Despite significant advances in the diagnosis and treatment of AE, little is known about markers of disease severity and their associations with outcomes. sNfL, a marker of axonal destruction, may fill this gap.
This is a longitudinal prospective case-control study of children presenting to a single tertiary center with AE (n=48) vs. an age-matched healthy control population (HC) (n=88). Clinical data and modified Rankin Scale (mRS) scores were collected using a standard CRF at baseline and at follow-up, up to one year. sNfL levels in stored samples were measured by Single Molecule Array Immunoassay (SIMOA). Volumetric analyses of key anatomic structures of brain MRIs were performed using FreeSurfer. Diffusion weighted MRI was assessed for restricted diffusion. Following standard diagnostic criteria, children were classified into those with no biological marker (antibody or genetic) and those with. We further dichotomized children into high vs. low sNFL levels. Descriptive statistics, group differences, and correlational analyses were performed using JASP version 0.16.3.
Baseline sNfL levels were significantly higher in patients with AE (no Ab), AE (MOG), and ANEC vs. HCs (log2 sNfL=4.3 AE(no Ab), 2.9 AE(NMDA), 5.6 AE(MOG), 6.3(ANEC), 2.4(HC), p<0.001). AE patients in the high sNfL group were more likely to be admitted to the ICU (p=0.02) and had significantly higher mRS scores at nadir (p=0.04), compared to patients in the low sNfL group. However, there was no significant difference in mRS scores at follow-up between groups. Baseline sNfL correlated significantly with baseline restricted diffusion (rs(43)=0.45, p=0.002) and thalamic volumes (rs(31)=0.45, p=0.009).
Baseline sNfL levels may serve as a marker of disease severity in patients with AE. Future studies are needed to evaluate their associations with long-term outcomes.