Objective:

Determine biomarkers of clinical course and outcomes in pediatric N-methyl-D-aspartate receptor encephalitis (NMDARE).

Background:

The identification of biomarkers that inform disease pathogenesis and progression in adult NMDARE has advanced. There has been limited progress, however, in discovering predictors of clinical course and outcome in pediatric NMDARE (pNMDARE). Identifying these biomarkers is essential to help guide patient care.

Design/Methods:

Biomarkers of neuronal (visinin-like protein 1/VILIP-1) and neuro-axonal damage (neurofilament light chain/NfL), neuro-inflammation (chitinase 3-like protein/YKL-40; monocyte chemoattractant protein-1/MCP-1), and synaptic function (synaptosomal associated protein-25/SNAP-25; neurogranin) were measured in cerebrospinal fluid (CSF) from 17 pNMDARE patients at diagnosis and 21 pediatric controls with other neurologic disease. Associations between biomarkers and modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were evaluated in pNMDARE cases.

Results:

In pNMDARE cases versus pediatric controls, biomarkers of neuro-inflammation (YKL-40) were elevated (p=0.028), whereas markers of neuronal injury (VILIP-1: p=0.001) and synaptic function (SNAP-25: p=0.005) were decreased. The log-transformed ratios of YKL-40/SNAP-25 and YKL-40/neurogranin optimally discriminated pNMDARE patients from pediatric controls (area under the curve [AUC] LogYKL-40/SNAP-25 0.89; 95% confidence interval [CI] 0.76, >0.99; AUC LogYKL-40/neurogranin 0.84; 95% CI 0.69, 0.98). Higher MCP-1 levels predicted higher mRS scores at 12 months, explaining 35.1% of the variance (p=0.036). Higher NfL (p=0.001) and MCP-1 (p=0.002) levels predicted higher CASE scores at 12 months, explaining 78.4% of the variance.

Conclusions:

In pNMDARE, there is neuro-axonal compromise and reduced synaptic function but intact neuronal integrity. Low levels of synaptic function biomarkers coupled with elevated neuro-inflammatory markers can effectively distinguish pNMDARE patients from those with other neurologic disorders. These findings align with previous research on adults with NMDARE. MCP-1 and NfL are associated with prognosis. Future directions include employing biomarkers to differentiate pNMDARE from other neuro-immunologic conditions and correlating these biomarkers with treatment response.