Background Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus responsible for unpredictable outbreaks of severe neurologic disease in animals and humans. While most human infections are asymptomatic or clinically nonspecific, a minority of patients develops encephalitic disease, a devastating illness with a mortality of at least 30%. No treatments are known to be effective. EEEV infection is rare in the United States, with an annual average nationwide incidence of 7 cases between 2009 and 2018. However, in 2019, 38 cases were confirmed nationwide, including 10 in Michigan. Methods Data from 8 cases identified by a regional network of physicians in southwest Michigan were abstracted from clinical records. Clinical imaging and histopathology were aggregated and reviewed. Results Patients were predominantly elderly and male. The initial arboviral CSF serology was frequently negative, and diagnosis was not made until a median of 24.5 days (range 13–38 days) after presentation, despite prompt lumbar punctures in all patients. Imaging findings were dynamic and heterogeneous, with abnormalities of the thalamus and/or basal ganglia, and one patient displayed prominent pons and midbrain abnormalities. 6 patients died, 1 patient survived the acute illness with severe neurologic sequelae, and 1 patient recovered with mild sequelae. A limited postmortem examination revealed diffuse meningoencephalitis, neuronophagia, and focal vascular necrosis. Conclusions Eastern equine encephalitis is a frequently fatal condition whose diagnosis is often delayed, and for which no effective treatments are known. Improved diagnostics are needed to facilitate patient care and encourage the development of treatments.

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