Clinical spectrum of voltage-gated potassium channel autoimmunity.
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.
Tan
K M
KM
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Lennon
V A
VA
Klein
C J
CJ
Boeve
B F
BF
Pittock
S J
SJ
D000236:Adenoma / Q000150:complications; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000276:immunology; D001480:Basal Ganglia Diseases / Q000209:etiology / Q000276:immunology; D002648:Child; D003389:Cranial Nerve Diseases / Q000209:etiology / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000276:immunology; D051663:Kv1.2 Potassium Channel / Q000276:immunology; D051667:Kv1.6 Potassium Channel; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000209:etiology / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000150:complications / Q000276:immunology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000276:immunology*; D051637:Shaker Superfamily of Potassium Channels / Q000276:immunology*; D013945:Thymoma / Q000150:complications; D013953:Thymus Neoplasms / Q000150:complications
D001323:Autoantibodies; C064389:KCNA6 protein, human; D051663:Kv1.2 Potassium Channel; D051667:Kv1.6 Potassium Channel; D051637:Shaker Superfamily of Potassium Channels; D051662:Kv1.1 Potassium Channel