Clinical spectrum of voltage-gated potassium channel autoimmunity

Neurology. 2008 May 13;70(20):1883-90. doi: 10.1212/01.wnl.0000312275.04260.a0.

Abstract

Objective: To document neurologic, oncologic, and serologic associations of patients in whom voltage-gated potassium channel (VGKC) autoantibodies were detected in the course of serologic 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 neurologic 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 (125)I-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. Neurologic manifestations were acute to subacute in onset in 71% and multifocal in 46%; 71% had cognitive impairment, 58% seizures, 33% dysautonomia, 29% myoclonus, 26% dyssomnia, 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, 5 adenomas, 1 thymoma, and 3 hematologic malignancies. Hyponatremia was documented in 36%, other organ-specific autoantibodies in 49%, and a co-existing autoimmune disorder in 33% (including thyroiditis 21%, type 1 diabetes mellitus 11%). Benefit was reported for 34 of 38 patients (89%) receiving immunotherapy and was marked in 50%.

Conclusions: The spectrum of neurologic manifestations and neoplasms associated with voltage-gated potassium channel (VGKC) autoimmunity is broader than previously recognized. Evaluation for VGKC antibodies is recommended in the comprehensive autoimmune serologic testing of subacute idiopathic neurologic disorders.

MeSH terms

  • Adenoma / complications
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / immunology
  • Basal Ganglia Diseases / etiology
  • Basal Ganglia Diseases / immunology
  • Child
  • Cranial Nerve Diseases / etiology
  • Cranial Nerve Diseases / immunology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hematologic Neoplasms / complications
  • Humans
  • Kv1.1 Potassium Channel / immunology
  • Kv1.2 Potassium Channel / immunology
  • Male
  • Middle Aged
  • Myoclonus / etiology
  • Myoclonus / immunology
  • Paraneoplastic Syndromes / complications
  • Paraneoplastic Syndromes / immunology*
  • Peripheral Nervous System Diseases / etiology
  • Peripheral Nervous System Diseases / immunology*
  • Shaker Superfamily of Potassium Channels / immunology*
  • Thymoma / complications
  • Thymus Neoplasms / complications

Substances

  • Autoantibodies
  • KCNA6 protein, human
  • Kv1.2 Potassium Channel
  • Shaker Superfamily of Potassium Channels
  • Kv1.1 Potassium Channel