MIAMI BEACH — It takes more than a positive serum IgM by enzyme-linked immunosorbent assay to make a definitive diagnosis of West Nile virus encephalitis in a patient with neurologic symptoms, Karen L. Roos, M.D., said at the annual meeting of the American Academy of Neurology.
For example, an elderly patient presents with 4 days of confusion and tremor, and her serum IgM is positive for West Nile virus on enzyme-linked immunosorbent assay (ELISA). Spinal fluid analysis indicates she has a lymphocytic pleocytosis. Does this patient have West Nile virus encephalitis?
Maybe not, according to Dr. Roos. “When I was in medical school, I learned that the IgM was positive early, became negative quickly, and then the IgG became positive. But West Nile isn't playing by the rules of medical school,” Dr. Roos said.
Serum West Nile IgM level on ELISA can remain positive for 6–12 months or longer after infection, and only 1 in 150 people develop neurologic symptoms from the virus, said Dr. Roos, professor of neurology at Indiana University, Indianapolis.
Serum IgM level is therefore not sufficient evidence to assume that the patient's symptoms are due to West Nile virus infection. “Don't put a lot of stake in a serum West Nile virus IgM,” Dr. Roos said.
The neurologic symptoms of this patient can be definitively attributed to West Nile virus infection if the virus is isolated in tissue, blood, or cerebrospinal fluid or IgM antibody is found in the cerebrospinal fluid. IgM antibody cannot cross the blood-brain barrier, so central nervous system infection should be “strongly suspected” if IgM antibody is found in cerebrospinal fluid.
Also, in the case of West Nile encephalitis or any viral encephalitis or meningitis where the causative virus is unknown, “if you send acute and convalescent titers in patients with viral meningitis or encephalitis, you will very often find the virus,” Dr. Roos said. There will be a fourfold increase in IgG antibodies between acute and convalescent serums.
This is not useful for diagnosis during the acute stage, but patients are considerably more able to put up with their headaches and other continuing symptoms in convalescence if they know which virus they had, Dr. Roos said.
A patient may not come to you in the acute phase, and there may be no serum findings from this phase. In this case, you may still be able to pin down the virus by demonstrating a stable elevated antibody titer.
If you order serology and can demonstrate that the patient maintains a stable antibody titer of more than 256 mg/dL, for example, “you can then say that's a presumptive diagnosis. … Realistically, this is the best we can do, sometimes,” she said.
In general, IgM or IgG serum antibody titers that are positive for West Nile virus on ELISA should be confirmed by plaque reduction neutralization assay in cell culture to eliminate false positives from cross-reactivity with other flaviviruses—particularly St. Louis encephalitis virus, she said.