Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.

BACKGROUND: Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS: BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS: Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS: The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

ARISE I Consensus Review on the Management of Intracranial Aneurysms.

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Corrigendum: Grade 3 Meningioma Survival and Recurrence Outcomes in an International Multicenter Cohort.

[This corrects the article DOI: 10.1055/s-0044-1779888.].

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort.

OBJECTIVE: Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients. METHODS: Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022. RESULTS: A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%-77%) and 37% (95% CI 28%-48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period. CONCLUSIONS: This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

Interventional Treatment of Symptomatic Vasospasm in the Setting of Traumatic Brain Injury: A Systematic Review of Reported Cases.

Traumatic subarachnoid hemorrhage (tSAH) is frequently comorbid with traumatic brain injury (TBI) and may induce secondary injury through vascular changes such as vasospasm and subsequent delayed cerebral ischemia (DCI). While aneurysmal SAH is well studied regarding vasospasm and DCI, less is known regarding tSAH and the prevalence of vasospasm and DCI, the consequences of vasospasm in this setting, when treatment is indicated, and which management strategies should be implemented. In this article, a systematic review of the literature that was conducted for cases of symptomatic vasospasm in patients with TBI is reported, association with tSAH is reported, risk factors for vasospasm and DCI are summarized, and commonalities in diagnosis and management are discussed. Clinical characteristics and treatment outcomes of 38 cases across 20 studies were identified in which patients with TBI with vasospasm underwent medical or endovascular management. Of the patients with data available for each category, the average age was 48.7 ± 20.3 years (n = 31), the Glasgow Coma Scale score at presentation was 10.6 ± 4.5 (n = 35), and 100% had tSAH (n = 29). Symptomatic vasospasm indicative of DCI was diagnosed on average at postinjury day 8.4 ± 3.0 days (n = 30). Of the patients, 56.6% (n = 30) had a new ischemic change associated with vasospasm confirming DCI. Treatment strategies are discussed, with 11 of 12 endovascularly treated and 19 of 26 medically treated patients surviving to discharge. tSAH is associated with vasospasm and DCI in moderate and severe TBI, and patients with clinical and radiographic evidence of symptomatic vasospasm and subsequent DCI may benefit from endovascular or medical management strategies.

Neutrophils: Novel Contributors to Estrogen-Dependent Intracranial Aneurysm Rupture Via Neutrophil Extracellular Traps.

Background Intracranial aneurysms (IAs) are more prevalent in women than men, and aneurysmal subarachnoid hemorrhage disproportionately affects postmenopausal women. These sex differences suggest estrogen protects against IA progression that can lead to rupture, but the underlying mechanisms are not fully understood. Although studies have demonstrated estrogen regulates inflammatory processes that contribute to IA pathogenesis, the role of neutrophils remains to be characterized. Using a murine model, we tested our hypothesis that neutrophils contribute to IA pathophysiology in an estrogen-dependent manner. Methods and Results We compared neutrophil infiltration in C57BL/6 female mice that develop IAs to those with a normal circle of Willis. Next, we investigated the estrogen-dependent role of neutrophils in IA formation, rupture, and symptom-free survival using a neutrophil depletion antibody. Finally, we studied the role of neutrophil extracellular trap formation (NETosis) as an underlying mechanism of aneurysm progression. Mice that developed aneurysms had increased neutrophil infiltration compared with those with a normal circle of Willis. In estrogen-deficient female mice, both neutrophil depletion and NETosis inhibition decreased aneurysm rupture. In estrogen-deficient female mice treated with estrogen rescue and estrogen-intact female mice, neither neutrophil depletion nor NETosis inhibition affected IA formation, rupture, or symptom-free survival. Conclusions Neutrophils contribute to aneurysm rupture in an estrogen-dependent manner. NETosis appears to be an underlying mechanism for neutrophil-mediated IA rupture in estrogen deficiency. Targeting NETosis may lead to the development of novel therapeutics to protect against IA rupture in the setting of estrogen deficiency.

How do children fare compared with adults? Comparing relative outcomes after thrombectomy for acute ischemic stroke due to large-vessel occlusion.

OBJECTIVE: Safety and efficacy data for endovascular thrombectomy for acute ischemic stroke secondary to large-vessel occlusion in children are lacking compared with those for adults. We undertook an updated systematic review and meta-analysis of endovascular thrombectomy in children and compared their outcomes with adult data. METHODS: We searched PubMed, Medline, and EMBASE databases to identify prospective and retrospective studies describing patients <18 years treated with endovascular thrombectomy for acute ischemic stroke due to large-vessel occlusion. RESULTS: Eight pediatric studies were included (n = 192). Most patients were male (53.1 %), experienced anterior circulation large-vessel occlusion (81.8 %), and underwent endovascular thrombectomy by stent retreiver (70.7 %). The primary outcome was change in National Institutes of Health Stroke Scale score from presentation to 24 h after thrombectomy. Secondary outcomes included modified Rankin scale score improvement and 90-day score, recanalization rates, procedural complications, and mortality rates. After treatment, 88.5% of children had successful recanalization; the mean National Institutes of Health Stroke Scale score reduction was 7.37 (95 % CI 5.11-9.63, p < 0.01). The mean reduction of 6.87 (95 %CI 5.00-8.73, p < 0.01) for adults in 5 clinical trials (n = 634) was similar (Qb = 0.11; p = 0.74). Children experienced higher rates of good neurological outcome (76.1 % vs. 46.0 %, p < 0.01) and revascularization (88.5 % vs. 72.3 %, p < 0.01), fewer major periprocedural complications (3.6 % vs. 30.4 %, p < 0.01), and lower mortality (1.0 % vs. 12.9 %, p < 0.01). CONCLUSIONS: Endovascular thrombectomy may be safe and effective treatment for acute ischemic stroke due to large-vessel occlusion in children. The aggregated data demonstrated high rates of revascularization, favorable long-term neurological outcomes, and low complication rates.

Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis.

Maladaptive inflammation underlies the formation and rupture of human intracranial aneurysms. There is a growing body of evidence that anti-inflammatory pharmaceuticals may beneficially modulate this process. Clopidogrel (Plavix) is a commonly used irreversible P2Y12 receptor antagonist with anti-inflammatory activity. In this paper, we investigate whether clopidogrel is associated with the likelihood of aneurysm rupture in a multi-institutional propensity-matched cohort analysis. Patients presenting for endovascular treatment of their unruptured intracranial aneurysms and those presenting with aneurysm rupture between 2015 and 2019 were prospectively identified at two quaternary referral centers. Patient demographics, comorbidities, and medication usage at the time of presentation were collected. Patients taking clopidogrel or not taking clopidogrel were matched in a 1:1 fashion with respect to location, age, smoking status, aneurysm size, aspirin usage, and hypertension. A total of 1048 patients with electively treated aneurysms or subarachnoid hemorrhages were prospectively identified. Nine hundred twenty-one patients were confirmed to harbor aneurysms during catheter-based diagnostic angiography. A total of 172/921 (19%) patients were actively taking clopidogrel at the time of presentation. Three hundred thirty-two patients were matched in a 1:1 fashion. A smaller proportion of patients taking clopidogrel at presentation had ruptured aneurysms than those who were not taking clopidogrel (6.6% vs 23.5%, p < .0001). Estimated treatment effect analysis demonstrated that clopidogrel usage decreased aneurysm rupture risk by 15%. We present, to the best of our knowledge, the first large-scale multi-institutional analysis suggesting clopidogrel use is protective against intracranial aneurysm rupture. It is our hope that these data will guide future investigation, revealing the pathophysiologic underpinning of this association.

Effect of Chronic Anticoagulation on Outcomes of Endovascular Treatment for Unruptured Intracranial Aneurysms-A Propensity-Matched Multicenter Study.

BACKGROUND AND OBJECTIVES: Endovascular treatment of unruptured intracranial aneurysms (UIAs) in patients receiving anticoagulant medications has not been well studied. Whether long-term anticoagulation (AC) use affects aneurysmal obliteration rates and treatment-related complications is unclear. METHODS: Patients with endovascular treatment for UIA from 4 academic centers were identified and divided into AC and non-AC groups. Periprocedural complications, radiographic and clinical outcomes, and retreatment rates were compared between the 2 groups before and after propensity score matching. RESULTS: The initial cohort consisted of 70 patients in the AC group and 355 in the non-AC group. After one-to-one nearest neighbor propensity matching, 38 pairs of patients were compared for periprocedural complications. The total number of complications were higher in the AC group yet not significant (18.4% vs 5.3%, P = .15). After adding imaging follow-up duration to matched variables, 36 pairs were obtained. There was no significant difference in Raymond-Roy occlusion rate between the 2 groups ( P = .74). However, retreatment rate trended higher in the AC group compared with the non-AC group (22.2% vs 5.6%, P = .09). When clinical follow-up duration was added among matched variables, 26 pairs of cases were obtained for long-term clinical outcomes. There was no significant difference in modified Rankin Scale score between the 2 groups ( P = .61). One-to-many nearest neighbor propensities matched analysis with bigger sample sizes yielded similar results. CONCLUSION: The use of anticoagulants does not affect occlusion rates or long-term outcomes in endovascular treatment of UIAs. Retreatment rates were higher in the AC group; however, this was not statistically significant.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Cost Comparison: Evaluating Transfemoral and Transradial Access for Diagnostic Cerebral Angiography.

BACKGROUND: Modern medicine necessitates the delivery of increasingly complex health care while minimizing cost. Transradial access (TRA) for neuroendovascular procedures is becoming more common as accumulating data demonstrate fewer complications, improved patient satisfaction, and high rates of treatment success compared with the transfemoral access (TFA) approach; however, disparities in cost between these approaches remain unclear. We compared supply and equipment costs between TRA and TFA for diagnostic cerebral angiography and evaluate the specific items that account for these differences. METHODS: We reviewed all adult patients who underwent diagnostic cerebral angiography from July 1, 2019 to December 31, 2019. Data related to patient demographics, vascular access site, catheters used, cost of catheters, arterial access sheath use, cost of sheaths, closure devices used, and cost of closure devices were collected. RESULTS: The transradial approach resulted in higher price of radial access sheath; however, the overall cost of closure devices was much lower in TRA group than in the TFA cohort. There was no significant difference in the cost of catheters. Overall, the total supply costs for TRA cerebral angiography were significantly lower than those of TFA cerebral angiography. The relative materials cost difference of using TRA was 20.9%. CONCLUSION: This study is the first itemized materials cost analysis of TRA versus TFA cerebral angiography. TRA necessitates the use of a more expensive access sheath device; however, this cost is offset by the increased cost of devices used for femoral arteriotomy closure. Overall, the supply and equipment costs were significantly lower for TRA than TFA.

The Evolution of Endovascular Therapy for Intracranial Aneurysms: Historical Perspective and Next Frontiers.

The history of cerebral aneurysm treatment has a rich and storied past with multiple notable luminaries contributing insights. The modern era has transitioned from primarily clip ligation to increasing use of endovascular therapy. Even more recently, the use of intrasaccular flow diverters has been introduced for the treatment of wide necked aneurysms. The field is continuing to transform, and bioactive coils and stents have resurfaced as promising adjuvants to promote aneurysm healing. Advanced imaging modalities are being developed that could further advance the endovascular arsenal and allow for porous memory polymer devices to enter the field. This focused review highlights notable historic contributions and advances to the point of futuristic technology that is actively being developed.

Inversed probability case-control analysis of operative burr hole evacuation versus subdural evacuating port system for chronic subdural hematomas: Clinical and economic outcomes.

INTRODUCTION: There are multiple treatments for a chronic subdural hematoma, a significant cause of neurosurgical morbidity that cost the healthcare system $5B in 2007, but few generalizable prospective studies. The purpose of this study was to examine outcomes of bedside Subdural Evacuation Port System (SEPS) placement as compared to operating room burr hole evacuation (BHE) to acquire data to support a randomized trial. METHODS: All procedures were performed in a single institution between 2011 and 2019. Patients were included if > 18 years of age, had chronic subdural hematoma, and were treated by SEPS or BHE. Patients with prior neurosurgical history, mass lesions or bilateral hematomas were excluded. Patients who met inclusion for SEPS (n = 55) or BHE (n = 105). Samples were propensity matched to account for variability. Non-inferiority tests compared outcomes. Cost data was obtained through billable charges. RESULTS: Patients with multiple comorbidities were more likely to undergo SEPS drainage. Noninferiority tests reported no statistically significant evidence to suggest SEPS drains were worse in reoperation-rate (18% vs 9%), post-operative seizure, or functional outcome. SEPS drain placement trended towards a faster time to procedure (3 h faster; p = 0.07) but the overall hospital stay was longer (4.23 vs 5.81, p = 0.01). SEPS drain placement costs are less than BHE, but these patients had 25% higher overall hospital costs (p = 0.01) due to comorbidities and increased hospital stay.

Sensorineural hearing loss due to delayed cerebral ischemia in bilateral auditory cortices following aneurysmal subarachnoid hemorrhage: illustrative case.

BACKGROUND: Recognizing rare signs of delayed cerebral ischemia (DCI) is crucial to caring for patients with subarachnoid hemorrhage. The authors presented a case of central hearing loss that occurred during the clinical course of a patient treated for aneurysmal subarachnoid hemorrhage. OBSERVATIONS: The patient had a ruptured right posterior communicating artery aneurysm successfully treated with coil embolization but later developed severe vasospasm and DCI. She developed bilateral hearing loss, and imaging revealed DCI to the left temporal lobe and the right auditory cortex. Computed tomography angiography and digital subtraction angiography demonstrated severe vasospasm of bilateral internal carotid arteries, bilateral middle cerebral arteries, and bilateral anterior cerebral arteries. One month after hospitalization, the patient had recovered fully neurologically intact except for persistent hearing loss. LESSONS: This case serves to teach important neuroanatomical features and discuss the unique pathophysiology of DCI affecting the auditory cortex.

Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment.

Intracranial atherosclerotic stenosis (ICAS) is one of the most frequent causes of stroke worldwide and confers one of the greatest risks of recurrent stroke compared with other causes of stroke. Asymptomatic ICAS is increasingly recognised as a risk factor for silent brain infarctions and dementia, magnifying the global burden of ICAS. Although ICAS is a lumen-based diagnosis, newer diagnostic imaging techniques, such as high-resolution MRI, might help to identify high-risk population subgroups to test interventions that might reduce the risk of stroke recurrence. Secondary stroke prevention in patients with ICAS currently consists of intensive management of modifiable risk factors and dual antiplatelet therapy, which is subsequently reduced to aspirin alone. Despite these therapies, the risk of recurrent stroke in patients presenting with stroke related to 70-99% ICAS exceeds 20% at 1 year; as such, better therapies are urgently needed. The optimal duration and combination of dual antiplatelet therapy in patients with ICAS is uncertain and is being investigated in addition to low-dose anticoagulation and aspirin. Other ongoing or planned studies will provide high-quality observational data on the role of transluminal angioplasty and stenting, submaximal balloon angioplasty alone, direct or indirect arterial bypass, and ischaemic conditioning for prevention of stroke in patients with ICAS.