{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:40:29Z","timestamp":1783539629653,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background\/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive\u2013compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS\/PANDAS. Methods: A structured narrative search of PubMed\/MEDLINE, Embase, the Cochrane Library, Google Scholar\/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein\u2013Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium\/calmodulin-dependent protein kinase II signaling, blood\u2013brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia\/CSTC circuit dysfunction, and gut\u2013oral\u2013brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials.<\/jats:p>","DOI":"10.3390\/idr18040069","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:53:46Z","timestamp":1783418026000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Infection-Associated Pediatric Acute-Onset Neuropsychiatric Syndrome: A Review of Immunological Mechanisms, Clinical Phenotypes, and Therapeutic Strategies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6349-4531","authenticated-orcid":false,"given":"Enoch Chi Ngai","family":"Lim","sequence":"first","affiliation":[{"name":"Translational Research Department, Specialist Medical Services Group, Earlwood, NSW 2206, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-6257","authenticated-orcid":false,"given":"Nga Chong Lisa","family":"Cheng","sequence":"additional","affiliation":[{"name":"Translational Research Department, Specialist Medical Services Group, Earlwood, NSW 2206, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-8154","authenticated-orcid":false,"given":"Chi Eung Danforn","family":"Lim","sequence":"additional","affiliation":[{"name":"Translational Research Department, Specialist Medical Services Group, Earlwood, NSW 2206, Australia"},{"name":"National Institute of Complementary Medicine Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia"},{"name":"Data Science Institute, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1176\/ajp.155.2.264","article-title":"Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases","volume":"155","author":"Swedo","year":"1998","journal-title":"Am. 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