title: An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre.
abstract: Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan's syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres <400 pM were seen with PNH (n = 15/22; 68 %) but also a heterogeneous range of central and/or peripheral nervous system disorders. Electromyography was supportive of PNH in 65 % of cases and symptomatic treatment was beneficial in 46 % of patients. Irrespective of titre, the rate of malignancy in patients with VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97-44.0 p<0.0001). Clinical phenotyping and antibody titres >400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.
authors.affiliation: Department of Neurology, Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazarkerley, Liverpool, L9 7LJ, UK, saif.huda@ndcn.ox.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Huda
authors.forename: S H
authors.initials: SH
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Pettingill
authors.forename: D
authors.initials: D
authors.lastname: O'Connell
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: M
authors.initials: M
authors.lastname: Steiger
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D053447:Channelopathies / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000276:immunology*; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024642:Potassium Channels, Voltage-Gated