Thrombolytic Therapy for Patients Who Wake-Up With Stroke

Abstract
Background and Purpose— Approximately 25% of ischemic stroke patients awaken with their deficits. The last-seen-normal time is defined as the time the patient went to sleep, which places these patients outside the window for thrombolysis. The purpose of this study was to describe our center’s experience with off-label, compassionate thrombolysis for wake-up stroke (WUS) patients. Methods— A retrospective review of our database identified 3 groups of ischemic stroke patients: (1) WUS treated with thrombolysis; (2) nontreated WUS; and (3) 0- to 3-hour intravenous tissue plasminogen activator-treated patients. Safety and clinical outcome measures were symptomatic intracerebral hemorrhage, excellent outcome (discharge modified Rankin score, 0–1), favorable outcome (modified Rankin score, 0–2), and mortality. Outcome measures were controlled for baseline NIHSS using logistic regression. Results— Forty-six thrombolysed and 34 nonthrombolysed WUS patients were identified. Sixty-one percent (28/46) of the treated WUS patients underwent intravenous thrombolysis alone whereas 30% (14/46) were given only intra-arterial thrombolysis. Four patients received both intravenous and intra-arterial thrombolysis (9%). Two symptomatic intracerebral hemorrhages occurred in treated WUS (4.3%). Controlling for NIHSS imbalance, treated WUS had higher rates of excellent (14% vs 6%; P =0.06) and favorable outcome (28% vs 13%; P =0.006), but higher mortality (15% vs 0%) compared to nontreated WUS. A second comparison controlling for baseline NIHSS between treated WUS and 174 intravenous tissue plasminogen activator patients treated within 3 hours of symptoms showed no significant differences in safety and clinical outcomes. Conclusion— Thrombolysis may be safe in WUS patients. Our center’s experience supports considering a prospective, randomized trial to assess the safety and outcome of thrombolysis for this specific patient population.