Objective: To document neurological, oncological, and serological associations of patients in whom voltage-gated potassium channel (VGKC) autoantibodies were detected in the course of serological evaluation for neuronal, glial, and muscle autoantibodies.

Methods: Indirect immunofluorescence screening of sera from ~130,000 patients performed on a service basis for markers of paraneoplastic neurological autoimmunity identified 80 patients whose IgG bound to the synapse-rich molecular layer of mouse cerebellar cortex in a pattern consistent with VGKC immunoreactivity. Antibody specificity was confirmed in all cases by immunoprecipitation of detergent-solubilized brain synaptic proteins complexed with 125I-alpha-dendrotoxin.

Results: Clinical information was available for 72 patients: 51% women, median age at symptom onset 65 years, and median follow-up period 14 months. Neurological manifestations were acute to subacute in onset in 71% and multifocal in 46%; 71% had cognitive impairment, 58% seizures, 33% dysautonomia, 29% myoclonus, 26% dysomnia, 25% peripheral nerve dysfunction, 21% extrapyramidal dysfunction, and 19% brainstem/cranial nerve dysfunction. Creutzfeldt-Jakob disease was a common misdiagnosis (14%). Neoplasms encountered (confirmed histologically in 33%) included 18 carcinomas, five adenomas, one thymoma, and three hematologic malignancies. Hyponatremia was documented in 36%, other organ-specific autoantibodies in 49%, and a co-existing autoimmune disorder in 33% (including thyroiditis 21%, hyperglycemia 11%). Benefit was reported for 34 of 38 patients (89%) receiving immunotherapy and was marked in 50%.

Conclusions: The spectrum of neurological and oncological associations with VGKC autoimmunity is broader than previously recognized. Evaluation for VGKC antibodies is recommended in the comprehensive serological testing of subacute idiopathic neurological disorders.