Abstract Details

Title CAMKV Autoimmune Paraneoplastic Encephalitis

Topic Autoimmune Neurology

Presentation(s) N1 - Neuroscience in the Clinic: Emerging Autoantibodies in Neurologic Disease (4:05 PM-4:15 PM)

Poster/Presentation
Number 003

Objective To report a novel paraneoplastic encephalitis associated with calmodulin kinase-like vesicle associated (CAMKV)-IgG antibody.

Background Uterine cancer is historically associated with paraneoplastic cerebellar ataxia but not encephalitis. High-throughput protein microarrays expedite novel neural antibody discovery.

Design/Methods Unclassified antibodies identified by murine brain-based indirect immunofluorescence assay (IFA) October 2022-September 2023 with cerebrum-restricted IgG staining (cerebellum negative) were screened by protein microarray and CAMKV identified as a high-ranking candidate antigen. Additional patient samples with an identical staining pattern were obtained retrospectively (serum, 3; CSF, 3). Western blot, confocal microscopy, immune-absorption and mass spectrometry were performed to elucidate CAMKV specificity further. Recombinant antigen-specific assays (cell-based assay [CBA], western blot) provided additional molecular confirmation.

Results Five patients with CAMKV-IgG were identified, 3 women; 2 men (median symptom-onset age was 59 years; range, 53-74). All samples (serum 4, CSF 3) were tissue IFA and CAMKV CBA positive. Onset was subacute (4) or acute (1). All had encephalitis manifesting with ≥1 of: behavioral change (3), seizures (3), psychosis (2), amnesia (2), hyperkinetic movements (tremor [1], choreiform movements [1]), insomnia (2). None had cerebellar ataxia. CSF revealed lymphocytic pleocytosis (median, 17; range, 8-74 [normal, ≤5]) in all 4 available. EEG was abnormal in 3 of 4 (subclinical electrographic seizures [2], bilateral epileptiform discharges [1]). T2 hyperintensities present in all patients were: mesial temporal (4), bilateral basal ganglia (3). Diffusion weighted lesions affected right paramedian frontal and parietal lobes (1), and bilateral anterior cingulate gyri (1). Cancers detected were uterine (3 patients: adenocarcinoma [2; 1 poorly differentiated], neuroendocrine [1]), bladder (1), non-Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All 5 demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]); 3 patients died from cancer.

Conclusions CAMKV-IgG is a biomarker of immunotherapy-responsive paraneoplastic encephalitis (limbic and extra-limbic) notably associated with uterine cancer.

Authors/Disclosures
Michael Gilligan, MBBS PRESENTER	Dr. Gilligan has nothing to disclose.
Connie Lesnick (Mayo Clinic)	Connie Lesnick has nothing to disclose.
Michael J. Bradshaw, MD, FAAN	Dr. Bradshaw has nothing to disclose.
Shafeeq Ladha, MD (Barrow Neurological Institute)	Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ladha has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurosense. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Rapa Therapeutics. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ladha has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Genentech. The institution of Dr. Ladha has received research support from Biogen. The institution of Dr. Ladha has received research support from Sanofi.
Maulik Shah, MD (UCSF Neurology)	Dr. Shah has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for National Football League.
J. Wittenborn, MD, FAAN	Dr. Wittenborn has nothing to disclose.
Shannon Hinson	Shannon Hinson has received intellectual property interests from a discovery or technology relating to health care. Shannon Hinson has received intellectual property interests from a discovery or technology relating to health care.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
John R. Mills, MD, PhD (Mayo Clinic)	The institution of Dr. Mills has received research support from Werfen Diagnostics. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.

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