Neurofilament as a biomarker of neurodegeneration in childhood Langerhans cell histiocytosis: A feasibility study on 273 patients

Neurodegeneration (ND) is a severe complication of Langerhans cell histiocytosis (LCH), often leading to progressive neurological decline. We evaluated the usefulness of using plasma and cerebrospinal fluid neurofilament light chain (p- and CSF-NFL) levels as biomarkers to identify and monitor ND-LCH. NFL levels were measured using the single-molecule array for a subset of patients from the French National LCH Registry. NFL levels in 692 plasma and 115 CSF samples from 273 registry-enrolled children were analysed. Based on 84 paired plasma and CSF samples from 67 patients, p- and CSF-NFL levels were strongly correlated (p < 0.0001). The areas under the receiver operating characteristics curves for ND-LCH were 72% (95% confidence interval [CI], 64%-78%) for p-NFL and 94% (95% CI, 88%-98%) for CSF-NFL. The highest p-NFL (13.7 vs. 7.2 pg/mL; z-score 2.3 vs. 0.6) and CSF-NFL (436.9 vs. 65.2 pg/mL) levels were significantly higher for ND-LCH than in no-ND-LCH patients, respectively (p < 0.0001). Plasma NFL levels were not elevated at LCH diagnosis. At LCH diagnosis, p-NFL was not predictive of ND, but it may serve as a minimally invasive screening tool for ND in LCH, although optimal timing remains to be determined.