Efficacy and safety of thrombolysis for stroke of unknown onset time: a meta-analysis

Current stroke treatment guidelines exclude unknown onset stroke (UOS) patients from thrombolytic therapy even though several studies have reported significant treatment efficacy and safety. We performed a meta-analysis of relevant studies retrieved by systematic searches of the PubMed, Embase, and Cochrane databases up to December 31, 2013. Dichotomized modified Rankin Scale (mRS) scores 0-1 at 90 days, mRS 0-2 at 90 days, overall mortality, and symptomatic intracranial hemorrhage (sICH) incidence were collected as primary outcome measures. Fixed effects meta-analytical models were used, and between-study heterogeneity was assessed. Eleven studies encompassing 1,832 patients were included. In case-control studies of UOS patients, thrombolysis was associated with a significant increase in the proportion of patients with mRS scores of 0-1 (OR 2.37; 95% CI 1.20-4.69; P = 0.013) and 0-2 (OR 2.03; 95% CI 1.26-3.30; P = 0.004) without increased mortality or sICH incidence. In studies comparing thrombolysis-treated UOS to thrombolysis-treated known onset stroke, however, fewer UOS patients had mRS scores of 0-1 (OR 0.70; 95% CI 0.51-0.97; P = 0.033) with no change in mortality, sICH incidence, or patients with mRS of 0-2. Subgroup analysis based on imaging criteria and time window of thrombolysis indicated that UOS patients treated within 3 h after first found abnormal and those with early ischemic changes restricted to <1/3 of the middle cerebral artery territory gained more benefit from thrombolysis treatment than the whole UOS population. Randomized controlled trials are warranted to confirm the efficacy of thrombolysis in this UOS subgroup.