West Nile virus encephalitis is endemic in parts of the United States, typically presenting with fever, headache, encephalopathy, and seizures. However, subtle or atypical presentations can complicate diagnosis. This case underscores how a seemingly isolated neurologic finding—spontaneous horizontal nystagmus—prompted further evaluation, ultimately leading to a diagnosis that was missed by multiple prior investigations.

Neurologic examination was normal except for a spontaneous episode of horizontal nystagmus lasting one minute, with no clear triggers or reproducibility upon positional change. The patient was febrile at 39°C. A lumbar puncture revealed 527 white blood cells (82% neutrophils), 263 red blood cells, and elevated protein at 59 mg/dL. She was empirically treated with ceftriaxone, vancomycin, acyclovir, and dexamethasone. CSF later returned positive for West Nile virus IgM. The patient received supportive care throughout her hospitalization and was discharged home after 21 days.

This case demonstrates the diagnostic value of isolated horizontal nystagmus, which led to the identification of West Nile virus encephalitis after multiple prior negative workups. While horizontal nystagmus is not commonly associated with specific central pathologies, its presence in this patient was a crucial clue. Clinicians should consider lumbar puncture for patients with unexplained neurologic symptoms, as early recognition and intervention in encephalitis can significantly improve outcomes.