Voltage-gated Potassium Channel Autoimmunity Mimicking Creutzfeldt-Jakob Disease
Manifestations of voltage-gated potassium channel (VGKC) autoimmunity may mimic Creutzfeldt-Jakob disease (CJD), especially in cases of subacute cognitive impairment and myoclonus. We describe 15 patients provisionally diagnosed with (CJD), prior to serological detection of (VGKC) autoantibodies, and favorable therapeutic responses in 12 of 13 cases.
In service serological evaluation for paraneoplastic autoantibodies, 2001-2007, the Mayo Clinic Neuroimmunology Laboratory identified 15 patients with a provisional diagnosis of CJD and high-titer VGKC autoantibodies. Clinical information was obtained by reviewing medical records.
Seven patients were women, median age at onset was 70 years (range, 58-84). Median follow-up was 11 months (range, 1-78). Median VGKC autoantibody titer by RIA was 1.53 nmol/L (range 0.16-51.9). Symptom onset was subacute (median 5 months; range, 0-13). All had cognitive impairment, 12 myoclonus, 12 seizures, 10 behavioral disturbance, 7 dysomnia, 6 tremor/parkinsonism, 6 dysautonomia, 5 ataxia, 5 hallucinations, 7 hyponatraemia, and 2 hyperphagia. Brain MRI was abnormal in 9 of 13; one had widespread cortical restricted diffusion. EEG revealed diffuse slowing in 9 of 13. CSF 14-3-3 protein or neuron-specific enolase were elevated in 6 of 8 patients. Active neoplasia was confirmed or suspected in 8 patients. Of 13 patients receiving immunomodulatory therapy (corticosteroids, plasmapheresis, IVIG), 12 showed improvement (5 marked, 6 moderate, 1 mild). Seven had relapses requiring ongoing immunotherapy.
VGKC autoantibody testing is justified in the evaluation of suspected CJD. Positive serology may obviate brain biopsy. Patients with VGKC autoimmunity generally have a beneficial response to antibody-depleting therapy.