Author(s): Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ
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.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/18474843
Author(s): Vernino S, Geschwind M, Boeve B
Author(s): Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, et al.
Author(s): Graus F, Saiz A, Dalmau J
Author(s): Geschwind MD, Tan KM, Lennon VA, Barajas RF Jr, Haman A, et al.
Author(s): Thieben MJ, Lennon VA, Boeve BF, Aksamit AJ, Keegan M, et al.
Author(s): Ances BM, Vitaliani R, Taylor RA, Liebeskind DS, Voloschin A, et al.
Author(s): Chan D, Henley SM, Rossor MN, Warrington EK
Author(s): Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, et al.
Author(s): Merchut MP