Calmodulin kinase-like vesicle-associated protein (CAMKV) autoimmune encephalitis: Neurological & oncological accompaniments, treatments & outcomes

BACKGROUND & OBJECTIVES: We previously reported CAMKV-IgG paraneoplastic encephalitis accompanying uterine and neuroendocrine-lineage carcinomas. Here, we describe 7 new cases (12 total) and report CSF cytokine/chemokine profiles and coexisting antibody frequency. METHODS: Patient samples demonstrating the CAMKV-specific murine tissue-based indirect immunofluorescence assay (TIIFA) staining pattern were tested by protein microarray and confirmed CAMKV-specific cell-based assay. CSF cytokines/chemokines were analyzed in 4 patients. RESULTS: Median symptom-onset age was 69 years (range 53-79); 8/12 were women. Common manifestations included altered mental status (7/12), hyperkinetic movements (6/12), seizures (5/12), psychiatric, and insomnia (4/12 each). Five patients had coexisting antibodies: tripartite motif-containing protein-9 (3), N-methyl-D-aspartate receptor (2), antineuronal nuclear antibody-type-1 (ANNA-1) and γ-aminobutyric acid B receptor (1 each). All 12 had cancer, including adenocarcinoma (6/12; uterine 4, lung 1, prostate 1), lymphoma (Hodgkin and non-Hodgkin), or other carcinoma (urothelial, Merkel cell, hepatocellular, and poorly differentiated (1 each). All 3 available cancers (uterine, 2; prostate adenocarcinoma, 1) were immunohistochemistry positive for CAMKV. 6/8 had CSF lymphocytic pleocytosis. MRIs revealed mesial temporal and basal ganglia T2 hyperintensities in 6/10 and 5/10, respectively. Among 7 immunotherapy-treated patients, 6 improved initially, although 5/7 with follow-up died from cancer. CSF IL-13 and GM-CSF were significantly elevated compared with non-inflammatory controls (FDR-adjusted P < 0.05). Four of 42 ANNA-1 positive samples with coexisting synaptic TIIFA staining were CAMKV-IgG positive. DISCUSSION: CAMKV-IgG is a paraneoplastic encephalitis autoantibody associated with diverse cancers. Neurologic improvement with immunotherapy is frequent, but prognosis is driven by cancer outcomes. Elevated IL-13 may indicate metastatic risk.