PANS as a Post-Infectious Autoimmune Disease: Benefit of IVIG

Background: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis given to children who have a dramatic – almost overnight – onset of neuropsychiatric symptoms. Recent findings suggest a relationship between a post-infectious response and behavioral changes, which may be a form of post-infectious autoimmunity, through molecular mimicry, resulting in various neurological symptoms. We’ve coined the term “Alzheimer’s of the Immune System,” or AIS, to identify this syndrome. As a result of our studies and observations, we’ve identified a number of common immune defects in patients with this presentation which suggests a new immune deficiency. Given our findings, we hypothesize that AIS is the underlying mechanism that leads to PANS.

Methods: Based on this hypothesis, we proposed a study to explore the use of intravenous immunoglobulin (IVIG)[Octagam 5%] for the treatment of PANS. The primary objective of the study was to assess the efficacy of IVIG in PANS over a period of 6 months (6 infusions) based on psychological evaluation scores using 6 different assessments (Figure 1). Secondary objectives included evaluation of the immunomodulatory effect of IVIG on key biomarkers associated with PANS.

Results: Our results indicate statistically significant reductions in symptoms from baseline to end of study (infusion 6) in all 6 assessments measured. Dramatic results can be seen in the PANSS-PI (Figure 2). Statistically significant reductions in symptoms were demonstrated beginning at infusion 3 through infusion 6 compared to baseline, with steady improvement from infusion 1 to infusion 6. Additional results from CY-BOCS indicated statistically significant reductions in obsessive compulsive symptoms, resulting in > 50% improvement, that were sustained 8 weeks after the final infusion (Figure 3).

Conclusion: In patients presenting with PANS, which may be associated with an underlying immune deficiency mechanism we term AIS, IVIG [Octagam 5%] successfully mediated psychological symptoms and dysfunction.