To present a case series that demonstrates the diverse neurological manifestations of the West Nile Virus (WNV).

Case 1 was a 39-year-old female with diffuse large B-cell lymphoma, who presented with fever, encephalopathy, and flaccid paraplegia. MRI showed T2 hyperintensities involving the bilateral thalami, temporal lobes, midbrain, pons, and spinal cord which was suspicious for CNS lymphoma. WNV was confirmed by PCR as her prior treatment with RCHOP made her serum and CSF serology falsely negative. In Case 2, a 49-year-old female presented with left sided ptosis and left arm weakness, suspicious for Horner’s syndrome. WNV was confirmed by CSF lymphocytic pleocytosis and positive WNV IgM. Case 3 was a healthy 79-year old male presenting with acute onset parkinsonism with positive CSF WNV IgM. Case 4 was a 31-year-old male who presented with uveo-meningitis syndrome with uveitis of the right eye, fever, headache, nuchal rigidity and CSF pleocytosis. An autoimmune cause was suspected till CSF showed WNV IgM. All 4 patients showed varying amounts of neurological recovery with supportive care. 

The myriad presentations of neuroinvasive WNV presents diagnostic challenges. Frequent alerts from the Nebraska DHHS prompted deliberate search for WNV infection in these cases. A high clinical suspicion for neuroinvasive WNV in endemic areas can prevent delays in diagnosis and appropriate care.