General Overview and Historical Context

Symptoms of PANDAS are hypothesized to result from immune dysfunction at one (or more) of three levels:

► Local dysfunction related to cross-reactive antibodies recognizing CNS antigens
► Regional dysfunction related to inflammation of the basal gangli
► Systemic abnormalities of chemokines or cytokines, with resultant disruption of CNS functions.

The hypotheses are based on the disease mechanisms proposed for Sydenham chorea (SC), the neurologic manifestation of rheumatic fever, and clinical observations demonstrating that obsessive-compulsive symptoms (OCD) appear in about two-thirds of SC patients. The OCD symptoms of SC patients begin 2 to 4 weeks before the onset of the chorea, suggesting that OCD might be a forme fruste of Sydenham chorea. A trial of immunomodulatory therapies for Sydenham chorea demonstrated benefits not only for the choreoathetoid movements, but also the OCD symptoms. Improvements were seen with plasmapheresis (5 single-volume exchanges over 8 to 10 days); intravenous immunoglobulin (IVIG at 1 gm/kg x 2 days); or prednisone treatment (21-day course of immunosuppressive doses, with taper).

A placebo-controlled trial of plasmapheresis and IVIG for PANDAS was conducted at the NIH in the late 1990’s, with children randomly assigned (by the NIH pharmacy) to receive plasmapheresis (unblinded) or IVIG/sham IVIG (see Perlmutter et al, 1999). The IVIG and sham IVIG (placebo) arms were blinded so that 18 of 19 of the subjects left the NIH Clinical Center believing that they had received active drug (10 had received placebo). At one month evaluations, there was no mistaking who had received active drug and who had received placebo. Placebo infusions produced no improvements in OCD or tic symptoms, while 100% of the children receiving IVIG or plasmapheresis were significantly improved. As shown in the graph below, the average improvement in OCD symptoms was 45% for the group receiving IVIG and nearly 65% for the children receiving plasmapheresis, with several subjects achieving complete symptom remission or symptoms improved to the subclinical level. The results of the trial were sufficiently robust to cause the American Society of Apheresis to include plasmapheresis as a treatment option for PANDAS, as well as for Sydenham chorea (see Weinstein, 2008). Although plasmapheresis and IVIG appear to provide the best long-term outcomes, they are expensive and involve risks which are not warranted in the treatment of mild to moderate cases of PANDAS; even for more severely ill patients, their use may be reserved for treatment of patients who fail to respond to antibiotics and other non-invasive therapies, as described below. For References, see PPN Library