To describe the clinical features of calmodulin kinase-like vesicle-associated protein (CAMKV)-IgG associated autoimmune paraneoplastic encephalitis.

Previously 5 were described. Here, we report our total clinical experience of 12 patients.

All patient samples had characteristic cerebrum-restricted IgG staining by tissue-based indirect immunofluorescence assay, confirmed by CAMKV-specific cell-based assay. Medical records were reviewed.

Median symptom-onset age for 12 patients were 69 years (range, 53 to 79); 8 were women. All patients presented with encephalopathy. Disorders were altered mental status (7/12), seizures (5/12), hyperkinetic movements (6/12), psychiatric features (4/12), memory loss (3/12), insomnia (4/12), gait instability (2/12), diplopia (2/12), dysmetria (2/12), hypermetric saccades (1/12) and ataxic dysarthria (1/12). Hyperkinetic movement disorders included oral dyskinesia (2/12), tremor, myoclonus, chorea, and opsoclonus (1 each). Cancer history (12/12) included uterine cancer (4/12: endometrial adenocarcinoma, 2; endometrial neuroendocrine adenocarcinoma, 1; endometrial undifferentiated carcinoma, 1); lymphoma, 2 (non-Hodgkin, 1; Hodgkin, 1), bladder urothelial carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, prostatic adenocarcinoma, metastatic undifferentiated carcinoma in lymph node (unknown primary), 1 each. Three patients developed encephalitis following immune checkpoint inhibitor therapy (atezolizumab [1], pembrolizumab [2]). Eight of 9 patients with solid organ malignancies had metastatic disease at the time of neurologic onset. Six of 8 patients with CSF result available had lymphocytic pleocytosis. Six of 7 patients who received immunotherapy had neurological improvements (corticosteroids [7], IVIG [5]). Despite this, 5 of 7 patients with follow-up data available died from cancer. After encountering a co-existent ANNA-1 (anti-Hu) and CAMKV-IgG sample, we retrospectively evaluated 42 ANNA-1 positive samples with accompanying unclassified synaptic IgG staining; 4 had coexisting CAMKV-IgG. Clinical data was available for 1/5, included among the 12 described.

CAMKV-IgG is a biomarker of paraneoplastic autoimmune encephalitis, with diverse cancer types (with emphasis on neuroendocrine-lineage and uterine carcinomas). Patients have good neurological responses to immunotherapy, but poor cancer outcomes.