Abstract
To obtain insights into the pathogenesis of ischemic stroke, we analyzed thromboemboli and other occlusive material retrieved acutely from the cerebral arteries of patients. The experimental design was an observational study in 25 consecutive patients with acute ischemic stroke treated by endovascular mechanical thromboembolectomy. Patients with acute occlusion of a proximal cerebral artery, a disabling neurologic deficit, and either initiation of therapy within 8 hours of onset or initiation of therapy beyond 8 hours if imaging demonstrated substantial residual penumbral tissue at risk were treated at a tertiary Comprehensive Stroke Center (the UCLA Stroke Center). Thrombus was removed by an endovascular mechanical embolectomy device (Merci® Retriever System, Concentric Medical, Mountain View, CA) after placement by angiographic catheter into the occluded intracranial carotid artery, middle cerebral artery or vertebral-basilar artery under fluoroscopic guidance. Our results show that the large majority (20 of 25) of extracted thrombi have similar histologic architecture, a complex of layered, sometimes serpentine, lengths of fibrin:platelet deposits interspersed with linear streaks of nucleated cells. This histology was prevalent with both cardioembolic and atherosclerotic etiologies, indicating the same pathogenetic influences of blood flow and shear in thrombus formation. This histologic pattern among thrombi was present in both the internal carotid artery (ICA) and the middle cerebral artery (MCA). Clots composed uniformly of erythrocytes were uncommon (3 of 25) and were observed only with incomplete extractions, suggesting that sampling was of the proximal thrombus tail where post-occlusion thrombosis had occurred under conditions of stagnant flow. Calcifications or cholesterol were not present. Thrombus size, not histology, predicted the site of arterial occlusion, with no thrombus larger than 3 mm width causing stroke limited to the MCA and no thrombus larger than 5 mm width removed from the ICA. Fungus-containing thrombus was extracted from one patient who had mycotic valvular disease, and an unusual complication occurred in another case, namely, scraping of a small atheroma and attached intima from the MCA, albeit without clinical consequence. We conclude that thromboemboli that cause acute ischemic stroke are of similar, complex structure, regardless of macroscopic dimensions, and are similarly influenced by blood flow, whether the primary etiology is cardioembolic or atherosclerotic. Embolus size is the critical aspect that determines its ultimate destination, those of more than 5 mm width appearing to bypass the cerebral vessels entirely. The mixed fibrin:platelet pattern present in the preponderance of thromboemboli provides foundation for the success of both antiplatelet and anticoagulant treatment strategies in stroke prevention.
Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke
