Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease

Michael D. Geschwind, K. Meng Tan, Vanda A Lennon, Ramon F. Barajas, Aissa Haman, Christopher Jon Klein, S. Andrew Josephson, Sean J Pittock

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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. Design: Observational, prospective case series. Setting: 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. Main Outcome Measures: 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.

Original languageEnglish (US)
Pages (from-to)1341-1346
Number of pages6
JournalArchives of Neurology
Volume65
Issue number10
DOIs
StatePublished - Oct 2008

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Voltage-Gated Potassium Channels
Creutzfeldt-Jakob Syndrome
Autoimmunity
Autoantibodies
Immunomodulation
Brain Diseases
Dementia
Magnetic Resonance Imaging
14-3-3 Proteins
Cerebrospinal Fluid Proteins
Myoclonus
San Francisco
Phosphopyruvate Hydratase
Hyponatremia
Hallucinations
Neurology
Neurologic Manifestations
Immunotherapy
Nervous System
Medical Records

ASJC Scopus subject areas

  • Clinical Neurology

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Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. / Geschwind, Michael D.; Tan, K. Meng; Lennon, Vanda A; Barajas, Ramon F.; Haman, Aissa; Klein, Christopher Jon; Josephson, S. Andrew; Pittock, Sean J.

In: Archives of Neurology, Vol. 65, No. 10, 10.2008, p. 1341-1346.

Research output: Contribution to journalArticle

Geschwind, Michael D. ; Tan, K. Meng ; Lennon, Vanda A ; Barajas, Ramon F. ; Haman, Aissa ; Klein, Christopher Jon ; Josephson, S. Andrew ; Pittock, Sean J. / Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. In: Archives of Neurology. 2008 ; Vol. 65, No. 10. pp. 1341-1346.
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abstract = "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. Design: Observational, prospective case series. Setting: 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. Main Outcome Measures: 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.",
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AB - 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. Design: Observational, prospective case series. Setting: 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. Main Outcome Measures: 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.

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