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Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

Reperfusion therapies, such as intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are crucial for improving outcomes in patients with acute ischemic stroke (AIS). However, access to these treatments can vary significantly due to ethnicity, socioeconomic status (SES), and geographical location, impacting patient outcomes. The Disparities in Access to Reperfusion Therapy for Acute Ischemic Stroke (DARTS) study aims to systematically assess disparities in access to IVT and EVT on the basis of ethnicity, SES, and geographical location. A comprehensive meta-analysis was conducted, incorporating data from 38 studies involving 5,256,531 patients with AIS. The analysis evaluated IVT and EVT utilization rates across ethnic groups, SES levels, and geographical locations. The findings reveal substantial disparities in access to reperfusion therapies. IVT and EVT utilization rates varied significantly by ethnicity (9% ethnic, 11% non-ethnic for IVT; 7% ethnic, 6% non-ethnic for EVT), SES (13% low SES, 16% high SES for IVT; 7% low SES, 10% high SES for EVT), and geography (9% rural, 12% urban for IVT; 1% rural, 4% urban for EVT). Black patients had significantly lower odds of receiving IVT (OR 0.69, p = 0.001) and EVT (OR 0.87, p = 0.005) compared with white patients. Similarly, patients with low SES and those from rural areas faced reduced odds of receiving IVT (OR 0.74, p < 0.001; OR 0.72, p = 0.002) and EVT (OR 0.74, p < 0.001; OR 0.39, p < 0.001). Rural patients also had significantly lower odds of timely hospital arrival (p < 0.001), posing a barrier to accessing reperfusion therapies. The DARTS study (and this meta-analysis) reveals significant access disparities in AIS treatment related to ethnicity, geography, and SES, particularly affecting Black communities, low SES individuals, and rural populations. Despite advances in reperfusion therapies, suboptimal implementation rates persist. To address these issues, we recommend the EQUITY framework: Educate, Ensure Quality, provide Universal Access, Implement Inclusive Policy Reforms, Enhance Timely Data Collection, and Yield Culturally Sensitive Care Practices. Adopting these recommendations will improve access, reduce disparities, and enhance stroke management and outcomes globally. Equitable access is essential for all eligible patients to fully benefit from reperfusion treatments.

Cerebral cavernous malformations are the most common vascular malformations and can be found in many locations in the brain. If left untreated, cavernomas may lead to intracerebral hemorrhage, seizures, focal neurological deficits, or headaches. As they are angiographically occult, their diagnosis relies on various MR imaging techniques, which detect different characteristics of the lesions as well as aiding in planning the surgical treatment. The clinical presentation and the location of the lesion are the most important factors involved in determining the optimal course of treatment of cavernomas. We concisely review the literature and discuss the advantages and limitations of each of the three available methods of treatment—microsurgical resection, stereotactic radiosurgery, and conservative management—depending on the lesion characteristics.

Abstract BACKGROUND: The biggest downside of cerebral aneurysm coiling is the high rates of recurrence and retreatments. With the increasing number of aneurysm recurrences after failed coiling procedures, the best retreatment strategy remains unknown. OBJECTIVE: To assess the efficacy and safety of the Pipeline Embolization Device (PED) in the treatment of recurrent previously coiled aneurysms. METHODS: Thirty-three patients who underwent treatment with the PED of a recurrent previously coiled aneurysm were retrospectively identified. Efficacy was assessed in terms of angiographic occlusion at the latest cerebral angiogram, recurrence and retreatment rates after PED placement, and clinical outcome at the latest follow-up. Safety was assessed by looking at the complications, morbidity, and mortality after PED treatment. RESULTS: The mean patient age was 53 years. The mean percent recurrence from coiling to PED placement was 34%. The mean time from coiling to PED placement was 40 months. PED treatment resulted in complete aneurysm occlusion in 76.7% of patients and near-complete aneurysm occlusion (≥90%) in 10%, for a total rate of complete and near-complete aneurysm occlusion of 86.7%. All patients, including those with incomplete aneurysm occlusion, had a significant reduction in aneurysm size. Two aneurysms required another retreatment after PED placement (6.2%). Ninety-seven percent of patients had a good clinical outcome. Complications were observed in 1 patient (3%), who suffered an intracerebral hemorrhage. There were no mortalities. CONCLUSION: The use of the PED in the management of recurrent, previously coiled aneurysms is safe and effective in achieving aneurysm occlusion.

The role of smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation and pathogenesis of stroke has not been determined. Cigarette smoke is a major risk factor for atherosclerosis, but potential mechanisms are unclear, and its role in SMC phenotypic modulation has not been established. In cultured cerebral vascular SMCs, exposure to cigarette smoke extract (CSE) resulted in decreased promoter activity and mRNA expression of key SMC contractile genes (SM-α-actin, SM-22α, SM-MHC) and the transcription factor myocardin in a dose-dependent manner. CSE also induced pro-inflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-α, IL-1β, NF-κB). CSE increased expression of KLF4, a known regulator of SMC differentiation, and siKLF4 inhibited CSE induced suppression of SMC contractile genes and myocardin and activation of inflammatory genes. These mechanisms were confirmed in vivo following exposure of rat carotid arteries to CSE. Chromatin immune-precipitation assays in vivo and in vitro demonstrated that CSE promotes epigenetic changes with binding of KLF4 to the promoter regions of myocardin and SMC marker genes and alterations in promoter acetylation and methylation. CSE exposure results in phenotypic modulation of cerebral SMC through myocardin and KLF4 dependent mechanisms. These results provides a mechanism by which cigarette smoke induces a pro-inflammatory/matrix remodeling phenotype in SMC and an important pathway for cigarette smoke to contribute to atherosclerosis and stroke.

Rapid reperfusion of ischemic penumbra in patients with acute stroke is critical to neurological recovery. Achieving reperfusion after first-pass mechanical thrombectomy has been associated with improved patient outcomes. However, the predictors for obtaining first-pass reperfusion are not well known. A single-institution retrospective study of all patients who underwent mechanical thrombectomy at a tertiary care center from January 2010 until March 2019 was conducted to assess for predictors of first-pass reperfusion. A total of 257 patients were reviewed. Successful reperfusion was obtained in 63.4% of patients, and in 38% of patients on the first pass. On multivariate analysis, increasing door-to-puncture time was a negative predictor of FPR (OR 0.989, 95% CI = 0.980–0.997) and use of combined thrombectomy technique with stent-retriever and aspiration was a positive predictor of FPR compared to aspiration or stent-retriever alone (OR 4.441, 95% CI = 1.001–19.699). Combination therapy using stent-retriever and aspiration may increase the chance of obtaining FPR, whereas delays in starting the procedure after patient arrival may decrease the odds of FPR. Rapid thrombectomy initiation and procedural technique may play in optimizing rates of FPR and ultimately patient outcomes, however, randomized controlled trials assessing these variables are necessary to determine optimal treatment strategies. •First pass reperfusion increases the odds of good outcome in thrombectomy.•Combined stent-retriever/aspiration increases the odds of first-pass reperfusion.•Delays in door-to-needle time decrease the odds of obtaining first-pass reperfusion.

BackgroundThe transradial approach (TRA) has gained increasing popularity for neuroendovascular procedures. However, the experience with TRA in neuroangiography is still in early stages in most centers, and the safety and feasibility of this approach have not been well established. The purpose of this study is to report the safety and feasibility of TRA for neuroendovascular procedures.MethodsWe reviewed charts from six institutions in the USA to include consecutive patients who underwent diagnostic or interventional neuroendovascular procedures through TRA from July 2018 to July 2019. Collected data included baseline characteristics, procedural variables, complications, and whether there was a crossover to transfemoral access.ResultsA total of 2203 patients were included in the study (age 56.1±15.2, 60.8% women). Of these, 1697 (77%) patients underwent diagnostic procedures and 506 (23%) underwent interventional procedures. Successfully completed procedures included aneurysm coiling (n=97), flow diversion (n=89), stent-assisted coiling (n=57), balloon-assisted coiling (n=19), and stroke thrombectomy (n=76). Crossover to femoral access was required in 114 (5.2%). There were no major complications related to the radial access site. Minor complications related to access site were seen in 14 (0.6%) patients.ConclusionIn this early stage of transforming to the ‘radial-first’ approach for neuroendovascular procedures, TRA was safe with low complication rates for both diagnostic and interventional procedures. A wide range of procedures were completed successfully using TRA.

Abstract Background: The risk factors predictive of intracranial aneurysm rupture remain incompletely defined. Objective: To examine the association between various nonmodifiable risk factors and aneurysm rupture in a large cohort of patients evaluated at a single institution. Methods: A retrospective analysis of patients admitted to a cerebrovascular facility between January 2006 and 2010 with a primary diagnosis of cerebral aneurysm. Aneurysms were divided into 2 groups: unruptured or ruptured. The dome diameter, aspect ratio (AR), location, sidedness, neck morphology, and multiplicity were entered into a central database. A full model was constructed, and a systematic removal of the least significant variables was performed in a sequential fashion until only those variables reaching significance remained. Results: We identified 2347 patients harboring 5134 individual aneurysms, of which 34.90% were ruptured and 65.09% were unruptured. On admission, 25.89% of aneurysms with a dome diameter <10 mm and 58.33% of aneurysms with a dome >10 mm were ruptured (P < .001). Of aneurysms with an AR >1.6, 52.44% presented following a rupture (P < .001). The highest incidence of rupture (69.21%) was observed in aneurysms with an AR >1.6, dome diameter <10 mm, and a deviated neck. Deviated neck-type aneurysms had a significantly greater incidence of rupture than classical necktype aneurysms (P < .001). Conclusion: An AR >1.6, dome diameter >10 mm, a deviated neck, and right-sidedness are independently associated with aneurysm rupture.

Aneurysms of the carotid-ophthalmic artery present unique challenges to cerebrovascular neurosurgeons given their proximity to vital anatomic structures. To report our experience with a combined-modality treatment of unruptured carotid-ophthalmic aneurysms over a 12-year period. A retrospective review of 161 patients who underwent open, endovascular, or combined treatment of 170 aneurysms from January 1997 to July 2009 was conducted. Medical records, operative reports, office notes, and follow-up angiograms were reviewed to obtain data on patient demographics, angiographic results, and clinical outcomes. One hundred forty-seven aneurysms were treated via endovascular techniques; 17 aneurysms (10%) were treated with microsurgical clip ligation; and 6 aneurysms (3.5%) were treated with a combined approach. Of the aneurysms treated via an endovascular approach alone, 81.6% of aneurysms had evidence of ≥ 95% occlusion on initial angiogram. There was a 1.4% rate of major complications associated with the initial procedure. Twenty-six of these aneurysms (18.9%) required further intervention on the basis of early angiographic results. Major complications occurred after 6 of 23 open microsurgical procedures (26.1%), including 2 instances of permanent visual loss. Nine clipped patients had long-term angiographic follow-up; none required further intervention. Endovascular treatment of carotid-ophthalmic aneurysms with modern endovascular techniques can be performed safely and efficaciously in the elective setting.

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.