_____In This Issue_____   • Watching for PANDAS (The Washington Post, Jun 18, 2002)   E-Mail This Article   Printer-Friendly Version   Subscribe to The Post

By Miriam E. Tucker
Special to The Washington Post
Tuesday, June 18, 2002; Page HE01

Instead of getting ready for school, the Kensington 13-year-old stood in his bedroom seven years ago, flipping the light switch on and off. Pushed along into the bathroom, he repeatedly stepped in and out of the shower. Next he put on his shirt and took it off, over and over. "I have to do this," he cried. "I can't stop."

His mother, a mental health professional, recognized the symptoms of obsessive-compulsive disorder (OCD). But, she said, "I didn't understand where it could have come from or how it could happen so suddenly."

Three years later, another local parent was grappling with the same question. Her son, then a District second-grader, suddenly developed a complex tic, stroking his forehead down to his nose, over and over. Certain words, like "Lord," "Jesus," "potty" or "body," would set off furious rounds of forehead-swiping, sometimes to the point of causing him to bleed.

Besides their sudden, bizarre behaviors, the two boys -- who were referred to The Post by Silver Spring behavioral therapist Charles Mansueto and whose names are being withheld at their families' request -- had something else in common. Both had been ill with sore throats shortly before their symptoms erupted.

Consequently, both were tentatively assigned a controversial diagnosis: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, or PANDAS for short.

First described in the mid-1990s by researchers at the National Institute of Mental Health (NIMH), the condition involves the emergence of OCD or a tic disorder after an untreated strep throat infection in pre-pubertal children. Which is to say, strep throat may somehow make a child suddenly appear to "catch" obsessive-compulsive disorder.

Now, a new study suggests that quick antibiotic treatment of strep throat in children who suddenly develop OCD or tics may prevent these behaviors from becoming chronic lifelong problems.

At a meeting of the Pediatric Academic Societies last month, a group of pediatricians from Rochester, N.Y., reported on 25 children who had been brought to the doctor's office primarily because they were acting strangely; only three complained of sore throats. Normally, odd behaviors wouldn't prompt a physician to suspect strep, but these doctors were looking for PANDAS: All 25 children tested positive for the infection. What's more, when doctors administered antibiotics, both the strep infections and the behaviors disappeared.

While acknowledging that the study sample was small and that more research will be needed, study co-author Michael E. Pichichero, director of Rochester's Elmwood Pediatric Center, said the findings are exciting because there is no known cure for either OCD or Tourette's syndrome, a disorder involving multiple tics.

"It would be amazing if a percentage of OCD, tics and Tourette's syndrome could have an infectious etiology that could be treated and made better," said Pichichero, an infectious disease specialist.

But some experts, like Stanford T. Shulman, chief of infectious diseases at Children's Memorial Hospital in Chicago, question whether PANDAS exists at all. In an era of increasing antibiotic resistance, they worry that parents who suspect their children might have the condition will push for the drugs even when they aren't necessary.

"In my view, the association between the neuropsychiatric issues and the strep infections is still unproven," Shulman said. Part of the problem in proving a link, he said, is that strep infections are extremely common: Depending on a child's age and the time of year, anywhere from 10 to 25 percent of children will test positive for strep despite feeling fine. Some are carriers, who always have the organism in their throats without its making them sick; others have had an infection in the past few weeks.

"If a kid falls and breaks his arm and you do a blood test, you'll often find evidence of a strep infection. It doesn't prove cause and effect," Shulman said.

Bacteria and the Brain

 

The PANDAS story began about 12 years ago, when Susan E. Swedo, now chief of the Pediatrics and Developmental Neuropsychiatry Branch at NIMH, and her institute associates began looking for evidence of strep infection in children already diagnosed with OCD or tics.

In February 1998, they published a description of 50 cases of what they called PANDAS and proposed five key criteria for diagnosis:

• the presence of OCD or a tic disorder;

• onset in pre-pubertal children;

• symptoms that wax and wane;

• association with strep infections; and

• other neurologic abnormalities.

Untreated strep infections might trigger the disorder, the researchers suggested, in much the way they cause rheumatic heart disease in a small number of children. In that disease, antibodies produced by the immune system to fight the infection mistakenly attack the heart valves. With PANDAS, researchers hypothesized, antibodies produced to fight the strep infection target a part of the brain called the basal ganglia, which is associated with movement and behavior. Each time a child incurs a new strep infection, they further speculated, the basal ganglia would come under renewed attack, and the OCD or tics would return or worsen.

If they were right, Swedo and her associates reasoned, preventing re-infection with antibiotics should also prevent the next OCD or tic flare-up. However, in a preliminary NIMH trial of 37 patients published in 1999, daily doses of penicillin given for four months had no impact on either subsequent strep infections or OCD/tic flare-ups.

Why, then, did antibiotics work in the Rochester patients? Because, Pichichero believes, he saw his PANDAS patients in an earlier and more treatable phase. The implication, he said, is that parents of children who suddenly exhibit bizarre behaviors should seek medical attention immediately. Physicians, in turn, should check for strep throat and at least consider antibiotic treatment if the test is positive.

But even Swedo urges caution here, saying that most children with OCD and tics do not have PANDAS, and that strep infection may be just one of many potential triggers of these brain disorders in children who are genetically predisposed toward such problems. Moreover, most children with strep, even if untreated, never develop OCD or tics. Swedos estimates PANDAS occurs in roughly 1 in 1,000 children, making it, in her words, "still a rare phenomenon."

The lack of clarity about PANDAS leaves pediatricians like Northern Virginia's Gary Bergman without guidance on what to do when they see a patient who meets the criteria for the disorder. Bergman, who has a special interest in the subject because his two sons have Tourette's syndrome, said the Rochester study's findings incline him to consider treating such children with antibiotics right away, rather than waiting to see how symptoms progress. But on the other hand, he said, "I'm also very cautious and worried that everyone will jump on the bandwagon and find PANDAS where it doesn't exist, and will inappropriately treat kids."

Still missing for Bergman and other physicians is a test that will definitively diagnose PANDAS, said Bennett Lavenstein, a pediatric neurologist who heads Children's National Medical Center's movement disorders program in Fairfax. Such a test would pinpoint the antibodies targeting the brain tissue and causing the abnormal behaviors. "You want a specific test you can send to a lab to establish the link, not just a loose association," he said.

Without that, Lavenstein said, PANDAS is "an interesting observation, but it's still a work in progress."

Seeking Answers

 

The next few years could help solve the puzzle. Swedo and her associates are now conducting a larger study in which children with recent onset of suspected PANDAS receive daily doses of either penicillin or azithromycin, which is more effective against strep. They hope this study will demonstrate more clearly whether antibiotics can reduce OCD and tic flare-ups. Results are expected within two years.

And at least three additional studies are seeking to better establish whether there are any links among strep infections, brain antibodies and OCD/tic symptoms.

Meanwhile, the Kensington and District boys are doing much better today, after receiving treatment at Mansueto's Silver Spring behavior therapy center. But they still struggle with their mental disorders.

The District boy, now 11, is still in behavior therapy. Since last fall, he also takes daily antibiotics, a treatment the NIMH advises against outside of clinical trials. However, his mother believes it important that her son avoid further strep infections, which she said exacerbate his tics.

The Kensington boy began taking an antidepressant and started behavior therapy about a month after his symptoms erupted. Within six weeks, he was better. By three months, he had learned techniques to control his fears until he was nearly symptom-free, his mother said.

Now 20, he just completed his sophomore year at college. He has good grades, friends and no longer receives any type of treatment. But he still has OCD. "When he gets anxious or has a bad thought, he still feels the impulse to perform a repetitive action, but now he pretty much controls it," according to his mother.

Another factor is in his favor, she said: He has matured. "As with any chronic illness, he now accepts that he will have to pay attention to it for the rest of his life."Miriam E. Tucker is a health writer in Bethesda.