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Abstract Details

Quantifying CSF Biomarkers of Neuronal Injury, Neuroinflammation and Synaptic Integrity in Antibody-Mediated Encephalitis
Autoimmune Neurology
P2 - Poster Session 2 (5:30 PM-6:30 PM)
15-001

To measure cerebrospinal fluid (CSF) biomarkers of neuronal injury, neuroinflammation and synaptic integrity in patients with antibody-mediated encephalitis (AME).
Recovering AME patients frequently exhibit persistent impairment in memory and executive function. Biomarkers that inform the contributors to long-term cognitive sequelae are needed to identify patients at-risk of long-term deficits.
Cerebrospinal fluid was collected from 46 patients at the time of diagnosis of NMDAR (n=35) or LGI1/CASPR-2 (n=11) AME, and 40 age- and gender-similar cognitively normal volunteers assessed at Washington University in St. Louis (USA); University of Toronto, Mitogen Diagnostics/University of Calgary (Canada); or Charité Hospital and University Hospital Magdeburg (Germany). Biomarkers of neuronal injury (total tau, VILIP-1), inflammation (YKL-40), and synaptic integrity (neurogranin, SNAP-25) were compared between patients and controls, controlling for age (univariate ANCOVA).
NMDAR encephalitis patients were younger (median, 26 years; range, 4.0-41.8) than patients with LGI1/CASPR2 AME (70.4 years, 60.6-83.2; p<0.001). Markers of neuronal injury were similar (mean total tau [95%CI]: 22.4 pg/ml [16.3-28.5]; vs. 20.2 pg/ml [13.7-26.8]; p=0.63) or decreased (VILIP-1: 42.5 pg/ml [31.4-53.6]; vs. 119.0 pg/ml [107.0-130.9]; p<0.001) in patients versus controls. The neuroinflammatory biomarker YKL-40 was elevated in patients compared to controls (YKL-40: 303.0 pg/ml [257.1-348.9] vs. 162.1 ng/ml [113.4-210.8]; p<0.001), while markers of synaptic integrity were decreased (SNAP-25: 1.54 pg/ml [1.19-1.89] vs. 3.20 pg/ml [2.83-3.58], p<0.001; neurogranin: 577.5 pg/ml [336.3-818.7] vs. 1462.9 pg/ml [1204.2-1721.7]; p<0.001). VILIP-1 levels differentiated patients with NMDAR (27.0 pg/ml [12.9-41.1]) from LGI1/CASPR2 AME (84.5 pg/ml [47.1-121.8]; p=0.02). No other biomarker differences were observed between patients.
Cerebrospinal fluid biomarkers suggest that neuronal integrity is acutely maintained in AME patients. Low-levels of biomarkers of synaptic integrity may reflect antibody-mediated internalization of cell-surface receptors, and may represent an acute correlate of antibody-mediated synaptic dysfunction underlying cognitive sequelae in recovering patients.
Authors/Disclosures
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic)
PRESENTER 		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.
No disclosure on file
No disclosure on file
No disclosure on file
Harald Pruss Harald Pruss has nothing to disclose.
Bob Bucelli, MD, PhD (Washington University) Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen . Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bucelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron. Dr. Bucelli has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Hamilton Weber. Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for O'Bryan Brown and Toner. Dr. Bucelli has stock in Neuroquestions.com. An immediate family member of Dr. Bucelli has stock in Neuroquestions.com. The institution of Dr. Bucelli has received research support from Biogen. The institution of Dr. Bucelli has received research support from Ionis.
No disclosure on file
Warren P. Mason, MD, FAAN (Princess Margaret cancer Centre) Dr. Mason has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novocure. Dr. Mason has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Mason has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Servier. Dr. Mason has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boeringher Ingelheim. Dr. Mason has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Therapeutics.
David F. Tang-Wai, MD, FRCPC (Toronto Western Hospital/University Health Network) Dr. Tang-Wai has nothing to disclose.
Claude Steriade, MD (NYU) The institution of Dr. Steriade has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for The Epilepsy Study Consortium. Dr. Steriade 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. Dr. Steriade has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for DOJ. The institution of Dr. Steriade has received research support from NIH. Dr. Steriade has received personal compensation in the range of $500-$4,999 for serving as a Consultant with Epitel. Dr. Steriade has received personal compensation in the range of $500-$4,999 for serving as a Consultant with Jazz Pharmaceuticals. Dr. Steriade has received personal compensation in the range of $10,000-$49,999 for serving as a Speakers Bureau with SK Life Sciences. Dr. Steriade has received personal compensation in the range of $5,000-$9,999 for serving as a Speakers Bureau with Neurelis. Dr. Steriade has received personal compensation in the range of $5,000-$9,999 for serving as a Advisory Board with Xenon Pharmaceuticals.
Julien Hebert, MD (Toronto Western Hospital (University Health Network)) Dr. Hebert has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Paladin Labs. Dr. Hebert has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Gowling WLG. The institution of Dr. Hebert has received research support from Praxis Precision Medicine.
Elizabeth Herries No disclosure on file
No disclosure on file
John C. Morris, MD, FAAN (Washington University) Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CBR International Advisory Board. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cure Alzheimers Fund. Dr. Morris has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LEADS Steering Commitee. The institution of Dr. Morris has received research support from NIH grants. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care. Dr. Morris has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file