Pediatric acute neuropsychiatric syndrome : diagnosis, biomarkers and treatment

Abstract

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) are proposed diagnoses combining a clinical picture of acute onset obsessive compulsive disorder, tics or eating disorders with a suggested inflammatory pathogenesis. However, it remains uncertain if patients with PANS or PANDAS differ from other psychiatric patients with regard to symptoms, disorder course or symptom load at onset. Furthermore, there is currently a diagnostic test in clinical use, which aims to diagnose PANS and PANDAS, but its clinical validity is yet unclear. The proposed inflammatory pathogenesis of the disorders motivates immunomodulatory treatments, but the evidence for using such treatments is lacking.

Aims: The aims of this thesis were to; describe a Swedish cohort of patients with PANS and PANDAS; evaluate the utility of the current diagnostic criteria for PANS and PANDAS; evaluate the diagnostic accuracy of the Cunningham Panel, a set of biomarkers aiming to diagnose PANS and PANDAS; establish if there are currently any evidence based treatments for PANS or PANDAS; and to describe the treatments given to a Swedish sample of patients with PANS and PANDAS, and the treatment effects.

Methods: This thesis comprises four studies with different study designs. Studies I, II and III were based on the same data collection. Study I is a case control study comparing Confirmed PANS (n=28), to Suspected PANS (n=29) and Never PANS (n=32) regarding symptoms, disorder onset and disorder course. Study II is a diagnostic accuracy study comparing Cunningham Panel results of Confirmed PANS (n=24), to Suspected PANS (n=29) and to a healthy comparison sample (n=21). Study III is a cross-sectional study of which treatments had been given to patients with Confirmed PANS (n=24) and Suspected PANS (n=29), treatment effects and patient satisfaction. Study IV is a systematic review of studies (n=12) and case reports (n=65) of treatment for PANS and PANDAS.

Results: In Study I we show that confirmed PANS (defined as acute onset) was associated to an episodic course and high symptom load at onset. According to the results of Study II the Cunningham Panel could not differentiate between Confirmed and Suspected PANS. In addition, healthy controls had elevated panel results on the Cunningham Panel. The results of Study III indicate that patients with PANS are possibly under-treated with standard psychiatric treatments. However, antibiotics and intravenous immunoglobulins were perceived as helpful by the participants. Treatment outcome predicted patient satisfaction. The literature reviewed in Study IV revealed that antibiotics, immunomodulatory medications and standard psychiatric treatment have been tried in PANS and PANDAS. The evidence for all studied treatments is inconclusive.

Conclusion: Episodic course, acute onset and high symptom load at onset are better specifiers of PANS than presence of specific symptoms. The Cunningham Panel is not a reliable diagnostic measure for PANS. When treating patients with PANS it is important to have knowledge of both psychiatric and immunomodulatory treatments. The lack of evidence based or effective treatments may lead to a low patient satisfaction. The field of PANS and PANDAS is in need of more and better research on the outcome of treatments. Key methodological issues include diagnostic challenges and lack of relevant outcome measures.