Limitations and confusing aspects of diagnostic testing for neurologic lyme disease in the United States

In the United States, laboratories frequently offer multiple different assays for testing of cerebrospinal fluid (CSF) samples to provide laboratory support for the diagnosis of central nervous system Lyme disease (CNSLD). Often included among these diagnostic tests are the same enzyme immunoassays and immunoblots that are routinely used to detect the presence of antibodies to Borrelia burgdorferi in serum. However, performing these assays on CSF alone may yield positive results simply from passive diffusion of serum antibodies into the CSF. In addition, such tests are only U.S. Food and Drug Administration cleared and well validated for testing serum, not CSF. When performed using CSF, positive results from these assays do not establish the presence of intrathecal antibody production to B. burgdorferi and therefore should not be offered. The preferred test to detect intrathecal production of antibodies to B. burgdorferi is the antibody index assay, which corrects for passive diffusion of serum antibodies into CSF and requires testing of paired serum and CSF collected at approximately the same time. However, this assay also has limitations and should only be used to establish a diagnosis of CNSLD in conjunction with patient exposure history, clinical presentation, and other laboratory findings.