RARE DISEASE
PANDAS
PANDAS
PANDAS
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Synonyms: Pediatric autoimmune disorders associated with Streptococcus infections, Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections
Drug discovery
1
drug
With orphan designation
Overview
PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections) is a post-infectious autoimmune condition characterized by the abrupt onset of obsessive-compulsive disorder (OCD) or tics following Group A streptococcal infection. Key diagnostic criteria include prepubertal onset, episodic symptom course, and neurological abnormalities (e.g., motor hyperactivity). It is distinguished from idiopathic OCD by rapid symptom escalation and concurrent neuropsychiatric manifestations [1][6][16].
Burden
Associated with severe psychiatric comorbidities (e.g., anxiety, developmental regression) and academic decline [1][4].
Economic impact includes high hospitalization costs (e.g., $2,049/day average in Illinois) [19] and prolonged care needs.
Families report significant emotional and logistical strain, exacerbated by diagnostic delays and limited specialist access [4][19].
Therapies
Medical: Antibiotics (targeting infections), IVIG/plasmapheresis (modulating immunity), NSAIDs (reducing inflammation) [8][13][18].
Behavioral: Cognitive-behavioral therapy (CBT) and exposure-response prevention (ERP) for OCD/anxiety [3][13].
Integrative: Probiotics, vitamin D, and dietary adjustments as adjunctive options [8].
Categories: rare neurological diseases
Research Papers
153 drug discovery papers about PANDAS, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
153 drug discovery papers about PANDAS, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-07-03 | Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.
Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.
2026-05-27 | Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host-microbiome interactions in modulating neuro-immune functions via gut-brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut-brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe-metabolite networks allied to gut-brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut-brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders.
2026-04-06 | Immune dysregulation in pediatric tic disorders: mechanisms, biomarkers, and therapeutic frontiers.
Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.
2022-12-02 | Therapeutic plasma exchange in adolescent and adult patients with autoimmune neuropsychiatric disorders associated with streptococcal infections.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal (PANDAS) infections and pediatric acute-onset neuropsychiatric syndrome (PANS) are typically diagnosed in childhood. Therapeutic plasma exchange (TPE) has been recommended to remove relevant antibodies and treat symptomatic presentations in children and adolescents, but there are no studies that evaluate the use of TPE in patients who are diagnosed later in life. It is therefore unclear if using an accepted treatment for pediatric PANS/PANDAS patients would be beneficial in adults with prolonged PANDAS/PANS symptomatic histories. This study investigated 16 late adolescent and adult PANDAS/PANS patients' responses to TPE. Improvement was noted in over half of the patients with available follow-up information.
2021-11-02 | Plasmapheresis, Rituximab, and Ceftriaxone Provided Lasting Improvement for a 27-Year-Old Adult Male with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a specific autoimmune response to group-A streptococcal (GAS) infections in children and adolescents with a sudden onset of neuropsychiatric disorders including obsessive-compulsive disorder (OCD) or tic-like symptoms. We present a case report of a 27-year-old male patient who had lasting improvement with plasmapheresis, rituximab, and ceftriaxone. Our patient first developed sudden psychosis and confusion after GAS infections at age 17. He had elevated anti-streptolysin O (ASO) titers, negative urine drug screen, no ETOH in blood, normal CBC, normal TSH, normal salicylate, normal acetaminophen, and a normal head CT. The tentative diagnosis of PANDAS was made, and the patient was thereafter treated with antipsychotics, antibiotics, tonsillectomy, and IVIG which resulted in remissions and relapses of his neuropsychiatric symptoms. Once he reached age 27, he received a trial of therapeutic plasma exchange (TPE), rituximab, and ceftriaxone. This eventually resulted in sustained benefit and minimal fluctuations of his clinical symptoms. Our report is noteworthy in three ways.One, he is a 27-year-old adult with PANDAS.Two, he improved after TPE, rituximab, and ceftriaxone. Our literature search yielded minimal data on the use of plasmapheresis for nonteenage adults with PANDAS. Three, he had unusual symptoms of PANDAS, as the typical OCD and/or tic-like symptoms were not observed.
antibodies
2026-06-01 | Sudden-Onset Obsessive-Compulsive Disorder in a Pediatric Patient: A Case-Based Literature Review on PANDAS and Immunomodulatory Treatment Strategies
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) describe a subset of prepubertal children who develop an abrupt onset of obsessive-compulsive symptoms and/or tics following a Group A Streptococcus (GAS) infection. Although the diagnosis remains controversial, the proposed pathophysiological mechanism involves an autoimmune response in genetically susceptible individuals, where molecular mimicry leads to the production of antibodies that cross-react with antigens in the basal ganglia. Nevertheless, this hypothesis has not been conclusively confirmed in current literature. Treatment is typically symptomatic, however, there is potential for clinical improvement with immunomodulatory and antibiotic therapies in selected cases. Objectives To describe a pediatric case of sudden-onset OCD with suspected autoimmune etiology and favorable response to antibiotic treatment, and to review the current literature on therapeutic strategies for PANDAS, including antibiotics and immunomodulatory interventions. Methods A narrative literature review was conducted using PubMed with the following terms: (“PANDAS” OR “PANS”) AND (“Obsessive-Compulsive Disorder” OR “OCD”) AND (“Antibiotic treatment” OR “Immunomodulatory therapy”). Twelve research studies involving treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids met inclusion criteria. Additionally, 65 case reports describing the use of antibiotics, immunomodulators, and/or psychotropics were identified. Results Twelve research studies met inclusion criteria, evaluating treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids. Additionally, 65 case reports described the use of antibiotics, immunomodulatory therapies, and/or psychotropic medications. While antibiotics and IVIG showed potential benefit in selected cases, the overall quality of evidence was low, with high risk of bias and lack of randomized controlled trials. Corticosteroids and NSAIDs were used in acute phases with variable outcomes, and plasma exchange was reserved for severe, refractory presentations. CBT remained a consistent component of symptom management across studies. Conclusions This case supports the hypothesis of an autoimmune mechanism in a subset of pediatric OCD presentations. Although various immunomodulatory strategies have been explored, including antibiotics, IVIG, corticosteroids, NSAIDs, and plasma exchange, rigorously conducted research remains scarce. Further investigation is needed to establish standardized diagnostic criteria and evidence-based treatment protocols for PANDAS and related autoimmune neuropsychiatric syndromes. Disclosure of Interest None Declared
2026-05-25 | Antibody Profiles in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is characterized by prepubertal abrupt onset of obsessive-compulsive disorder (OCD). The sine qua non is group A streptococcus (GAS) infection, which is hypothesized to elicit an IgG-class anti-GAS antibody response that cross-reacts with antigens in the basal ganglia. However, the association between GAS antibody (GAS-IgG) levels and PANDAS has been inconsistent, and qualitative differences in GAS-IgG profiles have not been carefully evaluated in well-phenotyped cohorts. Moreover, independent studies have yet to converge on anti-neural autoantibodies that are specific to PANDAS. Here, we used phage display immunoprecipitation sequencing (PhIP-Seq) to perform ultra-deep anti-pathogen antibody repertoire profiling of serum from definitive pediatric PANDAS patients (N = 34) collected as part of a prior double-blind, placebo-controlled clinical trial of intravenous immunoglobulin (IVIg). PANDAS cases were compared to pediatric controls without a history of neuropsychiatric illness (N = 31). To assess for objective evidence of neuroglial injury, serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels were compared to healthy pediatric controls. Within PANDAS, NfL and GFAP levels were compared between pre- and post-treatment sera. To evaluate for central autoantibodies, a subset of baseline cerebrospinal fluid (CSF) samples (N = 25) was profiled by full-length human protein microarray. Though GAS reactivity by PhIP-Seq was well correlated with clinical anti-DNaseB and anti-streptolysin O titers, there were no quantitative or qualitative differences in GAS-IgG profiles between PANDAS and controls. Furthermore, NfL and GFAP levels did not differ between cases and controls. Within PANDAS, changes in NfL or GFAP levels at six weeks did not differ between placebo and IVIg groups. However, CSF autoantibody profiling by protein microarray revealed infrequent but notable candidate autoantibodies. In one patient, we identified autoantibodies against Argonaute family proteins (AGO-IgG), a marker of autoimmune sensory neuropathy. Longitudinal measurement of AGO-IgG in sera revealed that titers were unchanged after placebo, but decreased after IVIg, coinciding with symptomatic improvement, including a decrease in that patient's CY-BOCS score. Overall, these results do not support an etiologic role for GAS-IgG in PANDAS. However, some individuals diagnosed with PANDAS may harbor anti-neural autoantibodies.
2026-02-12 | A unique case of food restriction and OCD diagnosed as PANDAS and a review of the literature.
Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is recognized as a significant causative element in the emergence of childhood-onset obsessive-compulsive disorder (OCD) and movement disorders, including tic disorders, and choreiform movement. It is associated with various behavioral and psychiatric manifestations in children, such as separation anxiety disorder, body dysmorphic disorder, attention deficit hyperactivity disorder, and eating disorders. We describe a unique case of progressive weight loss in a previously healthy 13-year-old child who had a sudden and dramatic onset of refusal to eat, induction of vomiting, emotional liability, anxiety disorder, and OCD over 6 months following fever and pharyngitis. His workup showed an elevation of antistreptolysin O (ASO) titer with a negative throat swab. PANDAS was considered. His irritability improved after a course of antibiotics, and abatement of all symptoms and progressive weight gain occurred after a course of intravenous immunoglobulin (IVIG) followed by monthly benzathine penicillin injections. This report could help to increase awareness among physicians, highlight the importance of early diagnosis, and promote treatment of PANDAS among patients who present with a combination of eating disorders and OCD.
2026-01-01 | Therapeutic impact and tolerability of intravenous immunoglobulin in pediatric autoimmune neuropsychiatric syndromes (PANS and PANDAS): an updatedsystematic review and meta-analysis
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are marked by the sudden onset of obsessive-compulsive behaviors, tics, anxiety, and cognitive or behavioral changes. PANDAS is linked to streptococcal infections, while PANS involves a broader range of immune or infectious triggers. Intravenous immunoglobulin (IVIG), with immunomodulatory and anti-inflammatory effects, has been studied as a potential treatment to reduce symptoms and improve functioning in affected children. This systematic review aimed to evaluate the effectiveness and safety of IVIG in treating neuropsychiatric symptoms in children with PANDAS or PANS. This review followed PRISMA 2020 guidelines. A comprehensive search of PubMed, Web of Science, Google Scholar, and Ovid (CENTRAL) covered October 1999–October 2024. Eligible studies included randomized controlled trials and cohort studies of pediatric patients (0–18 years) diagnosed with PANDAS or PANS receiving IVIG as the primary intervention. Studies evaluating IVIG in PANS/PANDAS showed significant improvement in symptom severity. The pooled mean difference in CY-BOCS scores was -10.91 (95% CI: -15.47 to -6.34; p-value=0.0001). CGI-S improved by -2.35 (95% CI: -2.73 to -1.97; p-value=0.0421), and CGI-I by -1.04 (95% CI: -2.31 to 0.23; p
2025-04-25 | An Uncommon Case of a Patient with CVID and PANDAS
Introduction Pediatric autoimmune neuropsychiatric disorder associated with Streptococcus infections (PANDAS), a subset of pediatric acute-onset neuropsychiatric syndrome (PANS), is characterized by new-onset neuropsychiatric symptoms temporally associated with Streptococcus infection. Some patients with PANS/PANDAS have also been found to have antibody deficiency (IgG, IgA, and vaccine antibody to Streptococcus pneumoniae). However, PANDAS in patients with common variable immunodeficiency (CVID) has not been previously reported. Case Presentation A 16-year-old male with CVID and psoriasis was diagnosed with PANDAS at 9 years old after a febrile illness with group A Streptococcus infection. Given his ongoing severe neuropsychiatric symptoms, including obsessive compulsive disorder, he transitioned from intravenous immunoglobulin (IVIG) dosing for CVID to a higher dose (2 gram/kg/month) for the treatment of PANDAS. He did not have additional major infections, and after approximately a year of higher dose IVIG treatment, his neuropsychiatric symptoms of PANDAS improved. Discussion The prevalence of PANDAS in children with CVID is unclear. The mechanism of IVIG in the treatment of PANDAS has not been elucidated. Mechanisms may involve the binding and neutralization of autoantibodies by anti-idiotypic antibodies and also the eradication and prevention of streptococcal infection. PANDAS should be considered on the differential for patients with CVID and antibody deficiency who develop new onset or suddenly worsening neuropsychiatric symptoms in the setting of an acute upper respiratory tract infection. Prompt diagnosis, timely treatment of an underlying streptococcal infection, and appropriate doses of IVIG, especially in patients with immunodeficiency, may prevent the development of severe PANDAS and improve the quality of life of patients.
small molecules
2025-12-30 | Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.
Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood-brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes.
2025-12-19 | Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence
<i>Background:</i> 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. <i>Objectives:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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.
2025-06-09 | Case Report: Special recoveries from major mental illness in childhood: a case series.
Sudden-onset, unexplained, and treatment-resistant neuropsychiatric symptoms have been reported in numerous pediatric patients. Prior to the identification of neuroimmune conditions including PANS and PANDAS, children with these conditions were diagnosed with psychiatric and neurological conditions and offered conventional psychiatric and therapeutic care. As connections between the immune and nervous systems become clearer, alternate curative treatments have emerged. This case series presents three pediatric patients' treatment experiences with sudden-onset severe neuropsychiatric symptoms such as disabling anxiety, tics, eating restriction, or hallucinations, and their full recoveries following treatment of their underlying infections, inflammatory responses, and gastrointestinal dysbiosis. Treatments included antimicrobials, nutraceuticals, probiotics, and dietary changes. Converging lines of research highlight the importance of considering neuroinflammatory conditions in the differential diagnosis of children with treatment-resistant neuropsychiatric symptoms.
2025-04-01 | PANDAS have claws too: A case report of an adolescent female with concurrent PANDAS and Mood Disorder
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) is an autoimmune disease caused by Group A Streptococcus bacteria. It usually affects children 3 to 12 years of age, however, have also been reported among adolescents. PANDAS presents with neuropsychiatric symptoms which can overlap or coincide with existing psychiatric disorders that often emerge further as children get older. Identifying the causation of events may be challenging making such cases difficult to manage. Objectives To understand the presentation of PANDAS with concurrent mood disorder and its management. Methods Clinical case report Results A 16-year-old female was initially admitted due to blank stares, disorganized behavior, paranoia, aggression, and depressive symptoms. Her EEG and MRI were normal. She did not tolerate Fluoxetine but improved with Olanzapine (12.5mg). At 17 years old, she had throat discomfort, colds, and headache with supportive management done. She felt depressed and suicidal due to school stress prompting her second admission. She was started on Escitalopram and Olanzapine was shifted to Quetiapine. Subsequently, she developed manic symptoms with hallucinations and worsened paranoia. Escitalopram was discontinued and Quetiapine was increased (300mg). Bipolar I Disorder with Psychotic Features was considered. Shortly after, she developed explosive motor and vocal tics, involuntary screeching with head gagging and jerking and urges to choke herself or hit her head on the wall. Quetiapine was discontinued and was placed on Clonazepam (0.25mg/8h). Work ups revealed normal EEG, positive ASO and ESR, and findings of Mild Rheumatic Heart Disease on 2D Echo, hence, the assessment of PANDAS. Treatment is multidisciplinary involving antimicrobial, immunomodulatory, and psychotherapeutic interventions. Medications were then adjusted to: Co-amoxiclav (625mg/10days) followed by Penicillin V (250mg/12h), Aripiprazole (15mg), and Divalproex Sodium (1000mg). Intravenous immunoglobulin was suggested due to her moderate to severe presentation. Henceforth, improvement of symptoms were noted and she was reintegrated back home. Conclusions Diagnosing PANDAS can be complex among adolescent due to concurrent issues with similar symptom presentation. PANDAS is episodic in nature but may also have sawtooth-like presentation which may indicate first admission as an episode and the second, a flare up. The case could have also been a combination of PANDAS and Bipolar Disorder thus the severity. Regardless, the interplay of biological and psychological facets have evidently magnified her predispositions leading to an intense manifestation of symptoms. Disclosure of Interest None Declared
2025-03-24 | The role of previous streptococcal infections in adult patients with obsessive-compulsive disorder: a research study.
Autoimmune processes have been documented in both childhood and adulthood patients with obsessive-compulsive disorder (OCD), with the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) representing the paradigm of this model.Given the limited information available, the present study aimed at assessing the characteristics of adult patients with OCD exposed to a previous group A β-hemolytic Streptococcus infection, together with some peripheral inflammatory biomarkers. Fifty-two subjects displaying antistreptolysin O (ASO) titer positivity were recruited from a sample of 247 adult OCD outpatients, diagnosed according to DSM-5 criteria and assessed by the Yale-Brown Obsessive-Compulsive Scale. Their clinical features were assessed and compared. The possible relationships between the different parameters were also examined. Thirty-six subjects who were on medication for OCD showed significantly lower ASO titers than the other. The neutrophil count was positively and negatively related to, respectively, the "distress associated with obsessive thoughts" item and to the patients' age. The lymphocyte count and folic acid levels were higher in 30 subjects with no perinatal insults. These results seem to suggest that OCD subjects with ASO titer-positivity show a chronic inflammatory state, in spite of no symptoms or recall of bacterial infections, that might be involved in both the onset and the maintenance of OCD, with immunological alterations being related to symptom dimension to be identified. They also support the notion of possible anti-inflammatory effects of some psychotropic compounds.
vaccines
2023-09-28 | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity.
Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits' brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial.
2023-08-31 | Symptom flares after COVID-19 infection versus vaccination among youth with PANS/PANDAS.
Background: Flares of autoimmune conditions can happen after coronavirus disease 2019 (COVID-19) infection and after COVID-19 vaccines. Patients and clinicians confront difficult decisions about vaccine safety when considering efforts to balance the risks of disease exacerbation after vaccines versus the protection that vaccines offer to potential serious life-threatening complications of COVID-19 infection. Objective: To examine symptom flares after COVID-19 infection and vaccines in the case of a form of autoimmune encephalitis that primarily affects children and young adults (pediatric acute-onset neuropsychiatric syndrome [PANS] / pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections [PANDAS]). Method: A cross-sectional study that used a survey distributed through PANS/PANDAS groups, organizations, and clinics. Results: Surveys were completed by 496 parents and/or caregivers of children with PANS/PANDAS. Among the children reported to have had a COVID-19 infection (n = 178), 43% reported severe flares of PANS/PANDAS symptoms, 23% reported mild flares, and 30% reported no symptom flares. Among those who had received COVID-19 vaccines (n = 181), 65% observed no changes in PANS/PANDAS symptoms after the vaccine, 19% reported mild flares, and 15% reported severe flares. Paired sample t-tests showed that, after COVID-19 infections, children with PANS/PANDAS were significantly more likely to experience a severe symptom flare than a mild flare or no change in symptoms. In contrast, after receiving COVID-19 vaccines, children were significantly more likely to experience no change in PANS/PANDAS symptoms than to endure a mild or severe symptom flare. In addition, children who recovered from PANS/PANDAS were significantly more likely to have no symptom change versus children who were managing the condition, both after COVID-19 infection (92% versus 25%) and vaccine receipt (100% versus 66%). Conclusion: These results support COVID-19 vaccination for most individuals with PANS/PANDAS given that the frequencies of symptom flares and setbacks after COVID-19 infection were significantly higher than after the COVID-19 vaccine. Nonetheless, further studies are needed to fully assess the risk-benefit balance and to provide a more individualized approach to disease prevention in people with immune vulnerabilities.
cell therapies
2026-07-03 | Therapeutic plasma exchange and immunomodulatory strategies in post-infectious syndromes: A review of immune dysregulation in PTLDS, long COVID, ME/CFS, and PANS/PANDAS.
Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute-onset neuropsychiatric syndrome (PANS)/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. Increasing evidence suggests that immune dysregulation-including persistent inflammation, autoantibody production, and cellular immune dysfunction-may underlie these conditions. This narrative review synthesizes peer-reviewed literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). Evidence supporting immune-targeted treatment strategies is strongest in subsets of patients with identifiable immunologic abnormalities. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification. TPE functions by removing circulating immune complexes, autoantibodies, and inflammatory mediators, and observational data suggest benefit in patients with demonstrable autoantibody burden. Further controlled studies incorporating immunologic phenotyping and early intervention are needed to define the therapeutic role of immune-directed interventions across these conditions.
2026-05-27 | Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host-microbiome interactions in modulating neuro-immune functions via gut-brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut-brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe-metabolite networks allied to gut-brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut-brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders.
2026-04-06 | Immune dysregulation in pediatric tic disorders: mechanisms, biomarkers, and therapeutic frontiers.
Tic Disorders (TDs) are common neurodevelopmental disorders characterized by complex pathophysiological mechanisms. A growing body of evidence in recent years suggests that immune system dysregulation plays a critical role in the pathogenesis and clinical course of TDs in a subset of pediatric patients. This review aims to systematically summarize the current understanding of the core mechanisms of immune dysregulation in pediatric TDs, potential biomarkers, and related therapeutic frontiers. We detail three core pathophysiological pathways, Post infectious autoimmunity, represented by the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) models. Its core mechanism involves the production of autoantibodies induced by molecular mimicry, which target basal ganglia neurons, such as cholinergic interneurons and dopamine receptors. Neuroinflammation is another critical pathway. This process involves T helper 17 (Th17) cell-mediated disruption of the blood-brain barrier and microglial activation. It is further characterized by elevated pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). Microbiota-gut-brain axis dysregulation, wherein gut dysbiosis and compromised intestinal barrier function influence central nervous system (CNS) function through the neuro immune endocrine network. Building upon this framework, we evaluate potential biomarkers across various dimensions, including the findings and limitations in serology (cytokines), cerebrospinal fluid analysis (oligoclonal bands, MCP-1), neuroimaging (volumetric changes in the basal ganglia and PET imaging of neuroinflammation), and genetics (variations in the IL-1RN gene). Finally, we discuss the evolution from conventional treatments to emerging immune-targeted therapies. This encompasses core immunomodulatory therapies (Intravenous Immunoglobulin (IVIG) and plasmapheresis) and promising future strategies, such as fecal microbiota transplantation (FMT), targeted B-cell therapies, and small-molecule anti-inflammatory drugs. In conclusion, a deeper understanding of the immunological basis of TDs is paving the way for the development of more precise diagnostic tools and novel, individualized immunomodulatory interventions.
2022-12-02 | Therapeutic plasma exchange in adolescent and adult patients with autoimmune neuropsychiatric disorders associated with streptococcal infections.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal (PANDAS) infections and pediatric acute-onset neuropsychiatric syndrome (PANS) are typically diagnosed in childhood. Therapeutic plasma exchange (TPE) has been recommended to remove relevant antibodies and treat symptomatic presentations in children and adolescents, but there are no studies that evaluate the use of TPE in patients who are diagnosed later in life. It is therefore unclear if using an accepted treatment for pediatric PANS/PANDAS patients would be beneficial in adults with prolonged PANDAS/PANS symptomatic histories. This study investigated 16 late adolescent and adult PANDAS/PANS patients' responses to TPE. Improvement was noted in over half of the patients with available follow-up information.
2021-11-02 | Plasmapheresis, Rituximab, and Ceftriaxone Provided Lasting Improvement for a 27-Year-Old Adult Male with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a specific autoimmune response to group-A streptococcal (GAS) infections in children and adolescents with a sudden onset of neuropsychiatric disorders including obsessive-compulsive disorder (OCD) or tic-like symptoms. We present a case report of a 27-year-old male patient who had lasting improvement with plasmapheresis, rituximab, and ceftriaxone. Our patient first developed sudden psychosis and confusion after GAS infections at age 17. He had elevated anti-streptolysin O (ASO) titers, negative urine drug screen, no ETOH in blood, normal CBC, normal TSH, normal salicylate, normal acetaminophen, and a normal head CT. The tentative diagnosis of PANDAS was made, and the patient was thereafter treated with antipsychotics, antibiotics, tonsillectomy, and IVIG which resulted in remissions and relapses of his neuropsychiatric symptoms. Once he reached age 27, he received a trial of therapeutic plasma exchange (TPE), rituximab, and ceftriaxone. This eventually resulted in sustained benefit and minimal fluctuations of his clinical symptoms. Our report is noteworthy in three ways.One, he is a 27-year-old adult with PANDAS.Two, he improved after TPE, rituximab, and ceftriaxone. Our literature search yielded minimal data on the use of plasmapheresis for nonteenage adults with PANDAS. Three, he had unusual symptoms of PANDAS, as the typical OCD and/or tic-like symptoms were not observed.
antibodies
2026-06-01 | Sudden-Onset Obsessive-Compulsive Disorder in a Pediatric Patient: A Case-Based Literature Review on PANDAS and Immunomodulatory Treatment Strategies
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) describe a subset of prepubertal children who develop an abrupt onset of obsessive-compulsive symptoms and/or tics following a Group A Streptococcus (GAS) infection. Although the diagnosis remains controversial, the proposed pathophysiological mechanism involves an autoimmune response in genetically susceptible individuals, where molecular mimicry leads to the production of antibodies that cross-react with antigens in the basal ganglia. Nevertheless, this hypothesis has not been conclusively confirmed in current literature. Treatment is typically symptomatic, however, there is potential for clinical improvement with immunomodulatory and antibiotic therapies in selected cases. Objectives To describe a pediatric case of sudden-onset OCD with suspected autoimmune etiology and favorable response to antibiotic treatment, and to review the current literature on therapeutic strategies for PANDAS, including antibiotics and immunomodulatory interventions. Methods A narrative literature review was conducted using PubMed with the following terms: (“PANDAS” OR “PANS”) AND (“Obsessive-Compulsive Disorder” OR “OCD”) AND (“Antibiotic treatment” OR “Immunomodulatory therapy”). Twelve research studies involving treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids met inclusion criteria. Additionally, 65 case reports describing the use of antibiotics, immunomodulators, and/or psychotropics were identified. Results Twelve research studies met inclusion criteria, evaluating treatments such as penicillin, azithromycin, intravenous immunoglobulin (IVIG), plasma exchange, tonsillectomy, cognitive behavioral therapy (CBT), NSAIDs, and corticosteroids. Additionally, 65 case reports described the use of antibiotics, immunomodulatory therapies, and/or psychotropic medications. While antibiotics and IVIG showed potential benefit in selected cases, the overall quality of evidence was low, with high risk of bias and lack of randomized controlled trials. Corticosteroids and NSAIDs were used in acute phases with variable outcomes, and plasma exchange was reserved for severe, refractory presentations. CBT remained a consistent component of symptom management across studies. Conclusions This case supports the hypothesis of an autoimmune mechanism in a subset of pediatric OCD presentations. Although various immunomodulatory strategies have been explored, including antibiotics, IVIG, corticosteroids, NSAIDs, and plasma exchange, rigorously conducted research remains scarce. Further investigation is needed to establish standardized diagnostic criteria and evidence-based treatment protocols for PANDAS and related autoimmune neuropsychiatric syndromes. Disclosure of Interest None Declared
2026-05-25 | Antibody Profiles in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is characterized by prepubertal abrupt onset of obsessive-compulsive disorder (OCD). The sine qua non is group A streptococcus (GAS) infection, which is hypothesized to elicit an IgG-class anti-GAS antibody response that cross-reacts with antigens in the basal ganglia. However, the association between GAS antibody (GAS-IgG) levels and PANDAS has been inconsistent, and qualitative differences in GAS-IgG profiles have not been carefully evaluated in well-phenotyped cohorts. Moreover, independent studies have yet to converge on anti-neural autoantibodies that are specific to PANDAS. Here, we used phage display immunoprecipitation sequencing (PhIP-Seq) to perform ultra-deep anti-pathogen antibody repertoire profiling of serum from definitive pediatric PANDAS patients (N = 34) collected as part of a prior double-blind, placebo-controlled clinical trial of intravenous immunoglobulin (IVIg). PANDAS cases were compared to pediatric controls without a history of neuropsychiatric illness (N = 31). To assess for objective evidence of neuroglial injury, serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels were compared to healthy pediatric controls. Within PANDAS, NfL and GFAP levels were compared between pre- and post-treatment sera. To evaluate for central autoantibodies, a subset of baseline cerebrospinal fluid (CSF) samples (N = 25) was profiled by full-length human protein microarray. Though GAS reactivity by PhIP-Seq was well correlated with clinical anti-DNaseB and anti-streptolysin O titers, there were no quantitative or qualitative differences in GAS-IgG profiles between PANDAS and controls. Furthermore, NfL and GFAP levels did not differ between cases and controls. Within PANDAS, changes in NfL or GFAP levels at six weeks did not differ between placebo and IVIg groups. However, CSF autoantibody profiling by protein microarray revealed infrequent but notable candidate autoantibodies. In one patient, we identified autoantibodies against Argonaute family proteins (AGO-IgG), a marker of autoimmune sensory neuropathy. Longitudinal measurement of AGO-IgG in sera revealed that titers were unchanged after placebo, but decreased after IVIg, coinciding with symptomatic improvement, including a decrease in that patient's CY-BOCS score. Overall, these results do not support an etiologic role for GAS-IgG in PANDAS. However, some individuals diagnosed with PANDAS may harbor anti-neural autoantibodies.
2026-02-12 | A unique case of food restriction and OCD diagnosed as PANDAS and a review of the literature.
Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is recognized as a significant causative element in the emergence of childhood-onset obsessive-compulsive disorder (OCD) and movement disorders, including tic disorders, and choreiform movement. It is associated with various behavioral and psychiatric manifestations in children, such as separation anxiety disorder, body dysmorphic disorder, attention deficit hyperactivity disorder, and eating disorders. We describe a unique case of progressive weight loss in a previously healthy 13-year-old child who had a sudden and dramatic onset of refusal to eat, induction of vomiting, emotional liability, anxiety disorder, and OCD over 6 months following fever and pharyngitis. His workup showed an elevation of antistreptolysin O (ASO) titer with a negative throat swab. PANDAS was considered. His irritability improved after a course of antibiotics, and abatement of all symptoms and progressive weight gain occurred after a course of intravenous immunoglobulin (IVIG) followed by monthly benzathine penicillin injections. This report could help to increase awareness among physicians, highlight the importance of early diagnosis, and promote treatment of PANDAS among patients who present with a combination of eating disorders and OCD.
2026-01-01 | Therapeutic impact and tolerability of intravenous immunoglobulin in pediatric autoimmune neuropsychiatric syndromes (PANS and PANDAS): an updatedsystematic review and meta-analysis
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are marked by the sudden onset of obsessive-compulsive behaviors, tics, anxiety, and cognitive or behavioral changes. PANDAS is linked to streptococcal infections, while PANS involves a broader range of immune or infectious triggers. Intravenous immunoglobulin (IVIG), with immunomodulatory and anti-inflammatory effects, has been studied as a potential treatment to reduce symptoms and improve functioning in affected children. This systematic review aimed to evaluate the effectiveness and safety of IVIG in treating neuropsychiatric symptoms in children with PANDAS or PANS. This review followed PRISMA 2020 guidelines. A comprehensive search of PubMed, Web of Science, Google Scholar, and Ovid (CENTRAL) covered October 1999–October 2024. Eligible studies included randomized controlled trials and cohort studies of pediatric patients (0–18 years) diagnosed with PANDAS or PANS receiving IVIG as the primary intervention. Studies evaluating IVIG in PANS/PANDAS showed significant improvement in symptom severity. The pooled mean difference in CY-BOCS scores was -10.91 (95% CI: -15.47 to -6.34; p-value=0.0001). CGI-S improved by -2.35 (95% CI: -2.73 to -1.97; p-value=0.0421), and CGI-I by -1.04 (95% CI: -2.31 to 0.23; p
2025-04-25 | An Uncommon Case of a Patient with CVID and PANDAS
Introduction Pediatric autoimmune neuropsychiatric disorder associated with Streptococcus infections (PANDAS), a subset of pediatric acute-onset neuropsychiatric syndrome (PANS), is characterized by new-onset neuropsychiatric symptoms temporally associated with Streptococcus infection. Some patients with PANS/PANDAS have also been found to have antibody deficiency (IgG, IgA, and vaccine antibody to Streptococcus pneumoniae). However, PANDAS in patients with common variable immunodeficiency (CVID) has not been previously reported. Case Presentation A 16-year-old male with CVID and psoriasis was diagnosed with PANDAS at 9 years old after a febrile illness with group A Streptococcus infection. Given his ongoing severe neuropsychiatric symptoms, including obsessive compulsive disorder, he transitioned from intravenous immunoglobulin (IVIG) dosing for CVID to a higher dose (2 gram/kg/month) for the treatment of PANDAS. He did not have additional major infections, and after approximately a year of higher dose IVIG treatment, his neuropsychiatric symptoms of PANDAS improved. Discussion The prevalence of PANDAS in children with CVID is unclear. The mechanism of IVIG in the treatment of PANDAS has not been elucidated. Mechanisms may involve the binding and neutralization of autoantibodies by anti-idiotypic antibodies and also the eradication and prevention of streptococcal infection. PANDAS should be considered on the differential for patients with CVID and antibody deficiency who develop new onset or suddenly worsening neuropsychiatric symptoms in the setting of an acute upper respiratory tract infection. Prompt diagnosis, timely treatment of an underlying streptococcal infection, and appropriate doses of IVIG, especially in patients with immunodeficiency, may prevent the development of severe PANDAS and improve the quality of life of patients.
small molecules
2025-12-30 | Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.
Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood-brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes.
2025-12-19 | Persistence of Basal Ganglia Dysfunction in PANS/PANDAS: Review of the Evidence
<i>Background:</i> 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. <i>Objectives:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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.
2025-06-09 | Case Report: Special recoveries from major mental illness in childhood: a case series.
Sudden-onset, unexplained, and treatment-resistant neuropsychiatric symptoms have been reported in numerous pediatric patients. Prior to the identification of neuroimmune conditions including PANS and PANDAS, children with these conditions were diagnosed with psychiatric and neurological conditions and offered conventional psychiatric and therapeutic care. As connections between the immune and nervous systems become clearer, alternate curative treatments have emerged. This case series presents three pediatric patients' treatment experiences with sudden-onset severe neuropsychiatric symptoms such as disabling anxiety, tics, eating restriction, or hallucinations, and their full recoveries following treatment of their underlying infections, inflammatory responses, and gastrointestinal dysbiosis. Treatments included antimicrobials, nutraceuticals, probiotics, and dietary changes. Converging lines of research highlight the importance of considering neuroinflammatory conditions in the differential diagnosis of children with treatment-resistant neuropsychiatric symptoms.
2025-04-01 | PANDAS have claws too: A case report of an adolescent female with concurrent PANDAS and Mood Disorder
Introduction Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) is an autoimmune disease caused by Group A Streptococcus bacteria. It usually affects children 3 to 12 years of age, however, have also been reported among adolescents. PANDAS presents with neuropsychiatric symptoms which can overlap or coincide with existing psychiatric disorders that often emerge further as children get older. Identifying the causation of events may be challenging making such cases difficult to manage. Objectives To understand the presentation of PANDAS with concurrent mood disorder and its management. Methods Clinical case report Results A 16-year-old female was initially admitted due to blank stares, disorganized behavior, paranoia, aggression, and depressive symptoms. Her EEG and MRI were normal. She did not tolerate Fluoxetine but improved with Olanzapine (12.5mg). At 17 years old, she had throat discomfort, colds, and headache with supportive management done. She felt depressed and suicidal due to school stress prompting her second admission. She was started on Escitalopram and Olanzapine was shifted to Quetiapine. Subsequently, she developed manic symptoms with hallucinations and worsened paranoia. Escitalopram was discontinued and Quetiapine was increased (300mg). Bipolar I Disorder with Psychotic Features was considered. Shortly after, she developed explosive motor and vocal tics, involuntary screeching with head gagging and jerking and urges to choke herself or hit her head on the wall. Quetiapine was discontinued and was placed on Clonazepam (0.25mg/8h). Work ups revealed normal EEG, positive ASO and ESR, and findings of Mild Rheumatic Heart Disease on 2D Echo, hence, the assessment of PANDAS. Treatment is multidisciplinary involving antimicrobial, immunomodulatory, and psychotherapeutic interventions. Medications were then adjusted to: Co-amoxiclav (625mg/10days) followed by Penicillin V (250mg/12h), Aripiprazole (15mg), and Divalproex Sodium (1000mg). Intravenous immunoglobulin was suggested due to her moderate to severe presentation. Henceforth, improvement of symptoms were noted and she was reintegrated back home. Conclusions Diagnosing PANDAS can be complex among adolescent due to concurrent issues with similar symptom presentation. PANDAS is episodic in nature but may also have sawtooth-like presentation which may indicate first admission as an episode and the second, a flare up. The case could have also been a combination of PANDAS and Bipolar Disorder thus the severity. Regardless, the interplay of biological and psychological facets have evidently magnified her predispositions leading to an intense manifestation of symptoms. Disclosure of Interest None Declared
2025-03-24 | The role of previous streptococcal infections in adult patients with obsessive-compulsive disorder: a research study.
Autoimmune processes have been documented in both childhood and adulthood patients with obsessive-compulsive disorder (OCD), with the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) representing the paradigm of this model.Given the limited information available, the present study aimed at assessing the characteristics of adult patients with OCD exposed to a previous group A β-hemolytic Streptococcus infection, together with some peripheral inflammatory biomarkers. Fifty-two subjects displaying antistreptolysin O (ASO) titer positivity were recruited from a sample of 247 adult OCD outpatients, diagnosed according to DSM-5 criteria and assessed by the Yale-Brown Obsessive-Compulsive Scale. Their clinical features were assessed and compared. The possible relationships between the different parameters were also examined. Thirty-six subjects who were on medication for OCD showed significantly lower ASO titers than the other. The neutrophil count was positively and negatively related to, respectively, the "distress associated with obsessive thoughts" item and to the patients' age. The lymphocyte count and folic acid levels were higher in 30 subjects with no perinatal insults. These results seem to suggest that OCD subjects with ASO titer-positivity show a chronic inflammatory state, in spite of no symptoms or recall of bacterial infections, that might be involved in both the onset and the maintenance of OCD, with immunological alterations being related to symptom dimension to be identified. They also support the notion of possible anti-inflammatory effects of some psychotropic compounds.
vaccines
2023-09-28 | Group A Streptococcus Vaccine Targeting the Erythrogenic Toxins SpeA and SpeB Is Safe and Immunogenic in Rabbits and Does Not Induce Antibodies Associated with Autoimmunity.
Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits' brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial.
2023-08-31 | Symptom flares after COVID-19 infection versus vaccination among youth with PANS/PANDAS.
Background: Flares of autoimmune conditions can happen after coronavirus disease 2019 (COVID-19) infection and after COVID-19 vaccines. Patients and clinicians confront difficult decisions about vaccine safety when considering efforts to balance the risks of disease exacerbation after vaccines versus the protection that vaccines offer to potential serious life-threatening complications of COVID-19 infection. Objective: To examine symptom flares after COVID-19 infection and vaccines in the case of a form of autoimmune encephalitis that primarily affects children and young adults (pediatric acute-onset neuropsychiatric syndrome [PANS] / pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections [PANDAS]). Method: A cross-sectional study that used a survey distributed through PANS/PANDAS groups, organizations, and clinics. Results: Surveys were completed by 496 parents and/or caregivers of children with PANS/PANDAS. Among the children reported to have had a COVID-19 infection (n = 178), 43% reported severe flares of PANS/PANDAS symptoms, 23% reported mild flares, and 30% reported no symptom flares. Among those who had received COVID-19 vaccines (n = 181), 65% observed no changes in PANS/PANDAS symptoms after the vaccine, 19% reported mild flares, and 15% reported severe flares. Paired sample t-tests showed that, after COVID-19 infections, children with PANS/PANDAS were significantly more likely to experience a severe symptom flare than a mild flare or no change in symptoms. In contrast, after receiving COVID-19 vaccines, children were significantly more likely to experience no change in PANS/PANDAS symptoms than to endure a mild or severe symptom flare. In addition, children who recovered from PANS/PANDAS were significantly more likely to have no symptom change versus children who were managing the condition, both after COVID-19 infection (92% versus 25%) and vaccine receipt (100% versus 66%). Conclusion: These results support COVID-19 vaccination for most individuals with PANS/PANDAS given that the frequencies of symptom flares and setbacks after COVID-19 infection were significantly higher than after the COVID-19 vaccine. Nonetheless, further studies are needed to fully assess the risk-benefit balance and to provide a more individualized approach to disease prevention in people with immune vulnerabilities.
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Drug Discovery Landscape
1 orphan drug designation for PANDAS.
1 orphan drug designation for PANDAS.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
sarcosine | small molecules | FDA | — | Guochuan Emil Tsai, MD, PhD |
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