A Multisystem Presentation of West Nile Neuroinvasive Disease: Lessons in Diagnostic Complexity.

West Nile virus (WNV) is an uncommon but serious case of encephalitis and meningitis, often presenting with nonspecific symptoms that can mimic a wide range of infectious, metabolic, and endocrine disorders. We present the case of a 61-year-old male with multiple comorbidities who arrived with 5 days of fever, chills, profuse diarrhea, black stools, and worsening confusion. Initial evaluation in the emergency department revealed hyponatremia, transaminitis, and concern for tick-borne illness, prompting empiric doxycycline. However, the patient denied any tick bites. Given his known thyroid nodule and Burch-Wartofsky screening score of 70, he was empirically treated for thyroid storm despite laboratory evidence of subacute hypothyroidism. During hospitalization, our patient developed acute hypoxic respiratory failure requiring emergent intubation, as well as second-degree heart block and supraventricular tachycardia following propranolol administration. Neurologic workup revealed moderate encephalopathy on EEG and an opening pressure of 36 cm H2O on lumbar puncture. CSF examination revealed pleocytosis with mixed neutrophilic and lymphocytic predominance. Despite broad-spectrum antibiotic coverage, initial testing, which included a tick panel, Monospot, respiratory studies, and viral PCR assays, was insignificant. On hospital day eight, CSF serologies were positive for WNV IgM with negative IgG, confirming acute WNV neuroinvasive disease presenting as meningitis. This case highlights the diagnostic complexity of WNV infection, which may initially resemble tick-borne illness, endocrine crisis, or bacterial meningitis. Early consideration of WNV in patients with unexplained encephalopathy, GI symptoms, hyponatremia, and CSF lymphocytic pleocytosis, especially during mosquito season, may reduce delays in diagnosis and prevent unnecessary interventions.