Gregory J. Velat

Early postmarket results after treatment of intracranial aneurysms with the pipeline embolization device: A US multicenter experience

BACKGROUND The pipeline embolization device (PED) is the latest technology available for intracranial aneurysm treatment. OBJECTIVE To report early postmarket results with the PED. METHODS This study was a prospective registry of patients treated with PEDs at 7 American neurosurgical centers subsequent to Food and Drug Administration approval of this device. Data collected included clinical presentation, aneurysm characteristics, treatment details, and periprocedural events. Follow-up data included degree of aneurysm occlusion and delayed (> 30 days after the procedure) complications. RESULTS Sixty-two PED procedures were performed to treat 58 aneurysms in 56 patients. Thirty-seven of the aneurysms (64%) treated were located from the cavernous to the superior hypophyseal artery segment of the internal carotid artery; 22% were distal to that segment, and 14% were in the vertebrobasilar system. A total of 123 PEDs were deployed with an average of 2 implanted per aneurysm treated. Six devices were incompletely deployed; in these cases, rescue balloon angioplasty was required. Six periprocedural (during the procedure/within 30 days after the procedure) thromboembolic events occurred, of which 5 were in patients with vertebrobasilar aneurysms. There were 4 fatal postprocedural hemorrhages (from 2 giant basilar trunk and 2 large ophthalmic artery aneurysms). The major complication rate (permanent disability/death resulting from perioperative/delayed complication) was 8.5%. Among 19 patients with 3-month follow-up angiography, 68% (13 patients) had complete aneurysm occlusion. Two patients presented with delayed flow-limiting in-stent stenosis that was successfully treated with angioplasty. CONCLUSION Unlike conventional coil embolization, aneurysm occlusion with PED is not immediate. Early complications include both thromboembolic and hemorrhagic events and appear to be significantly more frequent in association with treatment of vertebrobasilar aneurysms.

Vasospasm After Aneurysmal Subarachnoid Hemorrhage: Review of Randomized Controlled Trials and Meta-Analyses in the Literature

OBJECTIVE Cerebral vasospasm is a major source of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). A variety of therapies have been utilized to prevent or treat vasospasm. Despite the large number of clinical trials, few randomized controlled trials (RCTs) of sufficient quality have been published. We review the RCTs and meta-analyses in the literature regarding the treatment and prevention of cerebral vasospasm following aneurysmal SAH. METHODS A literature search of MEDLINE, the Cochrane Controlled Trials Registry, and the National Institutes of Health/National Library of Medicine clinical trials registry was performed in January 2010 using predefined search terms. These trials were critically reviewed and categorized based on therapeutic modality. RESULTS Forty-four RCTs and 9 meta-analyses met the search criteria. Significant findings from these trials were analyzed. The results of this study were as follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium channel blockers, including nicardipine, do not provide unequivocal benefit; triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics, endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies such as free radical scavengers and antifibrinolytics require additional study. Tirilazad is ineffective. CONCLUSIONS There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use. Nimodipine is the only treatment that provided a significant benefit across multiple studies.

Bottleneck factor and height-width ratio: association with ruptured aneurysms in patients with multiple cerebral aneurysms.

OBJECTIVEDetermining factors predictive of the natural risk of rupture of cerebral aneurysms is difficult because of the need to control for confounding variables. We studied factors associated with rupture in a study model of patients with multiple cerebral aneurysms, one aneurysm that had ruptured and one or more that had not, in which each patient served as their own internal control. METHODSWe collected aneurysm location, one-dimensional measurements, and two-dimensional indices from the computed tomographic angiograms of patients in the proposed study model and compared ruptured versus unruptured aneurysms. Bivariate statistics were supplemented with multivariable logistic regression analysis to model ruptured status. A total of 40 candidate models were evaluated for predictive power and fit with Wald scoring, Cox and Snell R2, Hosmer and Lemeshow tests, case classification counting, and residual analysis to determine which of the computed tomographic angiographic measurements or indices were jointly associated with and predictive of aneurysm rupture. RESULTSThirty patients with 67 aneurysms (30 ruptured, 37 unruptured) were studied. Maximum diameter, height, maximum width, bulge height, parent artery diameter, aspect ratio, bottleneck factor, and aneurysm/parent artery ratio were significantly (P < 0.05) associated with ruptured aneurysms on bivariate analysis. When best subsets and stepwise multivariable logistic regression was performed, bottleneck factor (odds ratio = 1.25, confidence interval = 1.11–1.41 for every 0.1 increase) and height-width ratio (odds ratio = 1.23, confidence interval = 1.03–1.47 for every 0.1 increase) were the only measures that were significantly predictive of rupture. CONCLUSIONIn a case-control study of patients with multiple cerebral aneurysms, increased bottleneck factor and height-width ratio were consistently associated with rupture.

Delayed intraparenchymal hemorrhage following pipeline embolization device treatment for a giant recanalized ophthalmic aneurysm

The pipeline embolization device has demonstrated clinical success in the management of complex intracranial aneurysms arising along the anterior intracranial circulation with a relatively low complication profile. A case report is presented which describes a novel complication of delayed intraparenchymal hemorrhage following deployment of a pipeline embolization device for the treatment of a previously ruptured partially thrombosed ophthalmic segment aneurysm.

Critical Care Guidelines on the Endovascular Management of Cerebral Vasospasm

Cerebral vasospasm and delayed cerebral ischemia account for significant morbidity and mortality after aneurysmal subarachnoid hemorrhage. While most patients are managed with triple-H therapy, endovascular treatments have been used when triple-H treatment cannot be used or is ineffective. An electronic literature search was conducted to identify English language articles published through October 2010 that addressed endovascular management of vasospasm. A total of 49 articles were identified, addressing endovascular treatment timing, intra-arterial treatments, and balloon angioplasty. Most of the available studies investigated intra-arterial papaverine or balloon angioplasty. Both have generally been shown to successfully treat vasospasm and improve neurological condition, with no clear benefit from one treatment compared with another. There are reports of complications with both therapies including vessel rupture during angioplasty, intracranial hypertension, and possible neurotoxicity associated with papaverine. Limited data are available evaluating nicardipine or verapamil, with positive benefits reported with nicardipine and inconsistent benefits with verapamil.

Comparison of N-butyl cyanoacrylate and onyx for the embolization of intracranial arteriovenous malformations: analysis of fluoroscopy and procedure times.

OBJECTIVE Intracranial arteriovenous malformations (AVM) may be managed through staged preoperative embolization and resection. Two commonly used liquid embolics are N-butyl cyanoacrylate (nBCA; Cordis Microvascular, Inc., New Brunswick, NJ) and Onyx (ev3, Inc., Irvine, CA). We sought to compare the utility of these agents in terms of fluoroscopy and procedure times. METHODS All intracranial AVMs embolized from 2002 to 2006 at the University of Florida were included in this study. Patients were stratified into three treatment groups: nBCA, Onyx, and patients who received both nBCA and Onyx during separate embolizations. Cohorts were compared by sex, age, Spetzler-Martin grade, AVM volume, fluoroscopy time, procedure time, surgical blood loss, and complications. RESULTS A total of 182 embolizations were performed on 88 patients (nBCA, 60 patients and 106 procedures; Onyx, 20 patients and 43 procedures; and nBCA/Onyx, eight patients and 16 nBCA and 17 Onyx procedures). There were no significant differences in patient demographics, AVM volumes, and Spetzler-Martin grades. Mean fluoroscopy and procedure times were increased for Onyx (57 min; 2.6 h) compared with nBCA (37 min; 2.1 h) embolizations (P < 0.0001 and P = 0.001, respectively). Cumulative mean fluoroscopy time was increased for Onyx (135 min) and nBCA/Onyx (180 min) cohorts relative to nBCA (64 min; P < 0.0001). Cumulative mean procedure time was increased in the nBCA/Onyx group (10.4 h) compared with nBCA (3.7 h) and Onyx (5.4 h; P < 0.0001). Seventy patients (80%) underwent AVM resection. No significant differences in surgical blood loss or complication rates were observed among the cohorts. CONCLUSION Onyx AVM embolization requires increased fluoroscopy and procedure times compared with nBCA. Further investigation is necessary to justify increased radiation exposure and procedure time associated with Onyx.

Surgical outcomes for moyamoya angiopathy at barrow neurological institute with comparison of adult indirect encephaloduroarteriosynangiosis bypass, adult direct superficial temporal artery-to-middle cerebral artery bypass, and pediatric bypass: 154 revascularization surgeries in 140 affected hemispheres

BACKGROUND Untreated, moyamoya angiopathy is a progressive vaso-occlusive process that can lead to ischemic or hemorrhagic stroke. OBJECTIVE To review 1 institutions surgical experience with both direct and indirect bypass (encephaloduroarteriosynangiosis) in adult and pediatric groups. METHODS A retrospective review was conducted of a consecutive series of patients treated for moyamoya angiopathy between 1995 and 2009. RESULTS Thirty-nine adult patients underwent indirect bypass as their initial therapy; 29 adult patients underwent direct bypass. Twenty-four pediatric patients included 20 indirect bypasses and 4 direct bypasses. Overall, 140 hemispheres were treated; 48 patients received revascularization of both hemispheres. There were 14 additional revascularization procedures (10% per hemisphere) performed over a site of continued hypoperfusion postoperatively. Fourteen postoperative ischemic strokes occurred during the entire follow-up (10% per hemisphere), and the Kaplan-Meier analysis was not significantly different between groups (P = .59). Four grafts (9.09%) had failed at radiographic follow-up of the 44 direct bypasses performed. Before the initial surgery, the modified Rankin Scale score was 1.58 ± 0.93, 1.48 ± 0.74, and 1.8 ± 1.1 in the pediatric, adult direct, and adult indirect groups (P = .39). At last follow-up, it was 1.29 ± 1.31, 1.09 ± 0.90, and 1.94 ± 1.51 (P = .04) in the pediatric, adult direct, and adult indirect groups. CONCLUSION This series demonstrates that both direct and indirect bypasses can be equally effective in preventing stroke. However, in adult patients, direct bypass patients had significantly greater improvement in symptoms, as seen in modified Rankin Scale scores. Pediatric patients, despite undergoing predominantly indirect bypasses, fared roughly the same as the adults in the direct bypass group.

Direct thrombolysis for cerebral venous sinus thrombosis

Cerebral venous sinus thrombosis (CVST) is an increasingly diagnosed disease with a wide range of symptoms, ranging from a mild headache to cerebral herniation. A potentially devastating syndrome, CVST has been associated with a mortality rate of 6-10%. In prospective studies, the overall rate of death and dependency from CVST ranges from 8.8 to 44.4%. Systemic anticoagulation remains the first-line treatment. However, a percentage of patients deteriorate despite medical therapy. These cases have resulted in the development of thrombolysis or endovascular treatment for CVST. Initial reports of the use of endovascular treatment of CVST have been promising. However, enthusiasm for the use of endovascular thrombolysis and thrombectomy should be tempered by an understanding of possible risks such as intracerebral hemorrhage and/or vessel dissection. The authors review the literature regarding endovascular treatment of CVST with a description of the chemical and mechanical thrombolytic techniques.

Stromal cell-derived factor-1 promoted angiogenesis and inflammatory cell infiltration in aneurysm walls.

OBJECT A small percentage of cerebral aneurysms rupture, but when they do, the effects are devastating. Current management of unruptured aneurysms consists of surgery, endovascular treatment, or watchful waiting. If the biology of how aneurysms grow and rupture were better known, a novel drug could be developed to prevent unruptured aneurysms from rupturing. Ruptured cerebral aneurysms are characterized by inflammation-mediated wall remodeling. The authors studied the role of stromal cell-derived factor-1 (SDF-1) in inflammation-mediated wall remodeling in cerebral aneurysms. METHODS Human aneurysms, murine carotid artery aneurysms, and murine intracranial aneurysms were studied using immunohistochemistry. Flow cytometry analysis was performed on blood from mice developing carotid or intracranial aneurysms. The effect of SDF-1 on endothelial cells and macrophages was studied by chemotaxis cell migration assay and capillary tube formation assay. Anti-SDF-1 blocking antibody was given to mice and compared with control (vehicle)-administered mice for its effects on the walls of carotid aneurysms and the development of intracranial aneurysms. RESULTS Human aneurysms, murine carotid aneurysms, and murine intracranial aneurysms all expressed SDF-1, and mice with developing carotid or intracranial aneurysms had increased progenitor cells expressing CXCR4, the receptor for SDF-1 (p < 0.01 and p < 0.001, respectively). Human aneurysms and murine carotid aneurysms had endothelial cells, macrophages, and capillaries in the walls of the aneurysms, and the presence of capillaries in the walls of human aneurysms was associated with the presence of macrophages (p = 0.01). Stromal cell-derived factor-1 promoted endothelial cell and macrophage migration (p < 0.01 for each), and promoted capillary tube formation (p < 0.001). When mice were given anti-SDF-1 blocking antibody, there was a significant reduction in endothelial cells (p < 0.05), capillaries (p < 0.05), and cell proliferation (p < 0.05) in the aneurysm wall. Mice given anti-SDF-1 blocking antibody developed significantly fewer intracranial aneurysms (33% vs 89% in mice given control immunoglobulin G, respectively; p < 0.05). CONCLUSIONS These data suggest SDF-1 is associated with angiogenesis and inflammatory cell migration and proliferation in the walls of aneurysms, and may have a role in the development of intracranial aneurysms.

Alpha-II spectrin breakdown products in aneurysmal subarachnoid hemorrhage : a novel biomarker of proteolytic injury

OBJECT Aneurysmal subarachnoid hemorrhage (ASAH) is a serious event with grave consequences. Delayed ischemic neurological deficits caused by cerebral arterial vasospasm contribute significantly to death and disability. Biomarkers may reflect brain injury and provide an early warning of impending neurological decline and stroke from ASAH-induced vasospasm. Alpha-II spectrin is a cytoskeletal protein whose breakdown products are candidate surrogate markers of injury magnitude, treatment efficacy, and outcome. In addition, all spectrin breakdown products (SBDPs) can provide information on the proteolytic mechanisms of injury. METHODS Twenty patients who received a diagnosis of Fisher Grade 3 ASAH were enrolled in this study to examine the clinical utility of SBDPs in the detection of cerebral vasospasm in patients with ASAH. All patients underwent placement of a ventriculostomy for continual cerebrospinal fluid drainage within 72 hours of ASAH onset. Cerebrospinal fluid samples were collected every 6 hours and analyzed using Western Blotting for SBDPs. Onset of vasospasm was defined as an acute onset of a focal neurological deficit or a change in Glasgow Coma Scale score of two or more points. All suspected cases of vasospasm were confirmed on imaging studies. RESULTS Both calpain- and caspase-mediated SBDP levels are significantly increased in patients suffering ASAH. The concentration of SBDPs was found to increase significantly over baseline level up to 12 hours before the onset of cerebral arterial vasospasm. CONCLUSIONS Differential expression of SBDPs suggests oncotic necrotic proteolysis may be predominant in acute brain injury after ASAH and cerebral arterial vasospasm.