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OBJECTIVEDual antiplatelet therapy is required for the treatment of intracranial aneurysms with the Pipeline embolization device (PED). Platelet function testing (PFT) is often used to assess the efficacy of the antiplatelet regimen prior to PED placement. The optimal impedance values for whole blood aggregometry in this setting have not been defined.METHODSA retrospective review of a prospectively maintained database was performed for the years 2011-2015 to identify patients with intracranial aneurysms treated with the PED who underwent pretreatment PFT using whole blood aggregometry. Antiplatelet therapy was not altered based on PFT results; all patients remained on standard doses of aspirin and clopidogrel. Clinical, radiographic, and laboratory data were analyzed to identify the optimal cutoff impedance value for clopidogrel responsiveness using the receiver operating characteristic curve and Youden's index.RESULTSForty-nine patients underwent 53 endovascular procedures for the treatment of 76 aneurysms using the PED. The majority of these aneurysms were located in the anterior circulation (90.8%) and affected the internal carotid artery (89.5%). Patients in 30 procedures (56.6%) were identified as clopidogrel responders based on the manufacturer cutoff value (< 6 Ω). Thromboembolic complications occurred in 13 (24.5%) procedures; patients in 6 (11.3%) cases were symptomatic and those in 3 (5.7%) cases had ischemic strokes. Eleven of the 13 (84.6%) thromboembolic complications occurred in clopidogrel nonresponders. An impedance value of ≥ 6 Ω was independently associated with thromboembolic complications. The optimal electrical impedance value was identified as ≥ 6 Ω (sensitivity 84.6%, specificity 70.0%, area under the curve 0.77) for identifying clopidogrel nonresponders.CONCLUSIONSThromboembolic complications are more common following PED placement in patients who do not respond adequately to clopidogrel. Clopidogrel nonresponders can be identified using pretreatment whole blood aggregometry. The optimal cutoff value to categorize a patient as a clopidogrel nonresponder when using whole blood aggregometry is ≥ 6 Ω.

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Neuroendovascular techniques for treating cerebral aneurysms and other cerebrovascular pathology are increasingly becoming the standard of care. Intraluminal stents, aneurysm coils, and other flow diversion devices typically require concomitant antiplatelet therapy to reduce thromboembolic complications. The variability inherent with the pharmacodynamic response to common antiplatelet agents such as aspirin and clopidogrel complicates optimal selection of antiplatelet agents by clinicians. This review serves to discuss the literature related to antiplatelet use in neuroendovascular procedures and provides recommendations for clinicians on how to approach patients with variable response to antiplatelet agents, particularly clopidogrel.

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OBJECTIVE Even though published data exist concerning the prevalence of ischemic lesions detected by diffusion-weighted imaging (DWI) following endovascular treatment of intracranial aneurysms, a single-center cross-evaluation of the different endovascular techniques has been lacking. The authors sought to prospectively evaluate the prevalence and clinical significance of ischemic lesions occurring after endovascular treatment of intracranial aneurysms and to compare the safety and effectiveness of a broad spectrum of currently accepted endovascular techniques in a single-center setting. METHODS This was a prospective cohort study involving consecutive patients treated for intracranial aneurysms exclusively by endovascular means, excluding treatments in the acute rupture phase, in a center featuring an endovascular-only treatment policy for intracranial aneurysms. All patients underwent MRI, including a 3-directional DWI sequence, before treatment, 24 hours postprocedure, and 6 months following endovascular embolization. Selective angiography was performed at 6 months' follow-up. RESULTS From January 2012 through December 2013, 164 aneurysms were treated in 128 consecutive patients. Endovascular techniques included coiling (14.6%), balloon-assisted coiling (20.1%), stent-assisted coiling (3.7%), low-profile stent-assisted coiling, flow diversion (38.4%), and very complex treatments (6.1%) involving 2 stents in Y or T configurations. On postprocedure MRI, the rates of occurrence of new DWI-positive lesions were 64.3% for coiling, 54.5% for remodeling, 61.1% for stent-assisted coiling, 53.7% for flow-diverting stents, and 75% for very complex treatments (p = 0.4962). The 6-month procedure-related morbidity and mortality rates were 6.25% and 0%, respectively. At 6 months' follow-up, 93% of the patients had modified Rankin Scale (mRS) scores of 0-2. Very complex treatments offered a higher complete occlusion rate (100%) than all other techniques (66.7%-88.9%). Age and length of procedure were independent factors for DWI lesion occurrence. The diameter of DWI lesions on 24-hour postprocedure MRI was positively correlated with mRS score at discharge. Among the DWI-positive lesions measuring less than 2 mm in diameter on the 24-hour MRI, 44.12% had regressed at 6 months. CONCLUSIONS Procedure-related DWI lesions are far more often encountered in silent forms than they are clinically evident. They do not seem to be significantly correlated with procedure-related complications, nor do they seem to impair clinical outcome, regardless of the endovascular technique. Small lesions (< 2 mm in diameter) may regress within 6 months. The use of the most adapted technique, in terms of aneurysm configuration, results in significant total occlusion rates, with acceptable safety.

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The Pipeline embolization device (PED) is the most widely used flow diverter in endovascular neurosurgery. In 2011, the device received FDA approval for the treatment of large and giant aneurysms in the internal carotid artery extending from the petrous to the superior hypophyseal segments. However, as popularity of the device grew and neurosurgeons gained more experience, its use has extended to several other indications. Some of these off-label uses include previously treated aneurysms, acutely ruptured aneurysms, small aneurysms, distal circulation aneurysms, posterior circulation aneurysms, fusiform aneurysms, dissecting aneurysms, pseudoaneurysms, and even carotid-cavernous fistulas. The authors present a literature review of the safety and efficacy of the PED in these off-label uses.

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OBJECTIVE Although the use of dual antiplatelet therapy with flow diversion is recommended and commonplace, the testing of platelet inhibition is more controversial. METHODS The authors reviewed the medical literature to establish and describe the physiology of platelet adhesion, the pharmacology of antiplatelet medications, and the mechanisms of the available platelet function tests. Additionally, they present a review of the pertinent neurointerventional and interventional cardiology literature. RESULTS Competing reports in the neurointerventional literature argue for and against the use of routine platelet function testing, with adjustments to the dosage or medications based on the results. The interventional cardiology literature has also wrestled with this dilemma after percutaneous coronary interventions, with conflicting reports of the benefits of platelet function testing. CONCLUSIONS Despite its prevalence, the benefits of platelet function testing prior to flow diversion are unproven. This practice will likely remain controversial until the level of evidence improves through more rigorous testing and reporting.

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OBJECTIVE: The incidence and risk factors of microembolic lesions on MR diffusion-weighted imaging (DWI) were analyzed after the endovascular coiling of unruptured intracranial aneurysms (UIAs). METHODS: Data obtained from 271 consecutive patients (70 men and 201 women; median age 57 years; range 23-79 years) who presented with UIA for coil embolization between July 2011 and June 2013 were analyzed. Two independent reviewers examined the DWI and apparent diffusion coefficient maps obtained the following day for the presence of restrictive diffusion spots and counted the number of spots. Multivariate analysis was then performed to identify independent risk factors for developing microembolism following the coiling of an aneurysm. RESULTS: Microembolic lesions were noted in 101 of 271 patients (37.3%). The results of the multivariate analysis showed that the following factors significantly influenced the risk for microembolism: age, diabetes, previous history of ischemic stroke, high-signal FLAIR lesions in the white matter, multiple aneurysms, and the insertion of an Enterprise stent (all ORs > 1.0 and all p values < 0.05). Previously known risk factors such as prolonged procedure duration, aneurysm size, and decreased antiplatelet function did not show any significant influence. CONCLUSIONS: The incidence of microembolism after endovascular coiling of UIA was not low. Lesions occurred more frequently in patients with vascular status associated with old age, diabetes, and previous stroke. Aneurysm multiplicity and the type of stent used for treatment also influenced lesion occurrence.

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OBJECT: Vertebrobasilar fusiform aneurysms (VFAs) are rare lesions characterized by abnormal dilation and tortuosity of the vertebral and/or basilar arteries. Untreated, these aneurysms have a tendency to progress, often resulting in neurological symptoms or rupture leading to subarachnoid hemorrhage. The microsurgical treatment of these lesions can be difficult due to their location and the circumferential involvement of the arteries. These features make microsurgical treatment prone to high morbidity. The Pipeline Embolization Device (PED) has gained popularity for the treatment of aneurysms of the internal carotid artery. Its use in the posterior circulation has been limited, likely due to a fear of perforating artery occlusion. METHODS: The authors retrospectively reviewed their database of patients treated with the PED and identified 12 patients who had VFAs. The clinical features, complications, and outcomes of these patients were analyzed. RESULTS: At an average follow-up of 11 months, the mean modified Rankin Scale score was 1.9. Complete aneurysm occlusion was seen in 90% of the patients with radiographic follow-up. Three patients suffered new neurological deficits postoperatively. One of these patients died, while the remaining 2 demonstrated significant clinical improvement at follow-up. CONCLUSIONS: With attention to the anatomy of perforating arteries, staged contralateral vertebral artery sacrifice, and adequate platelet inhibition, PED may be an effective treatment option-alone or in a hybrid construct with stents of less coverage for VFAs-with an acceptable complication rate.

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OBJECTIVES: Endovascular procedures are one of the important treatment options for steno-occlusive arteries in ischemic stroke patients. However, embolic complications after such procedures are always a concern. The authors investigated the association between serial change of residual platelet reactivity and silent embolic cerebral infarction (SECI) after endovascular treatment. METHODS: Ischemic stroke patients undergoing stenting of intra- or extracranial arteries were recruited prospectively. Residual platelet reactivity, represented by aspirin reaction units (ARUs) and P2Y12 reaction units (PRUs), was measured serially (6 hours before, immediately after, and 24 hours after the procedure). A loading dosage of aspirin (500 mg) and/or clopidogrel (300 mg) was given 24 hours before the procedure to patients naïve to antiplatelet agents, whereas the usual dosage (aspirin 100 mg and clopidogrel 75 mg) was continued for patients who had previously been taking these agents for more than a week. Diffusion-weighted MRI was performed before and 24 hours after the procedure to detect new SECIs. Clinical characteristics, baseline ARU and PRU values, and the change in ARU and PRU values after stenting were compared between patients with and without SECIs. RESULTS: Among 69 consecutive patients who underwent neurovascular stent insertion, 41 patients (59.4%) had poststenting SECIs. The lesion was located only at the vascular territory of the stented vessel in 21 patients (51.2%), outside the stented vessel territory in 8 patients (19.5%), and both inside and outside in 12 patients (29.3%). The occurrence of SECIs was not associated with the baseline ARU or PRU value, but was associated with PRU increase after stenting (36 ± 73 vs -12 ± 59, p = 0.007), deployment of a longer stent (31.1 ± 16.5 mm vs 21.8 ± 9.9 mm, p = 0.01), and stent insertion in extracranial arteries (78.1% vs 45.2%, p = 0.008). Stent length (OR 1.066, p = 0.01) and PRU change (OR 1.009, p = 0.04) were independently associated with the occurrence of SECI. CONCLUSIONS: Residual platelet reactivity after dual antiplatelet treatment measured before stenting did not predict poststenting SECI. However, the longer stent and the serial increase of PRU values after stenting were related to SECI. Continuous increase of platelet activation after endovascular procedure may be important in poststent cerebral infarction.

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