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June 22, 1998

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Brain Antibodies Provide New Clues To Origins of Tourette's

Some patients' tics may be triggered by an infection

Johns Hopkins researchers have found evidence that Tourette's syndrome, which causes involuntary muscle contractions and bursts of words and noise, may be triggered in part by an infection.

"We think antibodies made by the immune system in response to a bacterial infection may go on to attack brain nerve cells in a subset of the children who develop Tourette's," says Harvey Singer, M.D., professor of neurology and pediatrics, and lead author of a study in the June issue of Neurology. "The bacteria streptococcus is a leading suspect, but the search for a triggering factor should not be limited to it."

The antibodies Hopkins researchers identified could help scientists understand where the symptoms of Tourette's are created in the brain, find the infectious trigger, and develop new ways to treat or prevent Tourette's in a small number of affected children, according to Singer.

With funding from the National Institutes of Health and the Tourette's Syndrome Association, Singer's group took blood samples from 41 Tourette's patients and a group of 39 control subjects, and tested them for antibodies to proteins in ground-up human brain tissue.

The patients had significantly higher levels of antibodies against proteins from the putamen, an area at the base of the brain involved in movement. For two other brain areas studied, the caudate and the globus pallidus, there were no significant differences between patients and controls.

"Brain imaging studies have shown changes in the shape and size of the putamen in Tourette's patients, reinforcing the idea that these antibodies may contribute to the disorder," says Singer.

Strep infection is a leading suspect for the trigger in a small number of patients because scientists have already linked it to another, similar disorder, Sydenham's chorea, and patients have reported cases in which Tourette's began or became worse after a streptococcal infection.

Tourette's syndrome affects approximately five in every 10,000 persons. Because it occurs with high frequency in some families and identical twins, a genetic error has long been suspected as a cause. "However, based on family studies, it appears that for some individuals, an additional factor is required to cause the disease," says Singer.

One hypothesis is that people who have two copies of the Tourette's gene always develop the syndrome, while those who receive one copy of the gene, estimated at about 2 percent of the general population, develop Tourette's only after being exposed to another factor in the environment, such as an infection.

The Tourette's gene has not yet been isolated.

Further research is needed to confirm or clarify potential associations between the antibody and clinical symptoms or a particular infection, Singer says. He hopes to study antibody levels over time to see if they rise as tics become more pronounced. He also hopes to identify the putamen proteins the antibodies attack.

Other authors on the paper were J.D. Giuliano; B.H. Hansen; J.J. Hallett, M.D.; J.P. Laurino, Ph.D.; M. Benson; and L.S. Kiessling, M.D.

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