Feasibility of a study to determine the incidence, spectrum, course and outcome of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) in a diverse group of children - PROJECT SUMMARY/ABSTRACT The goal of this study is to determine the feasibility of a proposal to determine the incidence, breadth of clinical manifestations, course and outcome of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with group A Streptococcus (PANDAS) in a geographically and economically diverse population of children in the US. PANS is a relatively newly described clinical problem characterized by the acute onset of either obsessive-compulsive disorder (OCD) or food restriction (or both) plus two of 7 other neuropsychiatric/behavioral issues in children. PANS may be triggered by infectious or non-infectious stimuli. When Group A streptococcus (GAS) is the instigator event, it is referred to as PANDAS. The two cardinal features of PANDAS are tics and OCD. Intrinsic to both syndromes is the extremely acute onset of symptoms. Knowledge of the incidence, breadth, course and outcome of PANS/PANDAS has been hampered by the absence of both a biomarker and a registry. Most studies of clinical presentation have been retrospective and emerged from research/referral centers which provide an unavoidably skewed picture of the most severe cases which are catastrophic but may not be representative. In Specific Aim 1a we will demonstrate the feasibility of the prospective identification, enrollment and clinical description of children with PANS and PANDAS in geographically distinct populations of children in the US in order to determine the incidence, spectrum and course of these disorders. To accomplish this aim we will identify 2 different health systems which include a primary care population of children with an electronic health record (EHR) that is comprehensive. Using a combination of a ‘best practice alert’ and a tailored algorithm, pertinent EHRs will be reviewed every weekday. Applying stringent clinical criteria, we will enroll consecutive children with new and abrupt onset of tics, OCD or food restriction who fulfill the definitions for PANDAS/PANS and follow them. We will successfully enroll 85% of the children meeting criteria. In Specific Aim 1b we will demonstrate that GAS is an instigator event in at least 65% of cases of PANS. In Specific Aim 2 we will determine the feasibility of studying the course and outcome of children with PANS/PANDAS enrolled prospectively. Children identified in Aim 1 will be evaluated at baseline and every 6 months with the Child-Yale Brown Obsessive Compulsive scale (CY-BOC) if the child has OCD, the Yale Global Tic Severity Scale (YG- TSS) if the child has tics, the Clinical Global Impairment score (CGIS) and the Child Global Assessment Scale (CGAS). The compilation of these scales will allow classification of at least 85% of children at outcome as being in remission, or having mild, moderate or severe disease. This rigorous, prospective, observational study will demonstrate the feasibility of this approach in preparation for a larger multicentered study with more prolonged follow-up. A comprehensive understanding of the entire scope of illness will facilitate appropriate allocation of therapeutic resources and set the stage for randomized clinical trials to assess treatment modalities.
