Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma

Abstract

Patients with Langerhans cell histiocytosis (LCH) may develop progressive neurodegeneration in the central nervous system (ND-CNS-LCH). Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) is a promising biomarker to detect and monitor ND-CNS-LCH. We compared paired samples of NFL in plasma (p-NFL) and CSF in 10 patients (19 samples). Nine samples had abnormal CSF-NFL (defined as ≥380 ng/l) with corresponding p-NFL ≥ 2 ng/l. Ten samples had CSF-NFL < 380 ng/l; eight (80%) with p-NFL < 2 ng/l (p < 0.001; Fisher's exact test). Thus, our results suggest that p-NFL may be used to screen for ND-CNS-LCH. Further studies are encouraged, including the role of p-NFL for monitoring of ND-CNS-LCH.

Keywords: Langerhans cell histiocytosis; central nervous system (CNS); neurodegeneration; neurofilament light chain protein (NFL).

FIGURE 1

Plasma (p)‐NFL (neurofilament light protein) over time of three patients. The normal reference value for cerebrospinal fluid (CSF)‐NFL is <380 ng/l (depicted as a dotted line). The lower limit of detection for p‐NFL is 2 ng/l (depicted as a continuous line). The period marked BRAFi represents the time on BRAF‐inhibitor therapy. In addition, patient 7 received vinblastine, prednisolone and 6‐mercaptopurine at sampling 1, and 6‐mercaptopurine and methotrexate at sampling 5 while patient 9 was administered dexamethasone and cladribine between sampling 1 and sampling 2, and MEK‐inhibitor after sampling 2. Brief information on the three patients is provided in Text S1 [Colour figure can be viewed at wileyonlinelibrary.com]