Tests Do Not Differentiate Acute-Onset Neuropsychiatric Syndrome

Abstract

Source: Vasiljevic S, Winerdal ME, Wickström R, et al. Recommended medical investigations in pediatric acute-onset neuropsychiatric syndrome. JAMA Netw Open. 2026;9; (3):e262618;doi: 10.1001/jamanetworkopen.2026.2618..Investigators from Karolinska Institutet and Stockholm Health Care Services, both in Stockholm, Sweden, conducted a case-control study to assess whether the results of the recommended laboratory evaluation of children diagnosed with pediatric acute-onset neuropsychiatric syndrome (PANS) were different from those of patients diagnosed with relevant psychiatric conditions not thought to be associated with an immunologic pathogenesis. Cases were patients 4–18 years old meeting established diagnostic criteria for PANS, a condition defined by acute onset of obsessive-compulsive disorder (OCD), restricted food intake, and/or tics, in association with ≥2 neurologic or psychiatric symptoms. Controls were children diagnosed with idiopathic OCD, tic disorder, or both. Participants were enrolled at 1 of 2 specialized clinics in Stockholm. The laboratory evaluation of study children was based on published guidelines for PANS and included multiple blood tests, including immune-related markers, and a throat swab. For patients with PANS who had neurologic symptoms, cerebrospinal fluid (CSF) was obtained, and a brain MRI and electroencephalography (EEG) were performed. Laboratory tests were considered abnormal based on comparison to reference values. A total of 56 laboratory tests were included in the analysis, and the results of 31 core tests were statistically compared in case and control participants using chi-square, Fisher exact, and Mann-Whitney U tests. The number of children with PANS in whom an underlying diagnosis was made based on the results of the laboratory evaluation also was determined.Data were analyzed on 109 children, including 51 with PANS and 58 controls. The mean age of cases was 10.2 ±3.4 years, and 66.7% were boys. Control children had a mean age of 13.6 ±3.6 years, and 50% were boys; 53 were diagnosed with OCD, 21 with a tic disorder, and 16 with both. Among the 56 laboratory tests evaluated, 44 (86.3%) case patients and 56 (96.6%) controls had at least 1 abnormal value. The most common abnormal laboratory test results in children with PANS were low ferritin levels (28.6%), low leukocyte count (25.0%), and low levels of complement level C4 (21.4%). For those in the control group, the most common abnormal findings were low leukocyte count (41.4%), low orosomucoid levels (25.5%), and low vitamin D levels (25.5%). Throat cultures were positive for Group A streptococcus in 16.7% and 8.5% of cases and controls, respectively. There were no statistically significant differences between cases and controls for any of the 31 core laboratory tests assessed. Among those with PANS, 1 child was diagnosed with celiac disease, and another had EEG finding consistent with encephalitis.The authors conclude that the recommended laboratory evaluation for children with PANS did not differentiate them from those with idiopathic OCD or tic disorders.Dr Doolittle has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.PANS is a syndrome with a constellation of protean symptoms of variable intensity: obsessive-compulsive symptoms, severe eating restriction, anxiety, emotional lability, and developmental regression, as well as motor abnormalities such as tics.1 While the etiology for PANS is unknown, possible mechanisms include post-infectious auto-immune processes and primary neuroinflammation, with potentially a genetic, metabolic, psychosocial contribution.1Identifying a reliable laboratory value to increase the Bayesian post-test probability would be helpful in achieving a diagnosis. The current researchers evaluated many commonly ordered tests, such as ferritin, complement levels, vitamin D, and inflammatory markers. While many tests were abnormal in the affected group and controls, there were no statistically significant differences.It is not surprising that routine tests yielded no statistically significant differences. PANS is a complex neurological syndrome that impacts cortico-striato-thalamo-pathways.2 More-over, transient or local immune activation may escape detection in peripheral blood.2 More sophisticated approaches, such as cytokine profiling, autoantibody panels, or functional neuroimaging, may prove helpful.2 The current research is an important and necessary first step in refining a diagnostic approach. While the sample size was small, their method was sound: comparison with a control cohort of patients who had OCD and tics. Given the relatively rare prevalence of PANS, this is a difficult syndrome to investigate. While identifying a biomarker may guide diagnosis, the crucial aspect is how a biomarker may impact treatment.There are no apparent laboratory differences between children with PANS and those with idiopathic OCD or tic disorders.