Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder

Abstract

Post-infectious neuroinflammation has been implicated in multiple models of acute onset obsessive-compulsive disorder (OCD) including Sydenham’s chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by an infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

Prevalence of Neurological Soft Signs at Presentation in Pediatric Acute-Onset Neuropsychiatric Syndrome

“…Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are abrupt-onset neuropsychiatric disorders thought to be triggered by infection. 1,2 Basal ganglia inflammation may be an important mechanism in these disorders based on imaging studies demonstrating basal ganglia swelling in the acute stage, 3 microglia activation in the caudate and putamen, 4 and microstructural changes which are most prominent in the basal ganglia. 5,6 Additionally, sleep studies in this patient population indicating movements during rapid eye movement (REM) sleep [7][8][9] implicate basal ganglia pathology.…”

Ultrarare Variants in DNA Damage Repair Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome or Acute Behavioral Regression in Neurodevelopmental Disorders

“…While the criteria require 2 secondary symptoms, most patients have 5 to 6 secondary symptoms that start abruptly alongside the OCD and/or eating restriction. Autonomic instability (POTS, dilated pupils, increased urinary frequency, enuresis) and hypermobility have also been reported as co-morbid with PANS [13][14][15][16][17][18] . A deterioration in school performance occurs, exemplified by the loss of previously learned skills and/or new onset procedural learning challenges presumably relating to the basal ganglia inflammation PANS [9][10][11][12]19 .…”