A small but revealing study from Johns Hopkins Children’s Center challenges a controversial theory that strep infections cause a neuropsychiatric disorder in children marked by tics, jerking movements and obsessive-compulsive behaviors. The findings appear in the June issue of Pediatrics.

Working from the hypothesis that an overactive immune system in the wake of a strep infection mistakenly attacks a child’s brain and causes neuropsychiatric symptoms, researchers followed for two years 12 children diagnosed with PANDAS, (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections), but found no changes in the levels of immune proteins, the classic markers of autoimmune inflammation, during symptom exacerbation.  Moreover, researchers found no evidence of strep antibodies – the antibodies produced by the immune system against the streptococcus bacterium – binding to or interacting with brain tissue, a finding that makes an immune origin of PANDAS unlikely, investigators say.

“It is true that strep infections can send the immune system into overdrive, “ says lead investigator Harvey Singer, M.D., director of pediatric neurology at Hopkins Children’s, “but if an overactive immune system is truly behind this neuropsychiatric disorder, we would expect to see a spike in the blood levels of antibodies against brain proteins when children were having flare-ups of symptoms. We didn’t."

Researchers also compared levels of antibodies from six children whose symptoms got worse during strep infections to antibody levels from six children whose symptoms didn’t change during strep infections. They saw no marked difference between the two groups, which researchers say is yet another finding that makes post-strep inflammation an unlikely cause of PANDAS.

Speculating that symptoms could be unrelated to antibodies, Singer’s team measured changes in another inflammation marker – cytokines – proteins that regulate immune response. The researchers analyzed five carefully timed blood samples from each child: two samples drawn before flare-ups, one during peak of symptoms, and two after the symptoms subsided, finding no significant differences in cytokine levels before, during and after flare-ups, leading them to conclude that the symptom exacerbations were not related to cytokines. 

To further test the hypothesis that a misfiring immune system launches antibodies against brain tissue, investigators examined the reaction between strep antibodies key brain proteins, obtained from post-mortem brain tissue. Using blood from each of a child’s five samples drawn during the different stages of a flare-up, researchers saw no increase in reactivity between antibodies and brain proteins, which they say further shows lack of immune system involvement in PANDAS.

Finally, investigators studied how strep antibodies interact with gangliosides, types of complex sugars found mainly in nervous system cells, once again finding no increase in reactivity between antibodies and brain chemicals.

“We’ve tested the immune origin hypothesis on multiple fronts and found no evidence of immune system involvement,” Singer said. “It’s not that a strep infection cannot make symptoms of the condition worse, but so far there is no evidence to suggest that strep is the cause.”

Infections of any type can exacerbate tics, researchers say, but so can stress, fatigue and anxiety, and the fact that an infection makes symptoms worse does not mean it caused the disorder.

Because immune system involvement is unlikely, researchers say, treatments such as preventive antibiotics, immunoglobulin injections and plasmapheresis, a technique that filters antibodies from the blood, should not be used to treat children with PANDAS.

PANDAS, a relatively rare group of disorders believed to occur predominantly in young children and pre-teens, are marked by an explosive onset of symptoms, including tics and obsessive-compulsive behaviors.

The study was funded by the National Institutes of Health.

Other Hopkins investigators in the study: Colin Gause, B.S., Christina Morris, M.S., Pablo Lopez, Ph.D.