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Paraneoplastic Calmodulin Kinase-Like Vesicle-Associated Protein (CAMKV) Autoimmune Encephalitis.
- Source :
-
Annals of neurology [Ann Neurol] 2024 Jul; Vol. 96 (1), pp. 21-33. Date of Electronic Publication: 2024 Apr 18. - Publication Year :
- 2024
-
Abstract
- Objectives: To report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase-like vesicle-associated (CAMKV).<br />Methods: Serum and cerebrospinal fluid (CSF) samples harboring unclassified antibodies on murine brain-based indirect immunofluorescence assay (IFA) were screened by human protein microarray. In 5 patients with identical cerebral IFA staining, CAMKV was identified as top-ranking candidate antigen. Western blots, confocal microscopy, immune-absorption, and mass spectrometry were performed to substantiate CAMKV specificity. Recombinant CAMKV-specific assays (cell-based [fixed and live] and Western blot) provided additional confirmation.<br />Results: Of 5 CAMKV-IgG positive patients, 3 were women (median symptom-onset age was 59 years; range, 53-74). Encephalitis-onset was subacute (4) or acute (1) and manifested with: altered mental status (all), seizures (4), hyperkinetic movements (4), psychiatric features (3), memory loss (2), and insomnia (2). Paraclinical testing revealed CSF lymphocytic pleocytosis (all 4 tested), electrographic seizures (3 of 4 tested), and striking MRI abnormalities in all (mesial temporal lobe T2 hyperintensities [all patients], caudate head T2 hyperintensities [3], and cortical diffusion weighted hyperintensities [2]). None had post-gadolinium enhancement. Cancers were uterine adenocarcinoma (3 patients: poorly differentiated or neuroendocrine-differentiated in 2, both demonstrated CAMKV immunoreactivity), bladder urothelial carcinoma (1), and non-Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All treated patients (4) demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]), though 3 died from cancer.<br />Interpretation: CAMKV-IgG is a biomarker of immunotherapy-responsive paraneoplastic encephalitis with temporal and extratemporal features and uterine cancer as a prominent oncologic association. ANN NEUROL 2024;96:21-33.<br /> (© 2024 American Neurological Association.)
- Subjects :
- Humans
Female
Middle Aged
Aged
Male
Hashimoto Disease cerebrospinal fluid
Immunoglobulin G cerebrospinal fluid
Immunoglobulin G blood
Paraneoplastic Syndromes, Nervous System cerebrospinal fluid
Paraneoplastic Syndromes, Nervous System immunology
Mice
Encephalitis cerebrospinal fluid
Autoantibodies cerebrospinal fluid
Autoantibodies blood
Subjects
Details
- Language :
- English
- ISSN :
- 1531-8249
- Volume :
- 96
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Annals of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 38634529
- Full Text :
- https://doi.org/10.1002/ana.26943