Calmodulin Kinase-like Vesicle-associated Protein (CAMKV) Autoimmune Encephalitis: Neurological & Oncological Accompaniments, Treatments, & Outcomes
Diana Anissian1, Michael Gilligan1, Alise Carlson3, Christopher Hogge4, Timothy Bael5, Divyanshu Dubey2, John Mills1, Sean Pittock2, Anastasia Zekeridou2, Andrew McKeon2
1Department of Laboratory Medicine and Pathology, Mayo Clinic, 2Department of Neurology, Mayo Clinic, 3Mellen Center, Neurological Institute, Cleveland Clinic, 4Department of Neurology, Walter Reed National Military Medical Center (WRNMMC), 5Department of Oncology, Cayuga Medical Center
Objective:

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

Background:

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

Design/Methods:

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.

Results:

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.

Conclusions:

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.

10.1212/WNL.0000000000216000
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