Pediatric Acute-onset Neuropsychiatric Syndrome Research Articles

Clinical guidance for diagnosis and management of suspected Pediatric Acute‐onset Neuropsychiatric Syndrome in the Nordic countries

Pediatric acute-onset neuropsychiatric syndrome is a clinical concept used to describe a subgroup of children with sudden onset of psychiatric and somatic symptoms. The diagnostic term and especially management of children differs depending on the clinical setting to which they present, and the diagnosis and management is controversial. The aim of this paper is to propose a clinical guidance including homogenous diagnostic work-up and management of pediatric acute onset neuropsychiatric syndrome within the Nordic countries. The guidance is authored by a Nordic- UK working group consisting of pediatric neurologist, child psychiatrists and psychologists from Denmark, Norway, Sweden, and Great Britain and is the result of broad consensus. CONCLUSION: Consensus was achieved in the collaboration on work-up and treatment of patients with pediatric acute-onset neuropsychiatric syndrome, which we hope will improve and homogenise patient care and enable future collaborative research in the field.

Does Lyme Disease Cause PANS?

In 1994, Susan Swedo and colleagues described children who developed mental health issues following infection with Group A Streptococcus (GAS) infections, and in a subsequent report coined the term Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) [1,2]. In short order it was discovered that multiple microbes have the potential of triggering mental health issues in children and adolescents, and the nomenclature was updated to Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) [3]. The microbes that thus far have been associated with PANS include herpes simplex virus, influenza A virus, varicella virus, HIV, recurrent sinusitis, Epstein-Barr virus, the common cold, Mycoplasma pneumoniae and Bartonella henselae [4-6].

Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis in children who have an acute manifestation of varied neuropsychiatric symptoms, including obsessive compulsive disorder, eating disorders, tics, anxiety, irritability, and problems with attention/concentration. PANS may develop as a result of a postinfectious syndrome and may represent a new form of postinfectious autoimmunity. To test the hypothesis that multiple, consecutive infusions of intravenous immunoglobulin (IVIG) for PANS can be efficacious, a multisite, open-label study was designed.Methods: The primary endpoint was evaluation of the efficacy of IVIG [Octagam 5%] in PANS over a period of 6 months (six infusions) based on mean changes in psychological evaluation scores using 6 different assessments, including the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Clinical Global Impression of Severity, and the Parent-Rated Pediatric Acute Neuropsychiatric Symptom Scale (PANS Scale).Results: The final cohort consisted of 21 subjects (7 per site) with moderate to severe PANS. The mean age was 10.86 years (range: 4–16 years). Results demonstrated statistically significant reductions in symptoms from baseline to end of treatment in all six assessments measured. CY-BOCS results demonstrated statistically significant reductions in obsessive compulsive symptoms (p < 0.0001), resulting in >50% improvement sustained for at least 8 weeks after the final infusion and up to 46 weeks in a subset of subjects.Conclusions: In PANS, which may be associated with an underlying immune dysregulation, sequential infusions of IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks in a subset of subjects. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.

A Two-to-Five Year Follow-Up of a Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort

Little is known about the long-term prognosis of children with pediatric acute-onset neuropsychiatric syndrome (PANS). Out of the 46 eligible patients from the Karolinska PANS cohort, 34 consented to participate in a follow-up (median 3.3 years). Participants underwent a thorough clinical evaluation and were classified according to their clinical course. Resulting groups were compared on clinical characteristics and laboratory test results. We observed significant reductions in clinician-rated PANS symptom severity and improved general function. Two patients were classified as remitted, 20 as relapsing–remitting, and 12 as having a chronic-static/progressive course. The latter group had an earlier onset, greater impairment and received more pharmacological and psychological treatments. Although remission was rare, the majority of children with PANS were significantly improved over the follow-up period but a non-negligible minority of patients displayed a chronic-static/progressive course and required additional treatments. The proposed definitions of flare and clinical course may be useful in future clinical trials.

Patients with abrupt early-onset OCD due to PANS tolerate lower doses of antidepressants and antipsychotics

ObjectiveTo characterize drug tolerability in pediatric patients with an abrupt-onset of obsessive-compulsive disorder (OCD) meeting criteria for pediatric acute-onset neuropsychiatric syndrome (PANS). MethodsWe reviewed charts of 188 consecutive patients with PANS seen in the PANS clinic, collecting starting, side effect, and tolerated doses, as well as side effect profile for each antidepressant and antipsychotic trial. ResultsOf 188 included patients: 57% had trials of antidepressants and/or antipsychotics. Patients prescribed psychotropics were older at PANS onset (mean 9.5 vs 7.1 years, p < 0.01) and had had a longer delay before presenting to clinic (median 1.4 vs 0.5 years, p < 0.01). Antidepressant indications (n = 146) were OCD (48%), anxiety (44%), and depression (32%). Antipsychotic indications (n = 119) were aggression (34%), psychotic symptoms (28%), and OCD (24%). Side effects requiring medication change occurred in 54% of patients: in 38% of antidepressant trials and 49% of antipsychotic trials. Antidepressants' most common side effects were anxiety, agitation, aggression, and akathisia. Antipsychotics’ most common side effects were dystonia, aggression, self-injurious behavior, and movement abnormality. Side effects were common at doses lower than the suggested starting doses for these medications. Patients tolerated antidepressants and antipsychotics when doses were low. ConclusionWhen antidepressants and antipsychotics are prescribed to patients with PANS, intolerable side effects were noted at doses lower than or equal to suggested starting doses. Patients with PANS can benefit from these therapies. However, when treating these patients, clinicians are advised to start with significantly lower doses than they might use in other disorders.

A Case Study of Acute Onset Obsessive-Compulsive Symptoms in a Pediatric Patient

This is a case of a 10 year old boy who was seen in a clinic that specializes in childhood postinfectious encephalopathy (CPAE). The patient presented with new onset of obsessive-compulsive behaviors, severe separation anxiety and progressive eating restriction which led to dehydration and hospitalization. His mother reported that prior to onset of symptoms two months earlier, he was a happy, playful and engaging child who enjoyed friendships, family, school and karate. Differential diagnosis in such cases focuses on identifying the most likely primary underlying cause for the presenting symptoms. This is especially challenging because there are many potential etiologies including a variety of behavioral and environmental causes. Based on patient examination, laboratory findings and psychometric tests, diagnoses considered by the clinical team included new onset or exacerbation of previously not identified obsessive compulsive disorder (OCD) or anxiety, new onset of tic disorder, new onset of eating disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Group A Streptococcal infection (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). The presentation of OCD with an avoidant restrictive food intake disorder in combination with the acute onset of symptoms and the lack of documented strep infection led the team to a PANS diagnosis. When treated with a combination of anti-inflammatory and antibiotic medications, the patient demonstrated rapid improvement with a return to baseline functioning with resolution of OCD symptoms, separation anxiety, emotional lability, sleep disturbances and nocturnal enuresis. At 8 month follow up, school performance was reported to have returned to baseline.

Pediatric Acute-Onset Neuropsychiatric Syndrome with Capgras Syndrome.

Pediatric Acute-Onset Neuropsychiatric Syndrome with Capgras Syndrome.

Predictors and Prospective Course of PANS: A Pilot Study Using Electronic Platforms for Data Collection.

Objectives: Little is known about the longitudinal course of pediatric acute-onset neuropsychiatric syndrome (PANS) because existing literature is primarily cross-sectional. To begin to address this gap, two digital platforms were used to prospectively monitor neuropsychiatric symptoms in children with PANS. The aim was to identify baseline clinical characteristics that would predict the course of neuropsychiatric symptoms over 12 weeks. We compared relative compliance between two electronic data acquisition platforms and evaluated agreement between parent-child ratings of symptoms. Methods: For 12 weeks, 20 children with PANS and their parents completed weekly rating scales of neuropsychiatric symptoms on Research Electronic Data Capture (REDCap) and concurrently parents completed tri-weekly ratings on My Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Chart, a symptom monitoring website. Longitudinal data were analyzed by using regression analyses. Results: Greater duration of time between onset of PANS and study enrollment was associated with worsening of parent-rated neuropsychiatric symptoms over 12 weeks (p = 0.05). Higher scores on parents' Caregiver Burden Inventory at baseline predicted that children would report more severe symptoms over the 12-week period (p = 0.01). Compliance rates for parents were 86.3% for the weekly REDCap PANS Symptoms Rating Scale compared with 53.8% for the tri-weekly My PANDAS Chart ratings. There was moderate agreement between children and parents on the PANS Symptom Rating Scale (r = 0.55, p < 0.0001). Conclusion: Our study highlights the utility of electronic methods for tracking longitudinal symptoms in children with PANS and suggests that particular baseline characteristics (e.g., delay in identification and treatment of PANS, greater caregiver burden) may be indicative of a differential trajectory of PANS course, with more severe symptoms over the short term. clinicaltrials.gov NCT04382716.

Discovering prescription patterns in pediatric acute-onset neuropsychiatric syndrome patients

ObjectivePediatric acute-onset neuropsychiatric syndrome (PANS) is a complex neuropsychiatric syndrome characterized by an abrupt onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two concomitant debilitating cognitive, behavioral, or neurological symptoms. A wide range of pharmacological interventions along with behavioral and environmental modifications, and psychotherapies have been adopted to treat symptoms and underlying etiologies. Our goal was to develop a data-driven approach to identify treatment patterns in this cohort. Materials and methodsIn this cohort study, we extracted medical prescription histories from electronic health records. We developed a modified dynamic programming approach to perform global alignment of those medication histories. Our approach is unique since it considers time gaps in prescription patterns as part of the similarity strategy. ResultsThis study included 43 consecutive new-onset pre-pubertal patients who had at least 3 clinic visits. Our algorithm identified six clusters with distinct medication usage history which may represent clinician’s practice of treating PANS of different severities and etiologies i.e., two most severe groups requiring high dose intravenous steroids; two arthritic or inflammatory groups requiring prolonged nonsteroidal anti-inflammatory drug (NSAID); and two mild relapsing/remitting group treated with a short course of NSAID. The psychometric scores as outcomes in each cluster generally improved within the first two years. Discussion and conclusionOur algorithm shows potential to improve our knowledge of treatment patterns in the PANS cohort, while helping clinicians understand how patients respond to a combination of drugs.

Anti-inflammatory Augmentation Therapy in Obsessive-compulsive Disorder: A Review

Background: Obsessive-Compulsive Disorder (OCD) is considered as a serious disabling psychiatric disorder, influencing 2-3% of the total general population, with an unknown etiology. Methods: A comprehensive literature search in electronic databases was performed to investigate treatments targeting inflammation in patients suffering from OCD. Results: Recent studies display that inflammation processes and the dysfunction of the immune system are likely to play a role in the pathophysiology of OCD, indicating that the disturbances in neurotransmitters such as serotonin and dopamine cannot be alone involved in the development of OCD. Therefore, it seems that medications with anti-inflammatory effects have the potential to be evaluated as a new therapeutic strategy for OCD. However, this issue can be studied closely if OCD etiological factors are thoroughly understood. The present review study aims at gathering all obtained results concerning new treatments targeting inflammation in OCD patients. Reviewing the conducted studies shows that the use of agents with anti-inflammatory properties, including some NSAIDs, Minocycline and Atorvastatin, could lead to promising and intriguing results in the treatment of OCD. Curcumin also showed good efficacy in the reduction of OCD-like behavior when it has been used in an animal model. However, there is still no definitive and conclusive evidence for any of the medications proposed. Conclusion: More future studies are needed to investigate anti-inflammatory treatment strategies for OCD and its other subtypes such as Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS), and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS).

PANS/PANDAS: Clinical Experience in IVIG Treatment and State of the Art in Rehabilitation Approaches

Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition characterized by the abrupt, dramatic onset of obsessive–compulsive disorder (OCD) or eating restriction accompanied by equally abrupt and severe comorbid neuropsychiatric symptoms. PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection) is a heterogeneous syndrome identified as post-Streptococcus pyogenes infection (β-hemolytic Streptococcus group A) complications regarding the central nervous system with specific involvement of neuropsychiatric and behavioral skills. In the first part of our study, we share our experience in the treatment of a group of extreme-grade (according to CY-BOCS severity scale) symptomatic patients with intravenous immunoglobulin (IVIG), following the most recent studies regarding the dosage of the drug. Our contribution is to share our experience made on a sample of 55 patients all in the highest level of a severity grade. In the second part of our study, we also analyze the literature on PANS/PANDAS rehabilitation therapy, since in the literature there is no discussion of union and comparison on this method. Objective: This study aims to evaluate the clinical features of the patients observed from different Italian cohorts, with the attempt at evaluating clinical response to IVIG treatment in children with an extreme severity grade of PANS/PANDAS disease. Furthermore, after having analyzed the literature, we propose rehabilitation therapy as an added value to the pharmacological treatment. Materials and Methods: A total of 55 patients with a diagnosis of PANS/PANDAS, who belonged to an extreme grade of disease, were enrolled. All patients were administered with IVIG treatment at 2 g/kg per day for two consecutive days. Results: From our study, a noticeable improvement (until complete remission) of symptoms was evident for at least one year in 47 out of 55 (85%) observed children, while 11 out of these 43 (25%) showed an evident symptoms remission in a single attempt and the remaining 32 (75%) required a second administration to notice a lasting symptomatic improvement.

Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study. In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored. Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S. More stringent ferritin level cut-offs than the comparison CDC dataset were used. Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association. Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population. Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss. Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.

Antibodies against Group A Streptococcus, dopamine receptors, and ganglioside GM1 cross-react with a variety of food antigens, potentially interfering with biomarkers for PANS and PANDAS

Group A Streptococcus (GAS) is a bacteria that manifests itself in a variety of diseases, from strep throat to neuroautoimmune psychiatric disorders, such as pediatric acute-onset neuropsychiatric syndrome (PANS) or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). Dopamine 1 and dopamine 2 (D1 and D2) receptors and asialoganglioside (GM1) are used commercially as biomarkers in assessing neuropsychiatric diseases. However, some studies have found these antibodies in healthy subjects. Since previous research has shown cross-reactivity between foods and tissue antigens, we sought to determine whether or not cross-reactivity exists between GAS, D1, D2 receptors, GM1 and commonly consumed foods, and whether the presence of food antibodies may be responsible for the false positivity. We reacted antibodies against GAS, D1, D2 receptors, and GM1 with the antigens of 180 foods using the ELISA method. Anti-GAS antibodies had significant cross-reactivity with 17/180 foods, anti-D1 antibody with 26/180 foods, anti-D2 antibody with 20/180 foods, and anti-GM1 antibody with 47/180 foods. Our results indicate that the presence in blood of antibodies to GAS, D1, D2 and GM1 that cross-react with food antigens may not only interfere with the accurate measurement of these biomarkers of PANS and PANDAS, but show that these patients with these antibodies in their blood may not have these conditions at all, but just have innocuous antibodies against food antigens.

Pediatric Acute-Onset Neuropsychiatric Syndrome: A Data Mining Approach to a Very Specific Constellation of Clinical Variables.

Objectives: Pediatric acute onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder presenting with: unusually abrupt onset of obsessive compulsive disorder (OCD) or severe eating restrictions, with at least two concomitant cognitive, behavioral, or affective symptoms such as anxiety, obsessive-compulsive behavior, and irritability/depression. This study describes the clinical and laboratory variables of 39 children (13 female and 26 male) with a mean age at recruitment of 8.6 years (standard deviation 3.1). Methods: Using a mathematical approach based on Artificial Neural Networks, the putative associations between PANS working criteria, as defined at the NIH in July 2010 (Swedo et al. 2012), were explored by the Auto Contractive Map (Auto-CM) system, a mapping method able to compute the multidimensional association of strength of each variable with all other variables in predefined dataset. Results: The PANS symptoms were strictly linked to one another on the semantic connectivity map, shaping a central "diamond" encompassing anxiety, irritability/oppositional defiant disorder symptoms, obsessive-compulsive symptoms, behavioral regression, sensory motor abnormalities, school performance deterioration, sleep disturbances, and emotional lability/depression. The semantic connectivity map also showed the aggregation between PANS symptoms and laboratory and clinical variables. In particular, the emotional lability/depression resulted as a highly connected hub linked to autoimmune disease in pregnancy, allergic and atopic disorders, and low Natural Killer percentage. Also anxiety symptoms were shown to be strongly related with recurrent infectious disease remarking the possible role of infections as a risk factor for PANS. Conclusion: Our data mining approach shows a very specific constellation of symptoms having strong links to laboratory and clinical variables consistent with PANS feature.

Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging

Epidemiological studies indicate a link between obsessive-compulsive disorder and infections, particularly streptococcal pharyngitis. Pediatric acute-onset neuropsychiatric syndrome (PANS) manifests suddenly with obsessions, compulsions, and other behavioral disturbances, often after an infectious trigger. The current working model suggests a unifying inflammatory process involving the central nervous system, particularly the basal ganglia. To investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects microstructural abnormalities across the brain regions of children with PANS. Case-control study performed at a single-center, multidisciplinary clinic in the United States focusing on the evaluation and treatment of children with PANS. Sixty consecutive patients who underwent 3 Tesla (T) magnetic resonance imaging (MRI) before immunomodulation from September 3, 2012, to March 30, 2018, were retrospectively reviewed for study inclusion. Six patients were excluded by blinded investigators because of imaging or motion artifacts, 3 patients for major pathologies, and 17 patients for suboptimal atlas image registration. In total, 34 patients with PANS before initiation of treatment were compared with 64 pediatric control participants. Using atlas-based MRI analysis, regional brain volume, diffusion, and cerebral blood flow were measured in the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem. An age and sex-controlled multivariable analysis of covariance was used to compare patients with control participants. This study compared 34 patients with PANS (median age, 154 months; age range, 55-251 months; 17 girls and 17 boys) and 64 pediatric control participants (median age, 139 months; age range, 48-213 months); 41 girls and 23 boys). Multivariable analysis demonstrated a statistically significant difference in MRI parameters between patients with PANS and control participants (F21,74 = 6.91; P < .001; partial η2 = 0.662). All assessed brain regions had statistically significantly increased median diffusivity compared with 64 control participants. Specifically, the deep gray matter (eg, the thalamus, basal ganglia, and amygdala) demonstrated the most profound increases in diffusivity consistent with the cardinal clinical symptoms of obsessions, compulsions, emotional dysregulation, and sleep disturbances. No statistically significant differences were found regarding volume and cerebral blood flow. This study identifies cerebral microstructural differences in children with PANS in multiple brain structures, including the deep gray matter structures (eg, the thalamus, basal ganglia, and amygdala). Further study of MRI is warranted in prospective, clinical trials as a potential quantitative method for assessing patients under evaluation for PANS.

Benefits of IVIG in Pediatric Acute-Onset Neuropsychiatric Syndrome (2411)

Benefits of IVIG in Pediatric Acute-Onset Neuropsychiatric Syndrome (2411)

Current Approaches to PANS/PANDAS Diagnostics and Management

PANS, or Pediatric Acute-onset Neuropsychiatric Syndrome, is characterized by the sudden onset of obsessive-compulsive syndrome and accompanied by anxiety, emotional lability and other symptoms. PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections, is a subtype of PANS. Modern data on PANS/PANDAS etiology, pathogenesis, diagnostics and management is presented in this article. Therapeutic decisions on using anti-inflammatory and immunotropic therapy including non-steroidal anti-inflammatory drugs, glucocorticoids, intravenous immunoglobulin, plasmapheresis, rituximab and mycophenolate mofetil are analysed.

Pediatric Acute-onset Neuropsychiatric Syndrome and Mycoplasma Pneumoniae Infection: A Case Report Analysis with a Metabolomics Approach

Pediatric Acute-onset Neuropsychiatric Syndrome and Mycoplasma Pneumoniae Infection: A Case Report Analysis with a Metabolomics Approach

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

ObjectiveThis 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). MethodsIn 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. ResultsComparison 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. ConclusionThis 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.

Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a descriptive clinical entity defined by the abrupt onset of psychiatric and somatic symptoms leading to significant loss of function. Data on well-characterized PANS patients are limited, biomarkers have yet to be identified, and a solid evidence base to guide treatment is lacking. In this study, we present our experience of a systematic evaluation of the first 45 patients included in a Swedish cohort.Methods: During the period 2014–2018, our clinic received 100 referrals regarding suspected PANS. All patients underwent a standardized psychiatric/medical evaluation by a child/adolescent psychiatrist and a clinical psychologist or a nurse. Those with severe symptoms were also assessed by a pediatric neurologist and a pediatric rheumatologist. Laboratory tests were obtained at different time points in an attempt to capture an active disease state.Results: Of the 100 referrals, 45 met strict PANS criteria and consented to participate in a long-term follow-up study. The median age at intake was 7.2 years (range 3.0–13.1) and 56% were male. Ninety-three percent fulfilled both criteria for acute/atypical onset of PANS symptoms and having had an infection in relation to onset. Sixteen percent had an onset of an autoimmune or inflammatory disorder in temporal relation to the onset of PANS-related symptoms. The most common onset symptoms were obsessive-compulsive disorder (89%), anxiety (78%), and emotional lability (71%). Twenty-four percent had a preexisting autoimmune disease (AD) and 18% a preexisting psychiatric/neuropsychiatric diagnosis. Sixty-four percent of biological relatives had at least one psychiatric disorder and 76% at least one AD or inflammatory disorder. Complement activation (37%), leukopenia (20%), positive antinuclear antibodies (17%), and elevated thyroid antibodies (11%) were the most common laboratory findings.Conclusions: In our PANS cohort, there was a strong indication of an association with AD. Further work is needed to establish whether any of the potential biomarkers identified will be clinically useful. Long-term follow-up of these patients using the Swedish national registers will enable a deeper understanding of the course of this patient group.