Thrombolysis in Acute Stroke Patients with Cerebral Small Vessel Disease

Abstract

Background: 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. Summary: 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. Key Messages: 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.

Cerebral Computed Tomography-Graded White Matter Lesions Are Associated With Worse Outcome After Thrombolysis in Patients With Stroke

“…Three studies reported worse outcomes in ischemic stroke patients with WMLs after IVT in 400, 14 200, 13 164 patients. 12 However, in 1 study of 800 IVT-treated patients, severe van Swieten scores 3,4 were only associated with poor outcome (mRS, 2-6) or death in univariate, but not after adjusted analyses, whereas there remained a significant association after adjustments in the present study. 15 This difference is probably because of sample size because the cutoff values for severe WMLs on van Swieten scale covered only 71 (8.6%) patients in the cited study, whereas there were 481 (18.8%) patients with severe WMLs in the present study.…”

White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage

“…Our department's guidelines from the beginning of thrombolysis treatment have stated severe microangiopathy to be a relative contraindication for thrombolysis, although there is no evidence for WMLs being a contraindication for IVT, and this is not mentioned in the guidelines for the early management of patients with acute ischemic stroke. 1,6,8 For clinical use in CT-imaged patients with acute stroke our study supports the use of the Wahlund score with a cutoff of more than focal lesions at any frontal or parieto-occipital site (Wahlund any site score, >1).…”

“…5 Because of increased bleeding risk, WMLs are considered a relative, but not an absolute, contraindication for thrombolysis. 6,7 Yet, the attributable risk of WMLs to the risk of sICH in ischemic stroke patients treated with IVT in the general population is uncertain, 6 and major guidelines for treating acute ischemic stroke lack a statement on WMLs about IVT. 1,8 Considering the modest patient numbers and conflicting results in previous studies, we aimed to investigate the risk for sICH in the presence of WMLs in a large single-center cohort of ischemic stroke patients treated with IVT.…”

Intravenous Thrombolytic Therapy in Acute Stroke: Problems and Solutions

“…Thus, the presence of small vessel disease causes a poor prognosis by causing both increased bleeding risk and decreased recovery. Nevertheless, the results of IV tPA in such patients are still better and IV tPA should be administered (50).…”