Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies

Abstract

Introduction: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinically heterogeneous disorder with a number of different etiologies and disease mechanisms. Inflammatory and postinfectious autoimmune presentations of PANS occur frequently, with some clinical series documenting immune abnormalities in 75%-80% of patients. Thus, comprehensive treatment protocols must include immunological interventions, but their use should be reserved only for PANS cases in which the symptoms represent underlying neuroinflammation or postinfectious autoimmunity, as seen in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). Methods: The PANS Research Consortium (PRC) immunomodulatory task force is comprised of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and basic scientists with expertise in neuroimmunology and PANS-related animal models. Preliminary treatment guidelines were created in the Spring of 2014 at the National Institute of Health and refined over the ensuing 2 years over conference calls and a shared webbased document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with

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

“…There is a clear need for more treatment practice guidance for postinfectious autoimmune neuropsychiatric disorders. The recently published treatment guidelines for patients with PANS/PANDAS Thienemann et al, 2017;Frankovich et al, 2017;Cooperstock et al, 2017) and clinical and treatment information on the PANDAS Physician Network (PPN) ('PANDAS Physican Network'', 2018) will help establish a standard for treatment of these patients. Additionally, in order to help guide treatment decisions, we are systematically analyzing our biobank of over 8000 annotated samples to study how baseline data may help stratify patient populations into diagnostic subgroups for predicting treatment response.…”

Assessment and management of tic disorders and Tourette syndrome by Australian paediatricians

“…Although this entity is controversial, there are some patients who have a well‐documented acute onset of OCD and/or tics, often associated with sudden behavioural change and other functional deterioration. There is some evidence that these patients may respond to antibiotics or, in severe cases, to immune therapy with steroids or intravenous immunoglobulin, although more research is needed to be definitive. Until there is clear evidence of benefit, standardised measures of assessment, such as the Children's Yale‐Brown Obsessive Compulsive Scale and YGTSS, should be used to objectively evaluate response to treatment.…”

Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome

“…An overview of the management of PANS/PANDAS is presented in the Table 1. As shown, the first step is always a comprehensive evaluation, which should include a complete medical and psychiatric history, physical examination, laboratory testing of blood [and possibly, cerebrospinal fluid (CSF)], and selected paraclinical evaluations, such as magnetic resonance imaging, electrocardiogram/ echocardiography, electroencephalography, and polysomnography (see Chang et al 2015 for detailed description). The diagnosis of PANS should be made only when ''symptoms are not better explained by a known neurological or medical disorder,'' such as Sydenham chorea, autoimmune encephalitis, neuropsychiatric lupus, central nervous system vasculitis, and others.…”

“…By definition, PANS is always a diagnosis of exclusion. Thus, clinicians are encouraged to begin with a broad differential diagnosis and narrow it to PANS only after eliminating all other possibilities (Swedo et al 2012;Chang et al 2015).…”

“…P ediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinical condition defined by the unusually abrupt onset of obsessive-compulsive symptoms and/or severe eating restrictions and at least two concomitant cognitive, behavioral, or neurological symptoms (Swedo et al 2012). Because the PANS criteria define a broad spectrum of neuropsychiatric conditions, the syndrome is presumed to result from a variety of disease mechanisms and to have multiple etiologies, ranging from psychological trauma or underlying neurological, endocrine, and metabolic disorders to postinfectious autoimmune and neuroinflammatory disorders, such as pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), cerebral vasculitis, neuropsychiatric lupus, and others (Swedo et al 2012;Chang et al 2015). In cohorts of well-characterized PANS patients, evidence of postinfectious autoimmunity and/or neuroinflammation is found in more than 80% of cases (Frankovich et al 2015;Swedo et al 2015).…”