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Objective: Preclinical studies suggest that robotic carotid artery stenting (CAS) could be superior to manual CAS. However, very limited comparative data exist for patients who have undergone robotic versus manual CAS. In addition, no data exist comparing the costs of manual and robotic CAS., Methods: All robotic CAS cases at two academic neurosurgery centers were retrospectively reviewed and 1:1 propensity matched with manual CAS cases. Personnel costs, supply costs, and total procedure costs were collected in collaboration with hospital administration by using time-driven activity-based cost analysis., Results: A total of 24 robotic CAS operations were performed between 2019 and 2023. Comorbidities and baseline procedural characteristics were well matched between robotic and manual cases. Unplanned manual conversion was observed in only 1 robotic case (4.2%). Robotic CAS complications and outcomes were comparable to manual. Robotic CAS was associated with a significantly increased fluoroscopy time (29.0 vs 19.2 minutes; p < 0.001). Robotic procedure time (88.9 ± 18.2 minutes) was significantly (p = 0.003) longer than manual time (68.72 ± 22.4 minutes). Health personnel costs ($1589.71 ± $176.92 vs $1375.99 ± $233.39, p = 0.005); supply costs ($3918.25 ± $421.20 vs $2152.74 ± $1030.26, p < 0.001); and total procedure costs ($5306.11 ± $608.95 vs $3437.56 ± $1165.67, p < 0.001) were greater for robotic CAS., Conclusions: In the first multicenter study and largest sample to date, the authors show that robotic CAS, with a low rate of procedural failure and postoperative complications, is safe and feasible. In addition, robotic CAS achieves comparable clinical outcomes to manual CAS. Robotic CAS was associated with increased fluoroscopy time, but fluoroscopy time decreased as operators gained familiarity with the CorPath GRX system. Robotic CAS was associated with a greater procedural cost, which was driven by greater personnel and supply costs. Robotic CAS failed to show superiority to manual CAS. These findings set a foundation for randomized controlled trials of robotic CAS, and also highlight the need for further studies to optimize robotic CAS and reduce its associated costs.

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.

Background: Patient's age is an important factor in determining the risk of aneurysm rupture. However, there is limited data on how aneurysm morphology differs among age groups. We studied morphological characteristics of brain aneurysms among age groups in a large cohort., Methods: Aneurysms from the Stroke Thrombectomy and Aneurysm Registry (STAR) were analyzed. The following parameters were included: location, size, neck, width, height, aspect ratio, and regular versus irregular morphology. The risk of rupture presentation was estimated using logistic regression., Results: A total of 1407 unruptured and 607 ruptured saccular aneurysms were included. The most common locations of ruptured aneurysms in patients younger than 70 years-old were the middle cerebral artery (MCA) and the anterior communicating artery (ACOM). The most common location of ruptured aneurysms in patients older than 70 years-old were the posterior communicating artery (PCOM) and ACOM. The size of unruptured aneurysms increased with age (p < .001). Conversely, the size of ruptured aneurysms was similar among age groups (p = .142). Unruptured and ruptured aneurysms became more irregular at presentation with older age (p < .001 and p .025, respectively). Irregular morphology and location were associated with rupture status across all age groups in multivariate regression., Conclusions: Younger patients have small unruptured and ruptured aneurysms, and ruptured aneurysms are mostly located in the MCA and ACOM. Older patients have larger and more irregular unruptured aneurysms, and ruptured aneurysms are mostly located in the PCOM and ACOM. An irregular morphology increases the risk of rupture in all age groups.

Mechanical thrombectomy is established as standard of care in the management of acute ischemic stroke due to large vessel occlusion and evidence-based guidelines for mechanical thrombectomy have been defined. As research continues to further expand the eligibility criteria for thrombectomy and the number of thrombectomy procedures increase worldwide, there is also growing focus on innovation of thrombectomy devices, procedural techniques, and related outcomes. Thrombectomy primarily involves use of stent retrievers and distal aspiration techniques, but variations and different combinations of techniques have been reported. As this is a rapidly evolving area in stroke management, there is debate as to which, if any, of these techniques leads to improved clinical outcomes over another and there is a lack of data comparing them. In this review, currently published and distinct techniques of mechanical thrombectomy are described methodically along with illustrations to aid in understanding the subtle differences between the techniques. The perceived benefits of each variation are discussed.

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct., Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5., Design, Setting, and Participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score., Exposure: All patients underwent MT in one of the included centers., Main Outcomes and Measures: A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset)., Results: A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64)., Conclusions and Relevance: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race., Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days., Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72–84), compared with 63 years (54–74) for NHB, and 71 years (60–80) for NHW patients (P<0.001). Hispanic patients had a higher incidence of diabetes (41%; P<0.001) and hypertension (82%; P<0.001) compared with NHW and NHB patients. Median procedure time was shorter in Hispanics (36 minutes) compared to NHB (39 minutes) and NHW (44 minutes) patients (P<0.001). In multivariate analysis, Hispanic patients were less likely to have favorable outcome (odds ratio, 0.502 [95% CI, 0.263–0.959]), controlling for other significant predictors (age, admission National Institutes Health Stroke Scale, onset to groin time, number of attempts, procedure time)., Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have emerged over the past decades. Specifically, we discuss microcirculatory dysfunction, glymphatic impairment, inflammation, and neuroelectric disruption as pathological factors in addition to the canonical focus on cerebral vasospasm. This review intends to give clinicians and researchers a summary of the foundations of delayed cerebral ischemia pathophysiology while also underscoring the interactions and interdependencies between pathological factors. Through this overview, we also highlight the advances in translational studies and potential future therapeutic opportunities.

Introduction: We reviewed the literature on interventions for patients with medically refractory chronically occluded internal carotid artery (COICA) to assess the risks and/or benefits after recanalization via an endovascular technique (ET) or hybrid surgery (HS, i.e., ET plus carotid endarterectomy)., Methods: A systematic search of the electronic databases was performed. Patients with COICA were classified into 4 different categories according to Hasan et al classification., Results: Eighteen studies satisfied the inclusion criteria. Only 6 studies involved an HS procedure. We identified 389 patients with COICA who underwent ET or HS; 91% were males. The overall perioperative complication rate was 10.1% (95% confidence interval [CI]: 7.4%-13.1%). For types A and B, the successful recanalization rate was 95.4% (95% CI: 86.5%-100%), with a 13.7% (95% CI: 2.3%-27.4%) complication rate. For type C, the success rate for ET was 45.7% (95% CI: 17.8%-70.7%), with a complication rate of 46.0% (95% CI: 20.0%-71.4%) for ET and for the HS technique 87.6% (95% CI: 80.9%-94.4%), with a complication rate of 14.0% (95% CI: 7.0%-21.8%). For type D, the success rate of recanalization was 29.8% (95% CI: 7.8%-52.8%), with a 29.8% (95% CI: 6.1%-56.3%) complication rate. Successful recanalization resulted in a symmetrical perfusion between both cerebral hemispheres, resolution of penumbra, normalization of the mean transit time, and improvement in Montreal Cognitive Assessment (MoCA) score (ΔMoCA = 9.80 points; P  = 0.004)., Conclusions: Type A and B occlusions benefit from ET, especially in the presence of a large penumbra. Type C occlusions can benefit from HS. Unfortunately, we did not identify an intervention to help patients with type D occlusions. A phase 2b randomized controlled trial is needed to confirm these findings., (© 2019 The Author(s).)

Background and Purpose- Radial artery catheterization is an alternate route of access that has started to gain more widespread use for neuroendovascular procedures, and there have been few studies that describe its safety and efficacy. We present our institution's experience in performing neuroendovascular interventions via a transradial approach, with excellent clinical outcomes and patient satisfaction measures. Methods- We conducted a retrospective analysis and identified 223 patients who underwent 233 consecutive neuroendovascular interventions via radial artery access at our institution. The incidence of perioperative and postprocedural complications was investigated. We identified a subset of 98 patients who have undergone both transradial and transfemoral cerebral angiograms and compared clinical outcomes and patient satisfaction measures between the 2 groups. Results- The overall incidence of complications was low across all procedures performed via transradial access. Peri-procedurally, only 2 patients had symptomatic radial artery spasm, and there were no instances of iatrogenic complications (vessel dissection, stroke, and hemorrhage). In 10 cases (4.3%), the intended procedure could not be completed via a transradial approach, and, thus, femoral artery access had to be pursued instead. Ten patients complained of minor postprocedural complications, although none required therapeutic intervention. The mean procedure time was shorter for diagnostic angiograms performed via transradial versus transfemoral access (18.8±15.8 versus 39.5±31.1 minutes; P=0.025). Patients overall reported shorter recovery times with transradial access, and the majority of patients (94%) would elect to have subsequent procedures performed via this route. Conclusions- Radial artery catheterization is a safe and durable alternative to perform a wide range of neuroendovascular procedures, with a low rate of complications. On the whole, patients prefer transradial compared with transfemoral access.

We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin., (© 2016 American Heart Association, Inc.)

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.

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.

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.

Five patients were found to have spontaneous delayed migration/shortening of their Pipeline Embolization Devices on follow-up angiography. The device migrated proximally in 4 patients and distally in 1 patient. One patient had a subarachnoid hemorrhage and died as a result of migration of the Pipeline Embolization Device, and another patient presented with complete MCA occlusion and was left severely disabled. Mismatch in arterial diameter between inflow and outflow vessels was a constant finding. Migration of the Pipeline Embolization Device was managed conservatively, with additional placement of the device, or with parent vessel occlusion. Obtaining complete expansion of the embolization device by using a longer device, increasing vessel coverage, using adjunctive aneurysm coiling, and avoiding dragging and stretching of the device are important preventive measures. Neurointerventionalists should be aware of this potentially fatal complication and take all necessary preventive measures.

Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor necrosis factor-alpha (TNF-α) has been associated with aneurysms, but potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing myocardin induced expression of key SMC contractile genes (SM-α-actin, SM-22α, smooth muscle myosin heavy chain), while dominant-negative cells suppressed expression. Tumor necrosis factor-alpha treatment inhibited this contractile phenotype and induced pro-inflammatory/matrix-remodeling genes (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta). Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering RNA abrogated TNF-α activation of inflammatory genes and suppression of contractile genes. These mechanisms were confirmed in vivo after exposure of rat carotid arteries to TNF-α and early on in a model of cerebral aneurysm formation. Treatment with the synthesized TNF-α inhibitor 3,6-dithiothalidomide reversed pathologic vessel wall alterations after induced hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo and in vitro demonstrated that TNF-α promotes epigenetic changes through KLF4-dependent alterations in promoter regions of myocardin, SMCs, and inflammatory genes. In conclusion, TNF-α induces phenotypic modulation of cerebral SMCs through myocardin and KLF4-regulated pathways. These results demonstrate a novel role for TNF-α in promoting a pro-inflammatory/matrix-remodeling phenotype, which has important implications for the mechanisms behind intracranial aneurysm formation.

Background and Purpose: Stent-assisted coiling and balloon-assisted coiling are 2 well-established techniques for treatment of wide-neck intracranial aneurysms. A direct comparative analysis of angiographic outcomes with the 2 techniques has not been available. We compare the angiographic outcomes of wide-neck aneurysms treated with stent-assisted coiling versus balloon-assisted coiling., Materials and Methods: A retrospective review was conducted on 101 consecutive patients treated at our institution, 69 with stent-assisted coiling and 32 with balloon-assisted coiling. Two multivariate logistic regression analyses were performed to determine predictors of aneurysm obliteration and predictors of progressive aneurysm thrombosis at follow-up., Results: The 2 groups were comparable with respect to all baseline characteristics with the exception of a higher proportion of ruptured aneurysms in the balloon-assisted coiling group (65.6%) than in the stent-assisted coiling group (11.5%, P < .001). Procedural complications did not differ between the stent-assisted coiling group (6%) and the balloon-assisted coiling group (9%, P = .5). The rates of complete aneurysm occlusion (Raymond score 1) at the most recent follow-up were significantly higher for the stent-assisted coiling group (75.4%) compared with the balloon-assisted coiling group (50%, P = .01). Progressive occlusion of incompletely coiled aneurysms was noted in 76.6% of aneurysms in the stent-assisted coiling group versus 42.8% in the balloon-assisted coiling group (P = .02). Retreatment rates were significantly lower with stent-assisted coiling (4.3%) versus balloon-assisted coiling (15.6%, P = .05). In multivariate analysis, stented aneurysms independently predicted both complete aneurysm obliteration and progression of occlusion., Conclusions: Stent-assisted coiling may yield lower rates of retreatment and higher rates of aneurysm obliteration and progression of occlusion at follow-up than balloon-assisted coiling with a similar morbidity rate.

Background: 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., Methods and Results: 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., Conclusion: 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.

Head-of-bed (HOB) elevation is usually restricted in patients with aneurysmal subarachnoid hemorrhage (SAH). The goal of this study is to correlate HOB changes (0° and 90°) with cerebral blood flow using transcranial Doppler (TCD) and thermal diffusion probe in SAH patients. Thirteen patients with SAH were prospectively enrolled in the study. Eight patients underwent placement of a thermal diffusion probe for regional CBF measurement. CBF values were measured with the patients in flat (0°) and upright sitting positions (90°) at days 3, 7, and 10. The average increase in blood flow velocity when changing HOB from 0° to 90° was 7.8% on day 3, 0.1% on day 7, and 13.1% on day 10. The middle cerebral artery had the least changes in velocity. The average regional CBF measurement was 22.7 ± 0.3 mL/100 g/min in the supine position and 23.6 ± 9.1 mg/100 g/min in the sitting position. The changes were not statistically significant. None of the patients developed clinical cerebral vasospasm. Changing HOB position in the setting of SAH did not significantly affect cerebral or regional blood flow. These data suggest that early mobilization should be considered given the detrimental effects of prolonged bed rest.

Intracranial vertebral artery dissection (VAD) represents the underlying etiology in a significant percentage of posterior circulation ischemic strokes and subarachnoid hemorrhages. These lesions are particularly challenging in their diagnosis, management, and in the prediction of long-term outcome. Advances in the understanding of underlying processes leading to dissection, as well as the evolution of modern imaging techniques are discussed. The data pertaining to medical management of intracranial VADs, with emphasis on anticoagulants and antiplatelet agents, is reviewed. Surgical intervention is discussed, including, the selection of operative candidates, open and endovascular procedures, and potential complications. The evolution of endovascular technology and techniques is highlighted.

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.

Endovascular treatment of complex, wide-necked bifurcation cerebral aneurysms is challenging.  Intra/extra-aneurysmal stent placement, the "waffle cone" technique, has the advantage of using a single stent to prevent coil herniation without the need to deliver the stent to the efferent vessel. The published data on the use of this technique is limited. We present our initial and follow-up experience with the waffle cone stent-assisted coiling (SAC) of aneurysms to evaluate the durability of the technique. We retrospectively identified ten consecutive patients who underwent SAC of an aneurysm using the waffle cone technique from July 2009 to March 2011. Clinical and angiographic outcomes after initial treatment and follow-up were evaluated. Raymond Class I or II occlusion of the aneurysm was achieved in all cases with the waffle cone technique. No intraoperative aneurysm rupture was noted. The parent arteries were patent at procedure completion. Clinical follow-up in nine patients (median 12.9 months) revealed no aneurysm rupture. Two patients had a transient embolic ischemic attack at 18 hours and three months after treatment, respectively. Catheter angiography or MRA at six-month follow-up demonstrated persistent occlusions of aneurysms in seven out of eight patients. Another patient had stable aneurysm occlusion at three-month follow-up study. Our experience in the small series suggests the waffle cone technique could be performed on complex, wide-necked aneurysms with relative safety, and it allowed satisfactory occlusions of the aneurysms at six months in most cases.

Smoking is an established risk factor for subarachnoid hemorrhage yet the underlying mechanisms are largely unknown. Recent data has implicated a role of inflammation in the development of cerebral aneurysms. Inflammation accompanying cigarette smoke exposure may thus be a critical pathway underlying the development, progression, and rupture of cerebral aneurysms. Various constituents of the inflammatory response appear to be involved including adhesion molecules, cytokines, reactive oxygen species, leukocytes, matrix metalloproteinases, and vascular smooth muscle cells. Characterization of the molecular basis of the inflammatory response accompanying cigarette smoke exposure will provide a rational approach for future targeted therapy. In this paper, we review the current body of knowledge implicating cigarette smoke-induced inflammation in cerebral aneurysm formation/rupture and attempt to highlight important avenues for future investigation.

Tremendous insight into the molecular and genetic pathogenesis of cerebral cavernous malformations (CCMs) has been gained over the past 2 decades. This includes the identification of 3 distinct genes involved in familial CCMs. Still, a number of unanswered questions regarding the process from gene mutation to vascular malformation remain. It is becoming more evident that the disruption of interendothelial junctions and ensuing vascular hyperpermeability play a principal role. The purpose of this review is to summarize the current understanding of CCM genes, associated proteins, and functional pathways. Promising molecular and genetic therapies targeted at identified molecular aberrations are discussed as well.