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.

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models.

INTRODUCTION: Pediatric obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) have been associated with respiratory tract infections and alterations in the intestinal microbiome, respectively. Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) refers to the sudden onset of neuropsychiatric symptoms that are triggered by several infectious and non-infectious factors. Studies indicate that inflammation plays an important etiological role in PANS, as well as in ASD associated with gut dysbiosis. AREAS COVERED: The present review provides an overview of clinical studies of PANS and ASD associated with gastrointestinal symptoms, as well as existing strategies for investigating these syndromes in rodent models. The authors highlight similarities between these syndromes that may provide clues to common etiological mechanisms. EXPERT OPINION: Although data from animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and noninfectious triggers. The authors propose an animal modeling strategy that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.

Understanding parental stress among parents of children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) in Sweden.

PURPOSE: Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a relatively new diagnosis characterized by an abrupt and dramatic onset of obsessive-compulsive disorder (OCD), together with neuropsychiatric symptoms. Very little research has been done to understand the experience of being a parent of a child with PANS. The current study aimed to explore aspects related to parental stress in parents of children with PANS. METHOD: The study employed in-depth semi-structured individual interviews with 13 parents of children diagnosed with PANS. Parents were recruited via an announcement on the websites of patient organizations, and in waiting rooms at child medical clinics. An inductive qualitative content analysis approach was used as a guide for analysis of data. RESULTS: The analysis of interviews identified five categories of parents' experiences of stress related to: (1) being effected by the symptoms; (2) experiencing the symptoms over and over again; (3) having no control; (4) obtaining medical treatment is challenging; and (5) managing problems. The results are discussed in relation to the Transactional Theory of Stress and Coping. CONCLUSIONS: the study illuminates how parents' perceptions of the child's symptoms, parents' strategies for managing problems, as well as experiences related to healthcare providers, may increase or decrease parental stress.

Inflammatory neuropsychiatric disorders and COVID-19 neuroinflammation.

Neuropsychiatric sequalae to coronavirus disease 2019 (COVID-19) infection are beginning to emerge, like previous Spanish influenza and severe acute respiratory syndrome episodes. Streptococcal infection in paediatric patients causing obsessive compulsive disorder (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, widespread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long-term-specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favourable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease-modifying therapies are increasingly being applied to neuropsychiatric diseases characterised by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

Evaluation of women's worries in different strategies for the prevention of early onset group B streptococcal disease in neonates.

OBJECTIVE: Early onset group B streptococcal (EOGBS) disease is an important cause of neonatal morbidity and mortality. EOGBS preventive strategies aim to reduce the risk of neonatal complications. Two new strategies to prevent EOGBS were implemented in two regions in the Netherlands: a risk-based and a combination strategy and were compared to the Dutch strategy in a third region. Little is known how women feel about preventive EOGBS strategies, the consequences for management during labour, side effects such as harm caused by over prescribing of antibiotics or anxiety caused by screening. Women's worries in pregnancy overall and on women's worries related to GBS regarding the different strategies were explored. METHODS: Design - Setting - Participants - Interventions (if appropriate) - Before implementation of the two new strategies, all three regions worked according to the Dutch strategy. Women completed the Cambridge worry scale and a newly developed worry scale aimed to detect GBS related worries at 35 weeks of pregnancy before (T0) and after (T1) implementation of new strategies. Analyses were performed to test whether women's overall worries in pregnancy and their GBS related worries differed between the three strategies. MEASUREMENTS AND FINDINGS: In total 1369 women participated, 519 before implementation (T0) and 850 during implementation (T1) of EOGBS preventive strategies. Mean overall worries in pregnancy and GBS related worries were low during the whole study period in all three regions. No differences were found in total mean GBS related worries between the three strategies during implementation (T1). When looking at the combined 10% highest CWS and/or GBS related worries during implementation the adjOR were 1.94 (95% CI 1.21-3.12) for the combination strategy, 2.09 (95% CI 1.42-3.08 for primiparity and 6.37 (95% CI 2.98-13.60) for having a different country of origin. KEY CONCLUSIONS: Overall women had minor GBS related worries in all EOGBS preventive strategies. Implementation of the combination strategy, primiparity and having a different country of origin are associated with the highest levels of overall worries in pregnancy and GBS related worries. IMPLICATIONS FOR PRACTICE: The low level of women's worries combined with limited effects and cost effectiveness of the three strategies suggests that the strategy with the least costs and lowest antibiotic use should be implemented. A more tailored approach seems needed to address the specific needs of primiparous women and of women from different countries of origin when implementing the combination strategy.

Alterations in the Nervous System and Gut Microbiota after ß-Hemolytic Streptococcus Group A Infection-Characteristics and Diagnostic Criteria of PANDAS Recognition.

The objective of this paper is to review and summarize conclusions from the available literature regarding Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The authors have independently reviewed articles from 1977 onwards, primarily focusing on the etiopathology, symptoms, differentiation between similar psychiatric conditions, immunological reactions, alterations in the nervous system and gut microbiota, genetics, and the available treatment for PANDAS. Recent research indicates that PANDAS patients show noticeable alterations within the structures of the central nervous system, including caudate, putamen, globus pallidus, and striatum, as well as bilateral and lentiform nuclei. Likewise, the presence of autoantibodies that interact with basal ganglia was observed in PANDAS patients. Several studies also suggest a relationship between the presence of obsessive-compulsive disorders like PANDAS and alterations to the gut microbiota. Further, genetic predispositions-including variations in the MBL gene and TNF-α-seem to be relevant regarding PANDAS syndrome. Even though the literature is still scarce, the authors have attempted to provide a thorough insight into the PANDAS syndrome, bearing in mind the diagnostic difficulties of this condition.

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms.

OBJECTIVE: This retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). METHODS: In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. RESULTS: Comparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10-6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. CONCLUSION: This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.

Neuropsychiatric consequences of childhood group A streptococcal infection: A systematic review of preclinical models.

In recent years, clinical studies have shown strong epidemiological evidence of an increased risk of developing neuropsychiatric disorders after childhood exposure to streptococcal infection, including the Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS). New preclinical studies on group A streptococcus (GAS) exposure investigate how to disentangle the influences of immune activation to induce long-term neurobehavioral effects associated with neuropsychiatric disorders such as obsessive-compulsive disorder, schizophrenia or autism. The present systematic review collects neurobehavioral evidence regarding the use of GAS exposure in animal models to study the vulnerability to different neuropsychiatric disorders, improving our understanding of its possible causes and consequences, and compares its contribution with other preclinical models of immune activation in a variety of paradigms. Specifically, we reviewed the effects of postnatal GAS exposure, in comparison with post- and prenatal exposure to Lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly I:C), on the long-term effects concerning psychomotor, cognition and socioemotional outcomes in rodents. GAS exposure in animal models has revealed different behavioral alterations such as reduced locomotion and motor coordination, a deficit in sensorimotor gating, learning, working memory, altered social behavior, and increased anxiety and stereotyped behavior. Most of the results found are in accordance with other immune activation models -LPS and Poly I:C-, with some discrepancies. The systematic review of the literature supports the preclinical model of GAS exposure as a valid model for studying the neurobehavioral consequences of streptococcal infections. Future studies on streptococcal infection could contribute increasing our knowledge on preventive actions or treatments for neuropsychiatric disorders.

Inflammation in Tic Disorders and Obsessive-Compulsive Disorder: Are PANS and PANDAS a Path Forward?

This review and commentary is the product of an invited lecture called "Autoimmunity: PANS/PANDAS" presented at the 2018 Neurobiology of Diseases in Children Symposium in Chicago, IL. The talk addressed clinical and scientific questions and recently published data. At this time, among highly experienced and respected clinicians and researchers spanning relevant disciplines, there is substantial controversy regarding a role for inflammation in producing tics and obsessive-compulsive disorder. This commentary summarizes these controversies, discusses reasons for opposing views on best clinical practices, and concludes with suggestions for pathways forward.

Brain imaging can predict neurodevelopmental outcome of Group B streptococcal meningitis in neonates.

AIM: The association between cranial ultrasound (CUS) or magnetic resonance imaging (MRI) lesions and neonatal Group B streptococcal (GBS) meningitis outcome has not been studied in detail. METHODS: This retrospective study assessed CUS, cranial MRI and neurodevelopmental outcome in 50 neonates with GBS meningitis admitted to three neonatal intensive care units in the Netherlands between 1992 and 2014. Death, cognitive outcome and motor outcome below -1 SD were considered as adverse outcomes. RESULTS: CUS was available in all and MRIs in 31 infants (62%) with 28 CUS (56%) and 27 MRIs (87%) being abnormal. MRI lesions were multifocal (n = 10, 37%), bilateral (n = 22; 82%) and extensive (n = 11; 41%). A total of 10 died in the neonatal period. Median age at assessment was 24 months. Among survivors, abnormal cognitive outcome and motor outcome were seen in 23 and 20 patients, respectively. Abnormal CUS [odds ratio (OR) 5.3, p = 0.017], extensive bilateral deep grey lesions (OR 6.7, p = 0.035) and white matter lesions (OR 14.0, p = 0.039) correlated with abnormal motor outcome. Extensive bilateral deep grey matter lesions correlated with abnormal cognitive outcome (OR 8.1, p = 0.029). CONCLUSION: Abnormal CUS and the most severely affected MRIs were associated with poor neurodevelopmental outcome in neonatal GBS meningitis.

Hyperactive behavior in female rats in utero-exposed to group B Streptococcus-induced inflammation.

Group B Streptococcus (GBS) is one the most common bacterium responsible of maternal infections during pregnancy. Offspring in utero-exposed to GBS-induced placental inflammation displayed sex-specific forebrain injuries. Sex differences have been reported in several neuropsychiatric disorders. Hence, we hypothesized that female rats in utero-exposed to GBS may present sex-specific neurobehavioral impairments. Lewis rats were injected intraperitoneally every 12 h from gestational day (G) 19 to G22 with either saline (controls) or inactivated serotype Ia GBS (109 CFU). Before puberty, no difference in terms of spontaneous motor activity, exploratory or anxiety-related behaviors was noticed between experimental conditions. During puberty, GBS-exposed females - but not males - performed worse than same-sex controls in a forced motor task. During adulthood, GBS-exposed females - but not males - displayed increased spontaneous locomotor activity and decreased inhibition. In conclusion, our findings show for the first time that adult females - but not males - in utero-exposed to GBS-induced inflammation presented a hyperactive and disinhibited phenotype emerging after puberty.

Altered cerebral glucose metabolism normalized in a patient with a pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS)-like condition following treatment with plasmapheresis: a case report.

BACKGROUND: Pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed. CASE PRESENTATION: We present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized. CONCLUSIONS: This is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.

Antenatal vaccination against Group B streptococcus: attitudes of pregnant women and healthcare professionals in the UK towards participation in clinical trials and routine implementation.

INTRODUCTION: Maternal vaccination is increasingly part of antenatal care in the UK and worldwide. Trials of Group B streptococcus vaccines are ongoing. This study investigated the attitudes of pregnant women and healthcare professionals towards antenatal vaccination, both in routine care and a clinical trial setting. MATERIAL AND METHODS: Survey of 269 pregnant women, 273 midwives/obstetricians and 97 neonatal doctors across seven sites in the UK assessing attitudes towards antenatal vaccinations, knowledge of Group B streptococcus, a hypothetical Group B streptococcus vaccine, and participation in clinical vaccine trials. RESULTS: 68% of pregnant women intended to receive a vaccine during their current pregnancy (183/269) and 43% (of all respondents, 115/269) reported they would be very/fairly likely to accept a vaccine against Group B streptococcus despite only 29% (55/269) knowing what Group B streptococcus was. This increased to 69% after additional information about Group B streptococcus was provided. Twenty-four percent of pregnant women reported they would be likely to take part in a clinical trial of an unlicensed Group B streptococcus vaccine. Fifty-nine percent of maternity professionals and 74% of neonatologists would be likely to recommend participation in a Group B streptococcus vaccine trial to women, with the vast majority (>99%) willing to be involved in such a study. Incentives to take part cited by pregnant women included extra antenatal scans and the opportunity to be tested for Group B streptococcus. CONCLUSION: Pregnant women and healthcare professionals were open to the idea of an antenatal Group B streptococcus vaccine and involvement in clinical trials of such a vaccine. Education and support from midwives would be key to successful implementation.

Course of Neuropsychiatric Symptoms After Introduction and Removal of Nonsteroidal Anti-Inflammatory Drugs: A Pediatric Observational Study.

OBJECTIVE: Accumulating evidence suggests that anti-inflammatory interventions can modulate neuropsychiatric symptoms. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by an abrupt and dramatic onset of obsessive-compulsive (OC) symptoms and/or severely restrictive food intake and at least two coinciding, equally debilitating neuropsychiatric symptoms. When associated with group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). Here, we describe the course of neuropsychiatric symptoms in patients diagnosed with PANS and PANDAS after introduction or removal of nonsteroidal anti-inflammatory drugs (NSAIDs). STUDY DESIGN: We reviewed the electronic medical records (EMR) of 218 consecutive patients evaluated in our Stanford PANS Clinic for patients who met strict PANS or PANDAS research criteria and received NSAIDs for arthritis, pain, and/or psychiatric symptoms. We describe neuropsychiatric symptoms that were noted in the EMR before, during, and after NSAIDs were introduced or removed as the sole change in pharmacologic treatment. RESULTS: Seventy-seven patients were included in the current study. Of the 52 trials in which NSAID addition was the sole change in treatment, 16 (31%) coincided with an improvement in patients' neuropsychiatric symptoms. Of the 57 trials in which removal of NSAID treatment was the sole change in treatment, 20 (35%) coincided with escalation in patients' neuropsychiatric symptoms. Thirty patients (39%) experienced side effects, mainly mild gastrointestinal symptoms, which self-resolved after removal of NSAID, reduction of dose, or change in NSAID. CONCLUSIONS: Improvement in neuropsychiatric symptoms was evident in roughly one-third of NSAID treatment trials. A randomized clinical trial will be necessary to confirm whether NSAIDs are successful in reducing neuropsychiatric symptoms in youth with PANS.

Palatal Petechiae in the Absence of Group A Streptococcus in Pediatric Patients with Acute-Onset Neuropsychiatric Deterioration: A Cohort Study.

BACKGROUND: Palatal petechiae are 95% specific for streptococcal pharyngitis. Despite this, and despite prior research demonstrating that Group A Streptococcus (GAS) is a common antecedent to pediatric acute-onset neuropsychiatric syndrome (PANS) episodes, we anecdotally observed a low rate of documented GAS in patients with PANS and palatal petechiae. This retrospective chart review was conducted to formally report the rate of palatal petechiae and concurrent GAS in a cohort of patients with PANS and investigate other etiologic factors. METHODS: The clinical notes of 112 patients seen at the Stanford PANS Clinic who met PANS research criteria were reviewed for mention of palatal petechiae. The medical records of patients who demonstrated palatal petechiae on physical examination were reviewed for signs of infection, a clinical history of trauma, and laboratory results that could indicate other causes of petechiae. RESULTS: Twenty-three patients had documented palatal petechiae on physical examination (ages 5-16, 13/23 [57%] male). Fifteen patients had a rapid GAS test and GAS culture in the Stanford PANS clinic, all with negative results. Evidence of recent GAS infection was found in 8/23 (32%) patients (elevated GAS titers [n = 6] or documentation of a positive rapid GAS test at another facility [n = 2]), one of whom also had potential herpes simplex virus (HSV) infection. One patient had potential HSV infection and recent palatal trauma. No patients had thrombocytopenia. 14/23 (61%) of patients with palatal petechiae had no discernable cause of petechiae. 10/19 (53%) of patients had antihistone antibodies. CONCLUSIONS: Despite the established relationship between palatal petechiae and GAS, no patient with palatal petechiae in our clinic tested positive for GAS and only 32% had evidence of recent GAS. Most did not have an identifiable cause for the palatal lesions. This finding suggests the potential for alternative causes of palatal petechiae or undetectable GAS in our patient population. The high prevalence of palatal petechiae without GAS infection suggests that the pathogenesis of PANS is multifactorial and may involve disruption or inflammation of the microvasculature. Additional research is needed to further elucidate these findings.

A Survey of Pediatric Acute-Onset Neuropsychiatric Syndrome Characteristics and Course.

OBJECTIVE: To date, studies in the area of pediatric acute-onset neuropsychiatric syndrome (PANS; including pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection [PANDAS] and pediatric infection-triggered neuropsychiatric disorder [PITAND]) have been relatively small and hence unable to comprehensively address questions of disease heterogeneity (e.g., by age, gender), comorbidities, and progression. In this study, we investigated an internet survey sample to more fully characterize the phenotypic traits; medical, family, and developmental history; functional challenges; and clinical course associated with PANS. METHODS: Six hundred and ninety-eight patients with clinical diagnoses of PANS were included in this study. Participants, who included parents and legal guardians (for minors) or the PANS patients themselves (for those ages 18 and older), were asked to complete a 146-question survey designed to ascertain medical, developmental, and family history; PANS symptomatology; medical and nonmedical interventions for PANS; PANS course; PANS outcomes; and access to PANS care. RESULTS: Our results agree with previous findings concerning the core symptoms of PANS as well as its male predominance (65% in this survey) and infection-triggered onset, thus validating the study population. Infection was implicated as the primary inciting factor in 65% of patients; 54% of patients reported an association with group A streptococcus specifically. The results of this survey also revealed new findings, including a surprisingly strong impact of gender and pubertal status on symptom course and chronicity, a high rate of medical comorbidity suggesting generalized immune dysfunction, a profound impact of PANS episodes on functional status, and a role for early resolution of infection through antibiotic treatment in disease course. CONCLUSIONS: This study serves as the first survey of its size to provide insight into the global clinical picture and range of phenotypes of PANS patients. Significant results included the impact of gender and pubertal status on phenotype, affirmation of the role of the immune system in PANS pathology, and the role of timely resolution of infection in clinical outcomes. Understanding how PANS presents in a broad population-based sample, within the limitations of a self-selected and administered online survey, is an important step toward improving diagnosis, creating more targeted treatment options, educating the clinical and research community, and generating hypotheses for future prospective research.

Prevalence of Acute-Onset Subtypes in Pediatric Obsessive-Compulsive Disorder.

BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) is a common, debilitating illness. When childhood OCD symptom onset is described as acute and severe, diagnostic criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) should be considered. However, the frequency and differentiating features of these putative syndromes within pediatric OCD remain poorly understood. OBJECTIVES: To determine the prevalence and characteristics of those meeting PANDAS and/or PANS criteria within pediatric OCD, as determined by parent report and clinician interview. METHODS: Consecutive youth presenting to a subspecialty pediatric OCD clinic were rigorously assessed through the Anxiety Disorders Interview Schedule for DSM-IV, the Children's Yale-Brown Obsessive-Compulsive Scale, and through self- and parent-report measures, including a medical questionnaire. Strict diagnostic criteria for PANDAS and PANS were applied to determine prevalence rates, and comparative analyses were performed between subgroups. RESULTS: Among 136 youth with a lifetime OCD diagnosis, 5% (n = 7; 95% adjusted Wald interval: 1%-10%) met proposed criteria for PANDAS and/or PANS, of whom two met PANDAS criteria, four met PANS criteria, and one met criteria for both. Those in the PANDAS/PANS subgroup were more likely to have autoimmune illness, less likely to report symmetry factor symptoms, and had greater OCD-related family impairment during their worst OCD episode. CONCLUSION: A small yet significant percentage of pediatric OCD outpatients met criteria for PANDAS and/or PANS, justifying routine screening and attention to related characteristics during assessment and management. Longitudinal studies of these putative subtypes are warranted.