Recommended Medical Investigations in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Importance: The clinical utility of the comprehensive laboratory and medical investigations currently recommended for children with pediatric acute-onset neuropsychiatric syndrome (PANS) remains unclear. Notably, comparisons with relevant psychiatric control patients without suspected immunologic pathogenesis are lacking. Objective: To evaluate whether currently recommended laboratory investigations differentiate children with PANS from children with idiopathic obsessive-compulsive disorder (OCD) and/or tic disorders and whether the full set of recommended medical investigations identify underlying somatic conditions in children with PANS. Design, Setting, and Participants: This case-control study recruited children (aged 4-18 years) with PANS and children with idiopathic OCD and/or tic disorders (control group) from specialist PANS and OCD clinics in Stockholm, Sweden, between January 1, 2020, and September 19, 2023. The data analyses were performed between June 16, 2024, and August 19, 2025. Main Outcomes and Measures: Following published PANS guidelines, assessments included 56 laboratory variables from blood and throat cultures. Additional data from cerebrospinal fluid analysis, brain magnetic resonance imaging, and electroencephalography were available for a subsample of the PANS group. Laboratory findings were compared between the PANS and control groups. Results: Among 109 participants, the PANS group included 51 children (mean [SD] age, 10.2 [3.4] years; 34 boys [66.7%], and the control group included 58 children (mean [SD] age, 13.6 [3.1] years; 29 boys [50.0%]). Nearly all participants had at least 1 abnormal laboratory finding (44 [86.3%] in the PANS group, 56 [96.6%] in the control group), with no significant between-group differences. Most participants in the PANS group had 3 or more abnormal laboratory findings, while most in the control group had 4 or more. One participant with PANS was diagnosed with celiac disease; another showed electroencephalographic signs of neuroinflammatory activity without a definite diagnosis prior to the PANS assessment. Incidental, nonactionable findings were frequent. Conclusions and Relevance: In this case-control study of children with PANS and idiopathic OCD and/or tic disorders, abnormal laboratory findings were common in both groups and did not differ significantly. The full set of recommended medical investigations rarely identified underlying somatic conditions in children with PANS. These findings question the clinical utility of the comprehensive and costly medical investigations currently recommended for children with suspected PANS.