Nohra Chalouhi

Stent-Assisted Coiling of Intracranial Aneurysms Predictors of Complications, Recanalization, and Outcome in 508 Cases

Background and Purpose— Self-expanding stents are increasingly used for treatment of complex intracranial aneurysms. We assess the safety and the efficacy of intracranial stenting and determine predictors of treatment outcomes. Methods— A total of 508 patients with 552 aneurysms were treated with Neuroform and Enterprise stents between 2006 and 2011 at our institution. A multivariate analysis was conducted to identify predictors of complications, recanalization, and outcome. Results— Of 508 patients, 461 (91%) were treated electively and 47 (9%) in the setting of subarachnoid hemorrhage. Complications occurred in 6.8% of patients. In multivariate analysis, subarachnoid hemorrhage, delivery of coils before stent placement, and carotid terminus/middle cerebral artery aneurysm locations were independent predictors of procedural complications. Angiographic follow-up was available for 87% of patients at a mean of 26 months. The rates of recanalization and retreatment were, respectively, 12% and 6.4%. Older age, previously coiled aneurysms, larger aneurysms, incompletely occluded aneurysms, Neuroform stent, and aneurysm location were predictors of recanalization. Favorable outcomes were seen in 99% of elective patients and 51% of subarachnoid hemorrhage patients. Patient age, ruptured aneurysms, and procedural complications were predictors of outcome. Conclusions— Stent-assisted coiling of intracranial aneurysms is safe, effective, and provides durable aneurysm closure. Higher complication rates and worse outcomes are associated with treatment of ruptured aneurysms. Stent delivery before coil deployment reduces the risk of procedural complications. Staging the procedure may not improve procedural safety. Closed-cell stents are associated with significantly lower recanalization rates.

Biology of intracranial aneurysms: role of inflammation

Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

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.

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 …

Single center experience with pipeline stent: feasibility, technique, and complications.

BACKGROUND Endovascular coil embolization is an established method of treatment for intracranial aneurysms. The pipeline embolization device (PED) is a low-porosity endovascular stent designed to reconstruct the parent artery and decrease blood flow into the aneurysm. OBJECTIVE To report a series of 36 patients treated with the PED. METHODS Thirty-six patients underwent PED placement for aneurysm at the Jefferson Hospital for Neuroscience from October 2010 to November 2011. Clinical charts were reviewed. RESULTS Thirty-six patients with 42 aneurysms were treated (3 male; 33 female; ages, 34-82; mean age, 60.1 years). Forty-one aneurysms were located in the anterior circulation, whereas one was located at the vertebrobasilar junction. PED placement was successful in all patients and resulted in stasis within all treated aneurysms. Symptomatic postoperative complications were witnessed in 13.9% (n = 5) of patients. These complications included intracerebral hemorrhage (n = 4), dissection (n = 1), symptomatic stroke (n = 2), and death (n = 1). CONCLUSION Treatment of simple or complex intracranial aneurysms with PEDs alone or in conjunction with coil embolization is technically feasible, and the deployment technique requires a high degree of endovascular skills. Major perioperative adverse events must be studied. Respect for the indications of the procedure is crucial to justify the risk.

Safety and efficacy of endovascular treatment of basilar tip aneurysms by coiling with and without stent assistance: a review of 235 cases.

Background Endovascular therapy is now the preferred treatment option for basilar tip aneurysms (BTAs). Objective To compare the safety and efficacy of common endovascular techniques in the treatment of BTAs. Methods A retrospective review was conducted of 235 patients with BTAs treated with endovascular means in our institution between 2004 and 2011. Categorization was based on the presence and type of stent assistance (none, single, and Y stenting). The rates of perioperative complications, recanalization, rehemorrhage, and retreatment were analyzed. Results A total of 147 patients were treated with coil embolization and 88 patients with stent-assisted coiling (72 single stents, 16 Y stents). Thromboembolic complications occurred in 6.8% of patients in both groups. There was no associated mortality. Angiographic follow-up (mean, 23.5 months) was available in 172 patients (77.1%). Stented patients had significantly lower recanalization (17.2% vs 38.9%; P=.003) and retreatment (7.8% vs 27.8%; P=.002) rates compared with nonstented patients. Four rehemorrhages (2.7%) occurred in the coiled group, whereas none were noted in the stented group (P=.3). In paired comparisons, lower recanalization (8.3% vs 19.2%; P=.21) and retreatment (0% vs 9.6%; P=.19) rates were seen in the Y-stent group compared with the single-stent group. Thromboembolic complications occurred in 6.9% and 6.2% of patients in the single-stent and Y-stent groups, respectively (P=.91). In multivariate analysis, larger aneurysms, nonstented aneurysms, incomplete initial occlusion, and subarachnoid hemorrhage were predictors of aneurysm recanalization. Conclusion Stent-assisted coiling has significantly lower recurrence, retreatment, and rehemorrhage rates than coiling alone for the treatment of BTAs. Y stenting has the highest efficacy with low complication rates.

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.

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.