Clinical spectrum of voltage-gated potassium channel autoimmunity

被引:208
作者
Tan, K. M. [1 ,2 ]
Lennon, V. A. [1 ,2 ,3 ]
Klein, C. J. [1 ]
Boeve, B. F. [1 ]
Pittock, S. J. [1 ,2 ]
机构
[1] Mayo Clin, Neuroimmunol Lab, Coll Med, Dept Neurol, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Lab Med & Pathol, Coll Med, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Immunol, Coll Med, Rochester, MN 55905 USA
关键词
D O I
10.1212/01.wnl.0000312275.04260.a0
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 I-125-alphadendrotoxin. 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.
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页码:1883 / 1890
页数:8
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