David Hasan

Comparison of Flow Diversion and Coiling in Large Unruptured Intracranial Saccular Aneurysms

Background and Purpose— Flow diversion has emerged as an important tool for the management of intracranial aneurysms. The purpose of this study was to compare flow diversion and traditional embolization strategies in terms of safety, efficacy, and clinical outcomes in patients with unruptured, large saccular aneurysms (≥10 mm). Methods— Forty patients treated with the Pipeline Embolization Device (PED) were matched in a 1:3 fashion with 120 patients treated with coiling based on patient age and aneurysm size. Fusiform and anterior communicating artery aneurysms were eliminated from the analysis. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. Results— There were no differences between the 2 groups in terms of patient age, sex, aneurysm size, and aneurysm location. The rate of procedure-related complications did not differ between the PED (7.5%) and the coil group (7.5%; P=1). At the latest follow-up, a significantly higher proportion of aneurysms treated with PED (86%) achieved complete obliteration compared with coiled aneurysms (41%; P<0.001). In multivariable analysis, coiling was an independent predictor of nonocclusion. Retreatment was necessary in fewer patients in the PED group (2.8%) than the coil group (37%; P<0.001). A similar proportion of patients attained a favorable outcome (modified Rankin Scale, 0–2) in the PED group (92%) and in the coil group (94%; P=0.8). Conclusions— The PED provides higher aneurysm occlusion rates than coiling, with no additional morbidity and similar clinical outcomes. These findings suggest that the PED might be a preferred treatment option for large unruptured saccular aneurysms.

Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture

Background and Purpose— Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. Methods— Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case–control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results— A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18–0.87); reference group, no use of aspirin), patients in the “< once a month” group had an OR of 0.80 (95% CI, 0.31–2.05), and patients in the “> once a month to 2×/week” group had an OR of 0.87 (95% CI, 0.27–2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11–0.67; P=0.03) compared with those who never take aspirin. Conclusions— Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.

Review of Cerebral Aneurysm Formation, Growth, and Rupture

Cerebral aneurysms (CAs) occur in 3% to 5% of the general population and are characterized by localized structural deterioration of the arterial wall, with loss of the internal elastic lamina and disruption of the media.1 The most dreaded complication of CAs is rupture, the likelihood of which is related to several modifiable and nonmodifiable risk factors. Despite advances in surgical techniques and perioperative management, the mortality and morbidity associated with aneurysm rupture remain high.2 Current therapeutic options are limited to invasive therapies, namely microsurgical clipping and endovascular treatment, both of which carry a non-negligible risk of procedural morbidity. In recent years, it has become obvious that CAs are not passively enlarging vascular structures but exhibit prominent features of inflammation and tissue degeneration. Other factors mainly hemodynamic, genetic, hormonal, and environmental may also play an important role. Knowledge of the pathogenic pathways of CAs may pave the way for the development of noninvasive therapies. The purpose of this review is to summarize the most relevant data on the molecular mechanisms, genetics, and risk factors for aneurysm formation, growth, and rupture. Although there are different forms of CAs, the present discussion focuses on saccular aneurysms, which represent the most common type of CAs and are also the most common cause of subarachnoid hemorrhage (SAH). ### Cerebral Aneurysms: an Inflammatory Disease Increasing evidence points to inflammation as the leading factor in the pathogenesis of CAs. The inflammatory process is initiated by a hemodynamic insult and leads to matrix metalloproteinases (MMPs)–mediated degradation of the extracellular matrix and apoptosis of smooth muscle cells (SMCs), which are the predominant matrix-synthesizing cells of the vascular wall. These processes act in concert to weaken the arterial wall progressively, resulting in dilatation, aneurysm formation, and ultimately rupture (Figure; Table 1). The data supporting a major role for inflammation in CA pathogenesis are …

Clinical Course and Surgical Management of Massive Cerebral Infarction

OBJECTIVE:Acute occlusion of the proximal middle cerebral artery (MCA) can lead to rapid development of fatal brain swelling and ischemic strokes. Decompressive surgery, if performed early in this subpopulation of patients, can reduce mortality and result in a favorable outcome. In this article, we describe our surgical approach for treating malignant MCA syndrome and compare it with other management strategies. METHODS:This is a retrospective review of patients who developed acute occlusion of the proximal MCA and underwent aggressive surgical decompression (large craniectomy, anterior temporal lobectomy, resection of infarcted tissue, and duraplasty). The outcome of this management strategy is compared with the previously published outcomes of hemicraniectomy and dural augmentation. RESULTS:Twelve patients were included in the study. The group consisted of six men and six women (mean age, 46.8 yr). Nine patients had right MCA stroke, and three had left MCA infarction. The causes of the strokes were cardioembolic, iatrogenic, small-vessel occlusive disease, and others. The interval between infarction and clinical evidence of herniation varied from 24 hours to 10 days. Two patients died, five were independent or had moderate disabilities, and five had severe disability. CONCLUSION:Surgical decompression consisting of a large craniectomy, anterior temporal lobectomy, resection of infarcted tissue, and duraplasty is beneficial to a significant number of patients with massive MCA stroke and clinical signs of herniation.

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1–4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1–4.4) for panel members and 4.5 (95% CI 4.3–4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1–4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9–4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019–0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Extending the Indications of Flow Diversion to Small, Unruptured, Saccular Aneurysms of the Anterior Circulation

Background and Purpose— Flow diverters are currently indicated for treatment of large and complex intracranial aneurysms. The purpose of this study was to determine whether the indications of flow diversion can be safely extended to unruptured, small, saccular aneurysms (<10 mm) of the anterior circulation. Methods— Forty patients treated with the pipeline embolization device (PED) were matched in a 1:4 fashion with 160 patients treated with stent-assisted coiling based on patient age, sex, aneurysm location, and aneurysm size. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. Results— The rate of periprocedural complications was 5% in the PED group and 3% in the stent-coil group (P=0.7). In multivariable analysis, increasing age was the only predictor of complications. At follow-up, a higher proportion of aneurysms treated with PED (80%) achieved complete obliteration compared with stent-coiled aneurysms (70%) but the difference did not reach statistical significance (P=0.2). In multivariable analysis, increasing aneurysm size and aneurysm location were predictors of nonocclusion. The rate of favorable outcome (modified Rankin Scale, 0–2 and modified Rankin Scale, 0–1) was similar in the PED group and the coil group. Conclusions— The PED was associated with similar periprocedural risks, clinical outcomes, and angiographic results compared with stent-assisted coiling. These findings suggest that the indications of PED can be safely extended to small intracranial aneurysms that are amenable to conventional endovascular techniques. Larger studies with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and best clinical outcomes.

Risk of ventriculostomy-related hemorrhage in patients with acutely ruptured aneurysms treated using stent-assisted coiling.

OBJECT Intracranial stenting has improved the ability to treat wide-neck aneurysms via endovascular techniques. However, stent placement necessitates the use of antiplatelet agents, and the latter may complicate the treatment of patients with acutely ruptured aneurysms who demonstrate hydrocephalus and require ventriculostomy. Antiplatelet agents in this setting could increase the incidence of ventriculostomy-related hemorrhagic complications, but there are insufficient data in the medical literature to quantify this potential risk. The aim of this study was to directly quantify the risk of ventriculostomy-related hemorrhage in patients with acute aneurysmal subarachnoid hemorrhage treated with stent-assisted coiling. METHODS The authors retrospectively identified 131 patients who underwent endovascular treatment for an acutely ruptured aneurysm as well as ventriculostomy or ventriculoperitoneal (VP) shunt placement. The rate of hemorrhagic complications associated with ventriculostomy or VP shunt insertion was compared between patients who underwent coiling without a stent (Group 1) and those who underwent stent-assisted coiling and dual antiplatelet therapy (Group 2). RESULTS One hundred nine ventriculostomies or VP shunt placement procedures were performed in 91 patients in Group 1, and 50 procedures were undertaken in 40 patients in Group 2. The rates of radiographic hemorrhage and symptomatic hemorrhage were significantly higher in Group 2 (32% vs 14.7%, p = 0.02; and 8% vs 0.9%, p = 0.03, respectively). On multivariate analyses, Group 2 had 3.42 times the odds of a radiographic hemorrhage (95% CI 1.46-8.04, p = 0.0048) after adjusting for antiplatelet use prior to admission. CONCLUSIONS The application of dual antiplatelet therapy in stent-assisted coiling of acutely ruptured aneurysms is associated with an increase in the risk of hemorrhagic complications following ventriculostomy or VP shunt placement, as compared with its use in a coiling procedure without a stent.

The Pipeline Embolization Device: learning curve and predictors of complications and aneurysm obliteration.

BACKGROUND The Pipeline Embolization Device (PED) has emerged as a promising treatment for intracranial aneurysms. OBJECTIVE To assess the safety and efficacy of the PED, to analyze the effect of operator experience on the complication rate, and to identify predictors of complications and obliteration. METHODS A total of 109 patients with 120 aneurysms were treated with PED at our institution. The patient population was divided into 3 consecutive equal groups to assess whether overall and major complication rates decreased over time: group 1, patients 1 through 37; group 2, patients 38 through 73; and group 3, patients 74 through 109. RESULTS The number of PEDs used was 1.40 per aneurysm. Symptomatic and major procedure-related complications occurred in 11% and 3.7% of patients, respectively. The rate of complications decreased from 16.2% in group 1 to 5.6% in group 3, and the rate of major complications fell dramatically from 10.8% in group 1 to 0% in groups 2 and 3 (P < .05). Procedure time significantly decreased over time (P = .04). In multivariate analysis, previously treated aneurysms were predictive of procedural complications (P = .02). At the latest follow-up, 65.8% of aneurysms were completely occluded, 9.6% were nearly completely occluded, and 24.6% were incompletely occluded. In multivariate analysis, fusiform aneurysms (P = .05) and shorter angiographic follow-up (P = .03) were negative predictors of aneurysm obliteration. CONCLUSION PED therapy may have an acceptable safety-efficacy profile. The risk of complications appears to decrease dramatically with physician experience, supporting the existence of a learning curve. Patients with previously treated aneurysms have higher complication rates, whereas fusiform aneurysms achieve lower obliteration rates.

Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests unstable human cerebral aneurysm: a pilot study.

Background and Purpose— The clinical significance of early (ie, within the first 24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral aneurysms is not clear. The purpose of this study was to determine whether early uptake of ferumoxytol suggests unstable cerebral aneurysm. Methods— Thirty unruptured aneurysms in 22 patients were imaged with magnetic resonance imaging 24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72 hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from 4 patients with early magnetic resonance imaging signal changes, 5 patients with late signal changes, and 5 other patients with ruptured aneurysms. The tissue was immunostained for expression of cyclooxygenase-1, cyclooxygenase-2, microsomal prostaglandin E2 synthase-1, and macrophages. Results— In 23% (7/30) of aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were clipped. The remaining 3 aneurysms were managed conservatively; all 3 ruptured within 6 months. In 53% (16 of 30) of aneurysms, there was pronounced uptake of ferumoxytol at 72 hours. Eight aneurysms were surgically clipped, and 8 were managed conservatively; none ruptured or increased in size after 6 months. Expression of cyclooxygenase-2, microsomal prostaglandin E2 synthase-1, and macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol and ruptured aneurysms. Expression of these inflammatory molecules was significantly higher in aneurysms with early uptake of ferumoxytol versus aneurysms with late uptake. Conclusions— Uptake of ferumoxytol in aneurysm walls within the first 24 hours strongly suggests aneurysm instability and probability of rupture within 6 months, and may warrant urgent intervention.

Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results

BackgroundM1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture.MethodsTen patients with cerebral aneurysms (five ruptured and five unruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery (STA) was also removed and immunostained with monoclonal antibodies for M1, M2, and mast cells.ResultsAll ten aneurysm tissues stained positive for M1, M2, and mast cells. M1 and M2 cells were present in equal proportions in unruptured aneurysms. This contrasted with a marked predominance of M1 over M2 cells in ruptured aneurysms (p = 0.045). Mast cells were also prominently upregulated in ruptured aneurysms (p = 0.001). Few M1 and M2 cells were present in STA samples.ConclusionsM1/M2 macrophages and mast cells are found in human cerebral aneurysms; however, M1 and mast cell expression seems to markedly increase in ruptured aneurysms. These findings suggest that macrophage M1/M2 imbalance and upregulation of mast cells may have a role in the progression of cerebral aneurysms to rupture.