Medical Examiner

Strep Threat

Can a sore throat lead to Tourette’s syndrome?

Last February a happy, confident 8-year-old girl went to bed and woke up the next morning having turned into someone else. She came to her mother with a series of shocking confessions. She said she had licked people’s bottoms and drunk her own urine. She listed the people to whom she had shown her private parts. She asked if this made her a “bad person.”

The mother was horrified and baffled. She calmed the girl down and sent her to school. When her mother picked her up, the girl said she had spread her feces around the school. The mother casually checked with a teacher about the girl’s behavior and was told she was fine. This went on day after day. The girl said she had blinded her brother with a fork in his eye. She said she wanted to step in front of a bus. She said she had swear words stuck in her head. At first the mother suspected sexual abuse, but the daughter said no one had touched her, and the parents could find no evidence anyone had. The pediatrician said it sounded like a case of obsessive-compulsive disorder, a condition of unknown origin, and referred the family to a psychiatrist.

Surfing the Web, the mother discovered other cases just like her daughter’s: normal kids who suddenly become consumed by horrible thoughts or, in some cases, begin twitching uncontrollably. Doctors at the National Institutes of Health had a startling suspect: strep throat, one of the most common illnesses of childhood. Two months before the girl’s transformation, she had come down with strep throat four times.

Virtually all elementary-school-age children will get a sore throat, often many sore throats, caused by the Group A streptococcus bacterium, and the overwhelming majority will recover uneventfully. Many will get better without even seeing a doctor and getting antibiotics, the standard treatment. But there is growing evidence that a range of neurological disorders from temporary tics, such as eye-blinking and head-scratching, to full-blown OCD and Tourette’s syndrome are linked to the bacteria. The scientists who connected these neurological maladies to strep throat named the condition pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS. Some scientists even believe that strep throat might be a factor in some cases of anorexia nervosa.

It is estimated that about 2 percent of the population suffers from OCD and/or tics, which are diagnosed on the basis of behavior, making the conditions more common than schizophrenia and manic-depression. But many believe the incidence is likely far higher. No one knows the cause, and not even researchers in the field know to what degree strep might turn out to play a role in these cases.

That infections can trigger common mental illnesses is not a new idea. It is a very old one, discredited for most of the 20th century. In the middle of that century the cause for such disorders as schizophrenia, manic-depression, Tourette’s syndrome, and OCD was believed to be bad parents. One theory was that OCD was the result of punitive toilet training. Toward the end of the century, the blame shifted to bad genes. That idea, which is still the most widely held in the scientific community, is that the unfortunate few inherit a bad gene or genes that, in the case of schizophrenia, make people hear voices or, in the case of OCD, have obsessive thoughts. Yet, despite many seemingly promising leads, no one has been able to identify this blighted DNA.

But what if the problem isn’t bad genes but bad germs? Researchers are making the connection between OCD and tics with evidence of an infectious assault to the brain. For example, brain scans of children with PANDAS show that they have an inflammation in the basal ganglia, a portion of the brain that acts as a sort of gatekeeper for behavior and movement. It is the same inflammation seen in a rare neurological condition that arises from rheumatic fever, a disease caused by strep.

Scientists at both Brown Medical School and Yale University School of Medicine have infused rats with the blood serum of patients with Tourette’s and/or OCD. How it affected the rats’ thoughts is unknown, but the infused rodents exhibited the tics and grunts stereotypical of Tourette’s. And, as just reported in the Journal of the American Medical Association, researchers at the University of Rochester Medical Center identified a small group of children when they first exhibited signs of OCD and tics and eliminated the symptoms with early antibiotic treatment.

The researchers themselves warn that these studies, while intriguing, don’t prove the infection connection and that each step forward raises more questions. For instance, treatments that have been effective in the newly diagnosed have been failures in people with chronic cases. Is that because strep is responsible for only a small portion of these neurological illnesses? If so, what causes the rest? Or could chronic cases be linked to strep, but the available treatments are only effective when the brain is newly under assault?

Paul Ewald, a professor of biology at Amherst College, is a leading theorist of the germs-not-genes movement (read a full explanation of his theories here). But if bad genes aren’t responsible, why do disorders such as OCD/Tourette’s/tics run in families? Ewald says there is a place for genetics in the theory. He posits that genes determine how an individual’s immune system reacts—or overreacts—to any given infection. So, if that’s the case, in the end what’s the difference? Either some of us inherit a gene that makes us crazy, or some of us inherit a gene that makes us crazy because we got a certain infection. One crucial difference is if the cause is infection, there’s the possibility of prevention or cure (for now, genes can’t be fixed). Ewald says, for example, that the discovery of penicillin is the “biggest success story in all of psychiatry” because it ended one of the most common mental illnesses, syphilitic insanity.

For germ-theory proponents, the case that strep throat can cause a variety of mental disorders otherwise believed to be either psychological or genetic in origin is tantalizing. And a model for how that might happen already exists.

In the early 1990s, Dr. Susan Swedo, a senior investigator at NIH, was hoping to better understand OCD by studying a rare and ancient malady when a chance remark by a patient’s mother led to the description of PANDAS. Swedo was looking at Sydenham’s chorea, known in the Middle Ages as St. Vitus’ dance, a disorder that causes facial grimacing and flailing limbs. Sydenham’s occurs as a result of rheumatic fever, an autoimmune reaction to untreated strep throat that can cause inflammation of the heart. It was once the major killer of young children in the United States. But since the use of penicillin to treat strep throat became widespread in the 1940s, rheumatic fever incidence has declined dramatically. What intrigued Swedo about Sydenham’s is that before the onset of physical symptoms, the young victims often experience OCD.

About 25 years ago, researchers discovered the likely neurological basis of Sydenham’s. When we contract strep, our immune system recognizes the invading proteins on the outside of the bacteria, the antigens, and creates antibodies that attach themselves to the invader. That sends a signal to our white blood cells to kill the trespasser. But in an unfortunate quirk of nature known as “molecular mimicry,” proteins in the human heart closely resemble strep antigens. In vulnerable individuals, the immune system, instead of stopping when the strep is vanquished, continues on an autoimmune rampage against its own heart. In the case of Sydenham’s, the molecular mimicry, and the damage, is found in the neurons of the basal ganglia of the brain.

Swedo was evaluating a boy thought to have Sydenham’s. He didn’t, but he did have OCD and tics, and because these things often run in families, Swedo was not surprised to find that his older brother had Tourette’s syndrome. As Swedo was talking to the boys’ mother, the woman mentioned that it had become a family joke that whenever her kids’ tics got worse, it was time to take them in for a throat culture because an increase in tics inevitably meant a strep throat.

It clicked. Swedo theorized that Sydenham’s could just be one manifestation of neurological damage due to strep. Perhaps there were children who never got rheumatic fever or Sydenham’s but who got OCD or tics directly as a result of an unremarkable sore throat. If that was the case, it meant there might be something they could do to cure it. Antibiotics were not the answer for the patients Swedo saw. Because it was so long between the onset of symptoms and her patients’ arrival at NIH, the initial strep infection had cleared up. What was needed was a way to stop the autoimmune damage occurring in the brain.

So Swedo and her colleagues used a procedure called plasma exchange or plasmapheresis. It’s like a high-tech bloodletting. She performed a series of five on each patient—the patient’s blood was removed, and the fluid part, the plasma, where the antibodies are found, was discarded and replaced.

Swedo’s initial study was much too small to be considered definitive. In all, she has treated only about 30 children with the most devastating cases. But the results are striking. Last April, two months after the onset of her symptoms, the 8-year-old girl was admitted to NIH for a two-week course of plasma exchange. During her first three days in the hospital, she was unable to eat because of the extreme distress of seeing other sick people; she was convinced she had made all of them ill. By the third plasma exchange, the girl was less fraught with worry. By the fifth, she was almost herself again. Within a week of returning home she was completely better. Over the course of the plasma exchange study, 80 percent of the children receiving it maintained a remarkable improvement in their symptoms a year later.

Will there be other neurological disorders linked to strep infection? Dr. Mae Sokol, a specialist in eating disorders at Children’s Hospital in Omaha, Neb., believes some of her patients with anorexia nervosa had strep-triggered onset. Like the PANDAS patients, they tend to be preteens, and their parents can usually pinpoint exactly when, even to the day, the obsession with food began, usually within a few weeks of a strep infection. One 10-year-old patient, after an inadequately treated strep infection, became consumed with the idea that she couldn’t swallow solid food. As she began losing weight, she liked the result. Six months and 30 pounds after the onset of her symptoms, she was referred to Sokol. At that time, the girl had a sinus infection, and Sokol treated her with a high dose of antibiotics. The girl began eating two days later. Sokol says there is a possible physiological explanation for such cases: The part of the brain thought to be responsible for body image is close to the basal ganglia, which is inflamed in children with PANDAS.

Could other infections trigger PANDAS-like symptoms? Dr. Louise Kiessling, a professor at Brown Medical School, says there is some evidence Lyme disease can provoke similar behaviors. And once the immune system is primed to overreact, other invaders besides strep can set off the process. For example, says Kiessling, children with Sydenham’s have had recurrences of writhing after infection with the chicken pox virus or bacteria called Haemophilus influenzae.

While the connection between strep and neurological disorders is intriguing, it is far from proved. Research to find out to what degree strep is responsible for what percentage of OCD and tic disorders is continuing on everything from the chemical level to the epidemiological one. Researchers are trying to find out if there is a molecule produced in the brain unique to PANDAS patients. They are also following large groups of children to see if they can better correlate strep throat and subsequent behavior disorders. And if the work on a strep vaccine is successful, widespread inoculation could result in a dramatic decline of OCD and tics. (The doctors involved in the research all warn against rampant use of antibiotics, which is more likely to cause dangerous antibiotic resistance than prevent PANDAS.)

For now, Swedo doesn’t have much better advice than teaching children about washing their hands and not sharing drinking glasses, and for parents of children who have shown neurological symptoms following strep, even minor ones such as eye-blinking, to be vigilant about sore throats. As the mother of the 8-year-old says, “I can’t let her get strep.”