title: When should we test for voltage-gated potassium channel complex antibodies? A retrospective case control study.
abstract: Patients with voltage-gated potassium channel (VGKC)-complex antibodies are increasingly recognized as having central, peripheral or combined phenotypes. With increasing awareness, more patients are tested and the clinical spectrum is expanding. Consequently, clinicians may be uncertain as to which patients should or should not be tested. Previous studies have identified common clinical features, but none has looked at the usefulness of these in predicting seropositive disease. We conducted a case-control study of patients tested for VGKC-complex antibodies over 10years at a regional tertiary neurology centre determining which clinical/biochemical features were associated with antibody-positive disease. We found a marked increase in the numbers tested, although the percentage positive remained low. Antibody titre was highest in central disease (p<0.001). Time from presentation to testing was shorter in those with VGKC-disease (p=0.01). Seizures were present in 11 (69%) of those with VGKC-disease versus three (18%) without (odds ratio [OR] 10.3, 95% confidence interval [CI]: 2.0-52.7, p=0.005). There was an inverse correlation between the antibody titre and serum sodium. A multivariate model selected seizures and hyponatraemia as predictive of VGKC disease (sensitivity 75% and specificity 82%); faciobrachial dystonic movements were specific but insensitive. Interestingly serum alkaline phosphatase was higher in those with VGKC-disease (p=0.016) and highest in those with peripheral disease (p=0.015). An ALP>70u/L was strongly associated with antibody positivity (OR 4.11 95% CI: 1.43-11.8, p=0.007) with a sensitivity of 74.2%. The presence of seizures, faciobrachial movements, and hyponatraemia should raise suspicion of VGKC-disease; alkaline phosphatase may represent a novel biomarker, particularly in those with peripheral disease.
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: O'Sullivan
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: T
authors.initials: T
authors.lastname: Steele
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK; Department of Clinical Infection, Microbiology and Immunology, The Institute for Infection and Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Ellul
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: E
authors.initials: E
authors.lastname: Kirby
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Duale
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK; Department of Neuropathology, The Walton Centre NHS Foundation Trust Liverpool, UK.
authors.forename: G
authors.initials: G
authors.lastname: Kier
authors.affiliation: Department of Neuropathology, The Walton Centre NHS Foundation Trust Liverpool, UK.
authors.forename: D
authors.initials: D
authors.lastname: Crooks
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK; Department of Clinical Infection, Microbiology and Immunology, The Institute for Infection and Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, UK; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, UK.
authors.forename: T
authors.initials: T
authors.lastname: Solomon
authors.affiliation: Department of Neuroscience, The Walton Centre NHS Foundation Trust, Liverpool, UK; Department of Clinical Infection, Microbiology and Immunology, The Institute for Infection and Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, UK; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, UK; Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. Electronic address: benmic@liv.ac.uk.
authors.forename: B D
authors.initials: BD
authors.lastname: Michael
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004421:Dystonia / Q000209:etiology; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D024642:Potassium Channels, Voltage-Gated; D000469:Alkaline Phosphatase
keywords: Autoimmune; Clinical features; Diagnosis; Encephalitis