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Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study
  1. John G Hanly1,
  2. Murray B Urowitz2,
  3. Li Su3,
  4. Caroline Gordon4,
  5. Sang-Cheol Bae5,
  6. Jorge Sanchez-Guerrero2,
  7. Juanita Romero-Diaz6,
  8. Daniel J Wallace7,
  9. Ann E Clarke8,
  10. EM Ginzler9,
  11. Joan T Merrill10,
  12. David A Isenberg11,
  13. Anisur Rahman11,
  14. M Petri12,
  15. Paul R Fortin13,
  16. DD Gladman2,
  17. Ian N Bruce14,
  18. Kristjan Steinsson15,
  19. MA Dooley16,
  20. Munther A Khamashta17,
  21. Graciela S Alarcón18,
  22. Barri J Fessler18,
  23. Rosalind Ramsey-Goldman19,
  24. Susan Manzi20,
  25. Asad A Zoma21,
  26. Gunnar K Sturfelt22,
  27. Ola Nived22,
  28. Cynthia Aranow23,
  29. Meggan Mackay23,
  30. Manuel Ramos-Casals24,
  31. RF van Vollenhoven25,
  32. Kenneth C Kalunian26,
  33. Guillermo Ruiz-Irastorza27,
  34. Sam Lim28,
  35. Diane L Kamen29,
  36. Christine A Peschken30,
  37. Murat Inanc31,
  38. Chris Theriault32,
  39. Kara Thompson32,
  40. Vernon Farewell3
  1. 1Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  2. 2Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital and University of Toronto, Ontario, Canada
  3. 3MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK
  4. 4Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  5. 5Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
  6. 6Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
  7. 7Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  8. 8Divisions of Clinical Immunology/Allergy and Clinical Epidemiology, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec, Canada
  9. 9Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA
  10. 10Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma, USA
  11. 11Centre for Rheumatology Research, University College, London, UK
  12. 12Department of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA
  13. 13Division of Rheumatology, Centre Hospitalier Universitaire de Québec et Université Laval, Quebec City, Canada
  14. 14Arthritis Research UK Epidemiology Unit, School of Translational Medicine, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK
  15. 15Center for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland
  16. 16University of North Carolina, Chapel Hill, North Carolina, USA
  17. 17Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, King's College London School of Medicine, London, UK
  18. 18Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  19. 19Northwestern University and Feinberg School of Medicine, Chicago, Illinois, USA
  20. 20Division of Rheumatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  21. 21Lanarkshire Centre for Rheumatology, Hairmyres Hospital, East Kilbride, Scotland, UK
  22. 22Department of Rheumatology, University Hospital Lund, Lund, Sweden
  23. 23Feinstein Institute for Medical Research, Manhasset, New York, USA
  24. 24Josep Font Autoimmune Diseases Laboratory, IDIBAPS, Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain
  25. 25Department of Rheumatology, Karolinska Institute, Stockholm, Sweden
  26. 26UCSD School of Medicine, La Jolla, California, USA
  27. 27Autoimmune Disease Unit, Department of Internal Medicine, Hospital de Cruces, University of the Basque Country, Barakaldo, Spain
  28. 28Emory University, Atlanta, Georgia, USA
  29. 29Medical University of South Carolina, Charleston, South Carolina, USA
  30. 30University of Manitoba, Winnipeg, Manitoba, Canada
  31. 31Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
  32. 32Department of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada
  1. Correspondence to John G Hanly, Division of Rheumatology, Nova Scotia Rehabilitation Centre (2nd Floor), 1341 Summer Street, Halifax, Nova Scotia B3H 4K4, Canada; john.hanly{at}cdha.nshealth.ca

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-β2 glycoprotein-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.

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Footnotes

  • Ethics approval This study was conducted with the approval of the Capital Health Research Ethics Board, Halifax, NS, Canada.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Funding JG Hanly was supported by Canadian Institutes of Health Research grant MOP-57752 (Capital Health Research Fund). Li Su was supported by MRC (UK) U105261167. 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). The Montreal General Hospital Lupus Clinic was partially supported by the Singer Family Fund for Lupus Research. Dr Clarke is a National Scholar of the Fonds de la recherché en santé de Quebec. 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. Dr Ramsey-Goldman's work was supported by the National Institutes of Health (grants UL-1RR-025741, K24-AR-02318 and P60-AR-48098). Dr Ruiz-Irastorza was supported by the Department of Education, Universities and Research of the Basque Government.

  • Competing interests None.

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