First Indian single center experience with pipeline embolization device for complex intracranial aneurysms
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.149383
Source of Support: None, Conflict of Interest: None
Background: Flow diversion is a novel method of therapy wherein an endoluminal sleeve, the flow diverter stent is placed across the neck of complex aneurysms to curatively reconstruct abnormal vasculature. We present the first Indian single center experience with the pipeline embolization device (PED) and 6 months follow-up results of 5 patients. Subjects and Methods: Five complex or recurrent intracranial aneurysms in five patients were treated with PED. The patients were followed-up with magnetic resonance angiography (MRA) after 4 weeks and conventional angiography after 6 months. Feasibility, complications, clinical outcome, early 1-month MRA and 6 months conventional angiographic follow-up results were analyzed. Results: Of the five aneurysms treated, four were in the anterior circulation and one in the posterior circulation. All five patients were treated with a single PED in each, and additionally coils were used in one patient. At 1-month MRA follow-up, complete occlusion was seen in 2 (40%) of the five cases. Post 6 months conventional angiography showed complete occlusion of the aneurysm sac in all five cases (100%). Side branch ostia were covered in three patients, all of which were patent (100%). There was no incidence of major neurological morbidity or mortality. One patient (20%) who had basilar top aneurysm experienced minor neurological disability after 5 days which partially improved. Conclusions: Pipeline embolization device for complex and recurrent aneurysms is technically feasible, safe, offers low complication rate, and definitive vascular reconstruction. PED can be used without fear of occlusion of covered eloquent side branches and perforators.
Keywords: Complex aneurysm, flow diversion, parent artery dysplasia, pipeline embolization device, recurrent aneurysm, wide-necked aneurysm
Intracranial aneurysms are seen in approximately 2% of the general population  and are the most common cause of subarachnoid hemorrhage (SAH).  SAH is an acute neurological event resulting in a variety of clinical outcomes ranging from complete recovery to death. ,, The average annual incidence of rupture of the aneurysm is 1.1%.  Aneurysms with higher size ratio (aneurysm to average parent vessel diameter ratio) are more prone to rupture than smaller aneurysms.  Any ruptured intracranial aneurysm or incidentally detected unruptured aneurysm >5 mm is considered an indication for treatment either by endovascular or neurosurgical approach, ,, preferably through an endovascular route if feasible. 
However, there are certain subsets of aneurysms which cannot effectively be treated by either surgical clipping or endovascular coiling. These include wide-necked, fusiform, large and giant unruptured aneurysms, aneurysms with associated dysplastic parent vessel, aneurysms incorporating origin of eloquent side branches or perforators, recurrent aneurysms, and dissecting aneurysms with unexpendable parent artery. Endovascular reconstruction using a flow diverter is a novel effective way of treating these subsets of aneurysms. ,,,,,,,,,,,,
The purpose of this study was to present our initial experience with pipeline embolization device (PED) in five patients. This device is approved by Drug Controller General of India for use in cerebral aneurysms, CEmark approved for use in Europe since 2009, Food and Drug Administration approved for endovascular treatment in adults with large or giant wide-necked intracranial aneurysms in the internal carotid artery (ICA) from the petrous to the superior hypophyseal segments. This is the 1 st time in India that PED placement for aneurysm treatment has been performed.
Five patients presenting with unruptured or previously treated aneurysms not ideally suitable for endovascular coiling or surgical clipping were treated with PED in our institution. All the aneurysms were diagnosed, confirmed, and characterized by conventional and three-dimensional rotational angiography performed using Artis Zee Biplane cathlab system (Siemens AG, Muenchen, Germany).
The five aneurysms were [Table 1].
Case 1 [Figure 1]
Patient presented with left sided ptosis. Digital subtraction angiography (DSA) showed a 9 mm wide neck aneurysm arising from the cavernous segment of the left ICA. Location was not ideally suitable for surgical clipping.
Case 2 [Figure 2]
Patient had with SAH 5 years ago, DSA performed then showed a large posterior communicating artery (PCA) aneurysm which was coiled using balloon remodeling technique. Follow-up three-dimensional angiography showed a complex aneurysm arising from the base of the previously coiled aneurysm.
Case 3 [Figure 3]
Patient a known case of polycystic renal disease presented with SAH, DSA showed an aneurysm in the left A-1 segment of the anterior cerebral artery which showed features of rupture and was treated by surgical clipping. The patient presented a few weeks later with severe headache; repeat angiogram showed recurrence of aneurysm close to the area of clipping and required endovascular coiling to obliterate the residual lumen.
The angiogram also showed a 3 mm M1 segment aneurysm on the right side with a perforator arising from the fundus. Clipping or conventional coiling would result in neurological insult secondary to occlusion of the perforator.
Case 4 [Figure 4]
Patient presented with right-sided ptosis. The DSA showed a large right PCA aneurysm with dysplastic parent artery. The patient was posted for flow diverter; however, the aneurysm ruptured in the intervening period. Coils were placed predominantly in the fundus and body to prevent rebleed, and PED placement was planned subsequently to reconstruct the dysplastic segment.
Case 5 [Figure 5]
Patient presented with posterior circulation transient ischemic attacks in the form of episodes of visual disturbances and vertigo. Angiography performed showed a wide necked basilar top aneurysm which incorporated both the posterior cerebral and superior cerebellar arteries.
Before treatment, all patients were started on dual antiplatelets for 3 days consisting ticagrelor 90 mg q12h and aspirin 300 mg q24h. Ticagrelor was used in all patients secondary to an insufficient platelet suppression with clopidogrel 150 mg q24h as quantified by platelet aggregometry. The procedure was performed under general anesthesia. Routine systemic heparinization and standard triaxial access technique were followed, and a 3F Marksman microcatheter (ev3; Irvine, California, USA) was navigated across the neck of the aneurysm into the distal parent artery (MCA in the case of P-com aneurysms, distal ICA in cavernous segment aneurysm and right PCA in the case of basilar top aneurysm since left PCA was fetal in morphology) under roadmap guidance in the working angle. PED (ev3/Covidien, Irvine, California, USA) of a precalculated diameter and length was introduced into the Marksman microcatheter, positioned and deployed within the parent artery across the neck of the aneurysm using a method that incorporates uncovering with pushing to ensure complete expansion of the device. In addition, in one patient, the aneurysm was partially coiled through a microcatheter "jailed" within the aneurysm.
Dual antiplatelet regimen was continued for 6 weeks followed by aspirin 300 mg q24h alone for 6 months.
Patients underwent clinical review at 2 and 6 weeks post procedure. Follow-up magnetic resonance angiography (MRA) (Siemens Skyra 3T, Siemens AG, Muenchen, Germany) was performed after 1-month and follow-up conventional angiography was performed after 6 months in all five cases.
The technical feasibility, clinical and angiographic outcome, and complications were assessed.
Of the five cases, 3 (60%) were females, and the average age was 50.8 years (range, 38-72 years). Four were anterior circulation aneurysms (80%), and 1 (20%) was a basilar top aneurysm. The mean aneurysm size was 11.98 mm. Single PED was used in each of the cases and additionally, the basilar top aneurysm was partially filled with detachable coils. There was no technical difficulty in navigating the microcatheter to the parent artery distal to the neck of the aneurysm or in PED deployment in any case. Side branches were covered in three cases (anterior cerebral and choroidal arteries in two cases and bilateral superior cerebellar arteries in one case) and perforators were covered in one case. Contrast stasis within the aneurysm sac was seen immediately post PED deployment, and there was normal flow through the covered side branches [Table 2].
There was no mortality or severe disability. The patient with basilar top aneurysm had minor neurological deficit in the form of dysphasia and ataxia 6 days after treatment which improved partially over a period of 4 weeks. Magnetic resonance imaging at the onset of symptoms showed a small left superior cerebellar artery territory infarct. None of the cases had symptomatic or asymptomatic subarachnoid or intraparenchymal hemorrhage.
Magnetic resonance angiography at 1-month showed no flow signal in the aneurysm sac in two patients (40%). Flow signal was seen in covered side branches and perforators in all four cases [Table 3]. In MRA, the flow diverter was seen as thin parallel lines of signal void and due to susceptibility artefact, the vascular segment containing the flow diverter looks artifactually stenosed. No such stenosis was noted in the 6 months catheter angiography.
Conventional catheter angiography performed at 6 months showed complete obliteration of the aneurysm in all five cases (100%). The covered side branches and perforators showed good flow in all four cases (100% side branch preservation) [Table 3].
Significant observations made in this study are [Table 4]: Treatment with PED is a technically feasible option; achieved 100% aneurysm occlusion rate at 6 months; facilitated vessel reconstruction even in dysplastic vessel; and PED preserved covered side branches including small superior cerebellar arteries and still smaller middle cerebral artery perforators. There were no PED-associated complications like stenosis or thrombosis, and no antiplatelet regimen-related complications like intraparenchymal hemorrhage. Flow diversion requires optimal antiplatelet activity. Ticagrelor is a new reversible ADP P2Y12 platelet receptor inhibitor with no documented resistance and no additional adverse effects. 
A flow diverter achieves aneurysm occlusion by reconstructing the abnormal cerebral vessel, redirecting the flow away from an aneurysm, producing an environment contributory to thrombosis within the aneurysm and encouraging neo-intimal remodeling. ,,, Flow diverter adjusts the parent vessel altering the aneurysm inflow zone, redirecting the jet of blood away from the neck of the aneurysm,  thereby reducing the risk of recurrence or regrowth. Our experience with PED in recurrent post coiling P-com aneurysm has shown complete aneurysm occlusion and remodeling of the parent vessel.
Analysis of rabbit elastase-induced aneurysm models has suggested that optimal flow diversion requires porosity of 70% and pore density of 18 pores/mm 2 . , Animal studies using PED have shown better result with porosity of 65% rather than 70%.  The PED is a cylindrical metal sleeve made of 48 strands made of 25% platinum and 75% cobalt - nickel alloy, each strand measuring between 28 and 33 μm. It provides 30-35% metal coverage with pore size of 0.02-0.05 mm 2 when fully expanded. ,,, The collapsed device measures about 2.5 times the length of expanded device.  Accurate measurement of vessel to be treated is mandatory since oversizing will result in reduced wall coverage  and undersizing result in distal migration.
Pipeline embolization device does not necessitate intubating an aneurysm and forcing coils into it - thereby significantly reducing the risk of intraprocedural rupture. ,
In vitro studies have shown that flow diverters achieved higher reduction of flow into wide-necked aneurysm than coils  and hence, higher occlusion rates of aneurysm can be achieved with PED compared to coiling in large un-ruptured saccular aneurysms. 
Technical feasibility reached 97-100% in various studies. ,,,,, Technical feasibility in our study is 100%.
Literature has shown that occlusion rates at 6 months ranged between 64.3% and 94.4% ,,,,,,,,,, and at 1-year ranged between 90% and 96%. ,,, Our study showed complete occlusion rates of 40% and 100% at 1 and 6 months, respectively.
Pipeline embolization device has shown high occlusion rate in dissecting aneurysms and is considered when parent artery occlusion is not feasible. ,
Covered side branch preservation achieved ranged between 86% and 100% in multiple studies with good long-term outcome even in small branch occlusion. ,,, Covered side branch and perforator preservation in our study are 100%.
Pipeline embolization device proved to be financially favorable compared to endovascular coiling of large and giant aneurysms ,, of volume more than 0.9 cm 3 .  Since PED implantation is technically simpler, it significantly reduces fluoroscopy and procedure times, and radiation exposure. 
Mortality and major complication rates ranging from none to 18.5% and minor complications ranging from 3.5% to 26.7% have been reported in various studies. ,,,,,,, In our study, there has been no fatality or major neurological complication. The patient with complex basilar top aneurysm experienced mild ataxia and dysphasia 1-week postprocedure with partial recovery in 4 weeks. Studies have shown higher mortality and morbidity with posterior circulation flow diversion for giant fusiform aneurysms  and PED is reserved for cases not amenable for balloon or stent-assisted coiling. ,
The delay in occlusion coupled with the requirement of dual antiplatelets renders PED without coiling unsuitable for ruptured aneurysms. , However, studies performed on ruptured complex aneurysms and uncoilable very small aneurysms (<2 mm) have shown promising results with PED. ,,,
There is a proposed theoretical risk of aneurysm rupture after flow diversion secondary to increased leukocytic lytic enzymes in the red thrombus formed within the aneurysm - supporting the practice of placing a few coils within large aneurysms (>15 mm) in addition to flow diverter to facilitate white thrombus formation. ,
Partial expansion of PED is avoided by choosing appropriate sized PED and avoiding unnecessary stretching of the device. 
Delayed stenosis within the PED can be treated with balloon angioplasty if they are flow limiting. ,,, PED thrombosis is a dreadful event, and delayed thrombosis has been documented as late as 23 months after treatment. 
Flow diversion with PED is technically feasible, simpler compared to endovascular coiling, and has a low complication rate in treatment of complex, recurrent, and wide-necked aneurysms, in aneurysms with dysplastic parent artery and aneurysms with perforators arising from the dome. PED achieved 100% aneurysm occlusion and covered side branch and perforator preservation rates. Ticagrelor is an effective antiplatelet drug with no added risk of complications.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]