Murine typhus, caused by Rickettsia typhi, is a flea-borne zoonosis typically presenting with fever, headache, and myalgia, though central nervous system (CNS) involvement is uncommon and often mild. Radiologic findings resembling posterior reversible encephalopathy syndrome (PRES) are rare. This case highlights an atypical neuroinfectious presentation of murine typhus in a healthy young woman, emphasizing diagnostic challenges and the importance of maintaining a broad differential in patients with systemic and neurologic findings.

A 30-year-old woman with no significant history presented with severe retro-orbital headaches, intermittent fevers, tremors, dysarthria, and syncopal episodes. Initial CT head showed microvascular ischemic changes and right parietal hyperdensities. Brain MRI revealed bilateral parietal FLAIR hyperintensities suggestive of PRES. Lumbar puncture, autoimmune, and infectious panels were unremarkable, including negative meningoencephalitis PCR and CSF cultures.

Given ongoing fevers and a history of frequent plasma donation possibly contributing to transient immunoglobulin depletion, Infectious Disease initiated doxycycline for suspected atypical infection. The patient’s symptoms improved markedly within 48 hours. Post-discharge serology confirmed acute Rickettsia typhi infection (IgM 1:1024, IgG <1:64). She completed a 7-day doxycycline course with full resolution of symptoms.

Neurologic involvement in murine typhus occurs in fewer than 5% of cases, and PRES-like MRI findings are rare, especially in immunocompetent individuals. This case expands the clinical spectrum of murine typhus and illustrates how empiric doxycycline can be both diagnostic and therapeutic. The possible contribution of frequent plasma donation to immune susceptibility is a novel and underrecognized risk factor, warranting further study.