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Updated: Jun 16, 2026

Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Immune Checkpoint Inhibitor-Associated Kelch-Like Protein-11 IgG Brainstem Encephalitis
Albert Aboseif1, Nisa Vorasoot1, Marcus V Pinto1
1From the Center for Multiple Sclerosis and Autoimmune Neurology (A.A., N.V., Y.G., S.H., A.Z., J.J.C., D.D.), Department of Neurology; Department of Laboratory Medicine and Pathology (N.V., Y.G., A.Z., D.D.); Department of Neurology (N.V.), Mayo Clinic College of Medicine, Rochester, MN; Division of Neurology (M.V.P.), Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand; and Department of Ophthalmology (J.J.C.), Mayo Clinic College of Medicine, Rochester, MN.
Objectives:
Kelch-like protein-11 (KLHL11)-IgG is associated with rhombencephalitis and seminoma. It has not previously been described as a neurologic immune checkpoint inhibitor (ICI)-related adverse event (nirAE) or in association with esophageal adenocarcinoma.
Methods:
We describe a 61-year-old man with metastatic esophageal adenocarcinoma treated with folinic acid, fluorouracil, oxaliplatin (FOLFOX), and nivolumab, who subsequently developed diplopia, vertigo, and progressive gait ataxia after 8 weeks of treatment.
Results:
Owing to a concern for ICI-associated myasthenia gravis, nivolumab was held and he was treated with prednisone and pyridostigmine. EMG showed no neuromuscular junction dysfunction, and acetylcholine-receptor antibodies were negative. Brain MRI was unrevealing. Murine brain tissue immunofluorescence assay revealed KLHL11-IgG in both serum and CSF, confirmed by cell-based assay. Tumor histopathology demonstrated poorly differentiated, highly proliferative adenocarcinoma with increased mitotic figures and cytoplasmic KLHL11 immunoreactivity. He was initiated on 6 months of cyclophosphamide in addition to FOLFOX for post-ICI-associated KLHL11-IgG rhombencephalitis.
Discussion:
We report KLHL11-IgG rhombencephalitis associated with poorly differentiated esophageal cancer as a novel nirAE. Tumor staining revealed KLHL11 immunoreactivity, supporting a cancer-antigen-driven ICI-associated paraneoplastic syndrome. Recognition of novel nirAEs can expedite treatment and potentially prevent progressive neurologic disability.
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