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Only after 14-year-old Amanda (not her real name) had been hospitalized for the fourth time in one year after suffering from hallucinations did her mother think about Lyme disease. Months before her daughter became ill, a bull's-eye rash appeared on her leg – the characteristic marker of early Lyme disease – and she was treated with a short course of oral antibiotics. Could her psychiatric problems be related to her prior bout with Lyme disease? Anti-psychotic medications weren't working, so Amanda's mother asked for the opinion of Brian Fallon, M.D., M.P.H., a psychiatrist and Lyme expert at Columbia and the New York State Psychiatric Institute.

More patients like Amanda are now being evaluated at a new Lyme and Tick-borne Disease Evaluation Service at Columbia, which opened July 26. The service focuses on patients who are still experiencing symptoms after being diagnosed and treated for Lyme disease and patients who have unexplained psychiatric symptoms that may be due to Lyme or other tick-borne diseases. The goal is to provide a comprehensive evaluation seeking to also rule out other disorders that may cause the multisystemic symptoms. Along with Dr. Fallon, Carolyn Britton, M.D., associate professor of neurology, and Edward Dwyer, M.D., a rheumatologist and assistant professor of clinical medicine, will participate in the evaluation service.

In most cases of Lyme disease, early detection and a course of oral antibiotics is enough to get rid of the spirochete bacteria responsible for the disease. The symptoms – usually fever, fatigue, headaches and muscle and joint aches – disappear. If the disease is not caught early, however, the bacteria can spread and cause arthritis, cognitive disorders, or even personality changes, symptoms that suggest a course of intravenous antibiotics may be needed.

In a small percentage of cases, despite one or two courses of intravenous antibiotics, patients continue to experience nonspecific symptoms: fatigue, memory lapses, depression, and, sometimes, as in Amanda's case, severe psychiatric disturbances. These symptoms may be due to a small amount of persistent infection, an immune response to past infection, damage from the initial infection, or an unrelated secondary disorder.

Many doctors think these complaints arise from something other than the Lyme bacteria, B. burgdorferi, but some prescribe longer courses of intravenous or oral antibiotics in an effort to get rid of an organism they suspect continues to infect the patient's organs. But months and months of intravenous antibiotics are not benign; one woman died from an infected catheter while being treated for years for an unsubstantiated case of Lyme, according to a report in Clinical Infectious Disease.

Approaching Amanda's case, Dr. Fallon says he was skeptical, since most psychiatric illness is not caused by an infection. Blood tests for the bacteria, though, suggested the bacteria were still present. In addition, her brain SPECT imaging suggested that she had a diffuse central nervous system inflammatory process – a pattern that would be unexpected in a primary psychiatric disorder. Two years after the initial Lyme rash, Amanda's physician started her back on antibiotics. The progress over the subsequent year was dramatic: gradual and steady psychiatric improvement with no further hospitalizations. Within six months, she returned to her pre-illness baseline condition of health, resulting in normal socialization and awards for academic excellence.

"The big question in Lyme disease is what to do with these persistent cases," says Dr. Fallon. "Part of the issue, I think, is that the medical community has a hard time appreciating that an organism can cause a neuropsychiatric disorder, even though there are numerous precedents like syphilis, HIV, and the rabies virus."

Based on a small study Dr. Fallon published in 1999 on patients with persistent memory problems that suggested cognition improves with a repeated course of IV antibiotic therapy and on his functional imaging research that suggested Lyme disease causes a vasculitis-like pattern in the brain, Dr. Fallon received a $4.7 million grant from the NIH to test the hypothesis that repeated antibiotic therapy can help patients with persistent problems. In collaboration with Dr. Harold Sackeim, Ph.D., professor of clinical psychiatry, Robert DeLaPaz, M.D., professor of radiology, and Ronald Van Heertum, M.D., professor of radiology, Dr. Fallon has been conducting a randomized, double blind trial that compares 10 weeks of intravenous antibiotics with 10 weeks of intravenous placebo in patients with a verifiable history of Lyme who previously have been treated with at least three weeks of IV antibiotics and who have objective, persistent memory problems. This five-year study has just completed enrollment of its last 60 patients; data collection ends in October. Dr. Fallon says results from two other previously published trials have come up with conflicting results: One found antibiotics were effective, the other did not.

Another problem adding to the Lyme disease controversy is the lack of definitive tests that can identify an active infection. "There's no perfect test for detecting an active infection, so lots of educated guessing is going on."

The bacteria are usually not in the blood, where they would be easy to detect by PCR assays or culture, but instead invade deep tissues. "You're not going to do random biopsies to search for the organism, so the evidence for infection is often indirect and presumptive. What's evidence for one doctor is not evidence that convinces another doctor, so we have debates on proper treatments."

Dr. Fallon says he hopes the new evaluation center helps focus more research attention on the disease so these debates can be resolved. The Lyme Disease Association and its Connecticut affiliate, Time for Lyme, are currently raising $3 million to fund a Lyme disease research center at Columbia. "I'd like to see more basic research on the disease and be able to recruit additional scientists," Dr. Fallon says. "That would make Columbia the first place to focus on Lyme disease."

The clinical trial is supported by the NIH. To reach the Lyme Disease Evaluation Service, call Dr. Kathy Corbera, associate director, 212-543-6508.

—Susan Conova


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