Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence

Vicente Manuel Martínez Cárdenas

doi:doi:10.11648/j.frontiers.20250504.16

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Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence

Vicente Manuel Martínez Cárdenas^*

Published in Frontiers (Volume 5, Issue 4)

Received: 25 October 2025 Accepted: 4 November 2025 Published: 19 December 2025

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Abstract

Background: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are neuropsychiatric disorders characterized by abrupt onset or exacerbation of symptoms such as obsessive-compulsive behaviors, tics or severely restricted eating, often following infection. HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC11430956/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Proposed pathophysiological mechanisms include immune-mediated inflammation targeting the basal ganglia, with structural and functional alterations in these subcortical nuclei. Objectives: To review and synthesise the available literature (2013-2025) addressing the persistence of basal ganglia dysfunction (neuroanatomical, immunological and clinical) in PANS/PANDAS, and to identify gaps and implications for diagnosis and treatment. Methods: A narrative review of PubMed, Scopus, Web of Science, and Embase (January 2013-September 2025) was conducted using English and Spanish keywords: (“PANS” OR “PANDAS” OR “pediatric acute-onset neuropsychiatric syndrome” OR “pediatric autoimmune neuropsychiatric disorders”) AND (“basal ganglia” OR “autoantibodies” OR “neuroinflammation”). Titles and abstracts were screened manually, and eligible studies underwent full-text qualitative synthesis. Original articles, systematic reviews, meta-analyses, case series, and case reports addressing basal ganglia involvement in PANS/PANDAS were included. Data concerning neuroimaging findings, neurological soft signs, autoantibodies, and therapeutic outcomes were extracted and qualitatively analyzed. Results: Persistent abnormalities in the caudate nucleus and putamen have been documented, including volume enlargement and microstructural alterations, consistent with ongoing basal ganglia involvement. Functional neuroimaging (PET, SPECT) demonstrates hypoactivity or hypoperfusion in motor and emotional control regions of the basal ganglia. Immunological studies reveal autoantibodies targeting cholinergic interneurons in the striatum, along with microglial activation and blood-brain barrier disruption in animal models. Neurological soft signs (NSS) such as overflow movements have been reported in related basal-ganglia disorders, though their prevalence in PANS/PANDAS remains under-investigated. Heterogeneity in methodologies, small sample sizes and variable effect sizes limit generalisability of findings. HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC10609001/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Conclusions: The accumulated evidence supports a persistent, immune-mediated basal ganglia dysfunction underlying the clinical manifestations of PANS/PANDAS. Recognition of this involvement provides crucial pathophysiological insight and strengthens the rationale for early immunomodulatory and neuro-targeted interventions such as corticosteroids, IVIG, and plasmapheresis in selected cases. Nevertheless, well-designed prospective and controlled studies are needed to validate diagnostic biomarkers, quantify the prevalence and prognostic significance of neurological soft signs, and define standardized clinical and imaging endpoints that can guide future therapeutic trials and evidence-based management protocols.

Published in	Frontiers (Volume 5, Issue 4)
DOI	10.11648/j.frontiers.20250504.16
Page(s)	205-215
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

PANS, PANDAS, Basal Ganglia, Autoantibodies, Neurological Soft Signs (NSS)

References

[1]	Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998; 155(2): 264-271. https://doi.org/10.1176/ajp.155.2.264
[2]	Murphy TK, Gerardi DM, Leckman JF. Pediatric acute-onset neuropsychiatric syndrome (PANS). Psychiatr Clin North Am. 2014; 37(3): 353-74. Available from: https://doi.org/10.1016/j.psc.2014.06.001
[3]	American Academy of Pediatrics. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. 2025; 155(3): e2024070334. Available from: https://doi.org/10.1542/peds.2024-070334
[4]	Frick L, Pittenger C. Microglial dysregulation in OCD, Tourette syndrome, and PANDAS. J Immunol Res. 2016; 2016: 8606057. https://doi.org/10.1155/2016/8606057
[5]	Zheng J, Frankovich J, McKenna ES, Rowe NC, MacEachern SJ, Ng NN, 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. https://doi.org/10.1001/jamanetworkopen.2020.4063
[6]	Lázaro L, Calvo A, Ortiz AG, Andiarena A, Bargalló N, Morer A, et al. Microstructural brain abnormalities and symptom dimensions in child and adolescent patients with obsessive-compulsive disorder: a diffusion tensor imaging study. Depress Anxiety. 2014; 31(12): 1007-1017. https://doi.org/10.1002/da.22330
[7]	Gaughan T, Buckley A, Hommer R, Grant P, Williams K, Leckman JF, Swedo SE. Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). J Clin Sleep Med. 2016; 12(7): 1027-1032. https://doi.org/10.5664/jcsm.5900
[8]	Santoro JD, Frankovich J, Bhargava S. Continued presence of period limb movements during REM sleep in patients with chronic static Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). J Clin Sleep Med. 2018; 14(7): 1187-1192. https://doi.org/10.5664/jcsm.7222
[9]	Congiu P, Gagliano A, Carucci S, Lanza G, Ferri R, Puligheddu M. REM sleep atonia in patients with pediatric acute-onset neuropsychiatric syndrome: implications for pathophysiology. J Clin Sleep Med. 2025; 21(5): 757-764. https://doi.org/10.5664/jcsm.11544
[10]	Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013; 14(8): 744-748. https://doi.org/10.1016/j.sleep.2012.10.009
[11]	Kaiserova M, Grambalova Z, Kurcova S, Otruba P, Prikrylova Vranova H, Mensikova K, Kanovsky P. Premotor Parkinson's disease: overview of clinical symptoms and current diagnostic methods. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2021; 165(2): 103-112. https://doi.org/10.5507/bp.2021.002
[12]	Lewis MM, Harkins E, Lee EY, Stetter C, Snyder B, Corson T, Du G, Kong L, Huang X. Clinical progression of Parkinson's disease: insights from the NINDS Common Data Elements. J Parkinsons Dis. 2020; 10(3): 1075-85. https://doi.org/10.3233/JPD-201932
[13]	Postuma RB, Gagnon JF, Montplaisir J. REM sleep behavior disorder and prodromal neurodegeneration - Where are we headed? Nat Rev Neurol. 2013; 9(1): 40-49. https://doi.org/10.1038/nrneurol.2012.80
[14]	Xu J, Frankovich J, Liu RJ, Lee D, Bhargava S, Santoro JD, et al. Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome. Brain Behav Immun. 2024; 122: 241-255. https://doi.org/10.1016/j.bbi.2024.07.044
[15]	Chain JL, Alvarez K, Mascaro-Blanco A, Reim S, Bentley R, Hommer R, et al. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Front Psychiatry. 2020; 11: 564. https://doi.org/10.3389/fpsyt.2020.00564
[16]	La Bella S, Scorrano G, Rinaldi M, Di Ludovico A, Mainieri F, Attanasi M, et al. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease. Microorganisms. 2023; 11(10): 2549. https://doi.org/10.3390/microorganisms11102549
[17]	Dileepan T, Smith ED, Knowland D, Hsu M, Platt M, Bittner-Eddy P, et al. Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells. J Clin Invest. 2016; 126(1): 303-317. https://doi.org/10.1172/JCI80792
[18]	Eremija J, Patel S, Rice S, Daines M. Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome. Front Pediatr. 2023; 11: 1229150. https://doi.org/10.3389/fped.2023.1229150
[19]	Grandinetti R, Mussi N, Pilloni S, Ramundo G, Miniaci A, Turco E, et al. 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. Front Immunol. 2024; 15: 1420663. https://doi.org/10.3389/fimmu.2024.1420663
[20]	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 (Basel).2024; 11(9): 1043. https://doi.org/10.3390/children11091043
[21]	Swedo SE, Frankovich J, Murphy TK. Overview of treatment of pediatric acute-onset neuropsychiatric syndrome. J Child Adolesc Psychopharmacol. 2017; 27(7): 562-5. https://doi.org/10.1089/cap.2017.0042
[22]	Masterson EE, Miles K, Schlenk N, Manko C, Ma M, Farhadian B, et al. Defining clinical course of patients evaluated for pediatric acute-onset neuropsychiatric syndrome: phenotypic classification based on 10 years of clinical data. Dev Neurosci. 2025. https://doi.org/10.1159/000545598
[23]	Zych K, Burdan O, Ziomek WN, Białek AB, Wróbel J, Cieślik-Porębska M, et al. Current knowledge of PANDAS and PANS syndromes in paediatric patients - etiology, diagnosis and therapies. J Pre-Clin Clin Res. 2024; 18(4): 324-332. https://doi.org/10.26444/jpccr/193989
[24]	ASPIRE. ADHD-like symptoms & PANS/PANDAS. Aspire Care; c2023 [cited 2025 Jun 9]. Available from: https://aspire.care/families-parents-caregivers/adhd-pans-pandas/
[25]	Psychiatry Redefined. Sudden onset of obsessive-compulsive disorder and other mental health conditions in children: an overview of PANS/PANDAS. Psychiatry Redefined; 2025 Jul 3 [cited 2025 Jun 9]. Available from: https://www.psychiatryredefined.org/sudden-onset-of-obsessive-compulsive-disorder-and-other-mental-health-conditions-in-children-an-overview-of-pans-pandas/
[26]	Wang M, Yu J, Kim HD, Bautista Cruz A. Neural correlates of executive function and attention in children with ADHD: an ALE meta-analysis of task-based functional connectivity studies. Psychiatry Res. 2025; 345: 116338. https://doi.org/10.1016/j.psychres.2024.116338
[27]	Thorsson M, Galazka MA, Johnson M, Boersma M, Falkmer M. Visuomotor tracking strategies in children: associations with neurodevelopmental symptoms. Exp Brain Res. 2024; 242: 337-53. https://doi.org/10.1007/s00221-023-06752-0
[28]	LaRusso MD, Abadía-Barrero C. Developmental Impacts of PANS/PANDAS and Inadequate Support for Children and Families. Child Psychiatry Hum Dev. 2024; Jun 14. https://doi.org/10.1007/s10578-024-01723-0
[29]	Zebrack JE, Gao J, Verhey B, Tian L, Stave C, Farhadian B, Ma M, Silverman M, Xie Y, Tran P, Thienemann M, Wilson JL, Frankovich J. Prevalence of Neurological Soft Signs at Presentation in Patients With Pediatric Acute-Onset Neuropsychiatric Syndrome. JAMA Netw Open. 2024; 7(11): e2411166. https://doi.org/10.1001/jamanetworkopen.2024.11166
[30]	Gerez-Malo M, Tello A, Martín-Salas MJ, Castanedo L, Mendizábal A, Meneses Luna O, et al. Neurophysiological findings in Attention Deficit Hyperactivity Disorder, a Pandora’s box with therapeutic implications. Explor Neuroprot Ther. 2025; 5: 100499. https://doi.org/10.37349/ent.2025.100499
[31]	Prato G, Gulisano M, Scerbo S, Barone R, Vicario CM, Rizzo R. Diagnostic Approach to Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS): A Narrative Review of Literature Data. Front Pediatr. 2021; 9: 746639. https://doi.org/10.3389/fped.2021.746639
[32]	Eddy CM. Basal ganglia contributions to social cognition: evidence from movement disorders. Cogn Neuropsychiatry. 2025 Jan; 30(1): 1-14. https://doi.org/10.1080/13546805.2025.2490054
[33]	Longo R, Allegrini F, Gusson E, Morbio R, Di Gennaro G, Gozzi LA, Marchini G, Zoccante L. Visual-motor involvement in autism spectrum disorder: could the stereopsis deficit affect motor coordination? Front Psychiatry. 2023; 14: 1130185. https://doi.org/10.3389/fpsyt.2023.1130185
[34]	Cocuzza S, Maniaci A, La Mantia I, Nocera F, Caruso D, Caruso S, et al. Obsessive-Compulsive Disorder in PANS/PANDAS in Children: In Search of a Qualified Treatment—A Systematic Review and Meta-analysis. Children (Basel). 2022; 9(2): 155. https://doi.org/10.3390/children9020155
[35]	Gargano SP, Santos MG, Taylor SM, Pastis I. A closer look to neural pathways and psychopharmacology of obsessive compulsive disorder. Front Behav Neurosci. 2023; 17: 1282246. https://doi.org/10.3389/fnbeh.2023.1282246
[36]	Figee M, Vink M, de Geus F, Vulink N, Veltman DJ, Westenberg HG, Denys D. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol Psychiatry. 2011; 69(9): 867-74. https://doi.org/10.1016/j.biopsych.2010.12.003
[37]	Shi W, Tian Y, Yang H, Guo H, Wen B, Liu Z, Zhang Y, Han S, Cheng J. Abnormal static and dynamic functional connectivity of striatal subregions in patients with obsessive-compulsive disorder. Front Psychiatry. 2025 Feb 21; 16: 1529983. https://doi.org/10.3389/fpsyt.2025.1529983
[38]	van Velzen LS, Vriend C, de Wit SJ, van den Heuvel OA. Response prevention and interference control in obsessive-compulsive spectrum disorders. Front Hum Neurosci. 2014; 8: 419. Available from: https://doi.org/10.3389/fnhum.2014.00419
[39]	Wells L, O’Hara N, Frye RE, Hullavard N, Smith E. Folate receptor alpha autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) population. J Pers Med. 2024; 14(2): 166. https://doi.org/10.3390/jpm14020166
[40]	Wald ER, Eickhoff J, Flood GE, Heinz MV, Liu D, Agrawal A, Morse RP, Raney VM, Veerapandiyan A, Madan JC. Estimate of the incidence of PANDAS and PANS in 3 primary care populations. Front Pediatr. 2023; 11: 1170379. https://doi.org/10.3389/fped.2023.1170379
[41]	PANDAS Network. PANS/PANDAS statistics and prevalence estimates. PANDAS Network; 2025 [cited 2025 Oct 25]. Available from: https://pandasnetwork.org/get-involved/statistics/

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Cárdenas, V. M. M. (2025). Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers, 5(4), 205-215. https://doi.org/10.11648/j.frontiers.20250504.16

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Cárdenas, V. M. M. Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers. 2025, 5(4), 205-215. doi: 10.11648/j.frontiers.20250504.16

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Cárdenas VMM. Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers. 2025;5(4):205-215. doi: 10.11648/j.frontiers.20250504.16

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@article{10.11648/j.frontiers.20250504.16,
  author = {Vicente Manuel Martínez Cárdenas},
  title = {Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence},
  journal = {Frontiers},
  volume = {5},
  number = {4},
  pages = {205-215},
  doi = {10.11648/j.frontiers.20250504.16},
  url = {https://doi.org/10.11648/j.frontiers.20250504.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.frontiers.20250504.16},
  abstract = {Background: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are neuropsychiatric disorders characterized by abrupt onset or exacerbation of symptoms such as obsessive-compulsive behaviors, tics or severely restricted eating, often following infection.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC11430956/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Proposed pathophysiological mechanisms include immune-mediated inflammation targeting the basal ganglia, with structural and functional alterations in these subcortical nuclei. Objectives: To review and synthesise the available literature (2013-2025) addressing the persistence of basal ganglia dysfunction (neuroanatomical, immunological and clinical) in PANS/PANDAS, and to identify gaps and implications for diagnosis and treatment. Methods: A narrative review of PubMed, Scopus, Web of Science, and Embase (January 2013-September 2025) was conducted using English and Spanish keywords: (“PANS” OR “PANDAS” OR “pediatric acute-onset neuropsychiatric syndrome” OR “pediatric autoimmune neuropsychiatric disorders”) AND (“basal ganglia” OR “autoantibodies” OR “neuroinflammation”). Titles and abstracts were screened manually, and eligible studies underwent full-text qualitative synthesis. Original articles, systematic reviews, meta-analyses, case series, and case reports addressing basal ganglia involvement in PANS/PANDAS were included. Data concerning neuroimaging findings, neurological soft signs, autoantibodies, and therapeutic outcomes were extracted and qualitatively analyzed. Results: Persistent abnormalities in the caudate nucleus and putamen have been documented, including volume enlargement and microstructural alterations, consistent with ongoing basal ganglia involvement. Functional neuroimaging (PET, SPECT) demonstrates hypoactivity or hypoperfusion in motor and emotional control regions of the basal ganglia. Immunological studies reveal autoantibodies targeting cholinergic interneurons in the striatum, along with microglial activation and blood-brain barrier disruption in animal models. Neurological soft signs (NSS) such as overflow movements have been reported in related basal-ganglia disorders, though their prevalence in PANS/PANDAS remains under-investigated. Heterogeneity in methodologies, small sample sizes and variable effect sizes limit generalisability of findings.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC10609001/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Conclusions: The accumulated evidence supports a persistent, immune-mediated basal ganglia dysfunction underlying the clinical manifestations of PANS/PANDAS. Recognition of this involvement provides crucial pathophysiological insight and strengthens the rationale for early immunomodulatory and neuro-targeted interventions such as corticosteroids, IVIG, and plasmapheresis in selected cases. Nevertheless, well-designed prospective and controlled studies are needed to validate diagnostic biomarkers, quantify the prevalence and prognostic significance of neurological soft signs, and define standardized clinical and imaging endpoints that can guide future therapeutic trials and evidence-based management protocols.},
 year = {2025}
}

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TY  - JOUR
T1  - Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence
AU  - Vicente Manuel Martínez Cárdenas
Y1  - 2025/12/19
PY  - 2025
N1  - https://doi.org/10.11648/j.frontiers.20250504.16
DO  - 10.11648/j.frontiers.20250504.16
T2  - Frontiers
JF  - Frontiers
JO  - Frontiers
SP  - 205
EP  - 215
PB  - Science Publishing Group
SN  - 2994-7197
UR  - https://doi.org/10.11648/j.frontiers.20250504.16
AB  - Background: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are neuropsychiatric disorders characterized by abrupt onset or exacerbation of symptoms such as obsessive-compulsive behaviors, tics or severely restricted eating, often following infection.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC11430956/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Proposed pathophysiological mechanisms include immune-mediated inflammation targeting the basal ganglia, with structural and functional alterations in these subcortical nuclei. Objectives: To review and synthesise the available literature (2013-2025) addressing the persistence of basal ganglia dysfunction (neuroanatomical, immunological and clinical) in PANS/PANDAS, and to identify gaps and implications for diagnosis and treatment. Methods: A narrative review of PubMed, Scopus, Web of Science, and Embase (January 2013-September 2025) was conducted using English and Spanish keywords: (“PANS” OR “PANDAS” OR “pediatric acute-onset neuropsychiatric syndrome” OR “pediatric autoimmune neuropsychiatric disorders”) AND (“basal ganglia” OR “autoantibodies” OR “neuroinflammation”). Titles and abstracts were screened manually, and eligible studies underwent full-text qualitative synthesis. Original articles, systematic reviews, meta-analyses, case series, and case reports addressing basal ganglia involvement in PANS/PANDAS were included. Data concerning neuroimaging findings, neurological soft signs, autoantibodies, and therapeutic outcomes were extracted and qualitatively analyzed. Results: Persistent abnormalities in the caudate nucleus and putamen have been documented, including volume enlargement and microstructural alterations, consistent with ongoing basal ganglia involvement. Functional neuroimaging (PET, SPECT) demonstrates hypoactivity or hypoperfusion in motor and emotional control regions of the basal ganglia. Immunological studies reveal autoantibodies targeting cholinergic interneurons in the striatum, along with microglial activation and blood-brain barrier disruption in animal models. Neurological soft signs (NSS) such as overflow movements have been reported in related basal-ganglia disorders, though their prevalence in PANS/PANDAS remains under-investigated. Heterogeneity in methodologies, small sample sizes and variable effect sizes limit generalisability of findings.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC10609001/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Conclusions: The accumulated evidence supports a persistent, immune-mediated basal ganglia dysfunction underlying the clinical manifestations of PANS/PANDAS. Recognition of this involvement provides crucial pathophysiological insight and strengthens the rationale for early immunomodulatory and neuro-targeted interventions such as corticosteroids, IVIG, and plasmapheresis in selected cases. Nevertheless, well-designed prospective and controlled studies are needed to validate diagnostic biomarkers, quantify the prevalence and prognostic significance of neurological soft signs, and define standardized clinical and imaging endpoints that can guide future therapeutic trials and evidence-based management protocols.
VL  - 5
IS  - 4
ER  -

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Vicente Manuel Martínez Cárdenas

Children’s Medical Center, Lake City, USA

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Cárdenas, V. M. M. (2025). Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers, 5(4), 205-215. https://doi.org/10.11648/j.frontiers.20250504.16

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Cárdenas, V. M. M. Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers. 2025, 5(4), 205-215. doi: 10.11648/j.frontiers.20250504.16

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Cárdenas VMM. Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence. Frontiers. 2025;5(4):205-215. doi: 10.11648/j.frontiers.20250504.16

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@article{10.11648/j.frontiers.20250504.16,
  author = {Vicente Manuel Martínez Cárdenas},
  title = {Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence},
  journal = {Frontiers},
  volume = {5},
  number = {4},
  pages = {205-215},
  doi = {10.11648/j.frontiers.20250504.16},
  url = {https://doi.org/10.11648/j.frontiers.20250504.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.frontiers.20250504.16},
  abstract = {Background: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are neuropsychiatric disorders characterized by abrupt onset or exacerbation of symptoms such as obsessive-compulsive behaviors, tics or severely restricted eating, often following infection.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC11430956/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Proposed pathophysiological mechanisms include immune-mediated inflammation targeting the basal ganglia, with structural and functional alterations in these subcortical nuclei. Objectives: To review and synthesise the available literature (2013-2025) addressing the persistence of basal ganglia dysfunction (neuroanatomical, immunological and clinical) in PANS/PANDAS, and to identify gaps and implications for diagnosis and treatment. Methods: A narrative review of PubMed, Scopus, Web of Science, and Embase (January 2013-September 2025) was conducted using English and Spanish keywords: (“PANS” OR “PANDAS” OR “pediatric acute-onset neuropsychiatric syndrome” OR “pediatric autoimmune neuropsychiatric disorders”) AND (“basal ganglia” OR “autoantibodies” OR “neuroinflammation”). Titles and abstracts were screened manually, and eligible studies underwent full-text qualitative synthesis. Original articles, systematic reviews, meta-analyses, case series, and case reports addressing basal ganglia involvement in PANS/PANDAS were included. Data concerning neuroimaging findings, neurological soft signs, autoantibodies, and therapeutic outcomes were extracted and qualitatively analyzed. Results: Persistent abnormalities in the caudate nucleus and putamen have been documented, including volume enlargement and microstructural alterations, consistent with ongoing basal ganglia involvement. Functional neuroimaging (PET, SPECT) demonstrates hypoactivity or hypoperfusion in motor and emotional control regions of the basal ganglia. Immunological studies reveal autoantibodies targeting cholinergic interneurons in the striatum, along with microglial activation and blood-brain barrier disruption in animal models. Neurological soft signs (NSS) such as overflow movements have been reported in related basal-ganglia disorders, though their prevalence in PANS/PANDAS remains under-investigated. Heterogeneity in methodologies, small sample sizes and variable effect sizes limit generalisability of findings.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC10609001/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Conclusions: The accumulated evidence supports a persistent, immune-mediated basal ganglia dysfunction underlying the clinical manifestations of PANS/PANDAS. Recognition of this involvement provides crucial pathophysiological insight and strengthens the rationale for early immunomodulatory and neuro-targeted interventions such as corticosteroids, IVIG, and plasmapheresis in selected cases. Nevertheless, well-designed prospective and controlled studies are needed to validate diagnostic biomarkers, quantify the prevalence and prognostic significance of neurological soft signs, and define standardized clinical and imaging endpoints that can guide future therapeutic trials and evidence-based management protocols.},
 year = {2025}
}

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TY  - JOUR
T1  - Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence
AU  - Vicente Manuel Martínez Cárdenas
Y1  - 2025/12/19
PY  - 2025
N1  - https://doi.org/10.11648/j.frontiers.20250504.16
DO  - 10.11648/j.frontiers.20250504.16
T2  - Frontiers
JF  - Frontiers
JO  - Frontiers
SP  - 205
EP  - 215
PB  - Science Publishing Group
SN  - 2994-7197
UR  - https://doi.org/10.11648/j.frontiers.20250504.16
AB  - Background: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are neuropsychiatric disorders characterized by abrupt onset or exacerbation of symptoms such as obsessive-compulsive behaviors, tics or severely restricted eating, often following infection.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC11430956/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Proposed pathophysiological mechanisms include immune-mediated inflammation targeting the basal ganglia, with structural and functional alterations in these subcortical nuclei. Objectives: To review and synthesise the available literature (2013-2025) addressing the persistence of basal ganglia dysfunction (neuroanatomical, immunological and clinical) in PANS/PANDAS, and to identify gaps and implications for diagnosis and treatment. Methods: A narrative review of PubMed, Scopus, Web of Science, and Embase (January 2013-September 2025) was conducted using English and Spanish keywords: (“PANS” OR “PANDAS” OR “pediatric acute-onset neuropsychiatric syndrome” OR “pediatric autoimmune neuropsychiatric disorders”) AND (“basal ganglia” OR “autoantibodies” OR “neuroinflammation”). Titles and abstracts were screened manually, and eligible studies underwent full-text qualitative synthesis. Original articles, systematic reviews, meta-analyses, case series, and case reports addressing basal ganglia involvement in PANS/PANDAS were included. Data concerning neuroimaging findings, neurological soft signs, autoantibodies, and therapeutic outcomes were extracted and qualitatively analyzed. Results: Persistent abnormalities in the caudate nucleus and putamen have been documented, including volume enlargement and microstructural alterations, consistent with ongoing basal ganglia involvement. Functional neuroimaging (PET, SPECT) demonstrates hypoactivity or hypoperfusion in motor and emotional control regions of the basal ganglia. Immunological studies reveal autoantibodies targeting cholinergic interneurons in the striatum, along with microglial activation and blood-brain barrier disruption in animal models. Neurological soft signs (NSS) such as overflow movements have been reported in related basal-ganglia disorders, though their prevalence in PANS/PANDAS remains under-investigated. Heterogeneity in methodologies, small sample sizes and variable effect sizes limit generalisability of findings.  HYPERLINK "https://pmc.ncbi.nlm.nih.gov/articles/PMC10609001/?utm_source=chatgpt.com" \t "_blank" PubMed Central+2AAP Publications+2 Conclusions: The accumulated evidence supports a persistent, immune-mediated basal ganglia dysfunction underlying the clinical manifestations of PANS/PANDAS. Recognition of this involvement provides crucial pathophysiological insight and strengthens the rationale for early immunomodulatory and neuro-targeted interventions such as corticosteroids, IVIG, and plasmapheresis in selected cases. Nevertheless, well-designed prospective and controlled studies are needed to validate diagnostic biomarkers, quantify the prevalence and prognostic significance of neurological soft signs, and define standardized clinical and imaging endpoints that can guide future therapeutic trials and evidence-based management protocols.
VL  - 5
IS  - 4
ER  -

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