L. Fernando Gonzalez

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.

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.

Treatment of posterior circulation aneurysms with the pipeline embolization device.

BACKGROUND Treatment of complex intracranial aneurysms with the pipeline embolization device (PED) has become common practice in neurovascular centers. Very few studies have assessed the safety and efficacy of PED treatment for posterior circulation aneurysms. OBJECTIVE To retrospectively present our experience with use of the PED in the posterior circulation. METHODS A total of 7 patients harboring 7 posterior circulation aneurysms were treated with the PED at our institution between November 2011 and July 2012. RESULTS Aneurysm size was 14.1 mm on average. All patients had unruptured aneurysms. Three aneurysms arose from the vertebral artery, 2 from the basilar artery, and 2 from the vertebrobasilar junction. A single stent was used in 4 patients, 2 stents in 2 patients, and 3 stents in 1 patient. Treatment was successful in all 7 patients. No procedural complications or perforator infarcts were noted in the series. No patient experienced new neurological symptoms related to PED treatment during the follow-up period. Angiographic follow-up was available for 6 patients at a mean time point of 5.5 months. Follow-up angiography showed 100% aneurysm occlusion in 3 patients, marked decrease in aneurysm size in 2 patients, and no change in 1 patient. CONCLUSION In our initial experience, it appears that PED treatment in select patients with vertebrobasilar aneurysms may have a reasonable safety-efficacy profile. Larger studies are needed to confirm our findings.

Stent-assisted coiling of wide-necked aneurysms in the setting of acute subarachnoid hemorrhage: experience in 65 patients.

BACKGROUND Stent-assisted coiling in the setting of subarachnoid hemorrhage remains controversial. Currently, there is a paucity of data regarding the utility of this procedure and the risks of hemorrhagic and ischemic complications. OBJECTIVE To assess the utility of stent-assisted coil embolization and pretreatment with antiplatelet agents in the management of ruptured wide-necked aneurysms. METHODS A retrospective study of 65 patients with ruptured wide-necked aneurysms treated with stent-assisted coiling. Patients with hydrocephalus or a Hunt and Hess grade ≥ III received a ventriculostomy before endovascular intervention. Patients were treated intraoperatively with 600 mg of clopidogrel and maintained on daily doses of 75 mg of clopidogrel and 81 mg of aspirin. The Glasgow outcome scale (GOS) score was recorded at the time of discharge. We identified major bleeding complications secondary to antiplatelet therapy and cases of in-stent thrombosis that required periprocedural thrombolysis. RESULTS Of the aneurysms, 66.2% arose within the anterior circulation; 69.2% of patients presented with hydrocephalus or a Hunt and Hess grade ≥ III and required a ventriculostomy. A good outcome (GOS of 4 or 5) was achieved in 63.1% of patients, and the overall mortality rate was 16.9%. There were 10 (15.38%) major complications associated with bleeding secondary to antiplatelet therapy (5 patients, 7.7%) or intraoperative in-stent thrombosis (5 patients, 7.7%). Three (4.6%) patients had a fatal hemorrhage. CONCLUSION Our findings suggest that stent-assisted coiling and routine treatment with antiplatelet agents is a viable option in the management of ruptured wide-necked aneurysms.

Cigarette Smoke and Inflammation: Role in Cerebral Aneurysm Formation and Rupture

Smoking is an established risk factor for subarachnoid hemorrhage yet the underlying mechanisms are largely unknown. Recent data has implicated a role of inflammation in the development of cerebral aneurysms. Inflammation accompanying cigarette smoke exposure may thus be a critical pathway underlying the development, progression, and rupture of cerebral aneurysms. Various constituents of the inflammatory response appear to be involved including adhesion molecules, cytokines, reactive oxygen species, leukocytes, matrix metalloproteinases, and vascular smooth muscle cells. Characterization of the molecular basis of the inflammatory response accompanying cigarette smoke exposure will provide a rational approach for future targeted therapy. In this paper, we review the current body of knowledge implicating cigarette smoke-induced inflammation in cerebral aneurysm formation/rupture and attempt to highlight important avenues for future investigation.

TNF-α induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology

Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor necrosis factor-alpha (TNF-α) has been associated with aneurysms, but potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing myocardin induced expression of key SMC contractile genes (SM-α-actin, SM-22α, smooth muscle myosin heavy chain), while dominant-negative cells suppressed expression. Tumor necrosis factor-alpha treatment inhibited this contractile phenotype and induced pro-inflammatory/matrix-remodeling genes (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta). Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering RNA abrogated TNF-α activation of inflammatory genes and suppression of contractile genes. These mechanisms were confirmed in vivo after exposure of rat carotid arteries to TNF-α and early on in a model of cerebral aneurysm formation. Treatment with the synthesized TNF-α inhibitor 3,6-dithiothalidomide reversed pathologic vessel wall alterations after induced hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo and in vitro demonstrated that TNF-α promotes epigenetic changes through KLF4-dependent alterations in promoter regions of myocardin, SMCs, and inflammatory genes. In conclusion, TNF-α induces phenotypic modulation of cerebral SMCs through myocardin and KLF4-regulated pathways. These results demonstrate a novel role for TNF-α in promoting a pro-inflammatory/matrix-remodeling phenotype, which has important implications for the mechanisms behind intracranial aneurysm formation.

Open and Endovascular Treatment of Unruptured Carotid-Ophthalmic Aneurysms: Clinical and Radiographic Outcomes

BACKGROUND:Aneurysms of the carotid-ophthalmic artery present unique challenges to cerebrovascular neurosurgeons given their proximity to vital anatomic structures. OBJECTIVE:To report our experience with a combined-modality treatment of unruptured carotid-ophthalmic aneurysms over a 12-year period. METHODS:A retrospective review of 161 patients who underwent open, endovascular, or combined treatment of 170 aneurysms from January 1997 to July 2009 was conducted. Medical records, operative reports, office notes, and follow-up angiograms were reviewed to obtain data on patient demographics, angiographic results, and clinical outcomes. RESULTS:One hundred forty-seven aneurysms were treated via endovascular techniques; 17 aneurysms (10%) were treated with microsurgical clip ligation; and 6 aneurysms (3.5%) were treated with a combined approach. Of the aneurysms treated via an endovascular approach alone, 81.6% of aneurysms had evidence of ≥ 95% occlusion on initial angiogram. There was a 1.4% rate of major complications associated with the initial procedure. Twenty-six of these aneurysms (18.9%) required further intervention on the basis of early angiographic results. Major complications occurred after 6 of 23 open microsurgical procedures (26.1%), including 2 instances of permanent visual loss. Nine clipped patients had long-term angiographic follow-up; none required further intervention. CONCLUSION:Endovascular treatment of carotid-ophthalmic aneurysms with modern endovascular techniques can be performed safely and efficaciously in the elective setting.