A 76-year-old male with rheumatoid arthritis managed with rituximab infusions is brought in to the ED with altered mental status. Four days before presentation, he developed fevers up to 103°F and headaches about a week after he returned from a camping trip in rural Wyoming. He was seen in his primary care physician’s office 2 days ago for these symptoms and was noted to have a nonblanchable maculopapular rash over the left side of his trunk. He was managed symptomatically with antipyretics, but his headaches worsened and he was found to be confused this morning. On examination, he has limited ability to move his left lower extremity, which appears floppy. The rest of his examination is unremarkable, and no rash is seen. His complete blood profile and chemistry is normal. He has no risk factors for human immunodeficiency virus (HIV). Diagnostic workup is started for stroke, and he is empirically started on IV vancomycin, ceftriaxone, ampicillin, and acyclovir for possible meningoencephalitis. A CT head without contrast does not show an acute abnormality. An LP is performed, which reveals:
Gram stain is negative, and culture is pending. Brain MRI with gadolinium shows nonspecific enhancement of left basal ganglia. PCR for HSV on CSF is negative. Over the next 24 hours, his fevers persist, level of consciousness worsens, and he requires intubation for airway protection.
Which of the following laboratory tests is MOST likely to reveal the etiology of his presentation?
A. Echovirus PCR of CSFCorrect Answer: C
The patient has a classical presentation for West Nile virus meningoencephalitis. The diagnostic test of choice is measurement of West Nile IgM in the CSF unless there is concern for impaired antibody production in which case PCR on CSF can be helpful.
West Nile is the most common mosquito-borne illness in the United States. It was first reported in an outbreak in New York City in 1999, but the disease has spread rapidly across the continent and has now been reported from almost all continental states in the United States. Culex mosquitoes are primary vectors of transmission, which occurs seasonally in summer and fall. Transmission has also been reported via blood transfusion, organ transplantation, breastfeeding, and even transplacentally. Eighty percent of infections are asymptomatic and if present, symptoms are usually limited to a brief flulike illness with or without a nonspecific maculopapular rash, which is present for hours to days. Neuroinvasive disease is seen in less than 1% of cases and has three distinct presentations–acute flaccid paralysis, encephalitis, and meningitis (very rare in isolation)–although a combination of these presentation may also be seen. Meningismus is often absent, and LP usually reveals a mild aseptic meningitis picture without any predilection for lymphocyte or neutrophil predomination. When history is suggestive, diagnosis is usually made by West Nile virus IgM in the CSF. Serum IgM can also be supportive. Serologies may be negative early on in the disease, and a convalescent titer should be checked if suspicion remains high. IgM is not an option in the answers for this question; IgG in CSF or serum is insensitive in the acute phase. The next best diagnostic option is West Nile virus PCR in CSF. West Nile virus is notable in that unlike most other viruses, PCR is less sensitive and becomes negative very early on in the disease process. In patients who have known impairment of antibody production—either from an underlying disease such as chronic lymphocytic leukemia or iatrogenic (as in this case) from rituximab, antibody testing is not reliable and therefore PCR is very useful. It should be noted that West Nile virus is not included in most commercially available viral PCR panels and West Nile virus–specific PCR needs to be specifically sent to a reference laboratory. Most state labs and the Centers for Disease Control and Prevention (CDC) offer West Nile virus testing.
The above presentation of encephalitis with aseptic meningitis and flaccid paralysis following a prodrome of fevers, headaches, and transient maculopapular rash after a camping trip is not consistent with Echovirus or Coxsackie virus infection—these viruses typically cause self-limited aseptic meningitis.
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