Neuroinflammation in Obsessive-Compulsive Disorder Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome

摘要

Postinfectious neuroinflammation has been implicated in models of acute onset obsessive-compulsive disorder (OCD) in children since the description of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).1 Centuries before then, Sydenham chorea (SC) was recognized and eventually confirmed to be caused by a post-streptococcal autoimmune process.2 Pediatric acute-onset neuropsychiatric syndrome (PANS) (defined in 2015) has a broader definition than PANDAS and is agnostic to the triggering event. Triggers of most auto-immune/inflammatory diseases are often not knowable in individual cases. With SC, PANDAS and PANS, cortico-basal ganglia-thalamo-cortical (CBGTC) circuities are thought to become disrupted by immune dysfunction. Antibody studies3-16 imaging studies,17-20 and response to immunomodulation21 support this proposed pathogenic model, but much work remains to be done to discover and validate specific diagnostic and predictive biomarkers and treatment pathways.This article aimed to outline current research that provides evidence of an association of PANDAS and PANS with inflammation, immune dysregulation, and/or autoimmunity. We begin by discussing SC as an accepted model of a post-infection autoimmune response leading to neuropsychiatric symptoms. Data supporting neuroinflammation in SC strongly overlap with data in PANDAS and PANS, including a similar autoantibody profile, imaging data showing alterations in the basal ganglia, and observable data regarding the efficacy of immunomodulation. We then review the current clinical diagnostic criteria for PANDAS and PANS, as well as currently recommended evaluation pathways to rule out other diagnoses with established interventions. Next, we outline the accumulating evidence that neuroinflammation plays a role in these disorders, including work in animal models with patient-derived anti-neuronal autoantibodies and imaging studies showing changes in the basal ganglia. We conclude by providing current treatment recommendations for PANDAS and PANS and an agenda for future research targeting phase-specific mechanisms involved in the development and perpetuation of inflammation.