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

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.