Background: Therapeutic hypothermia for acute ischemic stroke is most likely to benefit patients with large vessel occlusion that require reperfusion. Until the recent success of endovascular trials with advanced imaging selection, noncontrast CT prior to intravenous (IV) thrombolysis has been the mainstay. We analyzed the ICTUS 2 trial CT findings before and after thrombolysis to disclose the impact of large vessel occlusion and subsequent edema formation.
Methods: Noncontrast CT findings at baseline and 36 hours after enrollment were analyzed by imaging variables linked with large vessel occlusion. Presence of hyperdensity artery sign (HAS) and ischemic changes were analyzed in hypothermia and normothermia arms of the randomized safety and efficacy trial. Data were presented using descriptive statistics and Fisher’s exact test for comparisons between treatment arms.
Results: 120 patients (median age 69±IQR 15 years; 51 (43%) women; median NIHSS 14±8 IQR) with acute stroke treated with IV thrombolysis were enrolled in ICTUS 2, including 63 randomized to hypothermia (H) and 57 to normothermia (N). CT abnormalities were balanced (68% H vs. 61% N, p=NS) across treatment arms, including hyperdense arteries (HAS) (33% H vs. 37% N, p=NS). At 36 hours, the vast majority of patients had CT abnormalities (92% H vs. 84% N, p=NS), including edema (52% H vs. 44% N, p=NS), hemorrhagic transformation (13% H vs. 19% N, p=NS) and HAS (22% H vs. 15% N, p=NS). Topography of ischemic changes at 36 hours was similar between arms, involving the insular cortex in 60%, frontal lobe 65%, parietal lobe 59% and temporal lobe 52%. Large vessel atherosclerosis was identified as cause of stroke in 29% of hypothermia and 19% normothermia subjects, p=NS. Serial CT changes from baseline to 36 hours based on topography were similar between arms. No interactions could be discerned between imaging findings, treatment allocation and 90-day mRS clinical outcomes.
Conclusions: ICTUS 2 selection criteria based on NIHSS yielded a substantial proportion of large vessel strokes. The relatively high rate of persistent hyperdense arteries and extensive ischemic changes suggest more effective reperfusion strategies than IV thrombolysis may be warranted and enhanced by advanced imaging surveillance.