Abstract Details

Title Longitudinal, Prospective Analysis of Neuronal Injury Biomarkers in a Patient with Paraneoplastic Anti-CRMP5 Antibody Transverse Myelitis with Associated Treatment Response

Topic Autoimmune Neurology

Presentation(s) Autoimmune Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 071

Objective

Here we prospectively evaluated neuronal injury biomarkers over 14 months in a patient with collapsing response-mediator protein-5 (CRMP5) transverse myelitis (TM) and report a correlation of neurofilament light (NfL) chain and glial fibrillary protein (GFAP) levels to treatment response and clinical symptoms.

Background

The paucity of known outcome-surrogate biomarkers is one major hurdle in the development of clinical trials in autoimmune and paraneoplastic neurological diseases. Neuronal injury biomarkers may demonstrate a quantitative treatment response.

Design/Methods

Patient diagnosed with paraneoplastic CRMP5 TM and enrolled into the autoimmune registry and biorepository at University of Colorado. Blood and CSF samples obtained at diagnosis with subsequent blood at times 7 months and 14 months during treatment. Using Quanterix Single Molecule Array (SIMOA) technique, 4-Plex assays provided neuronal injury biomarker concentrations for NfL (normal value ≤ 10 pg/mL), GFAP (normal value ≤100 pg/mL), Tau protein, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1).

Results

At the time of initial diagnosis, both plasma NfL (782.62 pg/mL) and GFAP (283.26 pg/mL) were significantly elevated. Treatment consisted of neuroendocrine tumor removal, chemotherapy, and radiation. TM treated with IV steroids and plasma exchange (PLEX) during hospitalization. After some initial improvement in rehabilitation, she experienced clinical worsening after completion of chemotherapy with persistently elevated, albeit improved, NfL (103.27 pg/mL and GFAP (211.58 pg/mL) levels. Whole body PET scan did not demonstrate recurrence of malignancy. After repeat PLEX and rituximab induction, clinical follow up at 14 months demonstrated improvements on neurological exam and improved patient symptoms; NfL 18.39 pg/mL and GFAP 100.61 pg/mL at this time demonstrating minimal elevation to high normal ranges.

Conclusions

To our knowledge, this is the first described longitudinal, prospective analysis of neuronal injury biomarkers and association of clinical treatment outcomes in CRMP5 myelitis. Findings suggestive of trends in clinical improvement correlated with NfL and GFAP concentrations.

Authors/Disclosures
Christopher S. Mizenko (University of Colorado) PRESENTER	Mr. Mizenko has nothing to disclose.
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine)	Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immpact Bio. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MIAC. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Bennett has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vindico. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Touch IME. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Efficient LLC. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marie Bush. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Marks Gray. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Knight, Nicastro, MacKay. The institution of Dr. Bennett has received research support from Alexion. The institution of Dr. Bennett has received research support from Genentech. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Timothy L. Vollmer, MD, FAAN	The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics.
Amanda L. Piquet, MD, FAAN (University of Colorado)	The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kyverna . The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Joe Jones Law Firm. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cortez & Associates. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Falk Waas. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. The institution of Dr. Piquet has received research support from Anokion. The institution of Dr. Piquet has received research support from UCB . The institution of Dr. Piquet has received research support from Foundation for Sarcoidosis. The institution of Dr. Piquet has received research support from Kyverna . Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Autoimmune Encephalitis Alliance (AEA) that is relevant to AAN interests or activities. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Stiff Person Syndrome Research Foundation (SPSRF) that is relevant to AAN interests or activities.

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