Dataset Information

Measuring clinical outcomes in children with pediatric acute-onset neuropsychiatric syndrome: data from a 2-5 year follow-up study.

ABSTRACT:

Background

It is unclear how to best measure the complex symptom presentation of pediatric acute-onset neuropsychiatric syndrome (PANS).

Methods

Well-characterized participants of a 2-5 year follow-up study (n = 34; 56% male) underwent clinical evaluations and completed scales assessing global symptom severity, functional impairment and specific psychiatric symptoms. We explored inter-correlations between the measures and used intraclass correlation coefficients to evaluate the agreement between clinician-, parent- and child ratings of the same constructs.

Results

Ratings on symptom-specific measures varied largely between participants. Agreement between informants was excellent on functional scales, fair-to-moderate on global severity scales and mixed on symptom-specific scales. Clinician-rated global and functional measures had stronger inter-correlations with parent- and child-rated functional measures than with symptom-specific measures.

Conclusions

General instruments assessing global severity and functioning are well suited for the assessment and follow-up of PANS, but should be complemented by symptom-specific scales representative of core symptoms.

SUBMITTER: De Visscher C

PROVIDER: S-EPMC8488538 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Measuring clinical outcomes in children with pediatric acute-onset neuropsychiatric syndrome: data from a 2-5 year follow-up study.

De Visscher Caroline C Hesselmark Eva E Rautio Daniel D Djupedal Ida Gebel IG Silverberg Maria M Nordström Selma Idring SI Serlachius Eva E Mataix-Cols David D

BMC psychiatry 20211004 1

<h4>Background</h4>It is unclear how to best measure the complex symptom presentation of pediatric acute-onset neuropsychiatric syndrome (PANS).<h4>Methods</h4>Well-characterized participants of a 2-5 year follow-up study (n = 34; 56% male) underwent clinical evaluations and completed scales assessing global symptom severity, functional impairment and specific psychiatric symptoms. We explored inter-correlations between the measures and used intraclass correlation coefficients to evaluate the ag ...[more]

PMID: 34607588

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Project description: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.

Project description:IntroductionPANS is a controversial clinical entity, consisting of a complex constellation of psychiatric symptoms, adventitious changes, and expression of various serological alterations, likely sustained by an autoimmune/inflammatory disease. Detection of novel biomarkers of PANS is highly desirable for both diagnostic and therapeutic management of affected patients. Analysis of metabolites has proven useful in detecting biomarkers for other neuroimmune-psychiatric diseases. Here, we utilize the metabolomics approach to determine whether it is possible to define a specific metabolic pattern in patients affected by PANS compared to healthy subjects.DesignThis observational case-control study tested consecutive patients referred for PANS between June 2019 to May 2020. A PANS diagnosis was confirmed according to the PANS working criteria (National Institute of Mental Health [NIMH], 2010). Healthy age and sex-matched subjects were recruited as controls.MethodsThirty-four outpatients referred for PANS (mean age 9.5 years; SD 2.9, 71% male) and 25 neurotypical subjects matched for age and gender, were subjected to metabolite analysis. Serum samples were obtained from each participant and were analyzed using Nuclear Magnetic Resonance (NMR) spectroscopy. Subsequently, multivariate and univariate statistical analyses and Receiver Operator Curves (ROC) were performed.ResultsSeparation of the samples, in line with the presence of PANS diagnosis, was observed by applying a supervised model (R2X = 0.44, R2Y = 0.54, Q2 = 0.44, p-value < 0.0001). The significantly altered variables were 2-Hydroxybutyrate, glycine, glutamine, histidine, tryptophan. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan metabolism, as well as glutamine and glutamate metabolism, exhibited the largest deviations from neurotypical controls.ConclusionWe found a unique plasma metabolic profile in PANS patients, significantly differing from that of healthy children, that suggests the involvement of specific patterns of neurotransmission (tryptophan, glycine, histamine/histidine) as well as a more general state of neuroinflammation and oxidative stress (glutamine, 2-Hydroxybutyrate, and tryptophan-kynurenine pathway) in the disorder. This metabolomics study offers new insights into biological mechanisms underpinning the disorder and supports research of other potential biomarkers implicated in PANS.

Project description:BackgroundPediatric obsessive-compulsive disorder (OCD) and eating disorder symptoms frequently overlap, clouding diagnostic certainty and hypothesized etiologic factors. Pediatric acute-onset neuropsychiatric syndrome (PANS) is defined by abrupt emergence of core obsessive-compulsive behaviours and/or food restriction with concurrent, ancillary cognitive and behavioral symptoms. Inflammatory and immune processes have putative roles in both PANS and a related described condition with cardinal obsessive-compulsive or tic symptoms, known as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). While prevalence of PANS and PANDAS has been examined in tic, movement disorder and OCD populations, this has not yet been systematically examined in a pediatric eating disorder sample.ObjectivesTo identify the lifetime prevalence of those meeting PANS and/or PANDAS criteria within a pediatric eating disorder cohort.MethodsConvenience sampling method was utilized to select consecutive youth (ages 8-18-years) presenting to an interdisciplinary pediatric eating disorder subspecialty program with a confirmed eating disorder and completed parent-report PANS/PANDAS questionnaire (n = 100). A parent-reported measure was used to establish lifetime prevalence rates for PANS and PANDAS. Descriptive and exploratory comparative analyses were conducted between PANS and non-PANS groups. Continuous measures were analyzed using two-tailed independent sample t-tests and categorical measures were analyzed using two-tailed Fisher's exact tests.ResultsAmong participants, 52% (n = 52) met PANS criteria and 0% (n = 0) met PANDAS diagnostic criteria. Core, abrupt-onset PANS symptoms included both food restriction and obsessive-compulsive symptoms in 63.5% (n = 33), food restriction only in 25% (n = 13), and obsessive-compulsive symptoms only in 11.5% (n = 6) of participants. In comparison to those who did not meet PANS criteria, those in the PANS subgroup were less likely to be male and more commonly prescribed a selective serotonin reuptake inhibitor medication. Significant group differences did not emerge for onset age, body mass index, eating disorder type or comorbid psychiatric/medical/autoimmune illness.ConclusionLifetime prevalence of symptoms in keeping with PANS diagnostic criteria within a pediatric eating disorder cohort was notably higher than that previously reported in OCD or tic disorder cohorts. The overlap between starvation effects and ancillary PANS symptoms may challenge the practical utility of this putative syndrome within the eating disorder population.

Project description: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.

Project description:Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Project description:Objective: Analyze the ultrasound features, single nucleotide polymorphism microarray (SNP-array) outcomes, pregnancy results, and follow-up data of fetuses with Xp22.31 deletions or duplications in mid to late pregnancy. Methods: A retrospective analysis was carried out on 10 cases diagnosed with Xp22.31 deletions and 11 cases with duplications, identified through single nucleotide polymorphism microarray (SNP-array) testing. The analysis focused on assessing ultrasound abnormalities, tracing parental origins, pregnancy outcomes, and postnatal follow-up conditions. Results: The deletion sizes in the 10 deletion cases ranged from 913 Kb to 1.81 Mb, while the duplication sizes in the 11 duplication cases ranged from 1.29 Mb to 2.35 Mb, encompassing 9 OMIM genes including STS, ANOS1, DXS1283E, VCS3B, and HDHD1A. Among the fetuses with deletions, four cases (40.0%, 4/10) exhibited ultrasound abnormalities, which included cardiovascular system malformations, lateral ventriculomegaly, clubfoot, increased nuchal translucency, and polyhydramnios. Notably, Case 5 involved a fetus with complex multi-organ malformations, including bilateral ventriculomegaly, a ventricular septal defect, and clubfoot. Among the 11 cases of duplications, three cases (27.3%, 3/11) exhibited ultrasound abnormalities, primarily featuring cardiovascular malformations, ventriculomegaly, and polyhydramnios. Of the 10 deletion cases, eight underwent parental origin testing, with seven cases inherited (six maternal and one paternal) and one case of de novo mutation. Among the 11 duplication cases, eight underwent parental origin testing, with seven cases being inherited (four maternal and three paternal) and one case representing a de novo mutation. Of the 10 deletion cases, six chose to terminate the pregnancy, while four decided to continue. Follow-up revealed that Case 6 was diagnosed with STS ichthyosis shortly after birth, and the sbling of Case 3 and Case 10 exhibited delayed walking and speech development. In the duplication group, one case opted for termination of pregnancy, while 10 continued with their pregnancies. Follow-up identified that Case 18 exhibited delayed walking and speech development. Conclusion: This study provides a preliminary assessment of the genotypes and phenotypes of fetuses with Xp22.31 deletions /duplications, expanding the phenotypic spectrum of Xp22.31 deletions /duplications syndrome. The findings indicate that prenatal Xp22.31 deletions in male fetuses are likely to manifest as STS ichthyosis after birth. Xp22.31 deletions and duplications may be associated with cardiovascular malformations. For fetuses with Xp22.31 deletions /duplications that appear phenotypically normal prenatally, postnatal monitoring of their neurological development is crucial.

Dataset Information

Measuring clinical outcomes in children with pediatric acute-onset neuropsychiatric syndrome: data from a 2-5 year follow-up study.

Background

Methods

Results

Conclusions

Publications

Measuring clinical outcomes in children with pediatric acute-onset neuropsychiatric syndrome: data from a 2-5 year follow-up study.

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