Efficacy and Safety of Alteplase on Treatment of Acute Single Small Subcortical Infarction.

Background: Single Small Subcortical Infarction (SSSI) is an isolated small infarction in the territory of perforating artery with a maximum diameter of 20 mm in axial Diffusion-Weighted Imaging (DWI). About 20 to 30% of SSSI patients were reported to have Early Neurological Deterioration (END) in the acute phase, which brought adverse effects on long-term outcomes. The effect of the alteplase on the outcome of SSSI, especially END and long-term outcomes, was ambiguous.

Objective: The study aims to find out the efficacy and safety of intravenous recombinant tissue Plasminogen Activator (rt-PA) on long-term and short- outcomes of patients with SSSI as compared to patients who received standard medical care.

Methods: The patients were retrospectively screened from a stroke registry of the neurology department of 1st Affiliated Hospital of Zhengzhou University from January 2013 to December 2020. Based on treatment modality, patients were dichotomized into alteplase and standard medical care groups. To minimize confounding factors in subgroups, a propensity score matching analysis was done. The primary outcome was the favorable functional outcome 3 months after stroke onset, defined by attaining a score of ≤2 points on the modified Rankin scale (mRS), secondary outcome was the prevention of occurrence of END, defined as an increase of ≥2 points in the total score or ≥1point on motor subunit in the National Institutes of Health Stroke Scale (NIHSS) score within 72 hours after admission, safety features were symptomatic intracranial hemorrhage (sICH) or death. Multivariate analysis was employed to find the efficacy and safety of alteplase in the treatment of SSSI.

Results: A total of 717 patients with anterior circulation SSSI were selected, and 132 were included in the final analysis. Forty-five patients were treated with alteplase within 4.5 hours and 87 with standard medical care, and 44 pairs were successfully matched by propensity score. Pre-match data showed that the alteplase thrombolysis group showed a higher proportion of favorable outcomes at 3-month follow-up [OR=0.315, 95%CI:0.106, 0.931, P = 0.037] but did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.033, 95%CI:0.417,2.554, P = 0.943]. Post-match data showed that the alteplase group also showed a higher proportion of favorable outcomes at 3-month follow-up [OR = 0.247, 95%CI: 0.074, 0.830, P = 0.024]; however, it did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.241, 95%CI: 0.433,3.554, P = 0.688]. There was one case of asymptomatic ICH in alteplase treated patients.

Conclusion: Patients with SSSI in the anterior circulation are more likely to achieve 3 months favorable outcomes than those who were treated with standard medical care; however, treatment with alteplase may not prevent the occurrence of END.