Acute ischemic stroke in Tsutsugamushi: understanding the underlying mechanisms and risk factors

Background: Tsutsugamushi (scrub typhus) is an acute infectious febrile disease common in the Asia-Pacific region. Common symptoms of tsutsugamushi include lymphadenopathy, fever, and myalgia, and it rarely causes acute ischemic stroke (AIS). However, we hypothesized that tsutsugamushi infection could trigger AIS. Method: We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over a 15-year period. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group and those (of similar age and sex) who did not develop AIS as the control group. The case and control groups consisted of 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 nonembolic. Results: Among the 19 patients, excluding three with transient ischemic stroke, 15 (78.9%) showed an embolic pattern. Although fever was common in the control group, it was less common in the case group. A higher D-dimer level at the time of hospitalization was associated with the development of AIS in patients with tsutsugamushi. Conclusions: AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. It was more likely to occur in patients with risk factors for stroke. Tsutsugamushi patients with AIS were likely to have no fever or high D-dimer levels. We hypothesized that D-dimers play an important role in the pathophysiology, where tsutsugamushi infection increases the likelihood of AIS.