To determine whether cerebrospinal fluid neopterin levels are associated with pediatric onset neuroinflammatory disorders and/or if elevations predict relapsing clinical courses.

Cerebrospinal fluid neopterin has been identified as a useful biomarker of central nervous system inflammation. However, there is currently no data comparing neopterin levels across different pediatric neuroinflammatory conditions or detailing how levels predict longitudinal outcomes.

A single-center cross-sectional study of neopterin levels in 189 children who underwent diagnostic lumbar puncture during evaluation for eventually confirmed neuroinflammatory disorders. Patients with history of malignancy, neurosurgical intervention, or who received immunotherapy or chemotherapy in the preceding six months were excluded. Confirmation of final diagnosis was made by two pediatric-trained neuroimmunologists. Significant correlations were probed using multiple linear and multiple logistic regression.

Amongst 20 different pediatric neuroinflammatory diagnoses, cerebrospinal fluid neopterin level was significantly elevated in children with myelin oligodendrocyte glycoprotein-associated disease (MOGAD), CNS vasculitis, opsoclonus-myoclonus syndrome (OMS) and autoimmune encephalitis (AE) (p = 1.5e-07, 95%CI:[22.3, 47.6]). A neopterin cut off value of 30 for making a diagnosis of MOGAD, AE, CNS Vasculitis, or OMS had a sensitivity of 73% and specificity of 74%. In evaluating the subgroup of patients with relapse, patients with diagnoses of MOGAD, AE, CNS Vasculitis and OMAS had a significant increase in neopterin level by 70.4 (p=1.6e-05, 95%CI:[40.6,100.3]) which held true even when accounting for neopterin level variation among different diagnoses. There is a sensitivity of 96% and specificity of 84% for using a neopterin of 33, 37 and 59 to predict relapse for AEs, CNS Vasculitis and MOGAD, respectively.

In a large and diagnostically diverse cohort of pediatric onset neuroinflammatory disorders, elevated neopterin levels were observed in MOGAD, CNS vasculitis, OMS and AE. Furthermore, elevated neopterin was associated with an increased risk of relapse, particularly in MOGAD, a disorder in which relapse risk remains poorly understood.