Jennifer Dearborn, MD

Pedder H, Vesterinen HM, Macleod MR, and Wardlaw JM. Systematic Review and Meta-Analysis of Interventions Tested in AnimalModels of Lacunar Stroke. Stroke. 2014

Lacunar stroke has a distinct pathophysiology from large artery strokes, and may present a unique opportunity for treatment. Lipohyalinosis and microatheroemboli represent a mechanism distinct from thrombosis in larger artery strokes. As Pedder et al. point out, little attention has been dedicated to developing treatments specific for small vessel stroke. In this meta-analysis, interventions in animal models of lacunar stroke were pooled to find evidence for testing candidate interventions in the future. They describe 43 interventions in 57 publications.

Lesions modeling lacunar stroke included those caused by occlusion or stenosis and by diseases modeling disease of perforating blood vessels, such as spontaneously hypertensive stroke-prone rats  (SHRSPs).  Studies including infarct size and neurobehavioral outcomes were included. The authors carefully controlled quality and risk of bias between studies. Examples of some of the interventions that improved outcomes were preclamol (dopamine receptor agonist); nicotiflorin (a flavinoid); hepatocyte growth factor; atorvastatin, among others. Studies that did not have a randomization technique had a significant increase in reported efficacy of therapy. The highest quality of studies had the lowest reports of efficacy. Interventions administered intraperitoneally were the most effective, and the highest efficacy was reported are studies using spontaneous strokes in SHRSPs.

It is not clear how to interpret the efficacy of these compounds, and more in vivo data is required prior to moving forward with clinical trials. The authors point out that there are limited measures to reduce bias, which compromises the internal validity of the results (e.g. randomization or blinding). Studies with the fewest measures to reduce bias had the largest effects reported. It was surprising to learn that four interventions actually improved neurobehavioral outcomes and infarct size, however none have been tested clinically yet, which may be appropriate as more animal data needs to be collected.  The SHRSP may be a good animal model to study lacunar stroke, but it is still not certain that the pathophysiology is similar to that in humans. Hopefully there will be translation of some of these compounds to patients in clinical trials, as we learn more from these animal models.