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Treatment of PANDAS based on pathogenesis of post-streptococcal autoimmunity The autoimmune pathophysiology proposed for PANDAS and Sydenham’s chorea, would support the use of immuno-modulation as possible therapy for children with PANDAS, such as plasma exchange, IV immunoglobulin, or corticosteriods. Corticosteriods are an unfavorable treatment modality because they worsen OCD and tic behavior. Therefore, plasma exchange (which filters out the antibodies) and IVIG (which binds receptors with pooled antibodies) were studied compared to placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms in the following study: “Therapeutic Plasma Exchange and Intravenous Immunoglobulin for Obsessive Compulsive Disorders and Tic Disorders in Childhood”, by Susan J. Perlmutter et al, The Lancet 1999, 345 (9185):1153-58. In this partial double-blind randomized trial, 30 children with severe infection-triggered exacerbations of OCD or tic disorders were randomly assigned treatment with plasma exchange (5 single volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (IV saline solution over 2 days). Psychiatric symptom severity was rated at baseline, at 1 month, and at 1 year after treatment by standard assessment scales for OCD, tic disorder, anxiety, depression, and global function. {Randomized by randomization chart} {Investigators and study participants were blinded to whether the child received IVIG or placebo, but were obviously aware of who received plasma exchange} After symptom ratings at 1 month were completed the IVIG/placebo masking was broken, and open treatment to IVIG and plasmapheresis was available for those not improving on saline (all of the subjects), therefore, there was no more placebo 1 year follow-up ratings. Results: ˇ 29 children completed the trial:10 received plasma exchange, 9 received IVIG, and ten placebo o at baseline, the three study groups were similar in age, primary diagnosis, duration of exacerbation, use of psychotropic medications, presence of antistreptococcal titers. ˇ 1 month follow up: striking improvements seen in plasma exchange and IVIG groups concerning obsessive-compulsive symptoms, anxiety, depression, emotional liability and global functioning. o Global change scores for children in the plasma exchange and IVIG groups improved by 48% and 41 % respectively, in contrast to placebo which showed no change in overall symptom severity o Improvement in obsessive-compulsive symptoms, rated by Yale-Brown OCD scale, seen in plasma exchange (33% improvement) and IVIG (35% improvement) groups o Anxiety improvement, as rated by the NIMH anxiety scale, significant in plasma exchange and IVIG groups, 31 % and 47% improvement respectively o Plasma exchange group showed significant improvement in tic severity over placebo, but IVIG did not ˇ 1 year follow up: psychiatric symptoms remained improved from baseline on all measures. o The most clinically meaningful improvements occurred in obsessive-compulsive symptoms (58 % and 70 % improvement from baseline; IVIG and plasmapheresis respectively), tic severity (53 % improvement plasmapheresis), and global measures of symptom severity (26 % and 45 % improvement) and psychological functioning (26 % and 47 % improvement). o The symptoms ratings and clinical impression of treatment of OCD favored plasmapheresis over IVIG o Parents report “ my child’s back to their old self again”, and children reported “things are a lot easier now”. Kids went from “symptom impairments in several social areas” to now “good functioning in all areas”. Conclusion: Both plasma exchange and IVIG were effective in significantly reducing the symptom severity of OCD and tic disorder for children with PANDAS. Possible mechanisms would be through blocking (via IVIG) or removing (via plasma exchange) the antistreptococcal antibodies that were cross-reacting to the neuronal tissue. Supporting the idea that PANDAS is a separate subgroup of OCD/tic disorder and may require a unique treatment plan. Also separating PANDAS from classic childhood onset OCD is the remission of symptoms after a single course of IVIG or plasma exchange. Typically, patients with OCD will have response to SSRIs and/or behavioral modification; however, the response is only partial and relapse is common after medication is discontinued. Further studies: Trials with more selective and specific immunomodulatory agents for children with PANDAS. Further Observations of treatment It has been documented in several case studies and a prospective study at a community pediatric practice that children with PANDAS respond readily to antibiotic treatment. The prospective study: “Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS)”, by Marie L. Murphy et al, Archives of Pediatric and Adolescent Medicine 156(4):356-61. Though this study only had a sample population of 12, all cases had documented active GABHS infections (by throat swab or culture, and/or rise GABHS Ab titers) associated with the initial episode of neuropsychiatric symptoms, and these neuropsychiatric symptoms (OCD, anxiety, ADHA, tic disorder) disappeared during antibiotic treatment for streptococcal-infected throat. The recurrences of neuropsychiatric behavioral symptoms were directly related to the recurrence of streptococcal throat infections, which again resolved with appropriate antibiotic treatment (amoxicillin or cephalosporin). There were no instances of new recurrence of OCD in the absence of new GABHS infection (throat cultures were also taken after initial treatment of antibiotics, when symptom free, and were negative). This study supports the linkage of GABHS infection to acute neuropsychiatric disorders, as described in the PANDAS sub-category; however, it slightly undermines the theory that PANDAS is caused by an autoimmune cross-reactivity to brain tissue, because rapid treament (within 2-14 days) with antibiotics does not target antibodies designed against GABHS/brain tissue. This leads one to believe there are several components to the pathophysiology of PANDAS, including genetic susceptibility of the host, an autoimmune reaction, and possibly a reaction to the toxins of the bacteria themselves or a certain strain of GABHS. Each of the delineated points can be the focus of diagnostic testing and therapeutic intervention. Currently, the NIMH is investigating the role of antibiotic prophylaxis against GABHS and its affects on the recurrence of neuropsychiatric symptoms in children with PANDAS. Website Design