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.

The evidence on the clinical significance of cerebral white matter changes (WMC) has mounted over the past few decades. WMC are recognized as one of the neuroimaging features of cerebral small vessel disease, and are associated with various disturbances and a poor prognosis. The Leukoaraiosis and Disability (LADIS) Study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration aimed at assessing the role of WMC as an independent predictor of the transition to disability in initially non-disabled patients aged 65-84 years. Besides the demonstration that severe WMC cause a more than double risk of transition from an autonomous to a dependent status after 3 years of follow-up, the LADIS Study has also provided evidence on the role of WMC in relation to the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, the presence of urinary disturbances, and various neurological abnormalities. The possible role of other lesions (lacunar infarcts, cerebral atrophy, corpus callosum morphology) and microstructural abnormalities (diffusion-weighted imaging changes in normal appearing brain tissue and in WMC) has also been investigated. In the present article, we review the main results of the LADIS Study and offer some considerations for future developments in the field, paying attention to the potential use of WMC progression as a surrogate marker in intervention trials in cerebral small vessel diseases. We also discuss some therapeutic perspectives regarding the beneficial impact of physical activity on the risk of vascular cognitive impairment in patients with WMC. Geriatr Gerontol Int 2015; 15 (Suppl. 1): 10-16.

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Leukoaraiosis (LA) is one of the neuroimaging features of cerebral small vessel disease and is associated with poor long-term prognosis. Areas covered: This narrative review focuses on the predictive role of LA on the evolution of the ischemic brain damage and on the clinical outcome in the subacute phase of stroke and in the short-term period afterwards. Expert commentary: LA predicts poorer tissue outcome and clinical prognosis also in acute and subacute stroke. In acute stroke, LA is associated with a less favorable fate of brain infarct and is a marker of increased risk of thrombolysis-related hemorrhagic transformation. The impaired cerebral microcirculation in LA patients may sustain the progression of ischemic lesion and enhance the bleeding risk. The short-term worse clinical outcome in ischemic stroke and intracranial hemorrhage patients with LA might be attributable to a state of altered brain connectivity. Endothelial failure, reduced micro-vessels density, and deficient collateral flow together with reduced functional reserve are some of the involved mechanisms. Future studies should aim at bridging the gap between the knowledge about LA pathophysiology and the therapeutic improvement of brain tissue perfusion and at producing data on early rehabilitation of stroke patients with LA at high disability risk.