Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

Impact of Intracerebral Hematoma Evacuation During Decompressive Hemicraniectomy on Functional Outcomes.

BACKGROUND AND PURPOSE: Decompressive hemicraniectomy has been used to treat spontaneous intracerebral hemorrhage, but the benefit of evacuating the hematoma during the procedure is unclear. We aim to evaluate the utility of performing clot evacuation during hemicraniectomy for spontaneous intracerebral hemorrhage. METHODS: Retrospective cohort of consecutive patients (2010-2019) treated with decompressive hemicraniectomy for a spontaneous supratentorial intracerebral hemorrhage at the University of Iowa. We compared hemicraniectomy alone to hemicraniectomy plus hematoma evacuation. We analyzed clinical features and hematoma characteristics. The outcomes at 6 months were dichotomized into unfavorable (Glasgow Outcome Scale score 1-3) and favorable (Glasgow Outcome Scale score 4-5). RESULTS: Eighty-three patients underwent decompressive hemicraniectomy for spontaneous intracerebral hemorrhage, 52 with hematoma evacuation, and 31 without hematoma evacuation. There were no statistically significant differences in clinical and radiographic characteristics between the 2 groups. Evacuating the hematoma in addition to hemicraniectomy did not change the odds of favorable outcome at 6 months (P=0.806). CONCLUSIONS: In this retrospective study, the performance of hematoma evacuation during decompressive hemicraniectomy for spontaneous intracerebral hemorrhage may not change functional outcomes over performing the hemicraniectomy alone.

Concentration of Lp(a) (Lipoprotein[a]) in Aneurysm Sac Is Associated With Wall Enhancement of Unruptured Intracranial Aneurysm.

BACKGROUND AND PURPOSE: Atherosclerotic remodeling of the aneurysm wall, which could be detected as aneurysm wall enhancement (AWE) by magnetic resonance-vessel wall imaging, is a part of degenerative change of unruptured intracranial aneurysms (UIAs). The purpose of this study was to determine whether the luminal concentrations of atherosclerotic proteins in the aneurysm sac were associated with increased wall enhancement of UIAs in vessel wall imaging. METHODS: We performed a prospective study of subjects undergoing endovascular treatments for UIAs. All subjects underwent evaluation using 3T-magnetic resonance imaging, including pre/postcontrast vessel wall imaging of the UIAs. Blood samples were collected from the aneurysm sac and the parent artery during endovascular procedures. Presence/absence of AWE was correlated with the delta difference in concentration for each atherosclerotic protein between the lumen of UIA and in the parent artery. RESULTS: A total of consecutive 17 patients with 19 UIAs were enrolled. The delta difference of lipoprotein(a) was significantly higher in UIAs with AWE compared with those without AWE (-6.9±16.0 versus -45.4±44.9 µg/mL, P=0.03). CONCLUSIONS: Higher luminal concentrations of lipoprotein(a) in the aneurysm sac were significantly associated with increased wall enhancement of UIAs. A larger study is needed to confirm these findings.

Detection and Quantification of Symptomatic Atherosclerotic Plaques With High-Resolution Imaging in Cryptogenic Stroke.

BACKGROUND AND PURPOSE: High-resolution vessel wall imaging (HR-VWI) is a powerful tool in diagnosing intracranial vasculopathies not detected on routine imaging. We hypothesized that 7T HR-VWI may detect the presence of atherosclerotic plaques in patients with intracranial atherosclerosis disease initially misdiagnosed as cryptogenic strokes. METHODS: Patients diagnosed as cryptogenic stroke but suspected of having an intracranial arteriopathy by routine imaging were prospectively imaged with HR-VWI. If intracranial atherosclerotic plaques were identified, they were classified as culprit or nonculprit based on the likelihood of causing the index stroke. Plaque characteristics, such as contrast enhancement, degree of stenosis, and morphology, were analyzed. Contrast enhancement was determined objectively after normalization with the pituitary stalk. A cutoff value for plaque-to-pituitary stalk contrast enhancement ratio (CR) was determined for optimal prediction of the presence of a culprit plaque. A revised stroke cause was adjudicated based on clinical and HR-VWI findings. RESULTS: A total of 344 cryptogenic strokes were analyzed, and 38 eligible patients were imaged with 7T HR-VWI. Intracranial atherosclerosis disease was adjudicated as the final stroke cause in 25 patients. A total of 153 intracranial plaques in 374 arterial segments were identified. Culprit plaques (n=36) had higher CR and had concentric morphology when compared with nonculprit plaques (P≤0.001). CR ≥53 had 78% sensitivity for detecting culprit plaques and a 90% negative predictive value. CR ≥53 (P=0.008), stenosis ≥50% (P<0.001), and concentric morphology (P=0.030) were independent predictors of culprit plaques. CONCLUSIONS: 7T HR-VWI allows identification of underlying intracranial atherosclerosis disease in a subset of stroke patients with suspected underlying vasculopathy but otherwise classified as cryptogenic. Plaque analysis in this population demonstrated that culprit plaques had more contrast enhancement (CR ≥53), caused a higher degree of stenosis, and had a concentric morphology.

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1ß, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.

Angiographic Features of Intracranial Aneurysms in Ecuador.

BACKGROUND: Most of the literature describing morphological features of intracranial aneurysms (IAs) is from North-America, East-Asia, and Europe. There is limited data from South-America. We describe the epidemiologic and angiographic features of ruptured and unruptured IAs in a cohort of patients from Ecuador. METHODS: We conducted a retrospective analysis of prospectively acquired databases from 3 different tertiary hospitals over a 3-year period (2014-2017). In a per-patient basis, odd ratios (ORs) of ruptured presentation for each variable using a univariate logistic regression model were calculated. An aneurysm-based multivariate analysis was performed to calculate rupture ORs for each variable. RESULTS: Our sample included 557 patients with 761 IAs. Mean patient age was 52.2 years (range 18-82). Sixty-eight percent were women, and almost 90% presented with ruptured aneurysms and concomitant subarachnoid hemorrhage (SAH). Mean size of all the IAs was 6.4 mm ± 3.98 mm. Most IAs were located in anterior circulation (96.6%): 28.4% medial cerebral artery, 24.4% anterior cerebral artery or anterior communicating artery (ACOM), and 23.5% posterior communicating artery (PCOM). Only 6 basilar tip aneurysms (0.8%) were reported. In the adjusted analysis, aneurysms located in the ACOM (OR 1.89, 95% CI 1.29-2.78) and PCOM (OR 1.84, 95% CI 1.25-2.71), size larger than 5 mm (OR 2.84, 95% CI 2.04-3.93) and 7 mm (OR 2.28, 95% CI 1.64-3.19), and those with non-saccular morphology (OR 9.87, 95% CI 2.21-44.14) were significantly associated with ruptured presentation. CONCLUSIONS: The prevalence of posterior circulation IAs in Ecuador, particularly basilar tip aneurysms, is low when compared to previous reports from developed countries. In our sample, IAs greater than 5 mm (and ≥7 mm) in size, ACOM and PCOM locations, and IAs with nonsaccular morphologies (blister and fusiform) were significantly associated with SAH presentation.

Absence of Collaterals is Associated with Larger Infarct Volume and Worse Outcome in Patients with Large Vessel Occlusion and Mild Symptoms.

BACKGROUND: Mechanical thrombectomy is the standard of care for patients with large vessel occlusion (LVO) presenting with severe symptoms; however, little is known about the best treatment for patients with LVO and mild symptoms. The absence of good collaterals has been associated with a worse outcome in patients with LVO. In this study, we aim to assess the use of collateral score to identify patients with LVO and mild symptoms that might benefit from mechanical thrombectomy (MT). METHODS: A retrospective review of prospectively collected data on patients presenting with mild ischemic stroke (National Institute of Health Stroke Scale [NIHSS] <6) and anterior circulation LVO between September 2015 and July 2017 was performed. Collected data included baseline demographics, NIHSS on admission, Alberta Stroke Program Early CT Score (ASPECTS), location of occlusion, collateral score using Tan scoring system, final infarct volume, and 90-day modified Rankin Scale (mRS). Patients who underwent MT were excluded from this analysis. Two multivariable models were used to assess outcomes. A gamma distributed generalized linear regression model with a log link was used to examine the impact on final infarct volume. To predict the odds of a positive 90-day outcome we estimated a logistic regression. RESULTS: Forty-one patients were identified. Mean age was 67.7-years with 56.1% males. Median NIHSS on admission was 3. The most common vessels involved were the middle cerebral artery (26), internal carotid artery (14), and anterior cerebral artery (1). Twelve patients received intravenous alteplase. Median ASPECTS score was 9, median collateral score was 2.3. Median infarct volume was 10.7 mL. A good functional outcome (mRS 0-2) at 90 days was achieved in 86.4% of patients. There was a negative relationship between collateral score and final infarct volume (-.3134, P = .046). Multivariable regression results showed that with a one-point increase in NIHSS on admission there was a 25% increase in final infarct volume. Higher infarct volume was associated with lower odds of achieving good functional outcome (mRS 0-2) (odds ratio .96, P = .049 [95% confidence interval .918-.999). CONCLUSIONS: Most patients with anterior circulation LVO and low NIHSS achieve good long-term functional outcome, however, approximately 15% had significant disability. The absence of collaterals correlates with a larger final infarct volume and a worse long-term functional outcome. Collateral score might be a useful tool in identifying patients with LVO and low NIHSS who might benefit from MT.

Disparities in Inter-hospital Helicopter Transportation for Hispanics by Geographic Region: A Threat to Fairness in the Era of Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is a time-dependent therapy that is only available at a limited number of hospitals. As such, patients that live at a considerable distance of those specialized centers often require rapid interhospital emergent evacuation with Helicopter Emergency Medical Services (HEMS) to be considered for MT. It is not known whether the use of HEMS is equitable across different groups of patients. METHODS: Acute ischemic stroke patients emergently transferred to another facility were identified in a retrospective review of a large Medicare claims database. Mode of transportation (HEMS, advanced, or basic ground ambulances) was determined by CPT codes. Distance from patient's residence to the closest center with MT capabilities was calculated. Generalized linear mixed logit models were used to determine the odds of HEMS relative to ground services for Hispanic and non-Hispanic black (NHB) patients relative to non-Hispanic white (NHW) patients while controlling for confounders. RESULTS: A total of 8027 patients that underwent emergent interhospital transportation were analyzed. HEMS utilization was 18.1% for NHB, 20.6% for Hispanics, and 21.6% for NHW (P = .054). In adjusted analyses for confounders, including distance to a MT-capable hospital, Hispanic patients were less likely than NHWs to be transported by HEMS. While that association had marginal significance for the whole United States (OR = .76; 95% CI, .57-1.01; P = .055), it was statistically significant for patients living in the southern region of the United States (OR = .6; 95% CI, .40-.92; P = .019). DISCUSSION: Our findings suggest there is a disparity in the use of HEMS in Hispanic stroke patients compared to NHW. Such a disparity may delay arrival to a MT-capable hospital, delay treatment times, or lead to ineligibility for MT altogether. Given the known benefit of MT and known existing disparities in stroke treatment and outcomes, it is important to further investigate and address disparities in mode of interhospital transportation.

Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Inflammation is a key element behind the pathophysiology of cerebral aneurysm formation and rupture. Aspirin is a potent inhibitor of cyclooxygenase-2 (COX), which plays a critical role in the expression of immune modulators known to contribute to cerebral aneurysm formation and rupture. Currently, there are no pharmacological therapies for patients with cerebral aneurysms. Both endovascular and microsurgical interventions may be associated with significant morbidity and mortality. Potentially, a medical alternative that prevents aneurysm progression and rupture may be a beneficial therapy for a significant number of patients. SUMMARY: In animal models, treatment with aspirin and genetic inactivation of COX-2 decreases aneurysm formation and rupture. Selective inhibition of COX-1 did not decrease aneurysm rupture, suggesting that selection inhibition of COX-2 may be critical in thwarting aneurysm progression. Walls of ruptured human intracranial aneurysms have higher levels of COX-2 and microsomal prostaglandin E2 synthase 1 (mPGES-1), both of which are known to be inhibited by aspirin. In a pilot study, patients undergoing microsurgical clipping had attenuated expression of COX-2, mPGES-1, and macrophages in aneurysm walls after 3 months of aspirin therapy versus those that did not receive aspirin. Additionally, in patients undergoing endovascular therapy, local circulating expression of chemokines and COX-2 were increased in blood samples taken from within aneurysm domes as compared to peripheral blood sample controls. Treatment with aspirin also resulted in decreased expression of COX-2 within leukocytes within aneurysms as compared to peripheral blood samples. Novel molecular imaging with ferumoxytol-enhanced MRI may help in the identification of patients at increased risk for aneurysm rupture and assessment of a response to aspirin therapy. Key Messages: Aspirin has been found to be a safe in patients harboring cerebral aneurysms and clinical studies provide evidence that it may decrease the overall rate of rupture. Furthermore, aspirin is an accessible and inexpensive medicine for patients who may not have access to endovascular or microsurgical treatment or for patients who are deemed low risk of aneurysm rupture, high risk for intervention, or both. Future clinical trials are indicated to determine the overall effect of aspirin on aneurysm progression and rupture. This review provides an update on the potential mechanisms and benefits of aspirin in the treatment of cerebral aneurysms.

Elective endovascular treatment of unruptured intracranial aneurysms: a management case series of patient outcomes after institutional change to admit patients principally to postanesthesia care unit rather than to intensive care.

BACKGROUND: Our intention in this case series was to review the postoperative care and neurologic outcomes of patients who had undergone elective endovascular treatment of unruptured intracranial aneurysms. The case series is unique managerially in that a progressively increasing percentage of patients were admitted to the postanesthesia care unit (PACU; 1:2 nurse-to-patient ratio) and subsequently to the neurosurgical ward (1:3 nurse-to-patient ratio) instead of directly to the intensive care unit (ICU; 1:1 nurse-to-patient ratio). METHODS: A retrospective review was performed of 170 consecutive elective endovascular procedures to treat unruptured intracranial aneurysms between July 2009 and September 2012. Data included patient, aneurysm, procedural characteristics, and adverse events within 96 hours after the procedure. Rates of ICU admission and perioperative neurologic adverse events were compared over time. RESULTS: Although direct ICU admission rates decreased over time (P < 0.0001) from 100% to 15%, perioperative neurologic event rates did not change (P = 0.79). Sixteen of 170 patients experienced perioperative neurologic events. The percentages of patients with neurologic events who died or had deficits that did not resolve before discharge were 38% (3 of 8) among patients directly admitted to the ICU versus 38% (3 of 8) among those first admitted to the PACU. Although the duration of anesthesia was greater among patients admitted to the ICU, duration was not useful in predicting decisions on the day of surgery for individual patients. The duration of anesthesia also was not meaningfully associated with information available preoperatively (i.e., for use when scheduling the case). CONCLUSIONS: In centers in which PACU and ward care are comparable to those in this case series, in the absence of intraoperative events with the potential for ongoing cerebral ischemia, most patients undergoing elective endovascular treatment of unruptured cerebral aneurysms can be managed without direct ICU admission. Scheduling all these procedures by using the mean historical anesthesia duration is reasonable.

Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. METHODS: A systematic review was carried out to identify studies employing venous stenting for IIH. RESULTS: From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4-20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5-5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7-5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8-80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1-96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0-89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5-4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4-12.4), resulting in restenting in 10 patients. CONCLUSION: In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH.

Critical role of TNF-α in cerebral aneurysm formation and progression to rupture.

BACKGROUND: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. METHODS: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining. RESULTS: TNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. CONCLUSIONS: These data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

The impact of regular aspirin use on aneurysm recanalization rates after endovascular coiling.

OBJECTIVE: Intracranial aneurysms (IAs) pose a significant health risk, often leading to subarachnoid hemorrhage and severe neurological outcomes. Endovascular coiling has been a principal treatment method, but it comes with the challenge of high recanalization rates. Aspirin has recently emerged as a potential agent to reduce these rates. In this study, the authors aimed to investigate the impact of regular aspirin use on aneurysm recanalization rates following endovascular coiling in a 10-year single-institution study. METHODS: A retrospective analysis was conducted on a dataset of 2236 aneurysms treated by a single neurosurgeon over a period of 10 years. The primary outcome measure was aneurysm recanalization, defined by a change in the Raymond-Roy Occlusion Classification of at least one grade. RESULTS: A total of 525 aneurysms were coiled, 109 of which involved patients who reported regular use of aspirin. The recanalization rate was significantly lower in the aspirin group (9.2%) compared with the control group (23.6%) (OR 0.33, 95% CI 0.15-0.66; p = 0.001). On analysis of the specific mechanisms of recanalization, aneurysm sac growth was less frequent in the aspirin group (5.5%) compared with the control group (18%) (OR 0.265, 95% CI 0.09-0.63; p = 0.002). Additionally, patients in the control group had a higher retreatment rate (18%) than patients in the aspirin group (5.5%) (OR 0.265, 95% CI 0.09-0.63; p = 0.002). CONCLUSIONS: Regular use of aspirin appears to be associated with reduced rates of aneurysm recanalization after endovascular coiling. However, caution is advised in interpretation of these results given the retrospective nature of this study. Further randomized controlled trials are needed to confirm these findings.

Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability.

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1ß and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log10 (IL-1.ra/IL-1ß). Based on the derivation cohort, multivariate logistic analysis showed that IL-1ß (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

Antithrombotic Therapy in Cerebral Cavernous Malformations: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

BACKGROUND: Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations. METHODS AND RESULTS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine single-center, nonrandomized cohort studies involving 2709 patients were included. Outcomes were analyzed using random-effects model, and a network meta-analysis was conducted for further insight. Of the 2709 patients studied, 388 were on antithrombotic therapy. Patients on antithrombotic therapy had a lower risk of presenting with intracranial hemorrhage (odds ratio [OR], 0.56 [95% CI, 0.45-0.7]; P<0.0001). In addition, the use of antithrombotic therapy was associated with lower risk of intracranial hemorrhage from a cerebral cavernous malformation on follow-up (OR, 0.21 [95% CI, 0.13-0.35]; P<0.0001). A network meta-analysis revealed a nonsignificant OR of 0.73 (95% CI, 0.23-2.56) when antiplatelet therapy was compared with anticoagulant therapy. CONCLUSIONS: Our study explores the potential benefits of antithrombotic therapy in cerebral cavernous malformations. Although the analysis suggests a possible role for antithrombotic agents, it is critical to note that the evidence remains preliminary. Fundamental biases in study design, such as ascertainment and assignment bias, limit the weight of our conclusions. Therefore, our findings should be considered hypothesis-generating and not definitive for clinical practice change.

Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study.

OBJECTIVE: Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. METHODS AND RESULTS: Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. CONCLUSIONS: Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.

Imaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: preliminary results.

BACKGROUND AND PURPOSE: Daily intake of aspirin was shown to decrease human cerebral aneurysm rupture by 60%. The feasibility of imaging macrophages in human cerebral aneurysm walls using ferumoxytol-enhanced MRI has been demonstrated. The goal of the present study is to image aspirin effect on macrophages in the wall of human cerebral aneurysm using ferumoxytol-enhanced MRI. MATERIAL AND METHODS: Five patients with known intracranial aneurysms underwent baseline imaging using T2(*) gradient-echo and T1 MRI sequences using ferumoxytol-enhanced MRI 72-hour post-ferumoxytol infusion. Patients then received 81 mg aspirin per os daily. After 3 months, imaging studies were repeated and analyzed by co-registration using a histogram and subtraction of follow-up images from baseline. RESULTS: In all five patients, after 3 months of treatment with aspirin, the signal intensity corresponding to the uptake of ferumoxytol by macrophages in the aneurysm wall was less intense than in the baseline images. This was confirmed by co-registration of images using histogram and subtraction of follow-up images from baseline. CONCLUSION: These preliminary results suggest the feasibility of imaging aspirin effect on macrophages localized in the wall of human cerebral aneurysm using ferumoxytol-enhanced MRI. The findings provide radiographic evidence of decreased inflammation in human cerebral aneurysms with daily intake of aspirin using macrophages as a surrogate marker for inflammation.

Volumetric surveillance of brain aneurysms: Pitfalls of MRA.

INTRODUCTION: Untreated brain aneurysms are usually surveilled with serial MR imaging and evaluated with 2D multiplanar measurements. The assessment of aneurysm growth may be more accurate with volumetric analysis. We evaluated the accuracy of a magnetic resonance angiography (MRA) segmentation pipeline for aneurysm volume measurement and surveillance. METHODS: A pipeline to determine aneurysm volume was developed and tested on two aneurysm phantoms imaged with time-of flight (TOF) MRA and 3D rotational angiography (3DRA). The accuracy of the pipeline was then evaluated by reconstructing 10 aneurysms imaged with contrast enhanced-MRA (CE-MRA) and 3DRA. This calibrated and refined post-processing pipeline was subsequently used to analyse aneurysms from our prospectively acquired database. Volume changes above the threshold of error were considered true volume changes. The accuracy of these measurements was analysed. RESULTS: TOF-MRA reconstructions were not as accurate as CE-MRA reconstructions. When compared to 3DRA, CE-MRA underestimated aneurysm volume by 7.8% and did not accurately register the presence of blebs. Eighteen aneurysms (13 saccular and 5 fusiform) were analysed with the optimized 3D volume reconstruction pipeline, with a mean follow-up time of 11 months. Artifact accounted for 10.2% error in volume measurements using serial CE-MRA. When this margin of error was used to assess aneurysms volume in serial imaging with CE-MRA, only two fusiform aneurysms changed in volume. The variations in volume of these two fusiform aneurysms were caused by intra-mural and intrasaccular thrombosis. CONCLUSIONS: CE-MRA and TOF-MRA 3D volume reconstructions may not register minor morphological changes such as the appearance of blebs. CE-MRA underestimates volume by 7.8% compared to 3DRA. Serial CE-MRA volume measurements had a larger margin of error of approximately 10.2%. MRA-based volumetric measurements may not be appropriate for aneurysm surveillance.