PANDAS AND PANS: PATHOGENESIS, DIAGNOSIS AND TREATMENT OF MYSTERIOUS DISEASES

Authors

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6223

Keywords:

Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections, PANDAS, Pediatric Acute-onset Neuropsychiatric Syndrome, PANS, Neuroinflammation, Autoantibodies, Post-streptococcal Sequelae

Abstract

PANDAS and PANS are rare conditions characterized by rapidly developing neuropsychiatric symptoms such as OCD and tics. To diagnose PANDAS, it is necessary to establish its relationship with group A Streptococcus infection. PANS, on the other hand, includes cases of various etiologies. Despite decades of research, many aspects of these conditions remain unclear.

Aim: The aim of this paper is to review the latest research on the pathogenesis, diagnosis, and treatment of PANS and PANDAS.

Materials and methods: A literature review was conducted using the PubMed and Google Scholar databases, focusing on articles published between 1998 and 2026.

Results: Research indicates that neuroinflammation in the basal ganglia is the cause of PANDAS and PANS development. Specific brain structures and autoantibodies involved in this process have been identified. Despite this, diagnosis of these syndromes remains difficult, and treatment, including antibiotic therapy, psychiatric treatment, and immunomodulatory therapy, is based on limited scientific evidence.

Conclusions: Further research is necessary to expand our understanding of the causes of PANDAS and PANS and to enable more effective diagnosis and treatment of this syndrome.

References

Baj, J., Sitarz, R., Forma, A., Wróblewska, K., & Karakuła-Juchnowicz, H. (2020). Alterations in the Nervous System and Gut Microbiota after β-Hemolytic Streptococcus Group A Infection-Characteristics and Diagnostic Criteria of PANDAS Recognition. International journal of molecular sciences, 21(4), 1476. https://doi.org/10.3390/ijms21041476

Baugh, R. F., Archer, S. M., Mitchell, R. B., Rosenfeld, R. M., Amin, R., Burns, J. J., Darrow, D. H., Giordano, T., Litman, R. S., Li, K. K., Mannix, M. E., Schwartz, R. H., Setzen, G., Wald, E. R., Wall, E., Sandberg, G., Patel, M. M., & American Academy of Otolaryngology-Head and Neck Surgery Foundation (2011). Clinical practice guideline: tonsillectomy in children. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 144(1 Suppl), S1–S30. https://doi.org/10.1177/0194599810389949

Ben-Pazi, H., Stoner, J. A., & Cunningham, M. W. (2013). Dopamine receptor autoantibodies correlate with symptoms in Sydenham's chorea. PloS one, 8(9), e73516. https://doi.org/10.1371/journal.pone.0073516

Board of Directors (2025). Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics, 155(3), e2024070334. https://doi.org/10.1542/peds.2024-070334

Bostan, A. C., & Strick, P. L. (2018). The basal ganglia and the cerebellum: nodes in an integrated network. Nature reviews. Neuroscience, 19(6), 338–350. https://doi.org/10.1038/s41583-018-0002-7

Brilot, F., Merheb, V., Ding, A., Murphy, T., & Dale, R. C. (2011). Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology, 76(17), 1508–1513. https://doi.org/10.1212/WNL.0b013e3182181090

Brouwer, S., Rivera-Hernandez, T., Curren, B. F., Harbison-Price, N., De Oliveira, D. M. P., Jespersen, M. G., Davies, M. R., & Walker, M. J. (2023). Pathogenesis, epidemiology and control of Group A Streptococcus infection. Nature reviews. Microbiology, 21(7), 431–447. https://doi.org/10.1038/s41579-023-00865-7

Brown, K., Farmer, C., Farhadian, B., Hernandez, J., Thienemann, M., & Frankovich, J. (2017). Pediatric Acute-Onset Neuropsychiatric Syndrome Response to Oral Corticosteroid Bursts: An Observational Study of Patients in an Academic Community-Based PANS Clinic. Journal of child and adolescent psychopharmacology, 27(7), 629–639. https://doi.org/10.1089/cap.2016.0139

Brown, K. D., Farmer, C., Freeman, G. M., Jr, Spartz, E. J., Farhadian, B., Thienemann, M., & Frankovich, J. (2017). Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic. Journal of child and adolescent psychopharmacology, 27(7), 619–628. https://doi.org/10.1089/cap.2016.0193

Calaprice, D., Tona, J., Parker-Athill, E. C., & Murphy, T. K. (2017). A Survey of Pediatric Acute-Onset Neuropsychiatric Syndrome Characteristics and Course. Journal of child and adolescent psychopharmacology, 27(7), 607–618. https://doi.org/10.1089/cap.2016.0105

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209.

Cesaroni, C. A., Pisanò, G., Rizzi, S., Pantani, A., Frattini, D., & Fusco, C. (2026). PANDAS Syndrome: A Narrative Review of the Diagnostic Conundrum in Children with Acute Neuropsychiatric Symptoms. International journal of molecular sciences, 27(10), 4612. https://doi.org/10.3390/ijms27104612

Chain, J. L., Alvarez, K., Mascaro-Blanco, A., Reim, S., Bentley, R., Hommer, R., Grant, P., Leckman, J. F., Kawikova, I., Williams, K., Stoner, J. A., Swedo, S. E., & Cunningham, M. W. (2020). Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Frontiers in psychiatry, 11, 564. https://doi.org/10.3389/fpsyt.2020.00564

Cocuzza, S., Maniaci, A., La Mantia, I., Nocera, F., Caruso, D., Caruso, S., Iannella, G., Vicini, C., Privitera, E., Lechien, J. R., & Pavone, P. (2022). Obsessive-Compulsive Disorder in PANS/PANDAS in Children: In Search of a Qualified Treatment-A Systematic Review and Metanalysis. Children (Basel, Switzerland), 9(2), 155. https://doi.org/10.3390/children9020155

Cooperstock, M. S., Swedo, S. E., Pasternack, M. S., & Murphy, T. K. (2017). Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III-Treatment and Prevention of Infections. Journal of child and adolescent psychopharmacology, 27(7), 594–606. https://doi.org/10.1089/cap.2016.0151

Cox, C. J., Sharma, M., Leckman, J. F., Zuccolo, J., Zuccolo, A., Kovoor, A., Swedo, S. E., & Cunningham, M. W. (2013). Brain human monoclonal autoantibody from sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease. Journal of immunology (Baltimore, Md. : 1950), 191(11), 5524–5541. https://doi.org/10.4049/jimmunol.1102592

Cox, C. J., Zuccolo, A. J., Edwards, E. V., Mascaro-Blanco, A., Alvarez, K., Stoner, J., Chang, K., & Cunningham, M. W. (2015). Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder. Journal of child and adolescent psychopharmacology, 25(1), 76–85. https://doi.org/10.1089/cap.2014.0048

Cunningham, M. W., & Cox, C. J. (2016). Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond. Acta physiologica (Oxford, England), 216(1), 90–100. https://doi.org/10.1111/apha.12614

Delice, S., Adaleti, R., Cevan, S., Alagoz, P., Bedel, A., Nuhoglu, C., & Aksaray, S. (2015). Detection of upper limit of normal values of anti-DNase B antibody in children's age groups who were admitted to hospital with noninfectious reasons. Northern clinics of Istanbul, 2(2), 136–141. https://doi.org/10.14744/nci.2015.39358

Dop, D., Marcu, I. R., Padureanu, R., Niculescu, C. E., & Padureanu, V. (2021). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (Review). Experimental and therapeutic medicine, 21(1), 94. https://doi.org/10.3892/etm.2020.9526

Esposito, S., Bianchini, S., Baggi, E., Fattizzo, M., & Rigante, D. (2014). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 33(12), 2105–2109. https://doi.org/10.1007/s10096-014-2185-9

Esposito, S., Masetti, M., Calanca, C., Canducci, N., Rasmi, S., Fradusco, A., & Principi, N. (2025). Recent Changes in the Epidemiology of Group A Streptococcus Infections: Observations and Implications. Microorganisms, 13(8), 1871. https://doi.org/10.3390/microorganisms13081871

Falcini, F., Lepri, G., Rigante, D., Bertini, F., & Matucci Cerinic, M. (2013). PReS-FINAL-2252: Descriptive analysis of pediatric autoimmune neuropsychiatric disorder associated with streptococcus infection (PANDAS) in a cohort of 65 Italian patients. Pediatric Rheumatology, 11(Suppl 2), P242. https://doi.org/10.1186/1546-0096-11-S2-P242

Franklin, M. E., Sapyta, J., Freeman, J. B., Khanna, M., Compton, S., Almirall, D., Moore, P., Choate-Summers, M., Garcia, A., Edson, A. L., Foa, E. B., & March, J. S. (2011). Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial. JAMA, 306(11), 1224–1232. https://doi.org/10.1001/jama.2011.1344

Frankovich, J., Swedo, S., Murphy, T., Dale, R. C., Agalliu, D., Williams, K., Daines, M., Hornig, M., Chugani, H., Sanger, T., Muscal, E., Pasternack, M., Cooperstock, M., Gans, H., Zhang, Y., Cunningham, M., Bernstein, G., Bromberg, R., Willett, T., Brown, K., … Thienemann, M. (2017). Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies. Journal of child and adolescent psychopharmacology, 27(7), 574–593. https://doi.org/10.1089/cap.2016.0148

Frankovich, J., Thienemann, M., Rana, S., & Chang, K. (2015). Five youth with pediatric acute-onset neuropsychiatric syndrome of differing etiologies. Journal of child and adolescent psychopharmacology, 25(1), 31–37. https://doi.org/10.1089/cap.2014.0056

Frick, L. R., Rapanelli, M., Jindachomthong, K., Grant, P., Leckman, J. F., Swedo, S., Williams, K., & Pittenger, C. (2018). Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain, behavior, and immunity, 69, 304–311. https://doi.org/10.1016/j.bbi.2017.12.004

Gagliano, A., Puligheddu, M., Ronzano, N., Congiu, P., Tanca, M. G., Cursio, I., Carucci, S., Sotgiu, S., Grossi, E., & Zuddas, A. (2021). Artificial Neural Networks Analysis of polysomnographic and clinical features in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): from sleep alteration to "Brain Fog". Nature and science of sleep, 13, 1209–1224. https://doi.org/10.2147/NSS.S300818

Garvey, M. A., Perlmutter, S. J., Allen, A. J., Hamburger, S., Lougee, L., Leonard, H. L., ... & Swedo, S. E. (1999). A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biological psychiatry, 45(12), 1564-1571. https://doi.org/10.1016/S0006-3223(99)00020-7

Gaughan, T., Buckley, A., Hommer, R., Grant, P., Williams, K., Leckman, J. F., & Swedo, S. E. (2016). Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 12(7), 1027–1032. https://doi.org/10.5664/jcsm.5942

Giedd, J. N., Rapoport, J. L., Garvey, M. A., Perlmutter, S., & Swedo, S. E. (2000). MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. The American journal of psychiatry, 157(2), 281–283. https://doi.org/10.1176/appi.ajp.157.2.281

Grandinetti, R., Mussi, N., Pilloni, S., Ramundo, G., Miniaci, A., Turco, E., Piccolo, B., Capra, M. E., Forestiero, R., Laudisio, S., Boscarino, G., Pedretti, L., Menoni, M., Pellino, G., Tagliani, S., Bergomi, A., Antodaro, F., Cantù, M. C., Bersini, M. T., Mari, S., … Esposito, S. (2024). Pediatric acute-onset neuropsychiatric syndrome and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections: a delphi study and consensus document about definition, diagnostic criteria, treatment and follow-up. Frontiers in immunology, 15, 1420663. https://doi.org/10.3389/fimmu.2024.1420663

Gromark, C., Harris, R. A., Wickström, R., Horne, A., Silverberg-Mörse, M., Serlachius, E., & Mataix-Cols, D. (2019). Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet. Journal of child and adolescent psychopharmacology, 29(8), 625–633. https://doi.org/10.1089/cap.2018.0127

Gromark, C., Hesselmark, E., Djupedal, I. G., Silverberg, M., Horne, A., Harris, R. A., Serlachius, E., & Mataix-Cols, D. (2022). A Two-to-Five Year Follow-Up of a Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort. Child psychiatry and human development, 53(2), 354–364. https://doi.org/10.1007/s10578-021-01135-4

Hesselmark, E., & Bejerot, S. (2017). Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS) - Sensitivity and specificity of the Cunningham Panel. Journal of neuroimmunology, 312, 31–37. https://doi.org/10.1016/j.jneuroim.2017.09.002

Hsu, C. J., Wong, L. C., & Lee, W. T. (2021). Immunological Dysfunction in Tourette Syndrome and Related Disorders. International journal of molecular sciences, 22(2), 853. https://doi.org/10.3390/ijms22020853

Jan, J. E., Reiter, R. J., Wasdell, M. B., & Bax, M. (2009). The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders. Journal of pineal research, 46(1), 1–7. https://doi.org/10.1111/j.1600-079X.2008.00628.x

Kalinowski, A., Tian, L., Pattni, R., Ollila, H., Khan, M., Manko, C., Silverman, M., Ma, M., Columbo, L., Farhadian, B., Swedo, S., Murphy, T., Johnson, M., Fernell, E., Gillberg, C., Thienemann, M., Mellins, E. D., Levinson, D. F., Urban, A. E., & Frankovich, J. (2023). Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome. Developmental neuroscience, 45(6), 315–324. https://doi.org/10.1159/000531707

Kataoka, Y., Kalanithi, P. S., Grantz, H., Schwartz, M. L., Saper, C., Leckman, J. F., & Vaccarino, F. M. (2010). Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. The Journal of comparative neurology, 518(3), 277–291. https://doi.org/10.1002/cne.22206

Kumar, A., Williams, M. T., & Chugani, H. T. (2015). 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. Journal of child neurology, 30(6), 749–756. https://doi.org/10.1177/0883073814543303

La Bella, S., Scorrano, G., Rinaldi, M., Di Ludovico, A., Mainieri, F., Attanasi, M., Spalice, A., Chiarelli, F., & Breda, L. (2023). Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease. Microorganisms, 11(10), 2549. https://doi.org/10.3390/microorganisms11102549

Latimer, M. E., L'Etoile, N., Seidlitz, J., & Swedo, S. E. (2015). Therapeutic plasma apheresis as a treatment for 35 severely ill children and adolescents with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Journal of child and adolescent psychopharmacology, 25(1), 70–75. https://doi.org/10.1089/cap.2014.0080

Lennington, J. B., Coppola, G., Kataoka-Sasaki, Y., Fernandez, T. V., Palejev, D., Li, Y., Huttner, A., Pletikos, M., Sestan, N., Leckman, J. F., & Vaccarino, F. M. (2016). Transcriptome Analysis of the Human Striatum in Tourette Syndrome. Biological psychiatry, 79(5), 372–382. https://doi.org/10.1016/j.biopsych.2014.07.018

Leonardi, L., Lorenzetti, G., Carsetti, R., Piano Mortari, E., Guido, C. A., Zicari, A. M., Förster-Waldl, E., Loffredo, L., Duse, M., & Spalice, A. (2024). Immunological characterization of an Italian PANDAS cohort. Frontiers in pediatrics, 11, 1216282. https://doi.org/10.3389/fped.2023.1216282

Lepri, G., Rigante, D., Bellando Randone, S., Meini, A., Ferrari, A., Tarantino, G., Cunningham, M. W., & Falcini, F. (2019). Clinical-Serological Characterization and Treatment Outcome of a Large Cohort of Italian Children with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute Neuropsychiatric Syndrome. Journal of child and adolescent psychopharmacology, 29(8), 608–614. https://doi.org/10.1089/cap.2018.0151

Lewin, A. B., Storch, E. A., Mutch, P. J., & Murphy, T. K. (2011). Neurocognitive functioning in youth with pediatric autoimmune neuropsychiatric disorders associated with streptococcus. The Journal of neuropsychiatry and clinical neurosciences, 23(4), 391–398. https://doi.org/10.1176/jnp.23.4.jnp391

Matera, M., Biagioli, V., Illiceto, M. T., Palazzi, C. M., Cavecchia, I., Manzi, A., Lugli, S., Pennazzi, L., Meocci, M., Pedaci, F. A., & Bertuccioli, A. (2025). Pediatric acute-onset neuropsychiatric syndromes and the gut-oral-brain axis: a narrative review of emerging microbiome-immune interactions and therapeutic perspectives. Frontiers in immunology, 16, 1726630. https://doi.org/10.3389/fimmu.2025.1726630

Mehta, N. D., Haroon, E., Xu, X., Woolwine, B. J., Li, Z., & Felger, J. C. (2018). Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results. Brain, behavior, and immunity, 73, 725–730. https://doi.org/10.1016/j.bbi.2018.07.026

Menendez, C. M., Zuccolo, J., Swedo, S. E., Reim, S., Richmand, B., Ben-Pazi, H., Kovoor, A., & Cunningham, M. W. (2024). Dopamine receptor autoantibody signaling in infectious sequelae differentiates movement versus neuropsychiatric disorders. JCI insight, 9(21), e164762. https://doi.org/10.1172/jci.insight.164762

Morris, C. M., Pardo-Villamizar, C., Gause, C. D., & Singer, H. S. (2009). Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls. Journal of the neurological sciences, 276(1-2), 45–48. https://doi.org/10.1016/j.jns.2008.08.032

Morris-Berry, C. M., Pollard, M., Gao, S., Thompson, C., Tourette Syndrome Study Group, & Singer, H. S. (2013). Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with PANDAS and Tourette syndrome: single-point and longitudinal assessments. Journal of neuroimmunology, 264(1-2), 106–113. https://doi.org/10.1016/j.jneuroim.2013.09.010

Murphy, T. K., Brennan, E. M., Johnco, C., Parker-Athill, E. C., Miladinovic, B., Storch, E. A., & Lewin, A. B. (2017). A Double-Blind Randomized Placebo-Controlled Pilot Study of Azithromycin in Youth with Acute-Onset Obsessive-Compulsive Disorder. Journal of child and adolescent psychopharmacology, 27(7), 640–651. https://doi.org/10.1089/cap.2016.0190

Murphy, T. K., Lewin, A. B., Parker-Athill, E. C., Storch, E. A., & Mutch, P. J. (2013). Tonsillectomies and adenoidectomies do not prevent the onset of pediatric autoimmune neuropsychiatric disorder associated with group A streptococcus. The Pediatric infectious disease journal, 32(8), 834–838. https://doi.org/10.1097/INF.0b013e31829062e2

Murphy, T. K., Storch, E. A., Lewin, A. B., Edge, P. J., & Goodman, W. K. (2012). Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The Journal of pediatrics, 160(2), 314–319. https://doi.org/10.1016/j.jpeds.2011.07.012

Nadeau, J. M., Jordan, C., Selles, R. R., Wu, M. S., King, M. A., Patel, P. D., Hanks, C. E., Arnold, E. B., Lewin, A. B., Murphy, T. K., & Storch, E. A. (2015). A pilot trial of cognitive-behavioral therapy augmentation of antibiotic treatment in youth with pediatric acute-onset neuropsychiatric syndrome-related obsessive-compulsive disorder. Journal of child and adolescent psychopharmacology, 25(4), 337–343. https://doi.org/10.1089/cap.2014.0149

Obregon, D., Parker-Athill, E. C., Tan, J., & Murphy, T. (2012). Psychotropic effects of antimicrobials and immune modulation by psychotropics: implications for neuroimmune disorders. Neuropsychiatry, 2(4), 331–343. https://doi.org/10.2217/npy.12.41

Oshima, T., Sasaki, M., Kataoka, H., Miwa, H., Takeuchi, T., & Joh, T. (2007). Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction. Cellular and molecular life sciences : CMLS, 64(23), 3139–3147. https://doi.org/10.1007/s00018-007-7268-7

Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014). Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nature reviews. Neuroscience, 15(6), 410–424.

Pavone, P., Rapisarda, V., Serra, A., Nicita, F., Spalice, A., Parano, E., Rizzo, R., Maiolino, L., Di Mauro, P., Vitaliti, G., Coco, A., Falsaperla, R., Trifiletti, R. R., & Cocuzza, S. (2014). Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment. International journal of immunopathology and pharmacology, 27(3), 371–378. https://doi.org/10.1177/039463201402700307

Pellegrini, C., Antonioli, L., Calderone, V., Colucci, R., Fornai, M., & Blandizzi, C. (2020). Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?. Progress in neurobiology, 191, 101806. https://doi.org/10.1016/j.pneurobio.2020.101806

Pelzer, E. A., Melzer, C., Timmermann, L., von Cramon, D. Y., & Tittgemeyer, M. (2017). Basal ganglia and cerebellar interconnectivity within the human thalamus. Brain structure & function, 222(1), 381–392. https://doi.org/10.1007/s00429-016-1223-z

Perlmutter, S. J., Leitman, S. F., Garvey, M. A., Hamburger, S., Feldman, E., Leonard, H. L., & Swedo, S. E. (1999). Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet (London, England), 354(9185), 1153–1158. https://doi.org/10.1016/S0140-6736(98)12297-3

Prosell, U., Norman, H., Sand, A., & McAllister, A. (2022). Infection and speech: Disfluency and other speech symptoms in Pediatric Acute-onset Neuropsychiatric Syndrome. Journal of communication disorders, 99, 106250. https://doi.org/10.1016/j.jcomdis.2022.106250

Quagliariello, A., Del Chierico, F., Russo, A., Reddel, S., Conte, G., Lopetuso, L. R., Ianiro, G., Dallapiccola, B., Cardona, F., Gasbarrini, A., & Putignani, L. (2018). 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. Frontiers in microbiology, 9, 675. https://doi.org/10.3389/fmicb.2018.00675

Rojas, M., Restrepo-Jiménez, P., Monsalve, D. M., Pacheco, Y., Acosta-Ampudia, Y., Ramírez-Santana, C., Leung, P. S. C., Ansari, A. A., Gershwin, M. E., & Anaya, J. M. (2018). Molecular mimicry and autoimmunity. Journal of autoimmunity, 95, 100–123. https://doi.org/10.1016/j.jaut.2018.10.012

Sankar, S. B., Pybus, A. F., Liew, A., Sanders, B., Shah, K. J., Wood, L. B., & Buckley, E. M. (2019). Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury. Neurobiology of disease, 124, 544–554. https://doi.org/10.1016/j.nbd.2018.12.018

Shaik, S. M., Schiro, G., Laubitz, D., Madan, J. C., Kelley, C. P., Daines, M., Rice, S. A., Ghishan, F. K., & Kiela, P. R. (2026). Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). Microorganisms, 14(5), 1036. https://doi.org/10.3390/microorganisms14051036

Shimasaki, C., Frye, R. E., Trifiletti, R., Cooperstock, M., Kaplan, G., Melamed, I., Greenberg, R., Katz, A., Fier, E., Kem, D., Traver, D., Dempsey, T., Latimer, M. E., Cross, A., Dunn, J. P., Bentley, R., Alvarez, K., Reim, S., & Appleman, J. (2020). Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms. Journal of neuroimmunology, 339, 577138. https://doi.org/10.1016/j.jneuroim.2019.577138

Sigra, S., Hesselmark, E., & Bejerot, S. (2018). Treatment of PANDAS and PANS: a systematic review. Neuroscience and biobehavioral reviews, 86, 51–65. https://doi.org/10.1016/j.neubiorev.2018.01.001

Silva-Costa, C., Friães, A., Ramirez, M., & Melo-Cristino, J. (2015). Macrolide-resistant Streptococcus pyogenes: prevalence and treatment strategies. Expert review of anti-infective therapy, 13(5), 615–628. https://doi.org/10.1586/14787210.2015.1023292

Snider, L. A., Lougee, L., Slattery, M., Grant, P., & Swedo, S. E. (2005). Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biological psychiatry, 57(7), 788–792. https://doi.org/10.1016/j.biopsych.2004.12.035

Spartz, E. J., Freeman Jr, G. M., Brown, K., Farhadian, B., Thienemann, M., & Frankovich, J. (2017). Course of neuropsychiatric symptoms after introduction and removal of nonsteroidal anti-inflammatory drugs: a pediatric observational study. Journal of Child and Adolescent Psychopharmacology, 27(7), 652-659. https://doi.org/10.1089/cap.2016.0179

Storch, E. A., Murphy, T. K., Geffken, G. R., Mann, G., Adkins, J., Merlo, L. J., Duke, D., Munson, M., Swaine, Z., & Goodman, W. K. (2006). Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial. Journal of the American Academy of Child and Adolescent Psychiatry, 45(10), 1171–1178. https://doi.org/10.1097/01.chi.0000231973.43966.a0

Swedo, S. E., Frankovich, J., & Murphy, T. K. (2017). Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. Journal of child and adolescent psychopharmacology, 27(7), 562–565. https://doi.org/10.1089/cap.2017.0042

Swedo, S. E., Leckman, J. F., & Rose, N. R. (2012). From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Therapeut, 2(2), 113. https://doi.org/10.4172/2161-0665.1000113

Swedo, S. E., Leonard, H. L., Garvey, M., Mittleman, B., Allen, A. J., Perlmutter, S., Lougee, L., Dow, S., Zamkoff, J., & Dubbert, B. K. (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. The American journal of psychiatry, 155(2), 264–271. https://doi.org/10.1176/ajp.155.2.264

Swedo, S., Menendez, C. M., & Cunningham, M. W. (2024). Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). In J. J. Ferretti (Eds.) et. al., Streptococcus pyogenes: Basic Biology to Clinical Manifestations. (2nd ed.). University of Oklahoma Health Sciences Center.

Swedo, S. E., Seidlitz, J., Kovacevic, M., Latimer, M. E., Hommer, R., Lougee, L., & Grant, P. (2015). Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. Journal of child and adolescent psychopharmacology, 25(1), 26–30. https://doi.org/10.1089/cap.2014.0073

Teixeira, A. L., Rodrigues, D. H., Marques, A. H., Miguel, E. C., & Fontenelle, L. F. (2014). Searching for the immune basis of obsessive-compulsive disorder. Neuroimmunomodulation, 21(2-3), 152–158. https://doi.org/10.1159/000356554

Trifiletti, R., Lachman, H. M., Manusama, O., Zheng, D., Spalice, A., Chiurazzi, P., Schornagel, A., Serban, A. M., van Wijck, R., Cunningham, J. L., Swagemakers, S., & van der Spek, P. J. (2022). Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing. Scientific reports, 12(1), 11106. https://doi.org/10.1038/s41598-022-15279-3

Vendhan, K., Bray, T. J., Atkinson, D., Punwani, S., Fisher, C., Sen, D., Ioannou, Y., & Hall-Craggs, M. A. (2016). A diffusion-based quantification technique for assessment of sacroiliitis in adolescents with enthesitis-related arthritis. The British journal of radiology, 89(1059), 20150775. https://doi.org/10.1259/bjr.20150775

Vreeland, A., Thienemann, M., Cunningham, M., Muscal, E., Pittenger, C., & Frankovich, J. (2023). Neuroinflammation in Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome. The Psychiatric clinics of North America, 46(1), 69–88. https://doi.org/10.1016/j.psc.2022.11.004

Wald, E. R., Eickhoff, J., Flood, G. E., Heinz, M. V., Liu, D., Agrawal, A., Morse, R. P., Raney, V. M., Veerapandiyan, A., & Madan, J. C. (2023). Estimate of the incidence of PANDAS and PANS in 3 primary care populations. Frontiers in pediatrics, 11, 1170379. https://doi.org/10.3389/fped.2023.1170379

Wilbur, C., Bitnun, A., Kronenberg, S., Laxer, R. M., Levy, D. M., Logan, W. J., Shouldice, M., & Yeh, E. A. (2019). PANDAS/PANS in childhood: Controversies and evidence. Paediatrics & child health, 24(2), 85–91. https://doi.org/10.1093/pch/pxy145

Williams, K. A., Swedo, S. E., Farmer, C. A., Grantz, H., Grant, P. J., D'Souza, P., Hommer, R., Katsovich, L., King, R. A., & Leckman, J. F. (2016). Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. Journal of the American Academy of Child and Adolescent Psychiatry, 55(10), 860–867.e2. https://doi.org/10.1016/j.jaac.2016.06.017

Xu, J., Liu, R. J., Fahey, S., Frick, L., Leckman, J., Vaccarino, F., Duman, R. S., Williams, K., Swedo, S., & Pittenger, C. (2021). Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. The American journal of psychiatry, 178(1), 48–64. https://doi.org/10.1176/appi.ajp.2020.19070698

Xu, M., Kobets, A., Du, J. C., Lennington, J., Li, L., Banasr, M., Duman, R. S., Vaccarino, F. M., DiLeone, R. J., & Pittenger, C. (2015). Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proceedings of the National Academy of Sciences of the United States of America, 112(3), 893–898. https://doi.org/10.1073/pnas.1419533112

Zheng, J., Frankovich, J., McKenna, E. S., Rowe, N. C., MacEachern, S. J., Ng, N. N., Tam, L. T., Moon, P. K., Gao, J., Thienemann, M., Forkert, N. D., & Yeom, K. W. (2020). Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging. JAMA network open, 3(5), e204063. https://doi.org/10.1001/jamanetworkopen.2020.4063

Downloads

Published

2026-09-28

How to Cite

Gąbka, M., Cieślik, A., Cieślik-Porębska , M. ., Cieślik, A. A., Cichocka, A. ., & Pelc, J. . (2026). PANDAS AND PANS: PATHOGENESIS, DIAGNOSIS AND TREATMENT OF MYSTERIOUS DISEASES. International Journal of Innovative Technologies in Social Science, 5(3(51). https://doi.org/10.31435/ijitss.3(51).2026.6223

Most read articles by the same author(s)