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Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

ABSTRACT: Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders.

SUBMITTER: Macerollo A

PROVIDER: S-EPMC3783973 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

Macerollo Antonella A Martino Davide D

Tremor and other hyperkinetic movements (New York, N.Y.) 20130925

Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between ...[more]

PMID: 24106651

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Project description:Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are subtypes of Obsessive-Compulsive Disorder (OCD) with suggested autoimmune etiology. Immunomodulatory treatments have been introduced as treatment options. A recent systematic review concluded that the evidence for all treatment options for PANS and PANDAS is inconclusive. However, case reports and clinical experience suggest that antibiotics and immunomodulatory treatment may be helpful. Treatment may also affect the patients' satisfaction with health care services offered. This study aims to describe the treatments given to a cohort of Swedish patients with suspected PANS and PANDAS, the patient rated treatment effects, and to establish if any specific treatment predicts higher patient satisfaction. Methods: Fifty-three patients (m?=?33, f?=?20, median age?=?14, age range?=?4-36) with suspected PANS or PANDAS were enrolled and assessed for PANS and PANDAS caseness, treatments given, treatment effects, global improvement, and patient satisfaction. Cases with confirmed and suspected PANS or PANDAS were compared regarding the frequency of treatments given and treatment effect. A linear regression model was used to see if treatments given or global improvement predicted patient satisfaction. Results: Twenty-four participants fulfilled criteria for PANS or PANDAS and 29 did not. The most common treatments given were antibiotics (88%), nonsteroidal anti-inflammatory drugs (67%), cognitive behavioral therapy (53%), and selective serotonin reuptake inhibitors (42%). There were no major differences between confirmed and suspected cases regarding what treatments they had received or their effect. Patient satisfaction was predicted by overall clinical improvement at the time of assessment. Antibiotics and intravenous immunoglobulin (IVIG) were rated as the most successful treatments by participants and were associated with higher patient satisfaction. Conclusions: It was more common that patients had received antibiotics than common psychiatric treatments for their psychiatric symptoms. Antibiotics and IVIG were experienced as effective treatments by the patients. Patient satisfaction was on average moderately low, and higher patient satisfaction was associated with global clinical improvement.

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:Importance:Streptococcal infection has been linked with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). However, previous studies of this association have been small, and the results have been conflicting. Objective:To investigate the risk of mental disorders, specifically OCD and tic disorders, after a streptococcal throat infection. Design, Setting, and Participants:A population-based cohort study was conducted using data from the nationwide Danish registers from January 1, 1996, to December 31, 2013, with up to 17 years of follow-up. The Danish National Health Service Register provided information on individuals with the registration of a streptococcal test. Data analysis was conducted from January 1, 2016, to February 28, 2017. Main Outcomes and Measures:Individuals were followed up in the nationwide Psychiatric Central Register for a diagnosis of any mental disorder, OCD, or tic disorders. Incidence rate ratios (IRRs) were calculated by Poisson regression analysis. Results:Of the 1?067?743 children (<18 years of age) included in the study (519?821 girls and 547?922 boys), 638?265 received a streptococcal test, 349?982 of whom had positive test results at least once. Individuals with a positive streptococcal test result had an increased risk of any mental disorder (n?=?15?408; IRR, 1.18; 95% CI, 1.15-1.21; P?<?.001), particularly of OCD (n?=?556; IRR, 1.51; 95% CI, 1.28-1.77; P?<?.001) and tic disorders (n?=?993; IRR, 1.35; 95% CI, 1.21-1.50; P?<?.001), compared with individuals without a streptococcal test. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a nonstreptococcal infection. Nonetheless, individuals with a nonstreptococcal throat infection also had an increased risk of any mental disorder (n?=?11?315; IRR, 1.08; 95% CI, 1.06-1.11; P?<?.001), OCD (n?=?316; IRR, 1.28; 95% CI, 1.07-1.53; P?=?.006), and tic disorders (n?=?662; IRR, 1.25; 95% CI, 1.12-1.41; P?<?.001). Conclusions and Relevance:This large-scale study investigating key aspects of the PANDAS hypothesis found that individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD and tic disorders. However, nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder, which could also support important elements of the diagnostic concept of pediatric acute-onset neuropsychiatric syndrome.

Dataset Information

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

Publications

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

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