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

Leonardi L, Perna C, Bernabei I, Fiore M, Ma M, Frankovich J, Tarani L, Spalice A. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children. 2024; 11(9):1043. https://doi.org/10.3390/children11091043

• PANS and PANDAS are overlapping neuroimmune conditions involving post-infectious inflammation, autoimmunity, and basal ganglia dysfunction, leading to OCD, eating restriction, tics, and cognitive/behavioral changes.
• Evidence points to immune dysregulation (autoantibodies, cytokines like IL-17, microglial activation) and blood–brain barrier disruption, allowing peripheral immune signals to affect the brain.
• The disorders often follow a relapsing-remitting course, though some patients develop persistent symptoms, reflecting ongoing inflammatory activity.
• Multiple triggers are implicated beyond strep, including other infections, environmental factors, and possibly gut microbiome changes, reinforcing a broader neuroimmune model.
• Findings suggest PANS/PANDAS may be part of a systemic inflammatory process, not just a psychiatric condition, with links to autoimmune features and other inflammatory diseases.
• While evidence supports an immune-mediated mechanism, research gaps, diagnostic challenges, and controversy remain, highlighting the need for better biomarkers and larger, rigorous studies.