Abstract
Background/Objective: Severity of white matter (WM) disease has been implicated in cerebral tissue and clinical outcomes of patients with acute ischemic stroke (AIS). We sought to assess whether WM disease burden is an independent predictor of outcome in patients with mild AIS and its effect on intravenous tissue plasminogen activator (IV TPA) treatment in this population. Methods: Patients with a National Instituted of Health Stroke Scale (NIHSS) score <8 (“mild AIS”) and acute brain ischemia on diffusion-weighted MRI were selected from the hospital-based, prospective AIS cohort. Normalized White Matter Hyperintensity Volumes (nWMHV) were obtained using a validated, semi-automated volumetric measurement tool. Bivariate and multivariate regression analyses were performed to identify independent predictors of full recovery on follow-up modified Rankin Scale (mRS) at 90 days. Interaction between nWMHV and IV TPA was tested in multivariate regression analysis. Results: Of 465 patients with mild AIS, 29 (6%) received IV TPA and 128 (33%) achieved full recovery (mRS 0) outcome. On bivariate analysis, greater nWMHV and admission NIHSS, as well as presence of hypertension, diabetes mellitus (DM), hyperlipidemia and prior stroke were associated with long-term persistence of symptoms (p<0.05). In multivariable analysis, higher admission NIHSS (OR 0.83, 95% CI 0.74-0.93), history of DM (OR 0.46, 95% CI 0.24-0.84) and prior stroke (OR 0.30, 95% CI 0.13-0.64), as well as increasing quartiles of nWMHV (OR 0.48, 95% CI 0.25-0.92) independently decreased the odds of favorable outcome. There was no interaction between nWMHV and IV TPA treatment (p=0.96). Conclusion: Patients with mild AIS often have worse functional outcomes than expected. Our data indicate that severe WM disease is an independent predictor of long-term full recovery in mild AIS, and nWMHV might be a useful tool to use for prognostic stratification and to gauge therapeutic intervention in this challenging population. IV TPA should not be precluded in mild AIS patients based on WM disease burden.
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