Robert A. Mericle

Rapid and effective labeling of brain tissue using TAT-conjugated CdS∶Mn/ZnS quantum dots

TAT (a cell penetrating peptide)-conjugated CdSratioMn/ZnS quantum dots (Qdots), intra-arterially delivered to a rat brain, rapidly (within a few minutes) labeled the brain tissue without manipulating the blood-brain-barrier (BBB). Qdot loading was sufficiently high that it allowed a gross fluorescent visualization of the whole rat brain using a low power hand-held UV lamp. Histological data clearly showed that TAT-conjugated Qdots migrated beyond the endothelial cell line and reached the brain parenchyma. Qdots without TAT did not label the brain tissue confirming the fact that TAT peptide was necessary to overcome the BBB. The present study clearly demonstrated the possibility of delivering a large amount of Qdot-based imaging agents to the brain tissue.

Stenting and secondary coiling of intracranial internal carotid artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE Endovascular stents have been successfully used in the treatment of fusiform and dissecting aneurysms of the peripheral circulation and extracranial carotid and vertebral arteries. Technical limitations related to the inability to navigate the stent and the delivery system through tortuous vascular segments has limited their application with intracranial lesions. Availability of new flexible and pliable stent systems might overcome these difficulties. CLINICAL PRESENTATION A 49-year-old woman presented with a dissecting pseudoaneurysm of the horizontal portion of the petrous internal carotid artery that increased in size, as revealed by serial angiographic studies. INTERVENTION The aneurysm was treated by deploying a new flexible stent across the aneurysm neck and by then packing the aneurysm sac with Guglielmi detachable coils that were delivered by a microcatheter positioned through the stent struts into the aneurysm lumen. CONCLUSION New flexible stents can be used to treat intracranial internal carotid artery aneurysms in difficult-to-access areas, such as the horizontal petrous segment. The stent may disrupt the aneurysm inflow tract, thereby inducing stasis and facilitating intra-aneurysmal thrombosis. In addition, the stent acts as an endoluminal scaffold to prevent coil herniation into the parent artery, which allows tight packing of even wide-necked and irregularly shaped aneurysms. The stent may also serve as a matrix for endothelial growth. We think this new generation of flexible stents and the use of this described technique will usher in the next era of endovascular management of intracranial aneurysms.

TAT conjugated, FITC doped silica nanoparticles for bioimaging applications

Water-in-oil (w/o) microemulsion synthesis of 70 nm size monodisperse TAT (a cell penetrating peptide, CPP) conjugated, FITC (fluorescein isothiocyanate) doped silica nanoparticles (TAT-FSNPs) is reported; human lung adenocarcinoma (A549) cells (in vitro) and rat brain tissue (in vivo) were successfully labeled using TAT-FSNPs.

Effect of Prophylactic Transluminal Balloon Angioplasty on Cerebral Vasospasm and Outcome in Patients With Fisher Grade III Subarachnoid Hemorrhage Results of a Phase II Multicenter, Randomized, Clinical Trial

Background and Purpose— Cerebral vasospasm continues to be a major cause of poor outcome in patients with ruptured aneurysms. Prophylactic Transluminal Balloon Angioplasty (pTBA) appeared to prevent delayed ischemic neurological deficit in a pilot study. A phase II multicenter randomized clinical trial was subsequently designed. Methods— One hundred and seventy patients with Fisher Grade III subarachnoid hemorrhage were enrolled in the study. Of these, 85 patients were randomized to the treatment group and underwent pTBA within 96 hours after subarachnoid hemorrhage. Main end points of the study included the 3-month dichotomized Glasgow Outcome Score (GOS), development of delayed ischemic neurological deficit (DIND), occurrence of Transcranial Doppler (TCD) vasospasm, and length of stay in the ICU and hospital. Results— The incidence of DIND was lower in the pTBA group (P=0.30) and fewer patients required therapeutic angioplasty to treat DIND (P=0.03). Overall pTBA resulted in an absolute risk reduction of 5.9% and a relative risk reduction of 10.4% unfavorable outcome (P=0.54). Good grade patients had absolute and relative risk reductions of respectively 9.5 and 29.4% (P=0.73). Length of stay in ICU and hospital was similar in both groups. Four patients had a procedure-related vessel perforation, of which three patients died. Conclusions— While the trial is unsuccessful as defined by the primary end point (GOS), proof of concept is confirmed by these results. Fewer patients tend to develop vasospasm after treatment with pTBA and there is a statistically significantly decreased need for therapeutic angioplasty. pTBA does not improve the poor outcome of patients with Fisher grade III subarachnoid hemorrhage.

Temporary balloon protection as an adjunct to endosaccular coiling of wide-necked cerebral aneurysms: technical note.

OBJECTIVE We present an endovascular technique for treating wide-necked cerebral aneurysms using Guglielmi detachable coils (Target Therapeutics, Fremont, CA) and simultaneous temporary balloon protection. The temporary balloon serves as a mechanical external force to mold the microcoils away from the parent artery. METHODS Two illustrative cases of wide-necked cerebral aneurysms treated with Guglielmi detachable coils and a temporary balloon are presented. Emphasis is placed on the technical aspects of the approach, with several variations. The first case involves a left posterior cerebral artery aneurysm at the P1/P2 segment, and the second case involves a left paraclinoid internal carotid artery aneurysm. Both patients suffered from subarachnoid hemorrhage, but neither was a candidate for craniotomy. In each case, the coils, when used alone, protruded into the parent artery and were therefore removed. Then a temporary balloon was inflated for mechanical protection during coil deployment. RESULTS The use of simultaneous temporary balloon protection allowed more dense intra-aneurysmal coil packing, especially in the neck, without parent artery compromise, than did the use of Guglielmi detachable coils alone. CONCLUSION Endovascular treatment of wide-necked cerebral aneurysms can be facilitated by simultaneous temporary balloon protection.

Onyx: a unique neuroembolic agent.

Rupture of a cerebral arteriovenous malformation can result in devastating hemorrhage with a possibility of serious neurological injury or death. Endovascular embolization is an important adjunct in the treatment of cerebral arteriovenous malformations, and in a small number of cases may provide definitive treatment. Currently available embolic agents have several shortcomings, including the possibility of recanalization, adhesiveness to the endovascular microcatheter and suboptimal handling at the time of surgical resection. Onyx® is an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide that was approved by the US FDA in July 2005 as an embolic agent for brain arteriovenous malformations. Although long-term follow-up is limited, this agent appears to offer several advantages over the other available embolic agents for the endovascular management of arteriovenous malformations and other vascular lesions.

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.

Defining the risk of retreatment for aneurysm recurrence or residual after initial treatment by endovascular coiling: a multicenter study.

OBJECTIVEEndovascular treatment of intracranial aneurysms is less invasive than surgical repair but poses a higher risk for aneurysm recurrence, which may necessitate retreatment, thus adding to the long-term risk. Cerebrovascular neurosurgeons from 8 institutions in the United States and Puerto Rico collaborated to assess the risk of retreatment for residual or recurrent aneurysms after the initial endovascular coiling. METHODSData were prospectively recorded for 311 patients with coiled intracranial aneurysms who underwent 352 retreatment procedures after angiographic or clinical recurrence (hemorrhage after initial coiling). Results analyzed included procedural complications and procedure-related morbidity. Morbidity was classified as major (modified Rankin scale score > 3) or minor, and temporary (<30 days) or permanent (>30 days). RESULTSRetreatment mortality was 0.85% per procedure and 0.96% per patient. Treatment-related rates were 0.32% per patient (0.28% per procedure) for permanent or temporary major disability; 1.29% for permanent minor disability (1.14% per procedure); and 1.61% for temporary minor disability (1.42% per procedure). Total risk for death or permanent major disability was 1.28% per patient and 1.13% per procedure. CONCLUSIONRetreatment poses a low risk for patients with recurrences of intracranial aneurysms after initial coiling; this risk is smaller than that posed by the initial endovascular therapy. The risk of disability associated with retreatment for aneurysm recurrence after coiling must be considered prospectively in the choice of treatment but with the recognition that its effects are low in the overall management risk.

Endovascular surgery for proximal posterior inferior cerebellar artery aneurysms: an analysis of Glasgow Outcome Score by Hunt-Hess grades.

OBJECTIVE:Proximal posterior inferior cerebellar artery (PICA) aneurysms represent a subset of posterior circulation aneurysms that can be routinely treated with either clipping or coiling. The literature contains limited numbers of patients with proximal PICA aneurysms treated with endovascular surgery. We report our experience with endovascular surgery of proximal PICA aneurysms with emphasis on patients with poor Hunt-Hess grades. METHODS:We reviewed 31 consecutive patients with proximal PICA aneurysms who were treated with endovascular surgery. The following data were analyzed: age, sex, size of aneurysm, Hunt-Hess grade at presentation, Fisher grade at presentation, angiographic result after embolization, complications, number of days hospitalized, duration of follow-up, angiographic follow-up results, and Glasgow Outcome Score at follow-up. RESULTS:Excellent angiographic occlusion was achieved in 30 of 31 (97%) patients. Clinical follow-up with Glasgow Outcome Score was performed on every patient an average of 10 months later. Twenty-one of 31 (68%) patients had good outcomes (Glasgow Outcome Score I or II) at follow-up. Of the patients who presented with a favorable clinical grade (Hunt-Hess 0–III), 13 of 15 (87%) had good outcomes at follow-up. Of the patients who presented with a poor clinical grade (Hunt-Hess Grade IV or higher), 8 of 16 (50%) had good outcomes at follow-up. CONCLUSION:This series demonstrates the safety and efficacy of endovascular surgery for proximal PICA aneurysms. Many patients with poor Hunt-Hess grades from ruptured PICA aneurysms ultimately had a good outcome. This could be secondary to early, aggressive treatment of hydrocephalus and the minimally invasive nature of the endovascular approach.

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.