Trifiletti’s fascination with the brain, combined with his love for children, led him into this often frustrating area of medicine. He likes the “long, continued contact” with his patients and their families; and with an MD/PhD from The Johns Hopkins University, he sometimes has the joy of discovering startlingly new information in his research that can change their lives. Recently, he has even had the thrill of inching
closer to the possibility of a cure for some of his young patients — and being a part of the discovery of a new way of approaching these mysterious disorders.
To most of us, pandas are majestic black and white bears that are native to China. But PANDAS — in the medical world meaning pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections — are also grabbing a remarkable measure of attention. Both the Wall Street Journal and The New York Times published articles in the past 12 months looking at the somewhat controversial research surrounding PANDAS.
Could infectious agents sometimes be the culprits when kids suddenly develop bizarre behavioral symptoms? Trifiletti says the science supporting this line of reasoning is credible. He points to the discovery that linked Helicobacter pylori (H. pylori) — a spiral-shaped bacterium that is found in the gastric mucous layer or adherent to the epithelial lining of the stomach — with more than 90 percent of duodenal ulcers and up to 80 percent of gastric ulcers. He explains that before the 1980s, when this bacterium was discovered, spicy food, acid, stress, and lifestyle were considered the major causes of ulcers, which affect more than 25 million Americans at some point in their lives. “That discovery changed our whole way of thinking about ulcers,” he states.
Trifiletti believes that one of the most exciting developments in OCD and Tourette’s research over the past decade has been the recognition that at least some of the cases may be associated with an infectious trigger. “Group A beta-hemolytic streptococcus, the bacterium responsible for common strep throat, is thought to be this trigger,” he comments.
The Tourette’s syndrome specialist goes on to explain that children with PANDAS often have a “burst of tics” or obsessive-compulsive behaviors following a bout of strep throat. Researchers have theorized that if the strep infection is
untreated, a build-up of antibodies may occur and these antibodies may ultimately cross-react with proteins in the brain, causing an array of bizarre symptoms.
The connection between movement disorders and infection with streptococcus was established about 50 years ago, when Sydenham’s chorea, a movement disorder, was linked to rheumatic fever — an inflammatory disease that sometimes develops after a strep infection. Sydenham’s chorea, initially called St. Vitus’ dance, causes uncontrollable movements of the muscles of the face, neck, trunk and limbs, restlessness and OCD-like symptoms, and generally follows a bout of acute rheumatic fever. Most of those affected completely recover without any treatment — even though it can take several months, and sometimes years.
Trifiletti says that patients with Sydenham’s chorea have been shown to have anti-streptococcal antibodies in their blood that cross-react with certain brain proteins, ultimately leading to the development of these strange movements. In other research — conducted at the National Institute of Mental Health in the 1980s — striking parallels between Sydenham’s chorea and OCD were established, suggesting that streptococcal infection might trigger OCD, at least in some cases, he explains.
The child neurologist points to the NIH research of Susan Swedo in providing the pivotal next step in the puzzle. In 1997, she and her team formalized the criteria for diagnosing PANDAS, which established a more definitive link between OCD and strep infection. Summarizing the five criteria the researchers put forth for a PANDAS diagnosis, Trifiletti says the term is used to describe two situations: a child who has had a Group A beta-hemolytic strep infection suddenly develops tics, obsessions and compulsions; or the tics, obsessions and compulsions of a child who has a tic disorder, such as Tourette’s syndrome or OCD, suddenly get worse after a strep infection. He says that diagnosing PANDAS may necessitate several
evaluations made over a period of six months to several years, because the symptoms can wax and wane.
This opened a whole new way of thinking about neuro-psychiatric disorders in children, comments Trifiletti. He and his research team have been studying the immune system in patients with OCD and Tourette’s syndrome. What they’ve discovered are changes in the immune system in these disorders that closely resemble those seen in Sydenham’s chorea.
The Tourette’s specialist says: “We examined more than 100 patients and found two antibodies to brain proteins. While only 15 percent of Tourette’s patients have antibodies to both proteins, 100 percent of them have antibodies to one of these two proteins.”
“We think that no more than 10 percent of patients without Tourette’s, OCD or PANDAS display antibodies to one or another of the proteins,” he continues.
Trifiletti says that if further studies corroborate the findings, the team may have identified a key molecule in the brain that could be the target of the abnormal immune response in Tourette’s. “And since it is an enzyme that can be turned off with specific drugs,” he explains, “this finding could result in new drug therapies.”
Current treatment relies on “neuroleptics — Haldol-like drugs,” he continues. “A child with Tourette’s would either have to live with the tics or take a very powerful drug with potentially serious side effects.”
Tourette’s will go away before the age of 18 in 80 to 90 percent of children who are affected whether it is treated or not, the neurologist explains. “But I have a patient, for instance, who shouts every 10 seconds. The family tried to live with it, but when they came to me they were distraught. You must do something for that child and his family.”
Trifiletti comments that in some cases, aggressive treatment with antibiotics, such as penicillin, can turn things around for a child with OCD and/or Tourette’s: “You give a short course of intensive therapy and then follow up with prophylactic treatment for a year.”
He says that 80 to 90 percent of those with OCD and Tourette’s are strep carriers. “They may not get a sore throat but they can shed the bacterium,” he explains. “Something is different about their immune system.”
Immunologic approaches are of great interest to the child neurologist, particularly the use of plasmapheresis, which removes circulating antibodies from the blood, and immunosuppressive drugs, which dampen down an immune system gone awry. Both have been shown to be effective in some cases of multiple sclerosis. “But side effects of immunotherapy can be bad, and so it should only be used when other therapies have failed,” Trifiletti advises.
He explains that Tourette’s and Parkinson’s are “Ying-Yang” diseases. “There is too much dopamine in the brain in Tourette’s, too little in Parkinson’s,” he comments. “We would like to find out what causes Tourette’s. What are the targets of the antibodies? We don’t know that yet.”
He would also like to do research on the incidence of Tourette’s among African Americans and Hispanics. “Is it rare? Is it under-recognized? There are no numbers on that,” he explains.
There is also a search ongoing for a Tourette’s gene or genes. Trifiletti says that like Parkinson’s, it is probably a two-punch hit of genes and one or more environmental factors that cause the disorder. One of these factors may be the strep A bacterium.
And although Trifiletti is still hesitant about using the word “cure,” he is nevertheless optimistic that scientists are on the right track to unraveling the complex origins of these devastating childhood neurologic disorders of mysterious origins.