Abstract Details

Title Paraneoplastic Cochleovestibulopathy: Clinical Presentations, Oncological and Serological Associations

Topic Autoimmune Neurology

Presentation(s) S41 - Autoimmune Neurology 3: Autoimmune Encephalitis, Paraneoplastic Neurologic Disorders, Antibody-Mediated Diseases, Immunology (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background Progressive hearing loss or vestibular dysfunction in the presence of malignancy or high-risk paraneoplastic antibody has been characterized as paraneoplastic cochleovestibulopathy.

Objective to evaluate the neural-specific antibody associations, clinical presentation, and outcomes of paraneoplastic cochleovestibulopathy.

Design/Methods Retrospective chart review of patients with hearing impairment and/or vestibulopathy who underwent serological evaluations for paraneoplastic antibodies between January 2007 and February 2021 was performed.

Results Twenty-six patients were identified (males, n=23; median age, 45 years, range: 28-70). Biomarkers detected included: KLHL11-IgG‌ ‌(n=20,‌ ‌77% [co-existing LUZP4-IgG, n=8]),‌ ‌‌ANNA1-IgG‌ ‌ ‌(n=3,‌ ‌12%),‌ ‌Amphiphysin-IgG‌‌ ‌(n=2,‌ ‌8%)‌ ‌and‌ ‌LUZP4-IgG‌‌ ‌(n=1,‌ ‌4%). ‌Malignancy‌‌evaluation‌ ‌revealed‌ ‌testicular‌ ‌and‌ ‌extra-testicular‌ ‌seminoma‌ ‌(n=13,‌ ‌50%),‌ ‌regressed‌ ‌germ-cell‌ ‌tumor‌ ‌(n=7,‌ 27%)‌ ‌and‌ ‌other‌ ‌tumors‌ ‌(n=5,‌ ‌19%).‌‌ Hearing‌ impairment (bilateral, 62%) was ‌present‌ ‌in‌ ‌all‌ ‌patients.‌ ‌Other‌ ‌symptoms‌ ‌included‌ ‌ataxia‌ ‌(n=26,‌ ‌100%),‌ ‌diplopia‌ ‌(n=20,‌ ‌77%)‌ ‌and‌ ‌vertigo‌ ‌(n=16,‌ ‌62%).‌ Fifteen patients (58%) had cochleovestibular dysfunction as their initial presentation before rhombencephalitis manifestations (hearing loss, 4; acute vertigo, 8; both, 3). ‌Brain‌ ‌MRI‌ ‌demonstrated‌ ‌internal‌ ‌auditory‌ ‌canal‌ ‌enhancement‌ ‌in‌ ‌4‌ ‌patients.‌ ‌Symptoms‌ ‌preceded‌ ‌tumor‌ ‌diagnosis‌ ‌in‌ ‌25‌ ‌out‌ ‌of‌ ‌26‌ ‌patients,‌ by a median ‌of‌ ‌8‌ ‌months‌ (range:‌ ‌3-29). Audiometry commonly revealed severe-profound bilateral sensorineural hearing loss. Most patients ‌had‌ a refractory course ‌despite‌ ‌immunotherapy‌ ‌and/or‌ ‌cancer‌ ‌treatment‌.

Conclusions Cochleovestibulopathy is a distinct paraneoplastic phenotype presenting with rapidly progressive bilateral hearing loss and/or acute vertigo, which is often treatment-refractory. KLHL11-IgG and seminoma are the most common serological and cancer associations, respectively. Recognition of this phenotype may aid in earlier diagnosis of paraneoplastic autoimmunity and associated cancer.

Authors/Disclosures
M Bakri Hammami, MD (Jacobi Medical Center) PRESENTER	Dr. Hammami has received intellectual property interests from a discovery or technology relating to health care.
Scott D. Eggers, MD	Dr. Eggers has received publishing royalties from a publication relating to health care.
Ajay Madhavan	No disclosure on file
Mayra Montalvo Perero, MD (University of Florida)	Dr. Montalvo Perero has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AMGEN.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.