To characterize neuroinvasive WNV cases presenting with unremarkable MRI findings.

West Nile Virus (WNV) is a neurotropic flavivirus and the leading cause of mosquito-borne neuroinvasive disease in the United States. The case-fatality rate of neuroinvasive WNV approaches 10% up to 50% of patients reporting long-term neurologic sequelae such as cognitive deficits, weakness, or seizures. 

Magnetic resonance imaging (MRI) findings in WNV meningoencephalitis are often variable and non-specific. Importantly, neuroinvasive WNV can also present with no acute MRI findings, representing a critical diagnostic gap that may delay recognition and worsen patient outcomes. We describe such a case and a systematic review of published reports examining the frequency and clinical profile of WNV with unremarkable MRI findings. 

PubMed and Google Scholar were searched through October 13, 2025, in accordance with PRISMA guidelines. Reports describing neuroinvasive WNV with unremarkable MRI findings were identified, and clinical data were summarized.

A 50-year-old female with ESRD on dialysis presented with intractable vomiting, and a seizure. Her mental status subsequently deteriorated; she became aphasic, required intubation, and remained comatose. CSF analysis revealed lymphocytic pleocytosis, mildly elevated protein (110 mg/dL), and was positive for WNV IgM. MRI with and without contrast at one and three weeks showed no acute abnormalities. Despite supportive care, she remained intubated without improvement.

We identified 85 cases of WNV with normal MRI findings. The mean age of the patients was 61.8 ± 9.1 years; 58.8% were female.  The most common presentations included seizures (85.9%), altered mental status (52.9%), headache (48.2%), and speech impairment (28.2%) with several patients exhibiting multiple of these symptoms.

Neuroinvasive WNV is a rising cause of encephalitis with no established treatment. Unremarkable MRI findings can delay recognition, leading to unnecessary empiric therapy and prolonged diagnostic uncertainty. Early LP with CSF analysis for WNV is essential for accurate diagnosis and management.