Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease

Neuroimmunology Laboratory, Hilton 3-78F, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Archives of neurology (Impact Factor: 7.01). 11/2008; 65(10):1341-6. DOI: 10.1001/archneur.65.10.1341
Source: PubMed

ABSTRACT Rapidly progressive dementia has a variety of causes, including Creutzfeldt-Jakob disease (CJD) and neuronal voltage-gated potassium channel (VGKC) autoantibody-associated encephalopathy.
To describe patients thought initially to have CJD but found subsequently to have immunotherapy-responsive VGKC autoimmunity.
Observational, prospective case series.
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.
Clinical features, magnetic resonance imaging abnormalities, electroencephalographic patterns, cerebrospinal fluid analyses, and responses to immunomodulatory therapy.
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.
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.


Available from: Michael D Geschwind, Jul 24, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the past 10 years, the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of 11 autoimmune encephalitic disorders, grouped by syndromes and approached from a clinical perspective. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases.
    Annals of the New York Academy of Sciences 10/2014; 1338(1). DOI:10.1111/nyas.12553 · 4.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We present a patient with rapidly progressive dementia (RPD) clinically suspicious for prion disease who met clinical criteria for probable and proposed MRI criteria for definite sporadic Creutzfeldt-Jakob disease (sCJD) but was found to have autoimmune encephalitis (AE).
    Neurology: Clinical Practice (Print) 10/2014; 4(6):493-495. DOI:10.1212/CPJ.0000000000000065
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND PURPOSE:Autoimmune voltage-gated potassium channel complex encephalitis is a common form of autoimmune encephalitis. Patients with seizures due to this form of encephalitis commonly have medically intractable epilepsy and may require immunotherapy to control seizures. It is important that radiologists recognize imaging characteristics of this type of autoimmune encephalitis and suggest it in the differential diagnosis because this seizure etiology is likely under-recognized. Our purpose was to characterize MR imaging findings in this patient population.MATERIALS AND METHODS:MR imaging in 42 retrospectively identified patients (22 males; median age, 56 years; age range, 8-79 years) with seizures and voltage-gated potassium channel complex autoantibody seropositivity was evaluated for mesial and extratemporal swelling and/or atrophy, T2 hyperintensity, restricted diffusion, and enhancement. Statistical analysis was performed.RESULTS:Thirty-three of 42 patients (78.6%) demonstrated enlargement and T2 hyperintensity of mesial temporal lobe structures at some time point. Mesial temporal sclerosis was commonly identified (16/33, 48.5%) at follow-up imaging. Six of 9 patients (66.7%, P = .11) initially demonstrating hippocampal enhancement and 8/13 (61.5%, P = .013) showing hippocampal restricted diffusion progressed to mesial temporal sclerosis. Conversely, in 6 of 33 patients, abnormal imaging findings resolved.CONCLUSIONS:Autoimmune voltage-gated potassium channel complex encephalitis is frequently manifested as enlargement, T2 hyperintensity, enhancement, and restricted diffusion of the mesial temporal lobe structures in the acute phase. Recognition of these typical imaging findings may help prompt serologic diagnosis, preventing unnecessary invasive procedures and facilitating early institution of immunotherapy. Serial MR imaging may demonstrate resolution or progression of radiologic changes, including development of changes involving the contralateral side and frequent development of mesial temporal sclerosis.
    American Journal of Neuroradiology 07/2013; 35(1). DOI:10.3174/ajnr.A3633 · 3.68 Impact Factor