Thrombolysis in acute stroke patients with cerebral small vessel disease

Thrombolytic treatment is of proven benefit in acute ischemic stroke. The term cerebral small vessel disease (SVD) refers to a group of pathological processes affecting the small arteries, arterioles, venules and capillaries of the brain, and encompasses both ischemic and hemorrhagic lesions. Lacunar stroke, an expression of SVD, is associated with an unfavorable long-term prognosis for an increased risk of death, recurrent stroke and cognitive dysfunction. Nonetheless, the efficacy and safety of intravenous thrombolysis in patients with lacunar stroke has been debated for two main reasons. First, among all ischemic stroke subtypes, lacunar strokes have been considered the most benign. Second, the efficacy of a pharmacological reperfusion has been questioned given the absence of a clear demonstration of thrombosis. Intracerebral hemorrhage (ICH) remains the most devastating and unpredictable complication related to thrombolysis, and neuroimaging evidence of SVD is nowadays recognized as one of the risk factors for thrombolysis-related ICH.

This review is structured in two parts dealing with the questions whether or not patients with lacunar stroke or SVD should be treated with thrombolysis. In the first part, we revised the literature concerning the efficacy of thrombolysis in patients with acute lacunar stroke. We included two types of studies: those in which patients with lacunar stroke receiving recombinant human tissue plasminogen activator (rt-PA) were compared with lacunar stroke patients receiving placebo, and those in which a comparison was made among different stroke subtype patients treated with rt-PA. In the second part, we reviewed the available evidence on the risk of ICH in patients treated with thrombolysis for ischemic stroke and presenting with neuroimaging evidence of SVD such as white matter lesions (WML) and cerebral microbleeds. We further questioned the extent to which WML and microbleeds could be used as reliable predictors of ICH and the feasibility of their detection in an acute setting.

The studies herein reviewed show that thrombolysis is an effective treatment in acute lacunar stroke, and that the presence of cerebral SVD increases the risk of ICH during thrombolysis but does not represent an absolute exclusion criterion. In the future, it can be assumed that the use of MRI on a routine basis might lead to a better quantitative definition of SVD and its correlates, permitting a step forward in thrombolysis decision making.