Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities

Abstract

Pediatric acute-onset neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), represent an overlapping group of disorders which is characterized by acute-onset obsessive compulsive disorders, eating restriction, tics, cognitive and behavioral deterioration which typically follows a relapsing-remitting course but some patients have a primary or secondary persistent progress. This condition is likely caused by heterogeneous inflammatory mechanisms (autoantibodies, complement activation, pro-inflammatory cytokine production) involving the basal ganglia as evidenced by imaging studies (patients vs. controls), sleep studies that found movements and/or atonia during REM sleep, and neurological soft signs that go along with basal ganglia dysfunction. The condition causes significant psychiatric and behavioral symptoms, caregiver burden and sleep abnormalities. Autoantibodies resulting from molecular mimicry of infectious agents (namely group A Streptococcus) and neuronal autoantigens that map to the basal ganglia play also a subtle role. This narrative review aims to describe the key immunological features documented thus far and that likely play a role in the pathogenesis and clinical manifestations of this disorder.

Keywords: IL-17; PANDAS; PANS; autoantibodies; autoimmune diseases; immunological features.

Figure 1

PANS/PANDAS overlapping criteria. GABHS = Group A Streptococcus Infection. PANS criteria are agnostic to infection but cases may be temporally associated with GABHS. PANDAS Criteria require that the condition is temporarily associated with GABHS; however, these criteria miss cases since patients often present after the window of opportunity to detect GABHS. These criteria are good for research but not practical for clinical care. Patients with abrupt-onset tics (when associated with GABHS) may satisfy PANDAS criteria but not PANS criteria. Patients with abrupt-onset eating restriction (regardless of the infectious trigger) satisfy PANS criteria but not PANDAS criteria. Both conditions are generally relapsing/remitting. PANS criteria require at least 2 other abrupt-onset neuropsychiatric symptoms in addition to OCD and or eating restriction but PANDAS criteria do not require adjunct symptoms. The PANS and PANDAS criteria strongly overlap since abrupt-onset OCD and preceding GABHS are highly prevalent in cohorts of patients meeting these criteria.