Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease.
BACKGROUND
Rapidly progressive dementia has a variety of causes, including Creutzfeldt-Jakob disease (CJD) and neuronal voltage-gated potassium channel (VGKC) autoantibody-associated encephalopathy.


OBJECTIVE
To describe patients thought initially to have CJD but found subsequently to have immunotherapy-responsive VGKC autoimmunity.


METHODS
Observational, prospective case series.


METHODS
Department of Neurology, Mayo Clinic, and the Memory and Aging Center, University of California, San Francisco. Patients A clinical serologic cohort of 15 patients referred for paraneoplastic autoantibody evaluation. Seven patients were evaluated clinically by at least one of us. Clinical information for the remaining patients was obtained by physician interview or medical record review.


METHODS
Clinical features, magnetic resonance imaging abnormalities, electroencephalographic patterns, cerebrospinal fluid analyses, and responses to immunomodulatory therapy.


RESULTS
All the patients presented subacutely with neurologic manifestations, including rapidly progressive dementia, myoclonus, extrapyramidal dysfunction, visual hallucinations, psychiatric disturbance, and seizures; most (60%) satisfied World Health Organization diagnostic criteria for CJD. Magnetic resonance imaging abnormalities included cerebral cortical diffusion-weighted imaging hyperintensities. Electroencephalographic abnormalities included diffuse slowing, frontal intermittent rhythmic delta activity, and focal epileptogenic activity but not periodic sharp wave complexes. Cerebrospinal fluid 14-3-3 protein or neuron-specific enolase levels were elevated in 5 of 8 patients. Hyponatremia was common (60%). Neoplasia was confirmed histologically in 5 patients (33%) and was suspected in another 5. Most patients' conditions (92%) improved after immunomodulatory therapy.


CONCLUSIONS
Clinical, radiologic, electrophysiologic, and laboratory findings in VGKC autoantibody-associated encephalopathy may be confused with those of CJD. Serologic evaluation for markers of neurologic autoimmunity, including VGKC autoantibodies, may be warranted in suspected CJD cases.
Neuroimmunology Laboratory, Hilton 3-78F, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Michael D
MD
Geschwind
K Meng
KM
Tan
Vanda A
VA
Lennon
Ramon F
RF
Barajas
Aissa
A
Haman
Christopher J
CJ
Klein
S Andrew
SA
Josephson
Sean J
SJ
Pittock
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000368:Aged; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D020274:Autoimmune Diseases of the Nervous System / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D053447:Channelopathies / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000503:physiopathology; D003704:Dementia / Q000209:etiology / Q000503:physiopathology; D003937:Diagnosis, Differential; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000276:immunology*; D011446:Prospective Studies
D048948:14-3-3 Proteins; D001323:Autoantibodies; D015415:Biomarkers; D024642:Potassium Channels, Voltage-Gated; D010751:Phosphopyruvate Hydratase