PANDAS and PANS: Pathophysiology, Diagnostics and Therapeutic Approaches in Pediatric Autoimmune Neuropsychiatric Disorders – a literature review
DOI:
https://doi.org/10.12775/JEHS.2025.79.57830Keywords
PANDAS, PANS, Obsessive-Compulsive Disorder, Group A Streptococcus, Neuroinflammatory DiseaseAbstract
Introduction and Purpose
PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) and PANS (pediatric acute-onset neuropsychiatric syndrome) are neuropsychiatric disorders that have been debated since their first descriptions. PANDAS is linked to Group A Streptococcus (GAS) infections and is characterized by the sudden onset of symptoms such as OCD and tics after GAS infection. PANS involves a broader spectrum of symptoms without a specific GAS trigger. Both conditions are under-researched, and diagnosing and treating them is challenging. This article summarizes the current knowledge on PANDAS and PANS, focusing on their etiology, diagnosis, and treatment.
Description of the State of Knowledge
PANDAS and PANS are marked by the sudden onset of OCD or severe food intake restrictions, alongside other neuropsychiatric symptoms. Clinical criteria for PANDAS were proposed in 1998, linking it to GAS infections, and in 2012, broader PANS criteria were introduced, expanding the possible causes. The pathophysiology remains unclear, with theories suggesting autoimmune processes or neuroinflammation. Diagnosis is complicated by symptom overlap with other disorders. Treatment often involves a multidisciplinary approach, including behavioral therapy and, in some cases, antibiotics for GAS infections. The effectiveness of immunomodulatory therapies remains debated.
Conclusions
PANDAS and PANS are complex disorders with sudden-onset symptoms, but diagnosing them is difficult due to unclear pathophysiology and overlapping symptoms. Further research is needed to better understand the underlying mechanisms and improve diagnostic and therapeutic approaches.
References
1. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases [published correction appears in Am J Psychiatry 1998 Apr;155(4):578]. Am J Psychiatry. 1998;155(2):264-271. doi:10.1176/ajp.155.2.264
2. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2):113.
3. Wald ER, Eickhoff J, Flood GE, et al. Estimate of the incidence of PANDAS and PANS in 3 primary care populations. Front Pediatr. 2023;11:1170379. Published 2023 Sep 21. doi:10.3389/fped.2023.1170379
4. McClelland M, Crombez MM, Crombez C, et al. Implications for Advanced Practice Nurses When Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Is Suspected: A Qualitative Study. J Pediatr Health Care. 2015;29(5):442-452. doi:10.1016/j.pedhc.2015.03.005
5. Swedo SE. Sydenham's chorea. A model for childhood autoimmune neuropsychiatric disorders. JAMA. 1994;272(22):1788-1791. doi:10.1001/jama.272.22.1788
6. Martino D, Giovannoni G. Antibasal ganglia antibodies and their relevance to movement disorders. Curr Opin Neurol. 2004;17(4):425-432. doi:10.1097/01.wco.0000137532.76491.19
7. Brilot F, Merheb V, Ding A, Murphy T, Dale RC. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology. 2011;76(17):1508-1513. doi:10.1212/WNL.0b013e3182181090
8. Singer HS, Hong JJ, Yoon DY, Williams PN. Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology. 2005;65(11):1701-1707. doi:10.1212/01.wnl.0000183223.69946.f1
9. Xu J, Liu RJ, Fahey S, et al. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. Am J Psychiatry. 2021;178(1):48-64. doi:10.1176/appi.ajp.2020.19070698
10. Xu J, Frankovich J, Liu RJ, et al. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome. Brain Behav Immun. 2024;122:241-255. doi:10.1016/j.bbi.2024.07.044
11. Zheng J, Frankovich J, McKenna ES, et al. Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging. JAMA Netw Open. 2020;3(5):e204063. Published 2020 May 1. doi:10.1001/jamanetworkopen.2020.4063
12. Cox CJ, Zuccolo AJ, Edwards EV, et al. Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2015;25(1):76-85. doi:10.1089/cap.2014.0048
13. Cunningham MW, Cox CJ. Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond. Acta Physiol (Oxf). 2016;216(1):90-100. doi:10.1111/apha.12614
14. Menendez CM, Zuccolo J, Swedo SE, et al. Dopamine receptor autoantibody signaling in infectious sequelae differentiates movement versus neuropsychiatric disorders. JCI Insight. 2024;9(21):e164762. Published 2024 Nov 8. doi:10.1172/jci.insight.164762
15. Kalinowski A, Tian L, Pattni R, et al. Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome. Dev Neurosci. 2023;45(6):315-324. doi:10.1159/000531707
16. Quagliariello A, Del Chierico F, Russo A, et al. Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. Front Microbiol. 2018;9:675. Published 2018 Apr 6. doi:10.3389/fmicb.2018.00675
17. La Bella S, Attanasi M, Di Ludovico A, et al. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Syndrome: A 10-Year Retrospective Cohort Study in an Italian Centre of Pediatric Rheumatology. Microorganisms. 2023;12(1):8. Published 2023 Dec 19. doi:10.3390/microorganisms12010008
18. Swedo SE, Seidlitz J, Kovacevic M, et al. Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. J Child Adolesc Psychopharmacol. 2015;25(1):26-30. doi:10.1089/cap.2014.0073
19. Chang K, Frankovich J, Cooperstock M, et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol. 2015;25(1):3-13. doi:10.1089/cap.2014.00841
20. Murphy TK, Patel PD, McGuire JF, et al. Characterization of the pediatric acute-onset neuropsychiatric syndrome phenotype. J Child Adolesc Psychopharmacol. 2015;25(1):14-25. doi:10.1089/cap.2014.0062
21. American Academy of Pediatrics Board of Directors . Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. Published online December 16, 2024. doi:10.1542/peds.2024-070334
22. Lougee L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE. Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). J Am Acad Child Adolesc Psychiatry. 2000;39(9):1120-1126. doi:10.1097/00004583-200009000-00011
23. Murphy TK, Storch EA, Turner A, Reid JM, Tan J, Lewin AB. Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder. J Neuroimmunol. 2010;229(1-2):243-247. doi:10.1016/j.jneuroim.2010.08.017
24. Hutanu A, Reddy LN, Mathew J, Avanthika C, Jhaveri S, Tummala N. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges. Cureus. 2022;14(8):e27729. Published 2022 Aug 6. doi:10.7759/cureus.27729
25. Giedd JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE. MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. Am J Psychiatry. 2000;157(2):281-283. doi:10.1176/appi.ajp.157.2.281
26. Kumar A, Williams MT, Chugani HT. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and tourette syndrome: a positron emission tomographic (PET) study using 11C-[R]-PK11195. J Child Neurol. 2015;30(6):749-756. doi:10.1177/0883073814543303
27. Swedo SE, Frankovich J, Murphy TK. Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. J Child Adolesc Psychopharmacol. 2017;27(7):562-565. doi:10.1089/cap.2017.0042
28. Thienemann M, Murphy T, Leckman J, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I-Psychiatric and Behavioral Interventions. J Child Adolesc Psychopharmacol. 2017;27(7):566-573. doi:10.1089/cap.2016.0145
29. Franklin ME, Sapyta J, Freeman JB, et al. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial [published correction appears in JAMA. 2012 Apr 25;307(16):1694]. JAMA. 2011;306(11):1224-1232. doi:10.1001/jama.2011.1344
30. Sukhodolsky DG, Woods DW, Piacentini J, et al. Moderators and predictors of response to behavior therapy for tics in Tourette syndrome. Neurology. 2017;88(11):1029-1036. doi:10.1212/WNL.0000000000003710
31. Toufexis MD, Hommer R, Gerardi DM, et al. Disordered eating and food restrictions in children with PANDAS/PANS. J Child Adolesc Psychopharmacol. 2015;25(1):48-56. doi:10.1089/cap.2014.0063
32. Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neurosci Biobehav Rev. 2018;86:51-65. doi:10.1016/j.neubiorev.2018.01.001
33. Cooperstock MS, Swedo SE, Pasternack MS, Murphy TK. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III-Treatment and Prevention of Infections. J Child Adolesc Psychopharmacol. 2017;27(7):594-606. doi:10.1089/cap.2016.0151
34. Frankovich J, Thienemann M, Pearlstein J, Crable A, Brown K, Chang K. Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients. J Child Adolesc Psychopharmacol. 2015;25(1):38-47. doi:10.1089/cap.2014.0081
35. Frankovich J, Swedo S, Murphy T, et al. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies. J Child Adolesc Psychopharmacol. 2017;27(7):574-593. doi:10.1089/cap.2016.0148
36. Williams KA, Swedo SE, Farmer CA, et al. Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. J Am Acad Child Adolesc Psychiatry. 2016;55(10):860-867.e2. doi:10.1016/j.jaac.2016.06.017
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