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Abstract Details

Biomarkers of Clinical Course and Outcomes in Pediatric N-Methyl-D-Aspartate Receptor Encephalitis
Autoimmune Neurology
P1 - Poster Session 1 (11:45 AM-12:45 PM)
8-007
Determine biomarkers of clinical course and outcomes in pediatric N-methyl-D-aspartate receptor encephalitis (NMDARE).
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.
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.
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.
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.
Authors/Disclosures
Sanam Zarei, MD (Children's National Medical Center)
PRESENTER 		Dr. Zarei has received intellectual property interests from a discovery or technology relating to health care.
Alexandra B. Kornbluh, MD (Children's National Hospital) Dr. Kornbluh has nothing to disclose.
Jonathan Santoro, MD (Department of Neurology, Children's Hospital Los Angeles) Dr. Santoro has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Santoro has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cycle Pharma. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Down Syndrome Society.
Claire Har, Jr., MPH Ms. Har has nothing to disclose.
Ilana L. Kahn, MD (Childrens National Medical Center) Dr. Kahn has nothing to disclose.
Elizabeth M. Wells, MD (Children'S National Medical Center) The institution of Dr. Wells has received research support from National Institute of Allergy and Infectious Diseases.
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic) Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has or had stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Amgen Pharmaceuticals. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with 好色先生. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing 好色先生, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Ionis Pharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a 好色先生al Case Development + Presentation (video) with PeerDirect (P\S\L Group). Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development / Presentation (non-CME) with MJH Life Sciences (NeurologyLive). Dr. Day has a non-compensated relationship as a Clinical Director with Anti-NMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.
Leigh N. Sepeta, PhD (Children'S National Health System) Dr. Sepeta has received personal compensation in the range of $500,000-$999,999 for serving as a Grant PI with Nih. Dr. Sepeta has a non-compensated relationship as a Special volunteer with Nih that is relevant to AAN interests or activities.