Grimshaw's finding that some OCD patients had a history of Sydenham's chorea is of interest in light of a more recent study by Rapoport (1989). There recently had been a resurgence of rheumatic fever in parts of the United States. A survey of 37 patients was conducted with rheumatic fever. About 20% of rheumatic fever patients develop Sydenham's chorea. This is an autoimmune response to the basal ganglia, leading to potential damage in that area (Rapoport, 1989). In her survey, 23 of the rheumatic fever patients developed Sydenham's chorea and 14 did not have chorea. In blind evaluations in which the interviewer did not know the medical diagnosis, scores for obsessional symptoms were significantly higher among those with Sydenham's chorea. In addition, three chorea patients, but no rheumatic fever patients without chorea, met diagnostic criteria for full-fledged OCD. This has been considered evidence that, at least  some patients, that dysfunction of the basal ganglia may be involved in OCD.

In children, such symptoms have been called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). They arise when antibodies directed against invading strep bacteria cross-react with basal ganglia structures, resulting in onset of or exacerbations of obsessive-compulsive or tic disorders. There is a report (Giedd et al, 1996) of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci. Serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. OCD symptoms were associated with acute basal ganglia enlargement. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAS patients.

Why do some patients develop OCD symptoms as a consequence of streptococcal infections and Sydenham=B9s chorea and others do not? Intriguing recent findings (Murphy et al, 1997) suggest that D8/17, a B lymphocyte antigen, may serve as a marker for susceptibility to some forms of childhood-onset OCD and Tourette syndrome, as well as rheumatic fever or Sydenham's chorea. The average percentage of B cells expressing the D8/17 antigen was significantly higher in patients (mean =3D 22%, SD =3D 5%) than in comparison subjects (mean =3D 9%, SD =3D 2%). When classified categorically, all patients but only one comparison subject were D8/17 positive. Patients with childhood-onset obsessive-compulsive disorder or Tourette syndrome had significantly greater B cell D8/17 expression than comparison subjects despite the absence of documented Sydenham's chorea or rheumatic fever.

Swedo et al (1997) wanted to further study whether this trait marker of rheumatic fever susceptibility (D8/17) could identify children with pediatric autoimmune neuropsychiatric disorders (OCD and tic disorders) associated with streptococcal infections (PANDAS). They obtained blood samples from 27 children with PANDAS, nine children with Sydenham's chorea, and 24 healthy children which were evaluated for D8/17 reactivity. Individuals were defined as D8/17 positive if they had 12% or more D8/17+ cells. They found that the frequency of D8/17-positive individuals was significantly higher in both patient groups than it was among the healthy volunteers. Eighty five percent of the children with PANDAS and 89% of the children with Sydenham's chorea, compared with 17% of the healthy children, were D8/17 positive. The mean number of D8/17+ cells was similar in the two patient groups and was significantly higher in these groups than in the group of healthy children. These results suggest that there may be a subgroup of D8/17-positive children who present with clinical symptoms of obsessive-compulsive disorder and Tourette syndrome, rather than Sydenham's chorea But who have similar poststreptococcal autoimmunity.

There are treatment implications of these findings. Researchers at the National Institute of Mental Health (oral communication) reported that a boy who had tested positive for a strep infection was enrolled in an experimental study in which he received intravenous gammaglobulin. A treatment that removes circulating strep antibodies in the body. Within three weeks, the child's obsessions had lessened, and within six weeks they had disappeared. So far 17 children - including the above 5-year-old boy - have been enrolled in a NIMH treatment trial being conducted the past several years. In a presentation of the data (American Psychiatric Association meeting, 5/97), Dr. Susan Swedo told psychiatrists that the results were dramatic. In a double-blind placebo controlled trial, there was virtually no change in either OCD or tics in those who received a placebo in an intravenous solution. There was a 45% decrease in behavioral symptoms in the majority of those who received gammaglobulin