Pediatric Acute-onset Neuropsychiatric Syndrome Research Articles

Implementing dietary changes with children affected by PANS/PANDAS

ABSTRACT PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) is characterized by acute-onset of obsessive-compulsive disorder (OCD) or disordered eating, as well as anxiety, tics, and developmental regressions, among other neuropsychiatric symptoms, after an infection or exposure to environmental triggers. PANS symptoms, which can be chronic and fluctuate in severity for several years, develop because of an aggressive autoimmune reaction to brain structures. Studies suggest that dietary changes, such as replacing industrialized foods with organic or eliminating gluten or dairy, can be important for autoimmune conditions. This mixed-method study examines dietary changes implemented as part of treatment for PANS and PANDAS (Pediatric Autoimmune Neuropsychiatric Syndrome Associated with Streptococcus), which is a subset of PANS, through in-depth interviews with families and clinicians and a caregiver survey. 64.7% of the 467 survey participants indicated that a healthcare provider recommended dietary changes as part of PANS/PANDAS treatment. 55.7% of the families did implement dietary changes and 69.6% reported at least one diet to be somewhat effective in helping with PANS/PANDAS symptoms, with 36% reporting dietary changes to be very effective, particularly gluten-free and sugar-free diets. However, some parents and clinicians highlighted children’s resistance to new diets and concerns about worsening OCD and food restrictive disorders as barriers to implementing dietary changes.

Psychometric Properties of the PANS 31-Item Symptom Rating Scale.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population.

The folate receptor alpha autoantibodies (FRAAs) are associated with cerebral folate deficiency (CFD) and autism spectrum disorder (ASD). Both of these syndromes have overlapping characteristics with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Thus, we propose that the FRAAs may contribute to the symptomatology of PANS/PANDAS. To test this hypothesis, 1 mL of serum from 47 patients (age range = 6-18 years old) clinically diagnosed with PANS/PANDAS was sent to Vascular Strategies (Plymouth Meeting, PA, USA) for analysis of FRAAs. Moreover, 63.8% of PANS/PANDAS patients (male = 15; female = 15) were found to have either the blocking and/or blinding FRAAs, with 25 (83.3%; male = 14; female = 11) having binding FRAAs, two (6.7%; all female = 2) having blocking FRAAs, and 3 (10%; male = 1; female = 2) having both binding and blocking. Furthermore, surprisingly, ASD was associated with a 0.76 lower binding titer (p = 0.02), and severe tics were associated with a 0.90 higher binding titer (p = 0.01). A case of a FRAA-positive patient is provided to illustrate that a treatment plan including leucovorin can result in symptom improvement in patients with PANS/PANDAS who are FRAA-positive. These data, for the first time, demonstrate that PANS/PANDAS is associated with FRAAs and suggest folate metabolism abnormalities may contribute to PANS/PANDAS symptomatology. Further studies investigating the therapeutic nature of leucovorin in the treatment of PANS/PANDAS are needed. Such studies may open up an alternative, safe, and well-tolerated treatment for those with the PANS/PANDAS diagnosis.

Neuropsychıatrıc dısorders assocıated wıth chıldhood ımmunologıc dysfunctıon

Introduction. These disease entities are known as pediatric neuropsychiatric syndromes because infectious pathogens other than streptococci have also been reported to be associated with neuropsychiatric symptoms. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS).
 Aim. The aim of this study was to evaluate neuropsychiatric disorders associated with immunologic dysfunction in childhood.
 Overview. PANS/PANDAS refers to the acute and dramatic onset of a neuropsychiatric syndrome in children, including OCD and/or tics. It is believed to be the result of an autoimmune reaction to the basal ganglia nuclei, initiated by infection with group A streptococci. Studies indicate neuroinflammatory reactions in the basal ganglia and related networks.
 Conclusions. Evaluating treatment strategies for PANS/PANDAS remains a challenge because it is a rare disease with few published high-quality studies. Little is known about its etiology, diagnostic methods, treatments or long-term effects. However, as hundreds of children and families suffer from the debilitating effects of the disease, infectious diseases should be carefully evaluated for PANS/PANDAS, especially in the pediatric age group. Even in the absence of evidence on which to base interventions, it is within the scope of advanced nursing practice to provide psychotherapeutic care with an empathetic perspective to children and families struggling with the frustration, fear and anxiety caused by illness.

Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objective: Children with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) experience sudden onset neuropsychiatric symptoms after infection or other triggers. Symptoms range from mild to severe, potentially lasting days, weeks, months, or longer. Exacerbation-related functional decline presents in many aspects of daily life, generally accompanied by family stress and caregiver burden. We sought to investigate the relationship between severity of PANS symptoms and caregiver burden/stress and the relationship between severity of PANS symptoms and degree of caregiver/child cohesion. Methods: This cross-sectional online study surveyed caregivers recruited from PANS-related social media support sites. The Pediatric Acute Neuropsychiatric Symptom Scale - Parent Version (PNSS) measured current severity. Caregiver Burden Inventory (CBI) and Caregiver Self-Assessment Questionnaire (CSAQ) assessed caregiver burden/stress. Inclusion of Other in the Self (IOS) scale determined caregiver-perceived current and desired cohesion with their child(ren) with PANS. Results: Of the 216 respondents 79.6% exceeded CBI threshold indicating need for respite in adult care receiver populations. On the CSAQ, 72.9% expressed high distress, 80.5% reported feeling overwhelmed, and 58.1% reported crying spells, meeting cutoffs for support/respite used in adult care receiver populations. Most caregivers reported not having the desired degree of cohesion with their child on the IOS (85.5%). Parents of children with more severe PNSS symptoms fared significantly worse on all measures (CBI: H = 57.83; CSAQ: F = 29.26; IOS: H = 38.04; p < 0.001 for all). Content analysis of comments revealed five themes: (1) severe caregiver and/or family emotional distress and trauma; (2) caregivers wondering what happened to their child; (3) lack of awareness and support among health and education professionals; (4) relationship strain with family, friends, and significant others; and (5) financial and/or legal struggles because of their child's diagnosis. Conclusion: There is strong need for support and respite for children with PANS and their families. Long-term effects including posttraumatic stress symptoms among family members should be studied.

Factors Associated with Symptom Persistence in PANS: Part I-Access to Care.

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) presents with abrupt neuropsychiatric symptoms, often after an immunologic trigger. A 2017 survey of 698 subjects found diagnostic delays to be associated with recurrences, suggesting that timely care impacts course. This secondary analysis explores the impact of barriers to care on symptom persistence. Methods: A 146-question online survey gathered history, symptomatology, intervention, and outcome data from subjects with PANS. Multivariate analyses examined associations between symptom persistence over the entire reported disease course, measured as % days symptom-free over reporting periods averaging approximately 4 years, and access-to-care history, reflected in availability of medical expertise and affordability of care. The impacts of time from symptom onset to treatment and effectiveness of initial antibiotics were also examined. Results: Among the 646 subjects analyzed, greater symptom persistence was associated with longer intervals between symptom onset and treatment (F = 4.43, p = 0.002). Thirty-four percent of subjects with the least symptom persistence (>75% symptom-free days), versus 13% of those with the most (symptoms every day), had been diagnosed by the first practitioner seen (likelihood ratio [L-R] χ2 = 36.55, p < 0.0001, for comparison across all groups). Diagnosis and treatment had not been impeded by lack of access to expertise for 52% of subjects with the least persistent symptoms, versus 22% of those with the most (L-R χ2 = 22.47, p < 0.0001). Affordability had not impacted diagnosis and treatment for 76% of subjects with the least persistent symptoms, versus 42% of those with the most (L-R χ2 = 27.83, p < 0.0001). The subjects whose PANS symptoms resolved with antibiotic treatment of the inciting infection experienced less symptom persistence than others (χ2 = 23.27, p = 0.0001). More persistently symptomatic subjects were more likely to have discontinued intravenous immunoglobulin (IVIG) treatment for access-to-care reasons. Conclusions: Unimpeded access to care for PANS is associated with more symptom-free days over reporting periods averaging approximately 4 years. Difficulty reaching expert providers, missed opportunities for diagnoses, and financial limitations may worsen outcomes. Practitioners, particularly primary providers, should adhere to published diagnostic and treatment guidelines promptly upon presentation.

Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is defined by acute onset of diverse neuropsychiatric manifestations, presumably in the setting of underlying immune dysfunction. We used standardized neuropsychological testing to assess how intravenous immunoglobulins (IVIG) impact neurological and cognitive functions in PANS patients by comparing pretreatment with post-treatment scores. A 5-year retrospective study was undertaken in Children's Postinfectious Autoimmune Encephalopathy Center at University of Arizona. We identified 12 children diagnosed with PANS and treated with immunomodulatory IVIG doses, who also completed neuropsychological testing before and after treatment. We tracked multiple patient characteristics, type/timeline of testing, and number of IVIG courses. Score change of 1 standard deviation in any tested domain/subdomain was considered improvement. We further reviewed records for laboratory signs of triggering infection and immune dysfunction. Improvement occurred in 11/12 patients, in one or multiple domains/subdomains, independently of time between disease onset and IVIG initiation (0-7 years). Participants received 1-7 IVIG courses. Improvement was primarily seen in memory (58%), sensory-motor (37%) and visual-motor integration (30%). In 5/12 patients we detected hypogammaglobulinemia requiring ongoing IVIG replacement, one patient had isolated low IgA. Only one patient had to discontinue IVIG therapy due to severe adverse effects. Standardized neuropsychological testing represents an important tool to objectively measure improvement in PANS patients. IVIG was tolerated well and showed efficacy in the vast majority of participants, independently from timelapse since disease onset, emphasizing impact of immunomodulation in PANS. Significant presence of baseline hypogammaglobulinemia in children with PANS emphasizes the presumed role of immune dysfunction in disease pathogenesis.

An Exploratory Study of Obsessive-Compulsive Behavior and School Problems Associated with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an increasingly studied disorder that has been linked to negative neuropsychiatric outcomes, with the most frequently cited consequence being rapid onset of obsessive-compulsive symptoms. Little is known, however, about the educational impacts of this disorder on school-aged children. This study aimed to learn (1) what school-related problems do parents report in children with PANS?; (2) with what frequency do school-aged children with PANS receive formal special services at school?; (3) what types and severity of obsessions and compulsions are exhibited by school-aged children with PANS?; and (4) does OCD symptom severity classification predict the presence of a school special service plan? Parents (n = 208) of children with PANS participated in this study by completing a survey that included the Children’s Yale-Brown Obsessive-Compulsive Scale Parent Report (CY-BOCS-PR) and additional questions regarding child school performance and participation in formal special services at school. Anxiety and inattention, among a variety of other school-based problems, are reported at school in this population. Approximately 60% of the children received some form of school special services across their educational career. A variety of mild to severe obsessive-compulsive behaviors were reported in the children, though the severity of those behaviors did not predict the existence of a school special services plan. School psychologists must be prepared to evaluate children with PANS and recommend evidence-based interventions.

Estimate of the incidence of PANDAS and PANS in 3 primary care populations.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute-Onset Neuropsychiatric syndrome (PANS) are presumed autoimmune complications of infection or other instigating events. To determine the incidence of these disorders, we performed a retrospective review for the years 2017-2019 at three academic medical centers. We identified the population of children receiving well-child care at each institution. Potential cases of PANS and PANDAS were identified by including children age 3-12 years at the time they received one of five new diagnoses: avoidant/restrictive food intake disorder, other specified eating disorder, separation anxiety disorder of childhood, obsessive-compulsive disorder, or other specified disorders involving an immune mechanism, not elsewhere classified. Tic disorders was not used as a diagnostic code to identify cases. Data were abstracted; cases were classified as PANDAS or PANS if standard definitions were met. The combined study population consisted of 95,498 individuals. The majority were non-Hispanic Caucasian (85%), 48% were female and the mean age was 7.1 (SD 3.1) years. Of 357 potential cases, there were 13 actual cases [mean age was 6.0 (SD 1.8) years, 46% female and 100% non-Hispanic Caucasian]. The estimated annual incidence of PANDAS/PANS was 1/11,765 for children between 3 and 12 years with some variation between different geographic areas. Our results indicate that PANDAS/PANS is a rare disorder with substantial heterogeneity across geography and time. A prospective investigation of the same question is warranted.

The PANDAS/PANS disorders. Is it time for more allergist-immunologists to get involved?

Background: The pediatric autoimmune neurologic disorders associated with streptococcal infections (PANDAS) comprise a group of patients who, after infection with group A β-hemolytic streptococci (GAS), exhibit a spectrum of neuropsychiatric symptoms that include obsessive thoughts, compulsive behaviors, tics, hyperactivity, inattention, and mild choreiform movements. More recently, a group of patients with a symptom complex similar to PANDAS without evidence of streptococcal etiology was given the acronym pediatric acute-onset neuropsychiatric syndrome (PANS). Despite more than several decades of study and increasing numbers of patients being identified with PANDAS and PANS, there are ongoing controversies, which range from disagreements about specific pathogenetic mechanisms to whether these entities actually exist. Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship(s) of immunologic host responses to infection and putative immunologic mechanisms involved in the pathogenesis of these disorders, to evaluate the effectiveness of anti-inflammatory and immunomodulatory therapies with intravenous immunoglobulin (IVIG), and to consider the extent to which allergist/immunologists might be involved in their management. Methods: An extensive literature review was conducted in medical literature data bases by applying terms such as PANDAS, PAN, autoimmune encephalitis, neuroinflammation, and autoimmune obsessive-compulsive disorders. Results: PANDAS and its later iterative form, PANS, continue to challenge clinicians, patients, and their families. Although the precise reason why these disorders develop remains unknown, both are considered to have an autoimmune basis related to the production of antibodies directed at antigens of the putative causative infectious disease agents that are cross-reactive with antigenic epitopes on selected brain nuclei, which lead to the neuroinflammatory sequelae responsible for the neuropsychiatric symptoms of these conditions, a phenomenon referred to as molecular mimicry. Conclusion: The PANDAS/PANS disorders are a continuing burden for growing numbers of patients, health-care providers, and the global health-care systems, and are a particular challenge for the allergist/immunologist who is increasingly being called upon for their management. Because of the importance of immunologic factors in the pathogenesis and treatment of these conditions with anti-inflammatory and immune-modulating treatments, the allergist/immunologist is well poised to offer consultative care.

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.

Caregiver Burden, Stress, &amp; Relationship Cohesion Among Caregivers of Children With Pediatric Acute-Onset Neuropsychiatric Syndrome

Abstract Date Presented 04/22/2023 Children with pediatric acute-onset neuropsychiatric syndrome (PANS) experience sudden neuropsychiatric symptoms after infection. This study investigated the relationship between children’s severity of symptoms and caregiver burden and degree of cohesion between the caregiver and care recipient. Primary Author and Speaker: Janice Tona Additional Authors and Speakers: Julie Ash, Emily Brown, Courtney Campagna, Kellie Kostek, Erin Lawton, Andrea Rieth

Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of comorbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) were used to assess whether the time to juvenile idiopathic arthritis (JIA) or autoimmune disease (AI) onset was a function of total C4A or C4B CN. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes, and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (hazard ratio = 2.7, p value = 0.004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis, and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.

Identifying Neurobiological Markers in Obsessive–Compulsive Disorder: A Study Protocol for a Cross-Sectional Study in Subgroups of Differing Phenotype

Obsessive–compulsive disorder (OCD) represents a frequent and highly disabling mental disorder. Past attempts to characterize different disease subgroups focused on the time of onset (late vs. early onset), presence of insight (poor insight), and post-infectious forms (pediatric acute-onset neuropsychiatric syndrome, PANS). Each subgroup may be associated with a differing impact on cognition, functioning, sleep quality, and treatment response profile. Certain lines of evidence suggest brain-derived neurotrophic factor (BDNF) levels may differ between individuals living with OCD as compared with controls, but there is a lack of evidence on the variation of BDNF levels in OCD subgroups. Lastly, the potential of assessing inflammatory states, electroencephalogram, and polysomnography to characterize these subtypes has been hardly explored. Estimates of drug-resistance rates indicate that 20% and up to 65% of affected adults and up to 35% of the pediatric population may not benefit from pharmacological treatments. At least part of the variability in treatment response could depend on the underlying biological heterogeneity. In the present project, we aim to increase the accuracy in characterizing the phenotypical and biological signature for the different OCD subtypes through clinical, cognitive, and sleep markers, along with other possible markers that may be biologically plausible.

Pediatric Acute-Onset Neuropsychiatric Syndrome: Current Perspectives.

Pediatric acute-onset neuropsychiatric syndrome (PANS) features a heterogeneous constellation of acute obsessive-compulsive disorder (OCD), eating restriction, cognitive, behavioral and/or affective symptoms, often followed by a chronic course with cognitive deterioration. Animmune-mediated etiology is advocated in which the CNS is hit by different pathogen-driven (auto)immune responses. This narrative review focused on recent clinical (ie, diagnostic criteria, pre-existing neurodevelopmental disorders, neuroimaging) and pathophysiological (ie, CSF, serum, genetic and autoimmune findings) aspects of PANS. We also summarized recent points to facilitate practitioners with the disease management. Relevant literature was obtained from PubMed database which included onlyEnglish-written, full-text clinical studies, case reports, and reviews. Among a total of 1005 articles, 205 were pertinent to study inclusion. Expert opinions are converging on PANS as the effect of post-infectious events or stressors leading to "brain inflammation", as it is well-established for anti-neuronal psychosis. Interestingly, differentiating PANS from either autoimmune encephalitides and Sydenham's chorea or from alleged "pure" psychiatric disorders (OCD, tics, Tourette's syndrome), reveals several overlaps and more analogies than differences. Our review highlights the need for a comprehensive algorithm to help both patients during their acute distressing phase and physicians during their treatment decision. A full agreement on the hierarchy of each therapeutical intervention is missing owing to the limited number of randomized controlled trials. The current approach to PANS treatment emphasizes immunomodulation/anti-inflammatory treatments in association with both psychotropic and cognitive-behavioral therapies, while antibiotics are suggested when an active bacterial infection is established. A dimensional view, taking into account the multifactorial origin of psychiatric disorders, should suggest neuro-inflammation as a possible shared substrate of different psychiatric phenotypes. Hence, PANS and PANS-related disorders should be considered as a conceptual framework describing the etiological and phenotypical complexity of many psychiatric disorders.

A novel tablet-based motor coordination test performs on par with the Beery VMI subtest and offers superior temporal metrics: findings from children with pediatric acute-onset neuropsychiatric syndrome

Neuropsychiatric and neurodevelopmental disorders are often associated with coordination problems. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) constitutes a specific example of acute and complex symptomatology that includes difficulties with motor control. The present proof-of-concept study aimed at testing a new, bespoke tablet-based motor coordination test named SpaceSwipe, providing fine-grained measures that could be used to follow-up on symptoms evolution in PANS. This test enables computationally precise and objective metrics of motor coordination, taking into account both directional and spatial features continuously. We used SpaceSwipe to assess motor coordination in a group of children with PANS (n = 12, assessed on in total of 40 occasions) and compared it against the motor coordination subtest from the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) 6th edition, traditionally used to follow-up symptomatology. Using a bivariate linear regression, we found that 33 s of the directional offset from tracking a moving target in SpaceSwipe could predict the Beery VMI motor coordination (VMI MC) raw scores (mean absolute error: 1.75 points). Positive correlations between the predicted scores and the VMI MC scores were found for initial testing (radj = 0.87) and for repeated testing (radj = 0.79). With its short administration time and its close prediction to Beery VMI scores, this proof-of-concept study demonstrates the potential for SpaceSwipe as a patient-friendly tool for precise, objective assessment of motor coordination in children with neurodevelopmental or neuropsychiatric disorders.

Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD): functional connectivity and cytokines associated with symptomatic improvements

IntroductionImmunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.ObjectivesWe aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).MethodsIn an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.ResultsNineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.ConclusionsAberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.Disclosure of InterestNone Declared

PANS et SREAT. À propos de deux entités rares neuropsychiatriques médiées par l’immunité : clinique et traitements

Many systemic diseases with psychiatric symptoms are considered rare in the general population but may be under-diagnosed in child and adolescent psychiatry. These conditions are important to know about, as they may lead to pharmacoresistance to psychiatric medication but also benefit from specific management. Through two clinical cases followed by data from the literature on their diagnosis and management, we present two rare immune-mediated disorders to be considered in the presence of obsessive-compulsive disorder or early-onset schizophrenia (respectively PANS – Pediatric Acute-onset Neuropsychiatric Syndrome – and SREAT – Steroid Responsive Encephalopathy Associated with Thyroiditis).

Untimely care: How the modern logics of coverage and medicine compromise children's health and development.

How do families manage when health care systems do not "cover" and clinicians do not acknowledge their children's condition? This article presents an ethnographic study in the Northeastern region of the United States with 20 families with children diagnosed with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). Two of the 20 families had moved to the U.S. seeking care. The for-profit structure of the U.S. health care system resulted in costly and lengthy therapeutic journeys to access a diagnosis and adequate treatments. In the U.S., PANS/PANDAS coverage depends on legislation, advocacy, clinical characteristics of each child, and how for-profit insurance companies react to an increased demand for a given service. Many medical professionals, both in the U.S. and in other countries, refuse to acknowledge the condition or offer effective treatments that lack "acceptable" evidence. We argue that the financial logic behind coverage exists across modern health care systems and imposes restrictions and exclusions that impede access to care. Thus, untimely care, the time gap from PANS/PANDAS symptoms to diagnosis and treatment is the result of the modern logics that structure medicine and coverage. The results of this study illustrate how modern medicine and coverage fail to protect families with children with PANS/PANDAS against catastrophic expenses and often block care that would prevent developmental disruptions and losses, avoid much suffering, and even save costs to health care systems. New and controversial conditions like PANS/PANDAS highlight the importance of separating the financial logics behind proposals such as "universal health coverage" from the provision of comprehensive forms of care that acknowledge uncertainty and prioritize action and flexibility.

Neuropsychiatric Testing Provides Objective Insight Into Beneficial Effects Of Intravenous Immunoglobulins In Patients With Pediatric Acute-Onset Neuropsychiatric Syndrome

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is defined by acute beginning of diverse neuropsychiatric symptoms, likely in the setting of underlying immune dysfunction. Thus, immunomodulatory interventions have a crucial therapeutic role, but objective post-treatment evaluations remain challenging given disease complexity. We used standardized neuropsychiatric testing to assess how intravenous immunoglobulins (IVIG) impact cognitive function.