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Background: It is unclear whether thrombolysis benefits patients with fluctuating neurologic symptoms., Objective: To evaluate the clinical course of patients with acute stroke who presented with marked fluctuations in neurologic status and received thrombolytic therapy., Design: Prospective analysis., Setting: London Health Science Centre University Hospital, London. Patients We prospectively identified patients who were treated with intravenous or intra-arterial recombinant tissue plasminogen activator between January 1, 2004, and January 1, 2006. For this analysis, we chose patients who had marked fluctuation in neurologic status at presentation and who received thrombolytic therapy. Main Outcome Measure Fluctuation of neurologic deficits, defined as a 4-point or greater increase or decrease in the National Institutes of Health Stroke Scale (NIHSS) score., Results: Among 127 patients, 13 (10.2%) had clinical fluctuations. Patients with fluctuations presented with a lower NIHSS score (median, 7; interquartile range, 10-17) compared with patients without fluctuations (median, 12; interquartile range, 10-17) (P < .001). Fluctuation of symptoms or signs ceased after thrombolysis. At 24 hours after stroke, the median NIHSS score was 2 (range, 1-12). All patients had favorable neurologic and functional outcomes at 3 months after thrombolysis (modified Rankin scale score, 0-2)., Conclusion: Thrombolysis may benefit patients with fluctuating symptoms or signs due to cerebral ischemia.