To evaluate serum neurofilament light chain (sNfL) in pediatric patients with anti-NMDA receptor (anti-NMDAR) autoimmune encephalitis (AIE), seronegative AIE, and first episode of psychosis (FEP) caused by psychiatric disease (pFEP) to determine the utility of sNfL as a diagnostic biomarker. 

Differentiating between AIE and pFEP presents a significant diagnostic challenge in patients presenting with FEP. sNfL is a marker of neuronal damage with elevated levels reported in patients with anti-NMDAR AIE compared to those with pFEP. It is recommended to obtain anti-NMDA antibody testing by lumbar puncture in patients with FEP and elevated sNfL based on these findings. Importantly, seronegative AIE presents a greater challenge as there is no clear serologic biomarker for definitive diagnosis. Finally, our understanding of sNfL in AIE is particularly limited in children. 

Pediatric patients clinically diagnosed with pFEP, seronegative AIE, and anti-NMDAR AIE with sNfL drawn within 90 days of symptom onset were included in a single-center retrospective chart review. 

Children with seronegative AIE have significantly higher sNfL (n=4, mean=100.4 pg/mL) compared to those with pFEP (n=8, mean=8.275 pg/mL, p<0.05). Patients with anti-NMDAR AIE had higher sNfL (n=9, mean=24.03 pg/mL) than those with pFEP (p=0.7870), however this failed to meet statistical significance. 

This pilot study suggests that sNfL may be a useful biomarker in the evaluation of patients presenting with FEP to aid in the diagnosis of seronegative AIE versus pFEP. Though previously reported, larger studies are needed to link sNfL to pediatric anti-NMDAR AIE in our cohort. A non-invasive biomarker may help support a clinical diagnosis of disorders that present with similar phenotypes and thus decrease the latency to appropriate therapies. Ultimately, this may reduce the use of inappropriate treatments and improve long-term outcomes.