A 53-year-old man with chronic hypertension, coronary artery disease, and left leg traumatic amputation presented with malaise and irritability of 2 weeks' duration followed by high fever (temperature, 40.5°C), dysuria, and severe frontal and cervical pain. A urinary tract infection was diagnosed and gatifloxacin (Tequin) was administered, but the patient showed no improvement. A few days prior to hospitalization, he had developed involuntary eye movements and jerking of the muscles in his upper limbs, along with intense, brief attacks of vertigo. On examination, the patient was an ill-looking, tremulous man with neck stiffness. He was hemodynamically stable and had no rash or lymphadenopathy. He had a fluctuating clouding of consciousness with confusion. There were no signs of meningeal irritation. His language was normal but he exhibited scanning speech. Muscle strength and tendon reflexes were normal and symmetrical, with a flexor right plantar response. There were prominent, involuntary, myoclonic muscle jerks, with intermittent action tremor in the upper extremities. When asked to look at a target, the patient's visual fixation was disrupted by bursts of high-frequency, conjugate ocular oscillations that had horizontal, vertical, and torsional components, all of which indicated opsoclonus (a video is available online at http://www.archneurol.com). Opsoclonus, but not myoclonus, was present during sleep (see the online video). The rest of the cranial nerve examination results were normal. He was unable to walk. Findings of a computed tomographic scan of the head were normal (a magnetic resonance image could not be obtained because of the patient's cardiac pacemaker). An analysis of cerebrospinal fluid showed lymphocytic pleocytosis (white blood cell count, 81/μL; 87% lymphocytes, 12% monocytes, and 1% neutrophils), with a total protein level of 0.11 g/dL and a glucose level of 52 mg/dL (3.1 mmol/L). Gram stain and cultures yielded negative results, including stains and cultures for fungi and Toxoplasma gondii. Polymerase chain reactions did not amplify any of the following viruses: herpes simplex, varicella-zoster, Epstein-Barr, Cytomegalovirus, or Enterovirus. Possible cross-reaction to encephalitis viruses (California, La Crosse, eastern equine, western equine, and St Louis) was eliminated by negative results of viral serology to both IgG and IgM antibodies. The patient had no recent history of travel or prior vaccination to yellow fever or Japanese B encephalitis viruses; thus, no further evaluation of these viruses was sought. Human immunodeficiency serology results were nonreactive. Paraneoplastic autoantibodies (anti-Ri, anti-Hu, anti-Yo, and anti–Ma-2) were undetectable in the serum. Electroencephalography (EEG) while the patients was in the awake state showed a mild slowing of the posterior dominant rhythm, with frequent prolonged runs of eye movements (Figure, B) corresponding to opsoclonus. The eye movements on EEG and the opsoclonus persisted during stage 2 sleep (note the sleep spindles in the Figure, A), although they were less frequent. The patient was initially treated with intravenous ceftriaxone sodium, vancomycin, ampicillin, and acyclovir. The use of these agents was discontinued after the detection of WNV on serologic analysis and after negative polymerase chain reaction results for herpes simplex and varicella-zoster viruses. Enzyme-linked immunosorbent assay results were positive for the presence of IgM antibodies to WNV and negative for the presence of IgG antibodies to WNV in the cerebrospinal fluid (ViroMed Laboratory, Minnetonka, Minn). Titers were not obtained on initial testing. The patient was discharged to a rehabilitation facility.