In Reply We thank Ospel and colleagues for their thoughtful comments on our article1 showing that more proximal occlusion and greater thrombus length predict early neurological deterioration of ischemic origin (ENDi) in patients with acute minor ischemic stroke with large-vessel occlusion treated with intravenous thrombolysis, with implications regarding how to best manage these patients. Although the precise pathophysiological links between more proximal occlusion, a longer thrombus, and ENDi are uncertain, we fully agree that a leading hypothesis is in situ thrombus extension leading to secondary hemodynamic compromise via occlusion of previously unaffected perforators or collaterals.2 Activation of the coagulation cascade triggered by blood stasis adjacent to the original thrombus (eg, because of slow collateral flow or inefficient angioarchitecture) is an attractive mechanism to explain thrombus extension and hence ENDi, but the lack of association between the hypoperfusion intensity ratio on perfusion imaging—a well-validated surrogate marker of collateral flow—and ENDi found in our study1 would not support this mechanism as prominent. To our knowledge, the association between thrombus length and collateral grade is not well documented so far and has only been described using single-phase computed tomography angiography, which overestimates thrombus length in patients with slow collaterals because of poor retrograde filling.3 Contrary to computed tomography angiography studies, we found no association between thrombus length measured on T2* magnetic resonance imaging and collateral grade.4 Thus, we believe there are insufficient data to propose thrombus length as a surrogate marker of collaterals, but further work using alternative imaging modalities is warranted to clarify the respective roles of thrombus length, collaterals, and angioarchitecture for ENDi prediction. Besides in situ thrombus extension, other factors might explain the association between ENDi and more proximal occlusion and longer thrombus, such as reembolization from a proximal source (eg, cervical carotid occlusion5) and blood pressure drops or hyperglycemia or hypoglycemia, which worsen neuronal status in hypoperfused tissue downstream of a persistent large-vessel occlusion.
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Seners P, Baron J, Turc G. Questions on Predicting Early Neurological Deterioration in Patients With Minor Stroke and Large-Vessel Occlusion—Reply. JAMA Neurol. 2021;78(8):1020–1021. doi:10.1001/jamaneurol.2021.2025
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