheric approach for clipping. Because this is a single case report, institutional review board approval was not needed. The patient consented to the procedure. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. Images at 7:19 and 7:49 in Surgical Video are used with permission from Lawton, Michael T.; Sanchez-Mejia, Rene O.; Pham, Diep; Tan, Jeffrey; Halbach, Van V. Tentorial Dural Arteriovenous Fistulae: Operative Strategies and Microsurgical Results for Six Types. Operative Neurosurgery 62(3): 110-125, 2008.

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.

Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort (P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts (P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

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.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

Hematologic and Inflammatory Predictors of Outcome in Patients with Brain Arteriovenous Malformations.

OBJECTIVE: This study investigated the prognostic value of admission blood counts for arteriovenous malformation (AVM) outcomes and compared admission blood counts for patients with ruptured and unruptured AVMs. METHODS: A retrospective analysis of patients who underwent surgical treatment for a ruptured cerebral AVM between February 1, 2014, and March 31, 2020, was conducted. The primary outcome was poor neurologic outcome, defined as a modified Rankin Scale score ≥2 in patients with unruptured AVMs or >2 in patients with ruptured AVMs. RESULTS: Of 235 included patients, 80 (34%) had ruptured AVMs. At admission, patients with ruptured AVMs had a significantly lower mean (SD) hemoglobin level (12.78 [2.07] g/dL vs. 13.71 [1.60] g/dL, P < 0.001), hematocrit (38.1% [5.9%] vs. 40.7% [4.6%], P < 0.001), lymphocyte count (16% [11%] vs. 26% [10%], P < 0.001), and absolute lymphocyte count (1.41 [0.72] × 103/µL vs. 1.79 [0.68] × 103/µL, P < 0.001), and they had a significantly higher mean (SD) white blood cell count (10.4 [3.8] × 103/µL vs. 7.6 [2.3] × 103/µL, P < 0.001), absolute neutrophil count (7.8 [3.8] × 103/µL vs. 5.0 [2.5] × 103/µL, P < 0.001), and neutrophil count (74% [14%] vs. 64% [13%], P < 0.001). Among patients with unruptured AVMs, white blood cell count ≥6.4 × 103/µL and absolute neutrophil count ≥3.4 × 103/µL were associated with a favorable neurologic outcome, whereas hemoglobin level ≥13.4 g/dL was associated with an unfavorable outcome. Among patients with ruptured AVMs, hypertension was associated with a 3-fold increase in odds of a poor neurologic outcome. CONCLUSIONS: Patients with ruptured and unruptured AVMs present with characteristic profiles of hematologic and inflammatory parameters evident in their admission blood work.