From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome)

Despite continued debates about the role of Group A streptococcal infections in the etiopathogenesis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections), experts on both sides of the controversy agree that a subgroup of children with obsessive-compulsive disorder (OCD) have an unusually abrupt onset of symptoms, accompanied by a variety of comparably severe and acute neuropsychiatric symptoms. The acuity of symptom onset is the hallmark feature of their clinical presentation and the basis for the name proposed for an expanded clinical entity: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). Modifying the PANDAS criteria to eliminate etiologic factors and to clarify the initial clinical presentation produced three potential diagnostic criteria for PANS. These three criteria are discussed in detail. The article also proposes strategies for applying the PANS criteria in clinical settings and evaluating their validity and reliability through prospective research investigations. *Corresponding author: Susan E. Swedo, Pediatrics & Developmental Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda MD, USA, E-mail: [email protected] Received December 06, 2011; Accepted January 30, 2012; Published February 02, 2012 Citation: Swedo SE, Leckman JF, Rose NR (2012) From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2:113. doi:10.4172/2161-0665.1000113 Copyright: © 2012 Swedo SE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction When the initial description of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) was published in 1998, it was a compilation of more than a decade of research by clinical investigators in the intramural research program of the National Institute of Mental Health (NIMH) [1]. Establishing a connection between childhood-onset obsessive compulsive disorder (OCD) and preceding infections with Group A streptococcal (GAS) infections was the result of two parallel lines of research longitudinal studies of OCD and a series of investigations of Sydenham chorea (SC) [2-4]. Prospective evaluations of children with OCD revealed that a subgroup had an atypical symptom course, characterized by an unusually abrupt onset (from no symptoms to maximum intensity within 24-48 hours), a relapsing-remitting symptom course, and significant neuropsychiatric comorbidity, including separation anxiety, ADHD-like symptoms and motor tics [1,2]. Often, the OCD symptoms were preceded by a bacterial or viral infection, such as influenza, varicella and Group A streptococcal (GAS) pharyngitis. The first case series suggested the name, “Pediatric Infection-Triggered Autoimmune Neuropsychiatric Disorders (PITANDS) “to reflect the variety of infectious organisms that had been observed [5]. Cases with onset of OCD symptoms following a GAS infection were of greatest interest to the NIMH investigators because of their concomitant research findings in SC which demonstrated that obsessions and compulsions were present in 60 – 75% of the affected children [3,6,7]. The children with SC reported that the obsessive-compulsive symptoms began 2 – 4 weeks prior to onset of the adventitious movements, leading the investigators to hypothesize that the neuropsychiatric symptoms might represent a forme fruste of SC and be manifest by children with a history of (untreated) GAS infections, even in the absence of chorea [6,7]. Dozens of post-GAS cases were subsequently identified and their unique clinical characteristics served as the basis for the diagnostic criteria for the PANDAS subgroup [1] (See Table 1). Subsequent research at a number of institutions revealed that not only are there clinical similarities between SC and PANDAS [811] but the two disorders also have similar profiles of cross-reactive antineuronal antibodies [12-15], responses to immunomodulatory therapies [16-17] and vulnerability to non-GAS recurrences [18-20]. Despite these commonalities, it is important to note that PANDAS is not equivalent to a “mild case of SC”, as the presence of chorea, rheumatic carditis or any of the other major manifestations of rheumatic fever (RF) is an exclusionary criterion for PANDAS [1,21]. By ruling out RF and SC before considering a diagnosis of PANDAS, decisions about antibiotic prophylaxis can be made appropriately. Clinical practice guidelines from the American Heart Association require antibiotics prophylaxis for all cases of RF, including those presenting only with chorea [22]. In contrast, antibiotics prophylaxis is not generally recommended for children in the PANDAS subgroup. Although two separate clinical trials in PANDAS demonstrated that All five diagnostic criteria must be met: 1) Presence of obsessive-compulsive disorder (OCD) or a tic disorder 2) Prepubertal symptom onset 3) Acute symptom onset and episodic (relapsing-remitting) course 4) Temporal association between Group A streptococcal infection and symptom onset/exacerbations 5) Associated with neurological abnormalities, (particularly motoric hyperactivity and choreiform movements) Table 1: PANDAS Diagnostic Criteria. Citation: Swedo SE, Leckman JF, Rose NR (2012) From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2:113. doi:10.4172/2161-0665.1000113