Acute Ischemic Stroke in Tsutsugamushi: Understanding the Underlying Mechanisms and Risk Factors

ABSTRACT Background Tsutsugamushi, also known as scrub typhus, is an acute infectious febrile disease common in the Asia–Pacific region. Its common symptoms include lymphadenopathy, fever, and myalgia. Tsutsugamushi rarely causes acute ischemic stroke (AIS); however, it has been reported to increase the likelihood of AIS development. Here, we aimed to test the hypothesis that tsutsugamushi infection could trigger AIS. Method We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over 15 years. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group; patients who did not develop AIS while being treated for tsutsugamushi at the same hospital and were of similar age and sex with the case group were categorized as the control group. The case and control groups had 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as non-embolic. Results Among the 19 patients, excluding three with transient ischemic attack, 15 (78.9%) showed an embolic pattern. Fever was common at the time of the visit in the control group; however, it was less common in the case group (93.8% vs. 27.3%, respectively; p<0.001). Multivariate analysis revealed that higher D-dimer levels at the time of hospitalization were associated with AIS development in patients with tsutsugamushi (adjusted odds ratio, 1.58; 95% confidence interval, 1.06–2.34; p=0.023). Discussion AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. This embolic pattern was more likely to occur in patients with stroke risk factors. These patients were unlikely to have a fever or high D-dimer levels. We speculated that D-dimers played a vital role in the pathophysiology, as tsutsugamushi infection increased the likelihood of AIS.