Basilar Terminus Research Articles

Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.

Y-Stent Rescue Technique for Failed Thrombectomy in Patients With Large Vessel Occlusion: A Case Series and Pooled Analysis.

Objective: Y-stent thrombectomy is a recent rescue technique for failed thrombectomy in patients with emergent large vessel occlusion. We presented case series of using Y-stent rescue technique at different sites and investigate its feasibility and safety through pooled analysis of collected case report or series.Methods: Twenty-eight cases were screened from stroke databank who underwent thrombectomy between January 2015 and June 2019. Clinical, procedural, and follow-up data were investigated and pooled analysis of published literature was analyzed.Results: The occlusion sites include carotid terminus in 14 patients; siphon segment in 3; middle cerebral artery (MCA) in 4; basilar terminus in 7. The overall recanalization rate reached 85.7% (arterial occlusive lesion score 2–3); and final reperfusion rate 85.7% (modified Thrombolysis in Cerebral Infarction 2b−3). After literature review, totally, 52 cases were included. Good clinical outcome was achieved in 26 (50%) and mortality in 7 (17.3%). There is no significant difference on the SAH complication at different sites. Literature review shows no difference between each site in the reperfusion and complication rate.Conclusion: Our case series results suggest that high recanalization rate can be effectively achieved with Y-stent rescue technique for patients with refractory emergent large vessel occlusion. The safety of using this technique at different sites needs further investigation for patients.

ECLIPs bifurcation remodeling system for treatment of wide neck bifurcation aneurysms with extremely low dome-to-neck and aspect ratios: a multicenter experience

BackgroundWide necked bifurcation aneurysms (WNBA) are among the most difficult aneurysms to treat. Very low dome-to-neck (DTN) and aspect ratios provide an even greater challenge in the management of WNBAs....

Adenosine-Induced Cardiac Arrest for Transvenous Embolization of Midbrain Arteriovenous Malformation.

Few studies describe the use of adenosine-induced cardiac systole for treatment of cerebrovascular pathologies.We describe a midbrain arteriovenous malformation (AVM) treated with transvenous embolization using adenosine-induced asystole to achieve transient systemic hypotension with the purpose of furthering discussion on the technique and operative considerations for adenosine use in endovascular AVM treatments. A 29-yr-old man presented with sudden onset of severe bilateral headache, blurred vision, and numbness on the right side of his face and tongue. Noncontrast head computed tomography revealed fourth ventricle hemorrhage. Diagnostic cerebral angiography revealed a high-flow midbrain AVM with a posterior wall perforator from the basilar artery terminus and a draining vein into the straight sinus. Transarterial AVM embolization was successful. The patient was discharged with no residual neurological deficits but returned 1 wk later with slurred speech and left-sided dysmetria. Repeat angiography revealed partial AVM filling. Attempts at transarterial embolization were unsuccessful. Thus, transvenous AVM embolization with adenosine-induced cardiac asystole and systemic hypotension was performed. A total of 60 mg of adenosine was administered, followed by 2 additional doses of 60 and 40 mg; and complete cardiac asystole with a mean arterial pressure of 40 mmHg was maintained, resulting in successful embolization of the AVM. No residual filling was visualized on postembolization arterial angiography runs. The patient was neurologically stable and discharged on postoperative day 2. With appropriate and safe dosing, adenosine-induced asystole and systemic hypotension may be a feasible, safe option to reduce flow and assist endovascular transvenous embolization of high-flow AVMs.

‘Railroad switch’ technique for stent-assisted coil embolization of a wide-neck bifurcation intracranial aneurysm: technical note

Preservation of the posterior cerebral arteries during endovascular treatment of wide-neck basilar bifurcation aneurysms remains a technical challenge despite recent device innovations. We present a novel stent deployment technique, the 'railroad switch', to protect both posterior cerebral arteries during treatment of a recurrent basilar bifurcation aneurysm. Following asymmetric basilar-posterior cerebral artery stent deployment, favoring distal placement in a posterior cerebral artery, advancement of a jailed microcatheter will advance the proximal stent into the aneurysm, protecting both posterior cerebral arteries and the native basilar terminus. This novel maneuver offers interventionalists another application of commonly used intracranial stents for endovascular management of complex basilar bifurcation aneurysms.

Abstract 201: Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-necked, Bifurcation Aneurysms

Background: The safety and probable benefit of the PulseRider ® (Pulsar Vascular, San Jose, CA) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, non-randomized, single arm clinical trial - the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction Trial (ANSWER). Objective: We present the results of the United States cases employing the PulseRider ® device as part of the ANSWER clinical trial. Methods: Aneurysms treated with the PulseRider ® device among U.S. sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study. Results: 34 patients were enrolled (29 female and 5 male) with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range 2.3 - 11.6 mm). In all patients the device was delivered and deployed. Immediate Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at six month follow up. A modified Rankin Score of 2 or less was seen in 94% of patients at 6 months. Conclusions: The results from the U.S. cases of the ANSWER trial demonstrate that the Pulse Rider® device is safe and effective as for the treatment of bifurcation aneurysms arising at the basilar apex or carotid terminus. As such, it represents a useful addition to the armamentarium of the neuroendovascular specialist.

Assessment of Vascular Geometry for Bilateral Carotid Artery Ligation to Induce Early Basilar Terminus Aneurysmal Remodeling in Rats.

Bilateral common carotid artery (CCA) ligation in rabbits is a model for basilar terminus (BT) aneurysm formation. We asked if this model could be replicated in rats. Fourteen female Sprague Dawley rats underwent bilateral CCA ligation (n=8) or sham surgery (n=6). After 7 days, 5 ligated and 3 sham rats were euthanized for histological evaluation of BT aneurysm formation, while the remaining rats were imaged with magnetic resonance angiography, euthanized, and subjected to corrosion casting of the Circle of Willis (CoW). 3D micro computed tomography images of CoW casts were used for flow simulations at the rat BT, and electron micrographs of the casts were analyzed for aneurysmal and morphological changes. Results from these analyses were compared to rabbit model data (n=10 ligated and n=6 sham). Bilateral CCA ligation did not produce aneurysmal damage at the rat BT. While the surgical manipulation increased rat basilar artery flow, fluid dynamics simulations showed that the initial hemodynamic stress at the rat BT was significantly less than in rabbits. Rats also exhibited fewer morphological and pathological changes (minor changes only occurred in the posterior CoW) than rabbits, which had drastic changes throughout the CoW. A comparison of CoW anatomies demonstrated a greater number of branching arteries at the BT, larger CoW arteries in relation to basilar artery, and a steeper BT bifurcation angle in the rat. These differences could account for the lower hemodynamic stress at the BT and in the cerebrovasculature of the rat. In conclusion, bilateral CCA ligation in rats does not recapitulate the rabbit model of early flow-induced BT aneurysm. We suspect that the different CoW morphology of the rat lessens hemodynamic insults, thereby diminishing flow-induced aneurysmal remodeling.

Endothelial Nitric Oxide Synthase and Superoxide Mediate Hemodynamic Initiation of Intracranial Aneurysms

BackgroundHemodynamic insults at arterial bifurcations are believed to play a critical role in initiating intracranial aneurysms. Recent studies in a rabbit model indicate that aneurysmal damage initiates under specific wall shear stress conditions when smooth muscle cells (SMCs) become pro-inflammatory and produce matrix metalloproteinases (MMPs). The mechanisms leading to SMC activation and MMP production during hemodynamic aneurysm initiation are unknown. The goal is to determine if nitric oxide and/or superoxide induce SMC changes, MMP production and aneurysmal remodeling following hemodynamic insult.MethodsBilateral common carotid artery ligation was performed on rabbits (n = 19, plus 5 sham operations) to induce aneurysmal damage at the basilar terminus. Ligated animals were treated with the nitric oxide synthase (NOS) inhibitor LNAME (n = 7) or the superoxide scavenger TEMPOL (n = 5) and compared to untreated animals (n = 7). Aneurysm development was assessed histologically 5 days after ligation. Changes in NOS isoforms, peroxynitrite, reactive oxygen species (ROS), MMP-2, MMP-9, and smooth muscle α-actin were analyzed by immunohistochemistry.ResultsLNAME attenuated ligation-induced IEL loss, media thinning and bulge formation. In untreated animals, immunofluorescence showed increased endothelial NOS (eNOS) after ligation, but no change in inducible or neuronal NOS. Furthermore, during aneurysm initiation ROS increased in the media, but not the intima, and there was no change in peroxynitrite. In LNAME-treated animals, ROS production did not change. Together, this suggests that eNOS is important for aneurysm initiation but not by producing superoxide. TEMPOL treatment reduced aneurysm development, indicating that the increased medial superoxide is also necessary for aneurysm initiation. LNAME and TEMPOL treatment in ligated animals restored α-actin and decreased MMPs, suggesting that eNOS and superoxide both lead to SMC de-differentiation and MMP production.ConclusionAneurysm-inducing hemodynamics lead to increased eNOS and superoxide, which both affect SMC phenotype, increasing MMP production and aneurysmal damage.

Bilateral common carotid artery ligation for creating basilar terminus aneurysm model in rabbits：a preliminary study

Objective To use bilateral common carotid artery ligation for creating an aneurysm model of the basilar terminus in New Zealand white rabbits.Methods Twenty-six adult New Zealand white rabbits were subjected to sham operation or bilateral common carotid artery ligation to increase basilar artery flow.Basilar artery flow velocity was monitored by transcranial Doppler before the operation,and 1d,1week,and 4weeks after surgery.Cerebral angiography was performed 4weeks after surgery to observe the changes of basilar arteries.The basilar arteries were harvested to observe the morphological changes of the arteries and the histological characteristics of the bifurcation tissues 1week and 4weeks after the surgery.Results All animals survived in the sham group,and80%(16/20)of the animals survived in the experimental group.The basilar artery flow velocity increased sharply one day after operation(increased by 226%)in the experimental group,and it kept increasing 1week after the operation until reaching a stable state4weeks after operation.The basal arteries were dilated obviously and displayed tortuous formation after one week in the experimental group,but there was no such change in the sham group.All rabbits in the experimental group presented with thinned media and absent,disrupted or thinned internal elastic lamina near the basilar terminus.Conclusion Blood flow increase at the basilar bifurcation caused by ligation of the bilateral common carotid arteries can lead to aneurysmal change at the basilar terminus of New Zealand white rabbits.

Aneurysmal Remodeling in the Circle of Willis after Carotid Occlusion in an Experimental Model

Carotid occlusions are associated with de novo intracranial aneurysm formation in clinical case reports, but this phenomenon is not widely studied. We performed bilateral carotid ligation (n=9) in rabbits to simulate carotid occlusion, and sham surgery (n=3) for control. Upon euthanasia (n=3 at 5 days, n=6 at 6 months post ligation, and n=3 at 5 days after sham operation), vascular corrosion casts of the circle of Willis (CoW) were created. Using scanning electron microscopy, we quantified gross morphologic, macroscopic, and microscopic changes on the endocasts and compared findings with histologic data. At 5 days, CoW arteries of ligated animals increased caliber. The posterior communicating artery (PCom) increased length and tortuosity, and the ophthalmic artery (OA) origin presented preaneurysmal bulges. At 6 months, calibers were unchanged from 5 days, PComs further increased tortuosity while presenting segmental dilations, and the OA origin and basilar terminus presented preaneurysmal bulges. This exploratory study provides evidence that flow increase after carotid occlusion produces both compensatory arterial augmentation and pathologic remodeling such as tortuosity and saccular/fusiform aneurysm. Our findings may have considerable clinical implications, as these lesser-known consequences should be considered when managing patients with carotid artery disease or choosing carotid ligation as a therapeutic option.

De Novo Cerebral Aneurysm Formation Associated With Proximal Stenosis

Hemodynamic insults--high wall shear stress (WSS) combined with high positive WSS gradient (WSSG)--have been proposed to link to cerebral aneurysm initiation. We report 4 cases of aneurysms with proximal stenosis, including 1 de novo aneurysm, that might be associated with hemodynamic insults caused by the proximal stenosis. In 4 clinical cases, the diameter stenosis was 37% to 49% (mean, 42%) located 2.7 to 4.7 mm (mean, 3.7 mm) from the apex. We performed computational fluid dynamics simulations for 2 cases: a ruptured basilar terminus aneurysm with proximal stenosis (which had an angiogram taken 15 years previously that showed no aneurysm and no stenosis) and a cavernous carotid artery aneurysm with proximal stenosis. In both cases, the stenosis caused unphysiologically high WSS (> 7 Pa) at the apex, nearly doubling the WSS and WSSG values. To investigate the relationship between stenosis and distal hemodynamic elevation, we created a series of T-shaped vascular models by varying the degree and location of stenosis. We found that stenosis > 40% by diameter located within 10 mm from the apex caused unphysiologically high WSS and WSSG. All 4 clinical cases satisfied these conditions. Proximal stenosis could produce high WSS and high positive WSSG at the apex, thus potentially inducing de novo aneurysm formation. BT, basilar terminusCFD, computational fluid dynamicsICA, internal carotid arteryWSS, wall shear stressWSS, wall shear stress gradient.

A Critical Role for Proinflammatory Behavior of Smooth Muscle Cells in Hemodynamic Initiation of Intracranial Aneurysm

BackgroundIntracranial aneurysm initiation is poorly understood, although hemodynamic insult is believed to play an important role in triggering the pathology. It has recently been found in a rabbit model that while macrophages are absent during hemodynamic aneurysm initiation, matrix metalloproteinases (MMPs) are elevated and co-localize with smooth muscle cells (SMCs). This study investigates whether SMCs play a mechanistic role in aneurysm initiation triggered by hemodynamics.MethodsAneurysmal damage was induced at the basilar terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7 sham controls). 16 ligated rabbits were treated with doxycycline to inhibit MMPs, 7 received clodronate liposomes to deplete circulating monocytes, and the rest received no drug. Effects of the treatments on aneurysm development were assessed histologically 5 days and 6 months after ligation. MMP production and expression of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ hybridization.ResultsTreatment with doxycycline attenuated aneurysmal development examined at 5 days and 6 months, suggesting that MMPs contribute to aneurysm initiation. However, systemic depletion of macrophages did not decrease MMPs or suppress aneurysmal development. Immunofluorescence showed that during aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ hybridization indicated that they were transcribed by SMCs. In regions of early aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and increased NF-κB and MCP-1 expressions.ConclusionsDuring aneurysm initiation triggered by hemodynamics, SMCs rather than macrophages are responsible for MMP production that is critical for aneurysmal lesion development. These SMCs exhibit proinflammatory behavior.

Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

Flow impingement at arterial bifurcations causes high frictional force [or wall shear stress (WSS)], and flow acceleration and deceleration in the branches create positive and negative streamwise gradients in WSS (WSSG), respectively. Intracranial aneurysms tend to form in regions with high WSS and positive WSSG. However, little is known about the responses of endothelial cells (ECs) to either positive or negative WSSG under high WSS conditions. We used cDNA microarrays to profile gene expression in cultured ECs exposed to positive or negative WSSG for 24 h in a flow chamber where WSS varied between 3.5 and 28.4 Pa. Gene ontology and biological pathway analysis indicated that positive WSSG favored proliferation, apoptosis, and extracellular matrix processing while decreasing expression of proinflammatory genes. To determine if similar responses occur in vivo, we examined EC proliferation and expression of the matrix metalloproteinase ADAMTS1 under high WSS and WSSG created at the basilar terminus of rabbits after bilateral carotid ligation. Precise hemodynamic conditions were determined by computational fluid dynamic simulations from three-dimensional angiography and mapped on immunofluorescence staining for the proliferation marker Ki-67 and ADAMTS1. Both proliferation and ADAMTS1 were significantly higher in ECs under positive WSSG than in adjacent regions of negative WSSG. Our results indicate that WSSG elicits distinct EC gene expression profiles and particular biological pathways including increased cell proliferation and matrix processing. Such EC responses may be important in understanding the mechanisms of intracranial aneurysm initiation at regions of high WSS and positive WSSG.

The artery of Percheron revisited: a cadaveric anatomical study

The artery of Percheron (AOP) is a single thalamoperforating arterial trunk that provides bilateral supply to the paramedian thalami and the rostral midbrain. As this rare anatomical variant artery may be involved in endovascular procedures or encountered surgically during basilar terminus aneurysms, the present study was warranted. Thirty-four adult (20 male and 14 female) formalin-fixed cadaveric brains underwent dissection of the 68 posterior cerebral arteries. Observations were made of the presence and the variations of the thalamoperforating arteries as well as the presence of the AOP. Thalamoperforating arteries arose from the superior or posterior surfaces of the P1 segment at a mean of a 1.87 mm (range, 0.39-5.25 mm) distance from the basilar apex and entered the brain through the posterior perforated substance. The average number was 4.25 (range 1-9), and the mean diameter was 0.73 mm (range 0.46-1.16 mm). Thalamoperforating arteries were classified into four different types according to their origin at the P1 segment: type I (bilateral multiple, n = 19), 55.8 %; type II (unilateral multiple, unilateral single, n = 4), 11.7 %; type III (bilateral single, n = 7), 20.5 %; type IV [one side with a single branch, the other side with no branches (the AOP), n = 4], 11.7 %. In three separate specimens with ruptured basilar artery aneurysms, the origin of the thalamoperforating arteries was incorporated not only into the posterior aspect of the aneurysm neck but also into the fundus. In about one tenth of cases the possibility of the presence of a single arterial trunk that supplies the two paramedian thalamic territories should be taken into consideration during treatment planning of basilar terminus aneurysms. Furthermore, our data show that the thalamoperforating arteries may take off from both the aneurysm neck and the fundus.

Lack of aneurysm formation after carotid artery ligation in rabbits: a polymer MICROFIL® study

Previous studies have noted formation of saccular aneurysms along the distal basilar artery/P1 segments after carotid ligation in rabbits. In this prospective study we employed MICROFIL®, a polymer, which was used to fill the entire arterial tree, to examine the incidence of microaneurysm formation following right common carotid artery (RCCA) ligation in rabbits. RCCA ligation was performed in 18 New Zealand White rabbits for 0 day (n = 2), 3 weeks (n = 6), or 16 weeks (n = 10). Three control rabbits without carotid surgery were sacrificed at 4 weeks. At the time of sacrifice, MICROFIL® MV-122 yellow was injected through left CCA to fill cerebral vasculature. After gross photographs were taken, specimens were embedded, sectioned, and stained for histopathological evaluation. Tissue and sections were carefully evaluated for microaneurysm formation, defined as a localized dilatation of the vessel wall, associated with fragmentation or complete loss of the internal elastic lamina (IEL), and/or medial degeneration. Gross examination with MICROFIL® opacification demonstrated no evidence of saccular aneurysm formation, but prominent perforating vessels were present in all 19 cases at, or adjacent to, the basilar terminus. Branches noted upon gross examination corresponded histologically to small, saccular contour defects, which demonstrated apparent loss of the IEL and apparent medial thinning. These observations, however, were a consequence of sectioning through the bases of perforating arteries, which simulated microaneurysm formation. Unilateral carotid ligation does not induce microaneurysm formation at the basilar terminus in rabbits. Prominent perforating arteries as well as tissue injury from the processing may simulate "aneurysms" histologically.

Characterization of Critical Hemodynamics Contributing to Aneurysmal Remodeling at the Basilar Terminus in a Rabbit Model

Hemodynamic insult by bilateral common carotid artery ligation has been shown to induce aneurysmal remodeling at the basilar terminus in a rabbit model. To characterize critical hemodynamics that initiate this remodeling, we applied a novel hemodynamics-histology comapping technique. Eight rabbits received bilateral common carotid artery ligation to increase basilar artery flow. Three underwent sham operations. Hemodynamic insult at the basilar terminus was assessed by computational fluid dynamics. Bifurcation tissue was harvested on day 5; histology was comapped with initial postligation hemodynamic fields of wall shear stress (WSS) and WSS gradient. All bifurcations showed internal elastic lamina loss in periapical regions exposed to accelerating flow with high WSS and positive WSS gradient. Internal elastic lamina damage happened 100% of the time at locations where WSS was >122 Pa and WSS gradient was >530 Pa/mm. The degree of destructive remodeling accounting for internal elastic lamina loss, medial thinning, and luminal bulging correlated with the magnitude of the hemodynamic insult. Aneurysmal remodeling initiates when local hemodynamic forces exceed specific limits at the rabbit basilar terminus. A combination of high WSS and positive WSS gradient represents dangerous hemodynamics likely to induce aneurysmal remodeling.

Mapping vascular response to in vivo Hemodynamics: application to increased flow at the basilar terminus

Hemodynamic forces play critical roles in vascular pathologies such as atherosclerosis, aneurysms, and stenosis. However, detailed relationships between the specific in vivo hemodynamic microenvironment and vascular responses leading to the triggering or exacerbation of pathological remodeling of the vessel remain elusive. We have developed a hemodynamics-biology co-mapping technique that enables in situ correlation between the in vivo blood flow field and vascular changes secondary to hemodynamic insult. The hemodynamics profile is obtained from computational fluid dynamics simulation within the vascular geometry reconstructed from three-dimensional in vivo images, whereas the vascular response is obtained from histology or immunohistochemistry on harvested vascular tissue. The hemodynamics field is virtually sectioned in the histological slicing planes and digitally co-mapped with the histological images, thereby enabling correlation of the specific local vascular responses with the inciting hemodynamic stresses. We demonstrate application of this technique to rabbit basilar terminus subjected to elevated flow. Morphological changes at the basilar terminus 5 days after the flow increase were co-mapped with the initial wall shear stress and wall shear stress gradient distributions, from which localization of destructive remodeling in a specific hemodynamic zone was noticed. This method paves the way for further investigations to determine the connection between in vivo mechanical stimuli and biological responses, such as initiation of aneurysmal remodeling.

Aneurysmal Changes at the Basilar Terminus in the Rabbit Elastase Aneurysm Model

We read the interesting report by Dai et al,[1][1] wherein the authors examined histology at the basilar terminus (BT) following right common carotid artery (RCCA) ligation as a part of a procedure to create an elastase aneurysm model in 30 consecutive New Zealand white rabbits at various time

Significance of Large Vessel Intracranial Occlusion Causing Acute Ischemic Stroke and TIA

Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score <or=2) was negatively predicted by LVO (0.33; 0.24 to 0.45; P<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to National Institutes of Health Stroke Scale and age, independently predicted outcome. Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.

Experience with Microaneurysm Formation at the Basilar Terminus in the Rabbit Elastase Aneurysm Model

Intracranial aneurysms have been induced in mice, rats, rabbits, and primates through carotid artery ligation. We reviewed our experience with RCCA ligation to quantify the rate of aneurysm formation in rabbits. In 30 consecutive New Zealand white rabbits, the RCCA was ligated during surgery to create elastase-induced aneurysms. The basilar artery and its bifurcation were harvested at various time points after surgery, including 8 weeks (n = 5), 13 weeks (n = 3), 14 weeks (n = 2), 16 weeks (n = 4), 17 weeks (n = 4), 30 weeks (n = 6), and 33 weeks (n = 6). All specimens were embedded in paraffin and sectioned at 5 microm in a coronal orientation, to show the basilar bifurcation and its branches. All sections were stained with HE. After the sections were evaluated and the photomicrographs were taken, the sections were de-stained and re-stained with VVG staining for elastin. The IEL was intact and continuous at the BT in all 30 rabbits, as was the medial layer. No bulge-like localized dilation, to suggest microaneurysm or nascent aneurysm formation, was observed at the BT in any subject. There were small (0.08 +/- 0.02 mm in diameter) concave structures along the P1 segments in 5 (16.7%) of 30 rabbits. On adjacent tissue sections, each of these 5 structures was shown to be branch vessels with intact IELs. In our rabbit model, unilateral RCCA ligation does not induce microaneurysm formation.