Efficacy and Safety of Intravenous Thrombolysis with Tenecteplase in Patients with Wake-Up Branch Atheromatous Disease

Branch atheromatous disease (BAD), a subtype of acute ischemic stroke (AIS), is associated with a high risk of early neurological deterioration (END) and poor prognosis. Wake-up stroke (WUS), comprising 20%-30% of AIS cases, is typically excluded from thrombolysis because of unknown onset time. Using diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR) mismatch, we evaluated the efficacy and safety of Tenecteplase (TNK) thrombolysis in patients with BAD-related WUS. We retrospectively recruited 1,062 patients from seven Zhengzhou hospitals between January 2021 and June 2025. The patients received either TNK (n = 338) or dual antiplatelet therapy (n = 724). Propensity score matching (PSM; 1:1, caliper 0.02) yielded 292 matched pairs. Early neurological changes were evaluated using the National Institutes of Health Stroke Scale (NIHSS), and 90-day outcomes were evaluated using the modified Rankin Scale (mRS). After PSM, TNK significantly reduced the risk of END (odds ratio [OR] = 0.425, 95% confidence interval [CI]: 0.262-0.689; P < 0.001). Patients treated with TNK were more likely to achieve good functional outcomes (modified Rankin Scale [mRS] 0-1 and 0-2) with fewer poor outcomes (mRS ≥ 4). There were no significant differences in symptomatic intracranial hemorrhage, other bleeding events, or mortality among the groups. DWI/FLAIR mismatch-guided TNK thrombolysis appears to overcome the limitations of an unknown onset time in WUS and may counteract the progressive pathophysiology of BAD. TNK intravenous thrombolysis may be a safe and effective treatment for patients with wake-up BAD and DWI/FLAIR mismatches.