Strep Throats and PANDAS Your daughter complains of a sore throat.

A few days later she begins acting like Jack Nicholson’s irrational character in the movie, “As Good As it Gets.” Suddenly she becomes obsessive-compulsive, with fears of contamination, ritual hand washing and counting, eye blinking, and the facial tics and hyperactivity suggestive of Tourette syndrome. What’s going on? Mental illness? Drugs? Toxins? How about strep throat? Strep throat is not an obvious reason for bizarre behaviors, but it is part of a medical theory linking a common bacterial infection to some uncommon psychiatric states in children. Young children who show a sudden onset of obsessive-compulsive disorder (OCD) and tics may be suffering from PANDAS: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. The PANDAS syndrome was first described by researchers at the National Institute of Mental Health in Bethesda. Since then PANDAS has attracted the attention of the general public and mainstream media. It has also attracted a fair number of critics in the pediatric and infectious disease communities, many of whom are quick to point to the weak link between cause (strep throat) and effect (behavior). That’s a good link to saw away at because causality is always difficult to prove. After all, everyone has had a strep throat but not everyone goes on to develop tics and OCD. Ten percent of school children are carriers of streptococcal bacteria, but remain healthy and without evidence of infection or behavioral changes. OCD and Tourette syndrome often seem to run in families and they tend to appear gradually among persons who show no evidence of prior or active strep infections. Causality is hard to spot in such a mix of people, genes, symptoms, and time intervals.

1

But let’s step back and look at just one piece of this puzzle: the bacteria. How would a common bacterial pathogen like Group A Streptococcus pyogenes cause changes in human behavior. S. pyogenes is a surprisingly effective pathogen and the agent of diverse illnesses. It’s the cause of strep throat and toxic shock syndrome. It is also the major cause of a horrific infection called necrotizing fasciitis or “flesh-eating disease.” Rheumatic fever and the damaged hearts seen in cases of rheumatic heart disease also are the work of S. pyogenes. Shielded from the body’s immune system by an array of proteins and sugary capsules, the bacteria produce a variety of toxins and enzymes to disable, destroy and spread through the host. Some of these streptococcal proteins are shaped to mimic the proteins of the human host. It is this “molecular mimicry” that probably leads to rheumatic heart disease. The immune system gets confused about who is who, and so the heart is damaged in the fight against the bacteria. Something similar may happen in PANDAS. In effect, PANDAS may be an autoimmune disease. Host antibodies made against streptococcal bacteria cross-react with the basal ganglia in the brain. The resulting damage and inflammation within this cluster of neurons then affects patient thoughts, movements and emotions. What’s the evidence for this? First, cross-reacting antibodies can be found in PANDAS patients. Second, episodes of PANDAS are typically preceded by a strep infection. Third, antibiotic treatments for strep throat will usually end or lessen an episode of PANDAS. Fourth, immune therapies designed to counteract autoimmune reactions (e.g., plasmapheresis and intravenous immunoglobulin) reduce the symptoms of PANDAS. Finally, a medieval aliment called St. Vitus’ Dance offers another clue. This neurological disorder (now called Sydenham’s

2

chorea) produces facial tics and flailing limbs, and episodes of OCD after a bout of rheumatic fever. Rheumatic fever is an autoimmune disease caused by Group A Strep. The connection between Strep and pediatric OCD sounds convincing, but not to everyone. Other experts contend the PANDAS theory is wrong or at least unproven. Last spring, two well known PANDAS critics were quoted in The New York Times as saying Strep and OCD are two things that are “true, true and unrelated.” (I know people on both sides of the PANDAS debate so I’m not taking sides.) The PANDAS debate is actually part of a larger effort to link some episodes of mental illness to an infectious disease. For example, a horse virus called Borna has been linked (tentatively) to depression in people. Leptospirosis, a bacterial infection, has been associated with depression, dementia, and psychosis. Neurocysticercosis, a parasitic infection, has been linked to seizures and epilepsy. Neuropsychiatric symptoms have also been associated with many cases of HIV. Of course, finding definitive proof of cause-and-effect is difficult. It would be nice to think that some mental illnesses could be treated or prevented with a vaccine or an antibiotic. That’s not likely to happen, but for cases of sudden changes in behavior or mental abilities it might be useful to consider the possibility of an underlying infection. Maybe even PANDAS.

3