Showing papers by "J Mocco published in 2011"

Hemodynamic-morphologic discriminants for intracranial aneurysm rupture.

Abstract: Background and purpose the purpose of this study was to identify significant morphological and hemodynamic parameters that discriminate intracranial aneurysm rupture status using 3-dimensional angiography and computational fluid dynamics. Methods one hundred nineteen intracranial aneurysms (38 ruptured, 81 unruptured) were analyzed from 3-dimensional angiographic images and computational fluid dynamics. Six morphological and 7 hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured aneurysms for each parameter. Significant parameters were examined by multivariate logistic regression analysis in 3 predictive models-morphology only, hemodynamics only, and combined-to identify independent discriminants, and the AUC receiver operating characteristic of the predicted probability of rupture status was compared among these models. Results morphological parameters (size ratio, undulation index, ellipticity index, and nonsphericity index) and hemodynamic parameters (average wall shear stress [WSS], maximum intra-aneurysmal WSS, low WSS area, average oscillatory shear index, number of vortices, and relative resident time) achieved statistical significance (P Conclusions all 3 models-morphological (based on size ratio), hemodynamic (based on WSS and oscillatory shear index), and combined-discriminate intracranial aneurysm rupture status with high AUC values. Hemodynamics is as important as morphology in discriminating aneurysm rupture status.

Delayed Thrombosis or Stenosis Following Enterprise-Assisted Stent-Coiling: Is It Safe? Midterm Results of the Interstate Collaboration of Enterprise Stent Coiling

Abstract: BACKGROUND Stent-assisted coiling of intracranial aneurysms with self-expanding stents has widened the applicability of neuroendovascular therapies to those aneurysms previously considered "uncoilable" because of poor morphology. The Enterprise Vascular Reconstruction Device and Delivery System (Cordis) has demonstrated promising initial short-term results. However, the rates of delayed in-stent stenosis or thrombosis are not known. OBJECTIVE To report midterm results of the Enterprise stent system. METHODS A 10-center registry was created to provide a large volume of data on the safety and efficacy of the Enterprise stent system. Pooled data were compiled for consecutive patients undergoing Enterprise stent-assisted coiling at each institution. Available follow-up data were evaluated for the incidence of in-stent stenosis, thrombosis, and aneurysm occlusion. RESULTS In total, 213 patients (176 females) with 219 aneurysms were treated with the Enterprise stent. One hundred ten patients had undergone delayed angiography (≥ 30 days from stent placement, mean follow-up 174.6 days). Forty percent of patients demonstrated total occlusion with 88% having ≥ 90% aneurysm occlusion. Six percent of patients had delayed (>30 days) angiographic findings, of which 3% demonstrated significant (≥ 50%) in-stent stenosis or occlusion. Seven delayed thrombotic events occurred (3%), along with 2 additional immediate periprocedural events. All 7 delayed events were concomitant to cessation of double-antiplatelet therapy. CONCLUSION Midterm occlusion rates are excellent, and stenosis and thrombosis rates are comparable to other available neurovascular stents. Interruption of antiplatelet therapy appears to be a factor in those developing delayed stenosis or thrombosis.

Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms.

Abstract: BACKGROUND Incomplete coil occlusion is associated with increased risk of aneurysm recurrence We hypothesize that intracranial stents can cause flow remodeling, which promotes further occlusion of an incompletely coiled aneurysm OBJECTIVE To study our hypothesis by comparing the follow-up angiographic outcomes of stented and nonstented incompletely coiled aneurysms METHODS From January 2006 through December 2009, the senior author performed 324 initial coilings of previously untreated aneurysms, 145 of which were Raymond classification 2 and 3 Follow-up angiographic studies were available for 109 of these aneurysms (75%) Angiographic outcomes for stented vs nonstented incompletely coiled aneurysms were compared A multivariate analysis was performed to identify factors related to the progression of occlusion at follow-up, with adjustment for aneurysm location, size, neck size, Hunt-Hess grade, stent use, initial Raymond score, packing density, age, sex, and medical comorbidities RESULTS Of the 109 aneurysms, 37 were stented and 72 were not stented With a median follow-up time of 154 months, 33 stented aneurysms (89%) progressed to complete occlusion compared with 29 nonstented aneurysms (40%) Recanalization rates were lower in the stented group (81%) compared with the nonstented group (375%; P < 001) On multivariate analysis, stent use (odds ratio, 185; 95% confidence interval, 43-769) and packing density (odds ratio, 1093; 95% confidence interval, 1021-1170) were significant predictors of the progression of occlusion Aneurysm size was negatively correlated with the progression of occlusion (odds ratio, 0844; 95% confidence interval, 0724-0983) CONCLUSION Stent-assisted coiling causes progression of occlusion, possibly by a flow remodeling effect The odds of progression of occlusion of stent-coiled aneurysms were 185 times that of nonstented aneurysms

Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial aneurysm initiation in a rabbit model.

Abstract: Background/Aims: Hemodynamics constitute a critical factor in the formation of intracranial aneurysms. However, little is known about how intracranial arteries respond to hemodynami

Unruptured cerebral aneurysms do not shrink when they rupture: multicenter collaborative aneurysm study group.

Abstract: BACKGROUND: The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage over 5 years, respectively. OBJECTIVE: To determine whether cerebral aneurysms shrink with rupture. METHODS: The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of ≥ 2 mm was considered a true change. RESULTS: Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms. None of the aneurysms had a significant decrease in size. One aneurysm decreased by 1.8 mm in maximum size after rupture (7.7%). Six aneurysms had an increase in maximum size of at least 2 mm after rupture (46.2%) with a mean increase of 3.5 mm (± 0.5 mm). CONCLUSION: Unruptured aneurysms do not shrink when they rupture. The large percentage of ruptured small aneurysms in previous studies were likely small before they ruptured.

Progressive aneurysm development following hemodynamic insult

Abstract: Object Hemodynamic insult has been speculated to be a key factor in intracranial aneurysm formation; however, it is unclear whether a sustained insult is necessary The authors examined whether aneurysmal degradation would continue despite the normalization of wall shear stress (WSS) by adaptive outward vascular remodeling Methods Twenty-five rabbits underwent either sham operation (5 animals) or bilateral common carotid artery ligation (20 animals) to augment basilar artery (BA) flow Basilar termini (BTs) were harvested at 5 days and 3, 12, and 27 weeks postoperation Histological changes at the BTs were quantified using an aneurysm development score (ADS) wherein the luminal length of the vessel wall exhibiting internal elastic lamina (IEL) loss, media thinning (> 30% media loss), and bulging was multiplied by the percentage of media thinning divided by the BA diameter This score and its component variables were evaluated over the specified time points and compared with the WSS time course obtained f

Lentivirus-mediated overexpression of angiotensin-(1–7) attenuated ischaemia-induced cardiac pathophysiology

Abstract: It is a well-established fact that components of the renin–angiotensin system (RAS) play a critical role in the progression of heart failure. Pharmacotherapeutic interventions with either angiotensin-converting enzyme (ACE) inhibitors (Haywood et al. 1997) or angiotensin type 1 receptor blockers (Steckelings et al. 2005; Ferreira et al. 2009) have demonstrated significant protection against myocardial infarction and heart failure in experimental animal models as well as in patients. Several studies have suggested that the beneficial effects observed with angiotensin-converting enzyme inhibitors are not only due to the reduction in the formation of the detrimental angiotensin II (Ang II), but are also due to significant elevation in the levels of angiotensin-(1–7) (Ang-(1–7); Keidar et al. 2007). Correlative studies have also shown that ACE2 and Ang-(1–7) levels are increased in the heart following myocardial infarction in both humans and rats (Averill et al. 2003; Burrell et al. 2005). A growing body of evidence indicates that Ang-(1–7) plays an active role in maintaining cardiovascular homeostasis, thus providing protection against heart diseases. This conclusion is supported by the following findings. Angiotensin-(1–7) has been shown to attenuate isoprenaline-induced cardiac hypertrophy (Santos et al. 2004). Chronic administration of Ang-(1–7) has been shown to improve coronary artery perfusion and endothelial function in a rat model for heart failure (Loot et al. 2002). Angiotensin-(1–7) was shown to reduce the incidence and the duration of postischaemic reperfusion arrhythmias in the isolated rat heart (Ferreira et al. 2001; De Mello, 2004). Intravenous infusion of Ang-(1–7) resulted in improved contractile function in rat hearts (Sampaio et al. 2003). Angiotensin-(1–7) has been demonstrated to attenuate cardiac remodelling significantly in terms of reducing myocyte hypertrophy and interstitial fibrosis (Santos et al. 2004; Tallant et al. 2005; Grobe et al. 2006, 2007b; Mercure et al. 2008; Ferreira et al. 2010; Giani et al. 2010). Furthermore, AVE0991, a synthetic mimetic of Ang-(1–7), has been shown to exert cardioprotective effects (Ferreira et al. 2007). Although Ang-(1–7) exerts beneficial effects against a range of cardiovascular diseases, the in vivo efficacy of this peptide is severely hampered owing to rapid degradation by peptidases. The half-life for Ang-(1–7) is very short and dependent on species. For example, following intravenous administration the half-life of Ang-(1–7) in humans is approximately 30 min (Kono et al. 1986; Rodgers et al. 2006), whereas in rodents it is approximately 20 s (Iusuf et al. 2008). To overcome this limitation, we have overexpressed Ang-(1–7) in the rodent heart shortly after birth, as we previously demonstrated (Methot et al. 2001; Diez-Freire et al. 2006), to evaluate its cardioprotective effects against myocardial infarction. Also, we hypothesize that Ang-(1–7) may exert its beneficial effects against myocardial infarction by restoring the balance between the deleterious ACE–Ang II–angiotensin II type 1 receptor (AT1R) axis and the beneficial ACE2–Ang-(1–7)–Mas axis of the RAS.

Midterm clinical and angiographic follow-up for the first Food and Drug Administration-approved prospective, Single-Arm Trial of Primary Stenting for Stroke: SARIS (Stent-Assisted Recanalization for Acute Ischemic Stroke).

Abstract: BACKGROUND Although early data demonstrate encouraging angiographic results following intracranial stent deployment for acute ischemic stroke, longer-term follow-up is necessary to evaluate the clinical outcomes, as well as the durability of angiographic results. OBJECTIVE We report 6-month clinical and radiologic follow-up data of the 20 patients prospectively enrolled in the Stent-Assisted Recanalization in acute Ischemic Stroke (SARIS) trial. METHODS Twenty patients were prospectively enrolled to receive self-expanding intra-arterial stents as first-line therapy for acute ischemic stroke treatment. Patients were scheduled for follow-up 6-months after treatment for clinical evaluation (modified Rankin Scale [mRS] score obtained by a trained certified research nurse/nurse practitioner) and repeat cerebral angiography. Angiographic interpretation was performed by an independent adjudicator. RESULTS At 6 months, the mRS score was ≤3 in 60% of patients (n = 12) and was ≤2 in 55% of patients (n = 11). Mortality at the 6-month follow-up was 35% (n = 7). Follow-up angiography was performed for 85% (11 of 13) of surviving patients. All patients undergoing angiographic follow-up demonstrated Thrombolysis in Myocardial Infarction 3 flow on digital subtraction angiography or stent patency on computed tomographic angiography. None of the patients demonstrated evidence of in-stent stenosis (≥50% vessel narrowing). CONCLUSION The midterm angiographic and clinical results following intracranial stent deployment for acute ischemic stroke are encouraging. Further study of primary stent-for-stroke treatment is warranted.

Intraluminal middle cerebral artery occlusion (MCAO) model for ischemic stroke with laser doppler flowmetry guidance in mice.

Abstract: Stroke is the third leading cause of death and the leading cause of disability in the world, with an estimated cost of near $70 billion in the United States in 2009 The intraluminal middle cerebral artery occlusion (MCAO) model was developed by Koizumi in 1986 to simulate this impactful human pathology in the rat A modification of the MCAO method was later presented by Longa Both techniques have been widely used to identify molecular mechanisms of brain injury resulting from ischemic stroke and potential therapeutic modalities This relatively noninvasive method in rats has been extended to use in mice to take advantage of transgenic and knockout strains To model focal cerebral ischemia, an intraluminal suture is advanced via the internal carotid artery to occlude the base of the MCA Retracting the suture after a specified period of time mimics spontaneous reperfusion, but the suture can also be permanently retained This video will be demonstrating the two major approaches for performing intraluminal MCAO procedure in mice in a stepwise fashion, as well as providing insights for potential drawbacks and pitfalls The ischemic brain tissue will subsequently be stained by 2,3,5-triphenyltetrazolium chloride (TTC) to evaluate the extent of cerebral infarction

Incidence of seizures or epilepsy after clipping or coiling of ruptured and unruptured cerebral aneurysms in the nationwide inpatient sample database: 2002-2007.

Abstract: BACKGROUND It is not clear whether treatment modality (clipping or coiling) affects the risk of seizures after treatment for cerebral aneurysms. OBJECTIVE To determine whether there is an increased risk of seizures after clipping vs coiling. METHODS Hospitalizations for clipping or coiling of ruptured and unruptured aneurysms were identified in the Nationwide Inpatient Sample Database for 2002 to 2007 by International Classification of Diseases 9th Revision codes for subarachnoid hemorrhage or unruptured cerebral aneurysm and codes for clipping or coiling. Clipping and coiling were compared for the combined primary endpoint of seizures or epilepsy. The analysis was adjusted for patient-specific and hospital-specific factors using generalized linear models with generalized estimated equations. RESULTS There were 10 899 hospitalizations for ruptured aneurysms (6593 clipping, 4306 coiling), and 9686 hospitalizations for unruptured aneurysms (4483 clipping, 5203 coiling). For ruptured aneurysm patients, clipping had a similar incidence of seizures or epilepsy compared with coiling (10.7% vs 11.1%, respectively, adjusted odds ratio: 0.596; 95% confidence interval: 0.158-2.248; P = .445 after adjustment for patient-specific and hospital-specific factors). For unruptured aneurysm patients, clipping was associated with a significantly higher risk of seizures or epilepsy (9.2%) compared with coiling (6.2%) (adjusted odds ratio: 1.362; 95% confidence interval: 0.155-1.606; P < .001 after adjustment for patient-specific and hospital-specific factors). Seizures or epilepsy were significantly associated with longer hospitalizations (P < .01) and higher hospital charges (P < .0001), except in coiled unruptured aneurysm patients, in which seizures or epilepsy were not significantly associated with hospital charges (P = .31). CONCLUSION In unruptured cerebral aneurysm patients, clipping is associated with a higher risk of seizures or epilepsy.

Interventional neurovascular disease: avoidance and management of complications and review of the current literature.

Abstract: There has been a substantial increase in the number of neuroendovascular procedures performed over the last 15 years. Although rare, complications of cerebral angiography and neuroendovascular procedures have the potential to be devastating. Fortunately, dedication to careful patient selection, meticulous attention to technical detail, and standardization of endovascular treatment protocols results in an acceptably low complication rate. Factors that may predispose one to complications with cerebral angiography include age, smoking, functional stats, medical comorbidities, and duration of the procedure. The most common complication of angiography is vascular access site complication, with a rate of up to 5%. The overall neurologic complication rate for diagnostic angiography is 1.3-2.6%, with a permanent neurologic deficit rate of 0.14-0.50%. Neuroendovascular interventions are more invasive, take longer to perform, and have higher rates of complication. Procedure specific complications include aneurysm rupture, arterial dissection, stroke, hemorrhage, thromboembolism, and microembolism, and rates of neurologic deficit are higher than those for diagnostic angiography. With knowledge of the common complications, strategies to minimize them, and a meticulous attention to the technical detail of the procedure, complications of neuroendovascular interventions can be minimized.

A prospective randomized single-blind trial of patient comfort following vessel closure: extravascular synthetic sealant closure provides less pain than a self-tightening suture vascular compression device

Abstract: Background and purpose The Mynx M5 (AccessClosure, Inc, Mountain View, California, USA), a novel vascular closure device (VCD) utilizing extravascular synthetic sealant, may effectively seal the arteriotomy while reducing the pain associated with arteriotomy closure seen with other VCDs To date, no studies exist comparing the pain associated with deployment between differing VCDs as a primary end point Methods A blinded, randomized controlled trial was performed comparing the Mynx and a popular VCD that utilizes a self-tightening suture, the Angio-Seal Evolution (St Jude Medical, St Paul, Minnesota, USA) Subjects were all adult patients undergoing diagnostic cerebral angiography via femoral access Local anesthesia and intraprocedural intravenous pain medication were standardized Pain was assessed using a horizontal visual analog scale both before and after VCD deployment Results 64 patients were enrolled with 32 in each treatment arm Both pain at closure and pain increase from baseline to closure were significantly higher in the Angio-Seal group (p=0009 and 0002, respectively) 88% of patients receiving an Angio-Seal reported closure as the most painful part of the procedure compared with only 34% of patients receiving the Mynx (p Conclusions In a blinded, randomized trial comparing the Mynx with the Angio-Seal Evolution, pain with device deployment at arteriotomy closure was significantly lower with the Mynx The reason for the large pain gradient between groups is likely due to the presence, and absence, of compression elements within the Angio-Seal and Mynx, respectively

A simple technique for morphological measurement of cerebral arterial circle variations using public domain software (Osiris).

Abstract: Th is article describes a straightforward method to measure the dimensions and identify morphological variations in the cerebral arterial circle using the general-purpose software program Osiris. This user-friendly and portable program displays, manipulates, and analyzes medical digital images, and it has the capability to determine morphometric properties of selected blood vessels (or other anatomical structures) in humans and animals. To ascertain morphometric variations in the cerebral arterial circle, 132 brains of recently deceased fetuses, infants, and adults were dissected. Th e dissection procedure was first digitized, and then the dimensions were measured with Osiris software. Measurements of each vessel's length and external diameters were used to identify and classify morphological variations in the cerebral arterial circle. The most commonly observed anatomical variations were uni- and bilateral hypoplasia of the posterior communicating artery. Th is study demonstrates that public domain soft ware can be used to measure and classify cerebral arterial circle vessels. Th is method could be extended to examine other anatomical regions or to study other animals. Additionally, knowledge of variations within the circle could be applied clinically to enhance diagnostic and treatment specifi city.

Recanalization therapy for acute ischemic stroke, part 1: surgical embolectomy and chemical thrombolysis

Abstract: Cerebral revascularization approaches for acute ischemic stroke greatly expanded during the past decade. Many new revascularization strategies are currently being assessed, while others continue to gain in popularity, offering hope to those with an otherwise refractory disease. We discuss historical and current progress toward successful recanalization, as well as the efforts being made to develop a safe and efficacious method of revascularization in the treatment of acute ischemic stroke.

Recanalization therapy for acute ischemic stroke, part 2: mechanical intra-arterial technologies

Abstract: Stroke therapy has been revolutionized in the past two decades with the widespread implementation of chemical thrombolysis for acute stroke. However, chemical thrombolysis continues to be limited in its efficacy secondary to relatively short time windows and a high associated risk of hemorrhage. In an attempt to minimize hemorrhagic complications and extend the available therapeutic window, mechanical devices designed specifically for thrombus removal, clot obliteration, and arterial revascularization have experienced a recent surge in development and utilization. As such, chemical thrombolytics now represent only one of many options in acute stroke therapy. These new mechanical devices have extended the potential treatment window and now provide alternatives to patients who do not respond to conventional intravenous thrombolysis. This review will discuss the development of these devices, supporting literature, and the individual strengths that each engenders towards a life-saving therapy for stroke.

Impact of intracranial self-expanding stents in the treatment of acute ischemic stroke: efficacy and limitations

Abstract: In recent years, endovascular self-expanding stents have become a viable option for neurointerventionalists treating acute ischemic stroke. Timely intervention for stroke could mean the difference between complete recovery and significant morbidity or death. Since 2006, a handful of clinical trials have demonstrated the potential of self-expanding stents in dependably achieving quick revascularization. These devices are expanding in utilization as new designs offer greater procedural flexibility and better clinical results. We discuss these clinical investigations, focusing on the procedural capabilities and limitations of each self-expanding stent design.

Delayed complication from a percutaneous vascular closure device following a neuro-interventional procedure.

Abstract: Percutaneous vascular closure devices are being increasingly used as alternatives to manual compression for the closure of femoral arteriotomy after endovascular procedures as they appear to reduce time to ambulate, improve patient's comfort, and are implicated with cost saving. However, vascular closure devices have been associated with an increased risk of complications including hematoma formation, local bleeding, arteriovenous fistula formation, pseudoaneurysm and arterial leg ischemia. To our knowledge, if the above complications occur it is usually within the first 30 days after the procedure. None have been reported in a delayed fashion ten months or longer after closure. We describe a 30-year-old man with a history of a giant basilar trunk aneurysm. He was placed on aspirin and clopidogrel prior to the procedure. He had bilateral femoral access with 6 French sheaths. Following the procedure, 6 French Angio-Seals (St. Jude Medical, St. Paul, MN, USA) were used for closure of bilateral femoral arteriotomies. Ten months after the procedure, the patient kicked a metal cart and developed a large right retroperitoneal iliopsoas hematoma. There was no evidence of pseudoaneurysm. The patient was managed conservatively and his serial hematocrit stayed stable. He did not require surgical intervention. Use of percutaneous vascular closure devices is associated with complications including risk of hematoma, pseudoaneurysm, intravenous fistula, rectal peritoneal hemorrhage, limb ischemia and possible surgical repair. Most complications occur peri-procedure or within 30 days post-procedure. This is the first reported case of a delayed complication at ten months after the initial procedure. Site-related complications associated with percutaneous vascular closure devices may occur in a delayed fashion, even ten months post-procedure, so should be considered in the management of patients.

Aggressive intervention to treat a young woman with intracranial hemorrhage following unsuccessful intravenous thrombolysis for left middle cerebral artery occlusion. Case report.

Abstract: Stroke patients whose condition does not improve after intravenous administration of tissue plasminogen activator (tPA) may be candidates for endovascular intervention. Patients with new intracerebral hemorrhage noted during such interventions pose a difficult challenge to neurointerventionists and are often sequestered as treatment failures and deemed inappropriate for intraarterial recanalization efforts. The authors present a case in which aggressive intervention was performed despite evidence of contrast extravasation on preintervention angiography. This 37-year-old woman presented with an occlusion of the M(1) segment of the left middle cerebral artery and a National Institutes of Health Stroke Scale score of 24. She received intravenous tPA without improvement. Angiography revealed M(1) thrombus as well as active contrast extravasation without arterial displacement. Thromboaspiration was performed in light of her known hemorrhage with excellent recanalization. Immediate postprocedure imaging demonstrated a large insular hematoma and emergent craniectomy and hematoma evacuation were performed. At 4 months' follow-up, the patient was living at home, was ambulating, and had excellent comprehension with mild expressive aphasia. There is little peer-reviewed data in the literature to aid in the decision-making process when contrast extravasation is recognized at the time of preinterevention angiography. Continuation of mechanical endovascular stroke intervention, in light of active contrast extravasation, may be warranted in young patients with major deficits and absence of arterial displacement or delayed global filling. Further thrombolytics are not advised. In select stroke patients, continuation of a planned attempt at mechanical recanalization without the further use of thrombolytics may be warranted in light of known intracerebral hemorrhage.