Adam Arthur

Monoclonal Antibodies Against ICAM-1 and CD18 Attenuate Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits

BACKGROUND AND PURPOSE Inflammatory responses have been implicated in the elaboration of several forms of central nervous system injury, including cerebral vasospasm after subarachnoid hemorrhage (SAH). A critical event participating in such responses is the recruitment of circulating leukocytes into the inflammatory site. Two of the key adhesion molecules responsible for the attachment of leukocytes to endothelial cells are intercellular adhesion molecule-1 (ICAM-1) and the common beta chain of the integrin superfamily (CD18). This study examined the effects of monoclonal antibodies on ICAM-1 and the effects of CD18 on cerebral vasospasm after SAH. METHODS A rabbit model of SAH was utilized to test the influence of intracisternally administered antibodies to ICAM-1 and CD18 on cerebral vasospasm. Antibodies were administered alone or in combination, and the cross-sectional area of basilar arteries was assessed histologically on day 2 post-SAH. RESULTS Treatment with antibodies to ICAM-1 or CD18 inhibited vasospasm by 22% and 27%, respectively. When administered together, the attenuation of vasospasm increased to 56%. All of these effects achieved statistical significance. CONCLUSIONS These findings provide the first evidence that the severity of cerebral vasospasm can be attenuated using monoclonal antibodies against ICAM-1 and CD18. The results reinforce the concept that cell-mediated inflammation plays an important role in cerebral vasospasm after SAH and suggest that therapeutic targeting of cellular adhesion molecules can be of benefit in treating cerebral vasospasm.

Utilization of Pipeline embolization device for treatment of ruptured intracranial aneurysms: US multicenter experience

Objective Utilization of the Pipeline embolization device (PED) in complex ruptured aneurysms has not been well studied. We evaluated the safety and effectiveness data from five participating US centers. Methods Records of patients with ruptured cerebral aneurysms who underwent PED treatment between 2011 and 2013 were retrospectively reviewed. Results 26 patients with ruptured aneurysms underwent PED treatment (mean age 51.4±13.2 years;16 women). At presentation, 8 patients (30.8%) had a Hunt–Hess grade of IV or above; 11 required extraventricular drain placement. Aneurysm morphologies were: 8 dissecting, 8 blister-like, 6 fusiform, and 4 saccular. There were 22 anterior circulation and 4 posterior circulation aneurysms. PED deployment was successful in all patients, with adjunctive coiling utilized in 12. Periprocedural complications occurred in 5 (19.2%), including 3 inhospital deaths. 23 patients (88.5%) had postoperative angiography at a mean of 5.9 months: 18 aneurysms (78.3%) were completely occluded, 3 (13.0%) had residual neck filling, and 2 (8.7%) had residual dome filling. All blister-type aneurysms were completely occluded at follow-up. Clinical follow-up was available for an average of 10.1 months (range 2–21 months), with one asymptomatic in-stent stenosis and one asymptomatic thromboembolic stroke noted. Good outcome (modified Rankin Scale (mRS) score of 0–2) was achieved in 20 patients (76.9%), fair (mRS 3–4) in 3 (11.5%), and 3 died (11.5%). Conclusions The PED can be utilized for ruptured aneurysms and is a good option for blister-type aneurysms. However, due to periprocedural complications, it should be reserved for lesions that are difficult to treat by conventional clipping or coiling.

Distal aspiration with retrievable stent assisted thrombectomy for the treatment of acute ischemic stroke

Objective Flexible large lumen aspiration catheters and stent retrievers have recently become available in the USA for the revascularization of large vessel occlusions presenting within the context of acute ischemic stroke (AIS). We describe a multicenter experience using a combined aspiration and stent retrieval technique for thrombectomy. Design A retrospective analysis to identify patients receiving combined manual aspiration and stent retrieval for treatment of AIS between August 2012 and April 2013 at six high volume stroke centers was conducted. Outcome variables, including recanalization rate, post-treatment National Institutes of Health Stroke Scale (NIHSS) score, symptomatic intracranial hemorrhage, discharge 90 day modified Rankin Scale (mRS) score, and mortality were evaluated. Results 105 patients were found that met the inclusion criteria for this retrospective study. Successful recanalization (Thrombolysis in Cerebral Infarction score 2B) was achieved in 92 (88%) of these patients. 44% of patients had favorable (mRS score 0–2) outcomes at 90 days. There were five (4.8%) symptomatic intracerebral hemorrhages and three procedure related deaths (2.9%). Conclusions Mechanical thrombectomy utilizing combined manual aspiration with a stent retriever is an effective and safe strategy for endovascular recanalization of large vessel occlusions presenting within the context of AIS.

Feasibility and Safety of Pipeline Embolization Device in Patients With Ruptured Carotid Blister Aneurysms

BACKGROUND Treatment of internal carotid ruptured blister aneurysms (IC-RBA) presents many challenges to neurosurgeons because of the high propensity for rebleeding during intervention. The role of a Pipeline Embolization Device (PED) in the treatment of this challenging aneurysm subtype remains undefined despite theoretical advantages. OBJECTIVE To present a series of 11 patients treated with a PED and to discuss the management and results of this novel application of flow diverters. METHODS Medical records of patients who presented with IC-RBA from May 2011 to March 2013 were retrospectively reviewed at 6 institutions in the United States. All relevant data were independently compiled. RESULTS A total of 12 IC-RBAs in 11 patients were treated during the study period. Nine (75%) were treated with a single PED; 1 was treated with 2 PEDs; 1 was treated with coils and 1 PED; and 1 was treated with coils and 2 PEDs. Three (27%) had major perioperative complications: middle cerebral artery territory infarction, vision loss, and death. Seven patients demonstrated complete obliteration of the aneurysm in postoperative imaging. Early clinical outcomes were favorable (modified Rankin Scale score, 0-2) in all 10 survivors. CONCLUSION This study demonstrates the feasibility and safety of using the PED to treat IC-RBA with fair initial results. The proper introduction and management of antiplatelet regimen are key for successful results. Bleeding complications related to dual antiplatelet therapy were similar to those in previous studies of stent-assisted coiling for the same population. Larger cohort analysis is needed to define the precise role of flow diverters in the treatment of IC-RBA.

Solitaire flow restoration thrombectomy for acute ischemic stroke: Retrospective multicenter analysis of early postmarket experience after FDA approval

BACKGROUND The promising results of the Solitaire Flow Restoration (FR) With the Intention for Thrombectomy (SWIFT) trial recently led to Food and Drug Administration (FDA) approval of the Solitaire FR stent retriever device for recanalization of cerebral vessels in patients with acute ischemic stroke. OBJECTIVE To report the early postmarket experience with this device since its FDA approval in the United States, which has not been previously described. METHODS We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between March 2012 and July 2012 at 10 United States centers where the Solitaire FR was used as a single device or in conjunction with other intraarterial endovascular approaches. RESULTS A total of 101 patients were identified (mean age, 64.7 years; mean admission National Institutes of Health Stroke Scale [NIHSS] score, 17.6). Intravenous thrombolysis was administered in 39% of cases; other endovascular techniques were utilized in conjunction with the Solitaire FR in 52%. Successful recanalization (Thrombolysis in Myocardial Infarction 2/3) was achieved in 88%. The rate of symptomatic intracranial hemorrhage within the first 24 hours was 15%. In-hospital mortality was 26%. At 30 days, 38% of patients had favorable functional outcome (modified Rankin scale score ≤2). Severity of NIHSS score on admission was a strong predictor of poor outcome. CONCLUSION Our study shows that a variety of other endovascular approaches are used in conjunction with Solitaire FR in actual practice in the United States. Early postmarket results suggest that Solitaire FR is an effective tool for endovascular treatment of acute ischemic stroke.

Embolectomy for stroke with emergent large vessel occlusion (ELVO): report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery

Stroke is the leading cause of adult disability in North America and is the fifth most common cause of death.1 ,2 The natural history of patients with acute ischemic stroke and occlusion of a major intracranial vessel such as the internal carotid artery (ICA), middle cerebral artery (MCA), or basilar artery is dismal, with high rates of mortality and low rates of disability-free survival.3 ,4 We introduce the term ‘Emergent Large Vessel Occlusion (ELVO)’ to describe this clinical scenario. Among acute ischemic stroke, ELVO accounts for the greatest proportion of patients with long-term disability. For the past two decades the use of endovascular therapy has been performed in many centers across the world. The therapies have spanned from infusion of thrombolytic agents5 ,6 to mechanical embolectomy with the introduction of first-generation devices,7 ,8 aspiration-based embolectomy techniques,9 ,10 and the use of stent-retriever based procedures.11 ,12 However, these embolectomy trials were single-arm trials demonstrating safety of the procedure and technique or superiority over another, without direct comparison with standard medical therapy alone. In the past 3 years, several major trials have been published comparing endovascular therapy with standard medical therapy alone. The purpose of this document is to summarize the results of these trials and synthesize the level of evidence supporting the use of embolectomy in patients with ELVO. This document was prepared by the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery, a multidisciplinary society representing the leaders in the field of endovascular therapy for neurovascular disease. The strength of the evidence supporting each recommendation was summarized using a scale previously described by the American Heart Association. ### Role of intravenous thrombolysis In 1996 the FDA approved the use of recombinant tissue plasminogen activator (tPA) for the treatment of acute ischemic stroke …

Should neurointerventional fellowship training be suspended indefinitely

> To bring about destruction by overcrowding, mass starvation, anarchy, the destruction of our most cherished values—there is no need to do anything. We need only do nothing except what comes naturally—and breed. And how easy it is to do nothing. Isaac Asimov The purpose of any training program is to provide a supply of skilled workers to address an unmet demand for their services. With respect to medical training, new physicians are required either to take the place of retiring physicians or to address an unmet demand for patient care. Evolving data strongly suggest that the supply of neurointerventional (NI) physicians is not only sufficient, but has exceeded the present need for services. Despite this, we continue to train new neurointerventionists (NIs) in unprecedented and increasing numbers every year. These new NI physicians are finding it progressively more difficult to secure employment and, once hired, face considerable challenges in building a practice and developing/maintaining their skills. Fellowship training is ingrained into the fabric of our academic practices and currently seems to be perpetuated more by inertia than a dynamic evaluation of the present workforce needs. It is the position of the authors that, if we do not re-evaluate this process, we are potentially doing a tremendous disservice to the people we are training, to patients in need of treatment (and maybe more importantly to those patients with lesions who are not in need of treatment), and finally to ourselves. One of the more difficult aspects of evaluating the NI workforce is obtaining accurate data to characterize the status of current supply and demand—such as the number of practicing NI physicians, the number and growth rate of neuroendovascular cases and the number of new graduates entering the market each year. These statistics must be triangulated using several available sources, the most …

Systemic Administration of the Endothelin-A Receptor Antagonist TBC 11251 Attenuates Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage: Dose Study and Review of Endothelin-based Therapies in the Literature on Cerebral Vasospasm

OBJECTIVE Increasing evidence implicates endothelin (ET)-1 in the pathophysiological development of cerebral vasospasm. This study examined the ability of TBC 11251 (TBC), a new ETA receptor antagonist, to prevent vasospasm in a rabbit model of subarachnoid hemorrhage (SAH). METHODS Eighty-five New Zealand White rabbits were assigned to 1 of 10 groups. SAH was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: 1) control (no SAH), 2) SAH alone, 3) SAH plus vehicle every 12 hours (BID), 4) SAH plus 5 mg/kg TBC BID, 5) SAH plus 10 mg/kg TBC BID, 6) SAH plus 20 mg/kg TBC BID, 7) SAH plus vehicle at 24 and 36 hours after SAH (24/36), 8) SAH plus 5 mg/kg TBC 24/36, 9) SAH plus 10 mg/kg TBC 24/36, and 10) SAH plus 20 mg/kg TBC 24/36. Animals were killed 48 hours after SAH, by perfusion-fixation, and then basilar arteries were histologically prepared and their cross-sectional areas were measured. RESULTS The mean basilar artery cross-sectional area was constricted from 0.332 mm2 in the control group to 0.131 mm2 in the SAH alone group, 0.132 in the vehicle 24/36 group, and 0.125 in the vehicle BID group. All groups treated with TBC showed an increase in cross-sectional luminal basilar artery area, relative to the vehicle-treated groups. The 5 mg/kg TBC BID group exhibited a mean basilar artery area of 0.217 mm2, and the 10 mg/kg TBC BID group showed a mean basilar artery area of 0.240 mm2; both groups were statistically improved, compared with the vehicle-treated groups (P < 0.05). No side effects were seen, and there were no differences in the mean arterial pressures between drug- and vehicle-treated groups. CONCLUSION These findings demonstrate that systemic administration of the ETA receptor antagonist TBC significantly attenuates cerebral vasospasm after SAH, thus providing additional support for the role of ET-1 in vasospasm.

Systemic Administration of the Iron Chelator Deferiprone Attenuates Subarachnoid Hemorrhage-induced Cerebral Vasospasm in the Rabbit

OBJECTIVE Iron catalyzed generation of injurious free radicals has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). The present study assessed the effects of the iron chelator deferiprone on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS Twenty-four rabbits were assigned to three groups as follows: SAH plus placebo (n = 8), SAH plus deferiprone (n = 8), or control plus placebo (n = 8). Deferiprone was administered to an additional group of three rabbits that were not subjected to SAH. Drug administration was initiated 8 hours after SAH was induced and was repeated at 8-hour intervals. The animals were killed using perfusion-fixation 48 hours after SAH. Cross-sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups. RESULTS In placebo-treated animals, the average luminal cross-sectional area of the basilar artery was reduced by 54% after SAH compared to controls (i.e., from 0.272 to 0.125 mm2). The vasospastic response after SAH was attenuated significantly in animals treated with deferiprone (0.208 mm2, representing a 24% reduction). CONCLUSION Previous experimental studies suggested that iron chelation can be effective in attenuating cerebral vasospasm after SAH. Deferiprone is a recently developed iron chelator that has been extensively evaluated for the treatment of patients requiring chronic blood transfusions. The present study demonstrates that deferiprone is effective in attenuating experimental cerebral vasospasm. Because of its stability, lipophilicity, and ability to penetrate the blood-brain barrier, deferiprone represents an attractive candidate for the treatment of cerebral vasospasm.

Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes

Background and Purpose— Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. Methods— We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. Results— A total of 100 patients were included in the final analysis (mean age, 63.5±14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2±8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score ⩽2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. Conclusions— Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization.