Beyond the borders—coma as a complication of imported Japanese encephalitis: a case report

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne flavivirus infection endemic to much of Asia and the Western Pacific. Although most infections are asymptomatic, less than 1% progress to clinical disease, typically presenting as acute encephalitis. The case fatality rate ranges from 20 to 30%, and up to half of survivors develop long-term neurological or psychiatric sequelae. While uncommon among travelers from non-endemic regions, risk increases with prolonged rural exposure or lack of vaccination. Immunocompromised individuals, including those with hematologic malignancies, may experience severe and rapidly progressive diseases. Awareness of this rare but life-threatening infection is essential when evaluating returning travelers with acute encephalopathy. CASE PRESENTATION: A 70-year-old Lao male living in the California Central Valley with a history of multiple myeloma, hypertension, and congestive heart failure presented with progressive confusion and weakness after travel to rural Laos. His trip exceeded the recommended duration, and his Japanese encephalitis virus (JEV) vaccination status was unknown. On admission, he was febrile and encephalopathic with new-onset rigidity. Computed tomography showed chronic calcifications consistent with prior neurocysticercosis, while magnetic resonance imaging revealed bilateral frontal and left insular cortical hyperintensities without thalamic involvement. Cerebrospinal fluid analysis conducted 9 days after his cognitive decline showed elevated protein without pleocytosis, and infectious and autoimmune panels were negative. Despite empiric antibiotics and supportive care, his condition deteriorated to coma, requiring intubation. Serologic testing later confirmed recent JEV infection with positive Immunoglobulin G (IgG) and low-titer Immunoglobulin M (IgM). After multidisciplinary discussions, comfort care was initiated, and he died in inpatient hospice. CONCLUSIONS: This case illustrates the diagnostic challenge of acute encephalopathy in immunocompromised travelers. Myeloma-related immune dysfunction, as suggested by his lack of pleocytosis, likely contributed to impaired viral clearance, leading to rapid progression. The absence of typical thalamic lesions and the presence of frontal and insular involvement represent an uncommon neuroimaging pattern in JE. Pre-existing neurocysticercosis may have further worsened neurologic outcomes, as prior studies suggest JEV co-infection can lead to worse prognosis. Our case highlights the importance of having a broad differential in an undifferentiated patient and the value of investigating a patient's history holistically. Imported JE should be considered in travelers returning from endemic regions, particularly those who are immunocompromised. A detailed travel history, broad infectious workup, and recognition of atypical imaging findings are key to diagnosis. Vaccination and mosquito precautions remain the most effective preventive measures against this often-fatal disease.