Fig. 1: Examples of MRI features evaluated and summary boxplots.

A, B T2 hyperintensity in bilateral middle cerebellar peduncles extending into cerebellum and pons (A, arrows) with associated gadolinium enhancement on T1 weighted images (B, arrows), defined as parenchymal brain involvement, with enhancement. C Gadolinium enhancement on T1 weighted images in subarachnoid spaces suggestive of leptomeningeal disease (C, arrow), defined in the study cohort as non-parenchymal CNS involvement, without parenchymal enhancement. D Large dural-based lesion with homogenous enhancement on T1 post-gadolinium sequences (D, arrow) with compression of brainstem and encasement of the vertebral artery, defined as non-parenchymal CNS involvement, without parenchymal enhancement. E Boxplot comparing cases to controls; neurofilament light chain (NfL) by Simoa assay transformed to Ella level plus Ella assay in patients with central nervous system (CNS) histiocytosis were significantly elevated compared to those with histiocytosis without CNS involvement (P < 0.0001). F NfL by Simoa assay transformed to Ella level plus Ella assay in patients with histiocytic disease without CNS involvement compared to those with CNS involvement with and without parenchymal involvement. NfL was significantly higher in those with parenchymal involvement than non-CNS histiocytosis (P < 0.0001). G NfL by Simoa assay transformed to Ella level plus Ella assay in patients with histiocytic disease without CNS involvement compared to those with CNS involvement with and without parenchymal enhancement. NfL was significantly higher in those with parenchymal enhancement than non-CNS histiocytosis (P < 0.0001).