Does the clopidogrel CYP2C19 genotype assay predict postprocedure stenosis in cerebral aneurysms treated with a flow diverter?

OBJECTIVE: Flow diverters have emerged as a popular modality for treating cerebral aneurysms but require dual antiplatelet therapy (DAPT) after placement. Clopidogrel is a common choice but is a prodrug that some patients may not convert into an active metabolite. The CYP2C19 genotype assay is used to predict activation speed; however, limited data exist showcasing whether this genotype accurately predicts postprocedure complications after flow diversion treatment of cerebral aneurysms. Therefore, the authors sought to characterize whether CYP2C19 genotype correlated with the development of postprocedure intimal hyperplasia (stenosis) after flow diverter placement. METHODS: Medical records were reviewed for patients who underwent flow diverter treatment of cerebral aneurysm at a single academic institution between January 1, 2012, and May 31, 2020. Patient demographics and comorbidities were reviewed alongside CYP2C19 genotype assay, DAPT regimen, and postprocedure angiogram data. Stenosis was defined based on review of angiogram data by two independent physicians. RESULTS: In this review of 120 unique cerebral aneurysms, 102 received DAPT with clopidogrel and 18 received DAPT with an alternative agent. Stenosis was present on 3-month follow-up angiogram for 35/102 (34.3%) aneurysms receiving DAPT with clopidogrel and in 11/18 (61.1%) aneurysms receiving an alternative DAPT regimen (p = 0.031). The CYP2C19 genotype did not correlate with postprocedure stenosis (p = 0.35). CONCLUSIONS: Clopidogrel was a significantly more effective DAPT agent for preventing stenosis when compared to nonclopidogrel DAPT regimens. The clopidogrel CYP2C19 genotype did not predict postprocedure stenosis in this cohort of 120 cerebral aneurysms treated with a flow diverter.

Acute ischemic stroke: emergency department management after the 3-hour window.

Acute ischemic stroke is a leading cause of morbidity and mortality in the United States, and a majority of acute ischemic stroke patients are evaluated for the first time by a clinician in the emergency department. Intravenous tissue plasminogen activator and mechanical thrombectomy are powerful tools for the treatment of acute ischemic stroke. Treatment algorithms for acute ischemic stroke are evolving rapidly, and strokes in select patients can now be treated up to 24 hours after last known well time. However, even in the setting of extended treatment times, the treatment effects of both intravenous tissue plasminogen activator and mechanical thrombectomy are time dependent. The emergency clinician must remain current with the newest treatment algorithms in order to provide expeditious and high-quality care to stroke patients.

Rabbit Elastase Aneurysm: Imaging and Histology Correlates for Inflammation and Healing.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage remains a devastating event with poorly understood pathophysiology. Previous studies have suggested that aneurysm wall inflammation may play a part in the development and potential rupture of aneurysms. The rabbit elastase aneurysm model is a well-established model, which produces aneurysms closely mimicking human cerebral aneurysms in flow dynamics and histopathology. The primary aim of this study was to correlate inflammatory changes after aneurysm formation using sequential vessel wall imaging with histopathologic analysis. A secondary aim was to evaluate the potential effect of gender and anti-inflammatory treatment with aspirin on this inflammatory response. METHODS: Twenty-seven New Zealand rabbits underwent surgery to create an aneurysm using elastase infusion at the right common carotid artery origin. Vessel wall imaging and histopathologic analysis was obtained at different time points after aneurysm creation. The rabbits were also randomized by gender and to treatment groups with or without aspirin. RESULTS: Histopathologic analysis revealed 3 distinct phases after aneurysm formation. These phases were an initial inflammatory phase, followed by a regeneration phase, and finally a connective tissue deposition phase. Vessel wall imaging demonstrated 2 distinct imaging patterns. No appreciable differences were seen in histology or imaging when comparing gender or treatment with aspirin. CONCLUSIONS: Inflammatory changes induced by the rabbit elastase aneurysm model can be correlated with histopathologic findings and observed on noninvasive vessel wall imaging. This may provide a method to study the inflammatory pathway as it pertains to aneurysmal development and subsequent rupture.

Endovascular intervention of acute ischemic stroke due to occlusion of fetal posterior cerebral artery.

A fetal posterior cerebral artery (FPCA) is an anatomic variant in which the posterior cerebral artery is an embryological derivative of the internal carotid artery. Although most cases of ischemic strokes in patients with FPCAs involve embolic infarcts, emergent large vessel occlusion of a FPCA is extremely rare. We present two cases of successful endovascular intervention for emergent occlusion of a FPCA, one of which is only the second reported case of a mechanical thrombectomy of a FPCA. We review the embryology of FPCA, the controversy regarding its association with cerebral infarcts, and various approaches used in the treatment of such occlusive lesions.