Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the abrupt onset of neuropsychiatric symptoms, including obsessive-compulsive disorder and/or restricted food intake, in response to infection or other triggers. This mixed methods systematic review synthesized evidence on the lived experience and psychosocial impacts of caring for a child with PANS. Seventeen publications of moderate to high quality met eligibility criteria. Four synthesized findings emerged from the qualitative meta-aggregation: (i) broad psychosocial impacts on caregivers and families; (ii) shock and ongoing uncertainty arising from the sudden, severe onset and unpredictable symptom flares; (iii) pervasive systemic barriers to timely diagnosis, treatment, and educational support; and (iv) caregivers' proactive responses to the challenges of navigating PANS. Narrative synthesis of quantitative findings highlighted increased caregiver burden, and elevated psychological distress and relationship dissatisfaction. Disease activity, diagnostic and treatment delays, and disruption to schooling and employment were associated with greater impact. Implications for improving clinical recognition and supporting caregiver and family wellbeing are discussed.

Vector-borne diseases (VBDs) caused by Borrelia spp., Bartonella spp., and Babesia spp. are associated with neuropsychiatric morbidity. Cerebral folate deficiency (CFD), primarily caused by folate receptor-α autoantibodies (FRAAs) impairing folate blood-brain barrier transport, is a treatable contributor to neurodevelopmental disorders including pediatric acute-onset neuropsychiatric syndrome (PANS) and autism spectrum disorder. Despite overlapping clinical manifestations, FRAA prevalence in VBD populations has not been investigated. This study aimed to determine the prevalence of FRAA in patients with confirmed VBDs. This retrospective cohort study included 68 VBD-positive patients with and without PANS evaluated at a single clinical practice. VBD testing was performed by IGeneX Laboratories; FRAA analysis including binding, blocking, and soluble folate receptor (sFR) testing was performed by Religen Laboratories (Plymouth Meeting, PA). Statistical associations were assessed using Fisher's exact test with Wilson 95% confidence intervals. Of the 68 VBD-positive patients, 42 (61.8%; 95% CI: 49.9-72.4%) were also FRAA-positive. Soluble folate receptor (sFR) was detected in eight patients (11.8%; 95% CI: 6.1-21.5%), all of whom were binding FRAA-positive, with 87.5% carrying confirmed evidence of Borrelia species infection. Neuropsychiatric symptoms were highly prevalent across both groups but did not significantly differentiate FRAA-positive from FRAA-negative patients (all p > 0.05). This study demonstrates a high prevalence of FRAA in a pediatric VBD cohort. The sFR was strongly associated with Borrelia species infection, suggesting a potential mechanistic link between spirochetal infection and folate receptor autoimmunity. These findings support the consideration of FRAA testing in patients with VBDs and warrant further investigation in larger prospective cohorts.

Background: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) shares numerous clinical features with Tourette syndrome (TS), notably the presence of tics and frequent comorbidities such as obsessive-compulsive disorder, irritability, and ADHD-like behaviors, often indistinguishable, particularly in the early stages of the two syndromes. Also, pathogenic similarities between PANS and TS constitute a diagnostic challenge, highlighting the need for biomarkers elucidating the underpinnings of the two disorders. In this context, metabolomics has emerged as a powerful tool for identifying distinct biochemical patterns in various diseases. We previously compared PANS, autism patients, and controls, identifying specific metabolic patterns. However, no studies have directly compared the metabolomic profiles of Tourette syndrome and PANS patients. The present study aims to compare the serum metabolomic profiles of TS patients with those of PANS and healthy controls to advance the molecular understanding and clinical differentiation of these two pediatric neuropsychiatric disorders. Methods: Thirty-four PANS patients and twenty-three Tourette patients were matched with twenty-five healthy subjects (C), and their blood samples were analyzed with 1H NMR spectroscopy. Subsequently, data were analysed with multivariate and univariate statistical approaches. Results: Supervised models indicated that the metabolomic profile of TS patients was significantly different from that of controls (p = 0.02), with altered concentrations of glutamate, glycerol, glycine, lactate, and proline. No significant differences were found in the comparison between PANS and TS patients. Conclusions: These preliminary data suggest that Tourette and Pans also seem to share the metabolic profiles, while differences were found in TS patients compared to controls. On the other hand, the PANS phenotype comprises symptoms that largely overlap with those of all other NDDs, including TS, outlining a spectrum of disorders that share common pathogenetic pathways. Larger studies are needed to confirm these findings.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by abrupt-onset neuropsychiatric symptoms, often infection-triggered. Intravenous immunoglobulin (IVIG) is recommended by expert guidelines in select cases, yet insurance denials and high out-of-pocket costs have been barriers to access. We surveyed 60 caregivers and adult PANS patients who pursued IVIG therapy, collecting data on insurance coverage, treatment protocols, financial strategies, and quality of life (QoL) before and after treatment. Most patients (88%) eventually received IVIG, 10% were still in pursuit, and 2% discontinued trying. Insurance approval without appeal occurred for 24%, often for patients with comorbidities for which IVIG is typically covered. Only 5% of those receiving IVIG for PANS alone were treated within a month of the doctor's order compared with 38% of those receiving IVIG for comorbidities plus PANS; 14% waited ≥9 months. Financial strain was routine: at least one-third of families without "substantial" insurance coverage (≥70% of expenses) reported extreme stress (10 on scale of 1 to 10), 58% borrowed money, and 21% sold major assets. Even families with substantial insurance coverage commonly depleted savings or took on additional work. Before IVIG, patient QoL ratings were poor (means 2.1-2.9 across domains), with over one-third selecting the lowest possible overall QoL rating. During the 6 months following IVIG initiation, mean ratings rose to 6.2-6.8, with over 60% reporting "good" to "exceedingly good" overall outcomes. Caregivers reported parallel gains, with family QoL ratings rising from 2.4-4.0 pretreatment to 5.7-6.6 posttreatment. Families pursuing IVIG for PANS reported prolonged delays, repeated denials, and financial strain, often resorting to loans, asset sales, and additional work. Despite these burdens, IVIG was correlated with marked improvements in perceived QoL for patients and caregivers.

Background: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a disorder with symptoms of obsessive-compulsive disorder and/or tic disorders associated with group A streptococcal infection. PANDAS is considered a subtype of pediatric acute-onset neuropsychiatric syndrome (PANS), and both can cause disabling symptoms. The influence of PANS/PANDAS on family function is significant, with parents reporting many adaptations and disruptions to the family, including extreme financial, emotional, and social impacts (Dolce et al., 2022; Tang et al., 2021). Despite the publication of evidential literature in 1998, there remains a lack of skilled providers who are confident in diagnosing and treating this disorder. Parents report that finding a skilled provider and confirming a timely diagnosis are significantly difficult. This can cause a treatment delay for years with indeterminate consequences (Tang et al., 2021). Objective: This quality improvement initiative aimed to assess changes in providers' awareness and comfort with diagnosing and treating PANDAS following an educational intervention implemented as part of a quality improvement effort. Methods: Pretest/posttest descriptive survey was used for providers participating in an educational intervention. The educational intervention was a recorded PowerPoint created using the published PANS/PANDAS Diagnostic and Treatment Guidelines. Results: After completing the provider educational intervention, participants' comfort in diagnosing and treating PANDAS improved. Conclusions: Access to a knowledgeable provider is a significant barrier for families of PANDAS patients. An educational intervention on PANDAS improved comfort in providing diagnoses and treatment in a small cohort of providers. Implications for Nursing: PANDAS education for providers may improve the comfort in diagnosing and treating PANDAS in primary care, thus positively impacting the quality of care families receive.

The clinical utility of the comprehensive laboratory and medical investigations currently recommended for children with pediatric acute-onset neuropsychiatric syndrome (PANS) remains unclear. Notably, comparisons with relevant psychiatric control patients without suspected immunologic pathogenesis are lacking. To evaluate whether currently recommended laboratory investigations differentiate children with PANS from children with idiopathic obsessive-compulsive disorder (OCD) and/or tic disorders and whether the full set of recommended medical investigations identify underlying somatic conditions in children with PANS. This case-control study recruited children (aged 4-18 years) with PANS and children with idiopathic OCD and/or tic disorders (control group) from specialist PANS and OCD clinics in Stockholm, Sweden, between January 1, 2020, and September 19, 2023. The data analyses were performed between June 16, 2024, and August 19, 2025. Following published PANS guidelines, assessments included 56 laboratory variables from blood and throat cultures. Additional data from cerebrospinal fluid analysis, brain magnetic resonance imaging, and electroencephalography were available for a subsample of the PANS group. Laboratory findings were compared between the PANS and control groups. Among 109 participants, the PANS group included 51 children (mean [SD] age, 10.2 [3.4] years; 34 boys [66.7%], and the control group included 58 children (mean [SD] age, 13.6 [3.1] years; 29 boys [50.0%]). Nearly all participants had at least 1 abnormal laboratory finding (44 [86.3%] in the PANS group, 56 [96.6%] in the control group), with no significant between-group differences. Most participants in the PANS group had 3 or more abnormal laboratory findings, while most in the control group had 4 or more. One participant with PANS was diagnosed with celiac disease; another showed electroencephalographic signs of neuroinflammatory activity without a definite diagnosis prior to the PANS assessment. Incidental, nonactionable findings were frequent. In this case-control study of children with PANS and idiopathic OCD and/or tic disorders, abnormal laboratory findings were common in both groups and did not differ significantly. The full set of recommended medical investigations rarely identified underlying somatic conditions in children with PANS. These findings question the clinical utility of the comprehensive and costly medical investigations currently recommended for children with suspected PANS.

Clinical Utility of Medical Investigations in Pediatric Acute-Onset Neuropsychiatric Syndrome

Individuals with both avoidant/restrictive food intake disorder (ARFID) and pediatric acute-onset neuropsychiatric syndrome (PANS) report restrictive eating. Inflammatory and immunological alterations may drive the onset of restrictive eating and comorbid obsessive-compulsive (OC) symptoms in PANS, while the etiology of restrictive eating in ARFID is unknown. Nevertheless, few studies have explored PANS and related OC symptoms among individuals with ARFID. We aimed to identify the frequency and nature of PANS and OC symptoms among those with full or subthreshold ARFID. We also explored associations between OC severity, ARFID profiles, and infection history. The study included 37 adolescents and young adults with subthreshold or full ARFID. We quantified the frequency of PANS/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection symptoms and diagnoses, as well as OC symptoms and severity, in our ARFID sample. We analyzed associations between ARFID profiles and OC severity, along with the relationship between infection history and OC severity. Two individuals (5%) met PANS criteria, and 17 (46%) reported lifetime mild-severe OC severity. The fear of aversive consequences profile was associated with a significant increase in log-transformed OC severity (β = 1.2, p = 0.04, adjusted R2 = 0.10) after adjusting for sensory sensitivity, lack of interest, and body mass index z-score. We did not find any associations between OC severity and infection history. In the first study to examine PANS and related symptoms among individuals with ARFID, we demonstrated salient overlap between PANS, OC symptoms, and ARFID. Further research is needed to examine the relationship between ARFID and PANS.

Introduction: We recently identified variants in 10 genes that are members of either the p53 pathway or Fanconi Anemia Complex (FAC), regulators of DNA repair (DNA damage response [DDR]) in 17 cases with pediatric acute-onset neuropsychiatric syndrome (PANS) or regression in autism spectrum disorder and other neurodevelopmental disorders (NDD). We aimed to identify additional cases with genetic vulnerabilities in DDR and related pathways. Methods: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 32 individuals were filtered and analyzed to identify ultrarare pathogenic or likely pathogenic variants. Results: Variants affecting DDR were found in 14 cases diagnosed with PANS or regression (CUX1, USP45, PARP14, UVSSA, EP300, TREX1, SAMHD1, STK19, MYTl1, TEP1, PIDD1, ADNP, FANCD2, and RAD54L). The CUX1 variant is de novo, as are two cases that had mutations in genes that affect mitochondrial functions that are connected directly or indirectly to mitophagy (PRKN and POLG), which can trigger the same innate immune pathways when disrupted as abnormal DDR. We also found pathogenic or likely pathogenic secondary mutations in several genes that are primarily expressed in the gut that have been implicated in gut microbiome homeostasis (e.g., LGALS4, DUOX2, CCR9). Conclusion: These findings align with previous genetic findings and strengthen the hypothesis that abnormal DDR and mitochondrial dysfunction underlie pathogenic processes in at least some cases of neuropsychiatric decompensation. The potential involvement of genetic variants in gut microbiome homeostasis is a novel aspect of our study. Functional characterization of the downstream impact of DDR deficits may point to novel treatment strategies.

ABSTRACT Introduction Despite increasing recognition of pediatric acute-onset neuropsychiatric syndrome (PANS), its neuropsychological underpinnings remain limited, particularly in relation to obsessive-compulsive disorder (OCD) symptoms. PANS manifests abruptly with severe OCD and/or eating restrictions alongside concurrent neuropsychiatric symptoms, causing distress and functional impairment. This study aimed to examine the relationship between neurocognitive performance and OCD symptom severity in children and adolescents with PANS. Method Twelve children and adolescents with PANS were assessed on a total of 39 occasions using a novel touchscreen-based button-choice reaction time task. The task was designed to capture subtle aspects of attentional focus, motor precision, and response speed. Analyses examined associations between OCD symptom severity, assessed for each testing session, and performance measures. Results Greater OCD symptom severity was associated with heightened attentiveness (noticing the lit-up button) and more centered touch positioning, but not with faster reaction times. A significant interaction was observed, whereby increased attentiveness and precision in touch placement were linked to longer reaction times, suggesting a trade-off between speed and perfectionistic response strategies. Conclusions Overall, while OCD symptom severity was not directly associated with reaction time, it significantly shaped response monitoring and touch positioning. These findings indicate a neurocognitive profile in PANS characterized by heightened self-monitoring and meticulousness, potentially reflecting mechanisms underlying OCD symptomatology. Our findings highlight the complex interplay between neurocognitive performance and OCD symptom severity in PANS, as revealed through digital assessment, contributing to a deeper understanding of the condition.

Abstract This article describes the clinical process of an interdisciplinary team approach to the comprehensive assessment and treatment of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). These complex conditions present with abrupt-onset behavioral and psychiatric symptoms that require simultaneous medical and behavioral intervention. The clinic’s overall process is described, along with the roles and responsibilities of each team member, and emphasis is placed on how behavior analysts are integrated into this health-care setting. Also discussed are challenges to interdisciplinary collaboration, along with methods employed by the team to maintain and deliver cohesive, patient-centered care.

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.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is defined by an abrupt onset of neuropsychiatric symptoms, traditionally viewed through the lens of obsessive-compulsive behaviors. However, it is also characterized by a state of extreme fear. While medical management addresses the biological triggers, this period creates a high-stakes emergency in human fear-learning that remains unaddressed by standard protocols. The current gold standard, exposure and response prevention (ERP), is theoretically mismatched to this unconditioned fear state. How do we help children endure and learn from pre-reflexive fear that is not cognitively mediated, not titratable, involuntary, and remains at peak without habituation? While we wait for the child to become "stable enough" for therapy, primitive learning is already occurring. The question is whether that learning is therapeutically guided or left to raw survival. This conceptual paper proposes Fear Rebalance Therapy (FRT), a theoretical framework requiring empirical validation. It is a developmentally unfolding framework that integrates co-regulation, survival learning and inhibitory learning principles. FRT guides the child to learn the safety of the external world even while the body signals imminent threat. Many of the initial symptoms may be reconceptualized as a threat-dominant physiological state, leading to a cascade of defensive reactions. The PANS index episode represents a critical branch point. Without guided learning, incidental conditioning can lead to chronic, sensitized disability. FRT aims to help children learn to regulate their emotional responses to these internal alarms. This framework proposes that while neuroimmune responses trigger the crisis, the nature of the learning during that crisis may determine trajectory. Early psychological intervention should be an active component of crisis management rather than a post-crisis adjunct to medical care. Importantly, FRT addresses psychological learning processes occurring during the acute episode, not the underlying neuroimmune mechanisms, which remains the domain of medical management.

<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.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by the sudden onset of obsessive-compulsive symptoms alongside a constellation of neuropsychiatric and somatic features. Disease progression typically includes flare and recovery states, with some patients exhibiting a persistent disease course (> 12 months of flare). We characterized circulating monocyte subsets during flare and recovery in pediatric patients with PANS, uncovering disease-state–dependent shifts in polarization and trafficking phenotypes. Inflammatory M1-like monocytes and monocyte-derived dendritic cells were elevated during flare, while anti-inflammatory M2-like monocytes were enriched in recovery. We also identified a circulating subset with a surface phenotype consistent with central nervous system (CNS) homing, which was reduced during flare and restored in recovery. These cells were detectable in the cerebrospinal fluid (CSF) of new-onset patients but not in persistent cases, suggesting differential compartmentalization during disease progression. Notably, monocyte phenotypes, including M2 polarization (monocytosis) and circulating CNS-homing profiles, exhibited striking sex-associated differences, particularly during recovery, with several subsets enriched in males but not females. Plasma from flare-phase patients modestly induced CNS-homing markers in monocytes from healthy donors, indicating the presence of circulating modulators. Together, these findings support a model in which distinct myeloid phenotypes—including sex-biased patterns—may contribute to both the pathogenesis and resolution of neuroinflammation in PANS.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12974-025-03549-6.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroimmune condition that significantly affects children's occupational performance across multiple domains. However, occupational performance is often overlooked in current PANS clinical frameworks, despite its critical role in daily functioning and well-being. To synthesize evidence on the occupational performance challenges experienced by children with PANS, the tools used to assess these challenges, and occupational therapy interventions used with these children. MEDLINE, CINAHL, Cochrane Library, PsycINFO, SCOPUS, ERIC, and EMBASE were searched from their inception through May 17, 2024. Peer-reviewed studies addressing PANS and occupational performance were included, with data categorized using the Occupational Therapy Practice Framework, 4th Edition. Of 3,431 records, 40 studies met inclusion criteria. Occupational performance challenges centered on communication, nutrition, education, rest/sleep, social participation, and toileting, with limited data on bathing, dressing, personal hygiene, and play and leisure. Assessments emphasized client factors, rarely using occupation-based tools. Only 2 studies mentioned occupational therapy interventions. PANS has a pervasive impact on children's occupational performance, highlighting the urgent need to prioritize it within clinical frameworks. Future research should focus on occupation-based intervention studies and assessments to enhance outcomes for children with PANS. Plain-Language Summary: Pediatric acute-onset neuropsychiatric syndrome (PANS) causes sudden, severe symptoms, such as obsessive-compulsive behaviors, eating difficulties, sensory and motor changes, and developmental regression, which significantly disrupt children's ability to perform daily activities. This study included 40 research articles addressing what is known about the impact of PANS on children's daily functioning and the role of occupational therapy in managing challenges. Results showed that most studies focused on communication, nutrition, education, sleep, social, and toileting challenges, but few addressed other daily tasks like bathing, dressing, personal hygiene, and play or leisure. Despite identified challenges, only two studies mentioned occupational therapy interventions, highlighting a major gap in the evidence. Assessments focused mainly on a child's skills and challenges, rather than looking at how the child participates in everyday activities. The findings highlight the need to better understand the challenges children with PANS face in their everyday activities and to provide practical strategies to help them succeed. Positionality Statement: Newby is a pediatric occupational therapist and researcher with both professional and personal experience of PANS. Her clinical work with children diagnosed with PANS, along with personal experience supporting a family member with this condition, has deepened her interest in the episodic fluctuations in occupational performance that occur during periods of exacerbation and remission. Haracz is an occupational therapist, academic, and researcher with a focus on mental health and the intersection between physical and psychological well-being. Lane is an occupational therapist, academic, and researcher who specializes in the neuroscience of developmental conditions and how sensory processing differences affect children's engagement in daily occupations. Tona is an occupational therapist and educational psychologist whose interest in neuroinflammatory disorders emerged following a family member's diagnosis with PANS. Her research explores the characteristics of PANS, treatment access, caregiver burden, and the role of occupational therapy in improving participation in both PANS and long-COVID populations.

ObjectivesPediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by infection-provoked abrupt-onset obsessive compulsive disorder (OCD) and neurodevelopmental regression. Owing to the neuroimmune hypothesis, we investigated the effects of IV immunoglobulin (IVIg) on cell-specific gene expression.MethodsSingle-cell RNA sequencing of peripheral immune cells was performed in 5 children with PANS (median age 8 (5.5–16) years), before and after administering open-label IVIg, compared with 4 controls (median age 13.5 [IQR 12–15] years).ResultsThe index PANS event (age 1.8–13 years) involved abrupt eating restriction (n = 5), developmental regression (n = 4), and OCD (n = 3). A total of 144,470 cells were sequenced and clustered into 11 cell types. Children with PANS before IVIg compared with controls showed downregulated immune pathways (defense response, innate immunity, secretory granules) in most cell types, with natural killer (NK) cells showing upregulated immune pathways (response to corticosteroid), supporting baseline “immune dysregulation.” Ribosomal pathways were upregulated in neutrophils and CD8 T cells but downregulated in NK cells. In children with PANS after IVIg, the baseline immune and ribosomal pathway abnormalities were reversed and histone modification pathways (histone methyltransferase, chromatin) were downregulated in neutrophils and NK cells.DiscussionWe propose that PANS is an epigenetic immune brain disorder with cellular epigenetic, ribosomal, and immune dysregulation. Epigenetic and immune-modulating therapies, such as IVIg, may have disease-modifying effects.

Pediatric acute-onset neuropsychiatric syndrome: A single-center retrospective study.

Introduction.We recently identified variants in 10 genes that are members of either the p53 pathway or Fanconi Anemia Complex (FAC), regulators of the DNA repair (DNA damage response; DDR) in 17 cases with Pediatric Acute-Onset Neuropsychiatry Syndrome (PANS) or regression in autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDD). We aimed to identify additional cases with genetic vulnerabilities in DDR and related pathways.Methods.Whole exome sequencing (WES) and whole genome sequencing (WGS) data from 32 individuals were filtered and analyzed to identify ultrarare pathogenic or likely pathogenic variants.Results.Variants affecting DDR were found in 14 cases diagnosed with PANS or regression (CUX1, USP45, PARP14, UVSSA, EP300, TREX1, SAMHD1, STK19, MYTl1, TEP1, PIDD1, ADNP, FANCD2, and RAD54L). The CUX1 variant is de novo, as are two cases who had mutations in genes that affect mitochondrial functions that are connected directly or indirectly to mitophagy (PRKN and POLG), which can trigger the same innate immune pathways when disrupted as abnormal DDR. We also found pathogenic or likely pathogenic secondary mutations in several genes that are primarily expressed in the gut that have been implicated in gut microbiome homeostasis (e.g., LGALS4, DUOX2, CCR9).Conclusion.These findings align with previous genetic findings and strengthen the hypothesis that abnormal DDR and mitochondrial dysfunction underly pathogenic processes in neuropsychiatric decompensation. The potential involvement of genetic variants in gut microbiome homeostasis is a novel aspect of our study. Functional characterization of the downstream impact of DDR deficits may point to novel treatment strategies.

Abstract Date Presented 04/04/2025 Examining the impact of pediatric acute-onset neuropsychiatric syndrome (PANS) exacerbation on occupational performance, we found typical performance at remission but significant declines at exacerbation. Thus, targeted OT interventions are needed. Primary Author and Speaker: Michelle J. Newby Contributing Authors: Shelly Lane, Janice Tona, Kirsti Haracz