Abstract Details

Title Immune Checkpoint Inhibitor-associated Kelch-like Protein-11 IgG Rhombencephalitis

Topic Autoimmune Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 14-002

Background ICIs are increasingly linked with several rare neural autoantibodies associated with autoimmune encephalitis. Kelch-like protein-11 (KLHL11)-IgG is an autoantibody usually associated with rhombencephalitis and seminoma. It has not previously been described in the setting of nirAE or in association with esophageal adenocarcinoma.

Objective

To report a novel immune checkpoint inhibitor (ICI)-associated seropositive neurological immune-related adverse effect (nirAE).

Design/Methods Case report.

Results A 61-year-old male was diagnosed with metastatic esophageal adenocarcinoma, and treated with folinic acid, fluorouracil, oxaliplatin (FOLFOX), and nivolumab. Two months after treatment initiation, he developed diplopia and vertigo. Due to a concern for ICI-associated myasthenia gravis, nivolumab was held, and he was started on prednisone and pyridostigmine. EMG showed no neuromuscular junction dysfunction, and acetylcholine-receptor antibodies were negative. MRI brain was unrevealing. Over the next three months, he developed progressive ataxia and gait instability, becoming walker dependent. Examination revealed bi-directional torsional nystagmus, a right upper-extremity wing-beating tremor, and a wide-based ataxic gait. His CSF was non-inflammatory. On further testing, murine brain tissue immunofluorescence assay revealed a neural-specific pattern with periventricular punctate staining consistent with KLHL11-IgG in both serum and CSF, with a titer of 1:7680 and 1:64 respectively, and confirmed by cell-based assay. Tumor histopathology demonstrated poorly differentiated and highly proliferative adenocarcinoma with increased mitotic figures and cytoplasmic KLHL11 immunoreactivity. His diagnosis was consistent with post ICI-associated KLHL11-IgG rhombencephalitis, and he was initiated on 6-months of cyclophosphamide in addition to FOLFOX.

Conclusions We report KLHL11-IgG rhombencephalitis associated with poorly differentiated esophageal cancer as a novel nirAE. Tumor staining revealed KLHL11 immunoreactivity, supporting an ICI-associated paraneoplastic syndrome. It is critical to recognize and report novel nirAEs, in an effort to initiate early treatment and prevent progressive neurological disability.

Authors/Disclosures
Albert Aboseif, DO (Mayo Clinic Rochester) PRESENTER	Dr. Aboseif has a non-compensated relationship as a AAN Autoimmune Neurology Section -- Education Workgroup with AAN that is relevant to AAN interests or activities.
Nisa Vorasoot, MD (Department of Neurology, Mayo Clinic)	Dr. Vorasoot has nothing to disclose.
Marcus Vinicius R. Pinto, MD (Mayo Clinic)	Dr. Pinto has nothing to disclose.
Yong Guo	No disclosure on file
Shemonti Hasan, MD (Mayo Clinic)	Dr. Hasan has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
John Chen	No disclosure on file
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.