National Institute of Mental Health (NIMH) researchers report that some children whose symptoms of obsessive-compulsive disorder (OCD) and tic disorders were worsened by a common strep infection have been successfully treated with plasma exchange (PEX) and intravenous immunoglobulin (IVIG). Dr. Susan Swedo and colleagues at the National Institutes of Health reported their findings in the October 2 issue of Lancet.

In previous studies, Dr. Swedo and others observed that in a small number of children suffering from the obsessional thoughts and compulsive behaviors typical of OCD and tic disorders, symptoms suddenly became worse following infection with Group A beta hemolytic streptococci. Evidence pointed to an autoimmune response to the infection, in which antibodies attack healthy as well as infected cells, leading to inflammation in the brain's basal ganglia, an area involving movement and motor control. The syndrome, known as PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, typically occurs in young children and is noted for its dramatic, sudden onset or exacerbation of symptoms and episodic course, in which periods of symptom worsening follow strep infections.

The investigation shows that plasma exchange and IVIG relieve neuropsychiatric symptoms in this subgroup of children with tics and obsessive-compulsive disorder. A few children were even able to discontinue all psychotropic medications after treatment," Dr. Swedo said. "The study does not, however, support using PEX and IVIG for all cases of tics or OCD. Nor does it suggest that all children with untreated strep infections will get OCD, tics, or Tourette syndrome. In fact, strep infections are very common and strep-triggered neuropsychiatric disorders are quite rare, so the vast majority of children with strep infections are not at risk for developing these disorders, particularly with prompt attention and treatment," according to Dr. Swedo.

Although the cause of obsessions, compulsions, and tics is unknown, evidence suggests a common origin for all of these symptoms, with genetic and nongenetic factors playing a role. Symptoms affect 1-2% of children, but the number involving PANDAS is unknown. The antistreptococcal antibodies reported in children with OCD and tic disorders are considered part of the unique syndrome of the subgroup PANDAS.

Thirty children ages 9 to 15 with severe, infection-induced worsening of OCD or tic disorders, including Tourette syndrome, participated in the double blind, placebo controlled study at NIH. After medical, neurological, and psychiatric assessments, the children were randomly assigned to plasma exchange, IVIG, or placebo (saline solution). PEX and IVIG were chosen as active treatments because of their safety and effectiveness in a variety of childhood and adult immune-related diseases. Researchers rated symptom severity at baseline and at one month and twelve months after treatment, using standardized assessments for OCD, tics, anxiety, depression, and normal behavior.

Of the 29 children who completed the trial (19 boys, 10 girls), 10 received PEX, 9 IVIG, and 10 placebo. Both PEX and IVIG produced substantial improvement in obsessive-compulsive symptoms, anxiety, and overall functioning; PEX also improved tic symptoms. Ratings done one month after treatment revealed that patients in both the PEX and IVIG groups were much improved. In contrast, symptoms changed little in children who received placebo. The treatment gains of PEX and IVIG remained at one-year follow-up, with 14 of 17 subjects "much" or "very much" improved over baseline.

The one-month follow-up consisted of a neurological examination to rate symptom severity. After that evaluation, if a child taking placebo had no symptom improvement, IVIG or PEX was offered, so one-year ratings are not available for the placebo group. At the one-year assessment, obsessive-compulsive symptoms, tic severity, psychosocial functioning, and symptom severity remained improved. Among subjects who received IVIG, there was a 58% improvement in OCD symptoms; with those who received PEX, a 70% improvement; 82% of the children had symptom reductions of at least 50%. On average, children now had good functioning in all social areas. Parents and children often reported, "My child's back to his old self again" or "Things are a lot easier now."

Susan J. Perlmutter, M.D., Marjorie A. Garvey, M.D., Susan Hamburger, M.S., M.A., Elad Feldman, B.S., and Henrietta L. Leonard, M.D., NIMH, and Susan F. Leitman, M.D., NIH Clinical Center, also participated in the study. Dr. Leonard is now affiliated with Rhode Island Hospital and Brown University.

10/25/99

The National Institute of Mental Health (NIMH) conducts and supports research nationwide on mental illness and mental health, including studies of the brain, behavior, and mental health services. NIMH is a part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIMH is a component of the U.S. Department of Health and Human Services.