Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study

• Type of Material: Article
• Authors: John G Hanly, Dalhousie University; Murray B Urowitz, University of Toronto; Li Su, University of Cambridge; Caroline Gordon, University of Birmingham; Sang-Cheol Bae, Hanyang University; Jorge Sanchez-Guerrero, University of Toronto; Juanita Romero-Diaz, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico; Daniel J Wallace, UCLA; Ann E Clarke, McGill University; EM Ginzler, SUNY Downstate; Joan T Merrill, Oklahoma Medical Research Foundation; David A Isenberg, University College, London; Anisur Rahman, University College, London; M Petri, Johns Hopkins University; Paul R Fortin, Université Laval; DD Gladman, University of Toronto; Ian N Bruce, University of Manchester; Kristjan Steinsson, Landspitali University Hospital; MA Dooley, University of North Carolina; Munther A Khamashta, King's College London; Graciela S Alarcón, University of Alabama at Birmingham; Barri J Fessler, University of Alabama at Birmingham; Rosalind Ramsey-Goldman, Northwestern University; Susan Manzi, University of Pittsburgh; Asad A Zoma, Hairmyres Hospital, Scotland; Gunnar K Sturfelt, University Hospital Lund; Ola Nived, University Hospital Lund; Cynthia Aranow, Feinstein Institute for Medical Research; Meggan Mackay, Feinstein Institute for Medical Research; Manuel Ramos-Casals, Hospital Clinic of Barcelona; RF van Vollenhoven, Karolinska Institute; Kenneth C Kalunian, UCSD; Guillermo Ruiz-Irastorza, University of the Basque Country; S Sam Lim, Emory University; Diane L Kamen, Medical University of South Carolina; Christine A Peschken, University of Manitoba; Murat Inanc, Istanbul University; Chris Theriault, Dalhousie University; Kara Thompson, Dalhousie University; Vernon Farewell, University of Cambridge
• Language: English
• Date: 2012-09-01
• Publisher: B M J PUBLISHING GROUP
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012, BMJ Publishing Group Ltd and the European League Against Rheumatism
• Final Published Version (URL): http://dx.doi.org/10.1136/annrheumdis-2011-201089
• Title of Journal or Parent Work: Annals of the Rheumatic Diseases
• Volume: 71
• Issue: 9
• Start Page: 1502
• End Page: 1509
• Grant/Funding Information: V Farewell was supported by MRC (UK) U105261167.; Dr Sang-Cheol Bae's work was supported by the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A080588).; JG Hanly was supported by Canadian Institutes of Health Research grant MOP-57752 (Capital Health Research Fund).; Dr Ruiz-Irastorza was supported by the Department of Education, Universities and Research of the Basque Government.; The Montreal General Hospital Lupus Clinic was partially supported by the Singer Family Fund for Lupus Research.; Li Su was supported by MRC (UK) U105261167.; Dr Paul R. Fortin is a Distinguished Senior Investigator of The Arthritis Society with additional support from the Arthritis Centre of Excellence, University of Toronto.
• Keywords: RHEUMATOLOGY; HYDROXYCHLOROQUINE; PROTEIN-S; ASSOCIATION; EDUCATION LEVEL; Science & Technology; DIAGNOSIS; ANTIPHOSPHOLIPID ANTIBODIES; Life Sciences & Biomedicine; NEUROPSYCHIATRIC EVENTS; Rheumatology; PREVALENCE; TIME; SURVIVAL
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

Objective: The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE). Methods: The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β 2glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions. Results: The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03). Conclusion: Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.