Mario Zanaty

Biology of Cerebral Arteriovenous Malformations with a Focus on Inflammation

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

Treatment of blister-like aneurysms with the pipeline embolization device.

BACKGROUND Endovascular vessel reconstruction with the pipeline embolization device (PED) has become common practice. Data on the safety and efficacy of the PED in blister-like aneurysms (BLAs) are limited. OBJECTIVE To retrospectively present our experience with use of the PED in BLAs. METHODS A total of 8 patients harboring 8 BLAs were treated with the PED at our institution between November 2011 and April 2013. RESULTS Aneurysm size was 2.5 mm on average. Five patients had sustained a subarachnoid hemorrhage (SAH), 1 patient presented with sentinel headaches, and in 2 patients the aneurysm was incidentally discovered. Seven aneurysms arose from the ICA and 1 from the basilar artery. Placement of the PED was successful in all 8 patients. There were no procedural or perioperative complications in any of the patients. At the latest follow-up, all 8 patients achieved a favorable outcome (mRS 0-2). Angiographic follow-up was available for 6 patients at a mean time point of 3.9 months. Follow-up angiography showed 100% aneurysm occlusion in 5 patients and marked decrease in aneurysm size in 1 patient. CONCLUSION The findings of this study suggest that the PED may be a safe and effective treatment for BLAs. Given the limitations of other treatment modalities and the challenging nature of BLAs, flow diversion may be a valuable option for these lesions.

Treatment of ruptured intracranial aneurysms with the pipeline embolization device.

BACKGROUND The pipeline embolization device (PED) has been used for treatment of unruptured aneurysms. Little is known about the use of the PED in ruptured aneurysms. OBJECTIVE To assess the safety and efficacy of the PED in ruptured intracranial aneurysms. METHODS This is a case series with prospective data collection on 20 patients with freshly ruptured aneurysms who were treated with PED (with or without adjunctive coiling) at 2 cerebrovascular centers. Patients were loaded with aspirin and clopidogrel or received an infusion of tirofiban intraoperatively. RESULTS Hunt and Hess grades were I in 7 patients (35%), II in 9 (45%), and III in 4 (20%). The mean duration from hemorrhage to PED placement was 7±7.0 days. A single device was used in all but 1 patient (95%). The procedure was staged in 20%. There was only 1 complication (5%); this was a fatal intraoperative aneurysm dome rupture that occurred during adjunctive coil deployment. Adjunctive coiling was used in 30%. No patient required an invasive procedure after PED placement. Follow-up angiography (mean, 5.3±4.2 months; range, 2-12 months) showed 100% occlusion in 12 (80%) and incomplete occlusion in 3 patients (20%). At latest follow-up, 19 patients achieved a favorable outcome (modified rankin scale 0-2). CONCLUSION In our preliminary experience, treatment of ruptured aneurysms with the PED was associated with low complication rates, high occlusion rates, and favorable outcomes. These findings suggest that PED may be a safe and effective option for patients with favorable Hunt and Hess grades and aneurysms difficult to treat with conventional methods.

Flow-Diversion Panacea or Poison?

Endovascular therapy is now the treatment of choice for intracranial aneurysms (IAs) for its efficacy and safety profile. The use of flow diversion (FD) has recently expanded to cover many types of IAs in various locations. Some institutions even attempt FD as first line treatment for unruptured IAs. The most widely used devices are the pipeline embolization device (PED), the SILK flow diverter (SFD), the flow redirection endoluminal device (FRED), and Surpass. Many questions were raised regarding the long-term complications, the optimal regimen of dual antiplatelet therapy, and the durability of treatment effect. We reviewed the literature to address these questions as well as other concerns on FD when treating IAs.

A Single Pipeline Embolization Device is Sufficient for Treatment of Intracranial Aneurysms

BACKGROUND AND PURPOSE: The Pipeline Embolization Device has emerged as an important treatment option for intracranial aneurysms. The number of devices needed to treat an aneurysm is uncertain and is the subject of vigorous debate. The purpose of this study was to compare rates of complications, aneurysm occlusion, and outcome in patients treated with a single-versus-multiple Pipeline Embolization Devices. MATERIAL AND METHODS: One hundred seventy-eight patients were treated with the Pipeline Embolization Device at our institution. Patients were divided into 2 groups: a single-device group (n = 126) and a multiple-device group (n = 52). RESULTS: There was no statistically significant difference between the 2 groups with respect to baseline characteristics except for age and aneurysm size (higher with multiple Pipeline Embolization Devices). Complications occurred more frequently with multiple (15%) versus a single device (5%, P = .03). In multivariate analysis, the use of multiple devices independently predicted complications. A similar proportion of patients achieved adequate aneurysm obliteration at follow-up in the single-device (84%) and the multiple-device groups (87%, P = .8). In multivariate analysis, age and follow-up time predicted obliteration. At follow-up, a significantly higher proportion of patients treated with a single device (97%) achieved a favorable outcome compared with those treated with multiple devices (89%, P = .03). In multivariate analysis, there was a strong trend for the use of a single device to predict favorable outcomes (P = .06). CONCLUSIONS: Treatment with a single Pipeline Embolization Device provides similar occlusion rates with less complications and better overall outcomes. These findings suggest that a single Pipeline Embolization Device is sufficient for treatment of most intracranial aneurysms.

Flow-diversion for ophthalmic segment aneurysms.

BACKGROUND The use of flow-diversion to treat ophthalmic segment aneurysms (OSA) has not been well evaluated. OBJECTIVE To assess the visual outcomes, the obliteration rate, and the need for retreatment of OSA treated by the pipeline embolization device (PED). METHODS Patients who underwent treatment with PED for OSA from 2009 to 2014 were selected and retrospectively reviewed. Patients age, sex, mode of presentation, and aneurysm size were recorded. The complication rates, the need for retreatment (due to recurrence of the aneurysm or worsening symptoms), the aneurysm occlusion rates, the evolution of visual symptoms, and the evolution of headache/retro-orbital pain were registered. RESULTS Forty-one patients harboring 44 OSA treated by flow-diversion were identified. Females constituted 87.80% (37/41) of the cohort. The mean age was 59.16 ± 12.54 years. At final angiographic follow-up, 77.27% (34/44) had complete occlusion, 6.81% (3/44) had near-complete occlusion, and 15.90% (7/44) had incomplete occlusion. Of the 22 symptomatic OSA, complete resolution or significant improvement was noted in 72.72% (16/22), while worsening of symptoms occurred in 4.54% (1/22). Five patients out of 22 (22.72%; 5/22) had no significant changes in their symptoms. The complication rate was 2.27% (1/44). The mortality rate was 0%. CONCLUSION The low complication rate, the high obliteration rate, and the high rate of improvement in the visual symptoms make flow-diversion an appealing option for the treatment of OSA.

Flow Diversion Versus Conventional Treatment for Carotid Cavernous Aneurysms

Background and Purpose— Several endovascular treatment options are available for cavernous carotid aneurysms. We compared pipeline embolization device (PED) versus conventional endovascular treatment in terms of evolution of mass effect, complications, recurrence, and retreatment rate. Methods— One hundred fifty-seven patients harboring 167 cavernous carotid aneurysms were treated using PED placement, coiling, stent-assisted coiling, and carotid vessel destruction. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. Results— There were no difference in age, sex, and mean aneurysm size between those treated with PED and those treated with conventional endovascular procedures. The patients treated with PED had a significantly lower proportion of small-size aneurysms (<10 mm) and a shorter follow-up duration. Multivariate analysis revealed treatment other than PED (PED: odds ratio [OR], 0.03; P=0.002) and size >15 mm (OR, 4.27; P=0.003) to be predictors of no improvement in symptoms. The rate of complete occlusion was 81.36% (48 of 59) for PED, 42.25% (39 of 71) for stent-assisted coiling, 27.27% (6 of 22) for coiling, and 73.33% (11 of 15) for carotid vessel destruction. Retreatment was needed in patients with aneurysm size >15 mm (OR, 2.67; P=0.037) and those who were not treated with PED (PED: OR, 0.16; P=0.006). The rate of major complications was 6.6% (11 of 167). Patients who were treated with PED or stent-assisted coiling had 3.84 lower odds to develop complications (OR, 0.26; P<0.05). Conclusions— The use of PED should be encouraged, especially in symptomatic patients. We found PED to be associated with less need for future treatment, higher improvement in symptoms rate, and lower rate of complications.

Fate of the Ophthalmic Artery After Treatment With the Pipeline Embolization Device.

BACKGROUND Flow diverters have emerged as a major tool in the treatment of cerebral aneurysms. A crucial issue with the use of flow diverters is the patency of side branches covered by the device, most importantly the ophthalmic artery (OA). OBJECTIVE To assess the patency of the OA after coverage with the pipeline embolization device (PED). METHODS All patients who had a PED covering the OA and in whom angiographic follow-up was available were included in the study. The patency of the OA at follow-up was systematically evaluated by 2 authors who were not involved in the procedure. RESULTS Of 95 treated patients, the OA was covered by 1 PED in 81 patients (85%) and by 2 PEDs in 14 patients (15%). Mean angiographic follow-up was 7.5 months, ranging from 3 to 24 months. At the latest follow-up, the OA remained patent in 85 patients (89%), showed diminished flow in 4 patients (4%), and was occluded in 6 patients (7%). Only 1 patient had clinical symptoms related to OA occlusion. In multivariable analysis, larger aneurysm size predicted OA occlusion (P = .04). There was also a strong trend for younger age (P = .06) and coverage by more than 1 device (P = .07). CONCLUSION Treatment of internal carotid artery aneurysms with the PED preserves the patency of the OA in most cases. The occlusion of the OA in the few cases where it occurs is usually a clinically irrelevant event. Minimizing the number of PEDs across the OA is crucial to preserve its patency.

Cerebral Arteriovenous Malformations: Evaluation and Management

There has been increased detection of incidental AVMs as result of the frequent use of advanced imaging techniques. The natural history of AVM is poorly understood and its management is controversial. This review provides an overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management of AVMs. The authors discussed the imaging techniques available for detecting AVMs with regard to the advantages and disadvantages of each imaging modality. Furthermore, this review paper discusses the factors that must be considered for the most appropriate management strategy (based on the current evidence in the literature) and the risks and benefits of each management option.

Aneurysm geometry in predicting the risk of rupture. A review of the literature

Abstract The management of unruptured aneurysms (UAs), whose incidence is increasing, is still a controversial issue. Many studies have been investigating the link between the geometry of the aneurysm and the risk of future rupture in order to bring forth a clear decision plan. The different estimators studied are the aneurysm’s geometry and hemodynamic features on one hand, and the patient’s clinical characteristics on the other. We reviewed the literature while focusing on the different geometrical parameters that have been used in estimating the future risk of rupture. These include mainly the size ratio (SR), the aspect ratio, the non-sphericity index (NI), the undulation index (UI), and the vessel aneurysm inclination angle (AA), to name a few.