592 - Predictors of Seizures in Systemic Lupus Erythematosus

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
John G. Hanly1, Murray B. Urowitz2, Li Su3, Caroline Gordon4, Sang-Cheol Bae5, Jorge Sanchez-Guerrero6, Juanita Romero-Diaz7, Daniel Wallace8, Ann E. Clarke9, Sasha Bernatsky10, E.M. Ginzler11, Joan T. Merrill12, David A. Isenberg13, Anisur Rahman13, M. Petri14, Paul R. Fortin15, Dafna D. Gladman16, Ian N. Bruce17, Kristjan Steinsson18, M.A. Dooley19, Munther A. Khamashta20, Graciela S. Alarcon21, Barri J. Fessler21, Rosalind Ramsey-Goldman22 and Susan Manzi23, 1Dalhousie University and Capital Health, Halifax, NS, 2Toronto Western Hospital and University of Toronto, Toronto, ON, 3MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK, Cambridge, United Kingdom, 4University of Birmingham, Birmingham, United Kingdom, 5Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea, 6Mount Sinai Hospital/University Health Network, Toronto, ON, 7INCMNSZ, Mexico city, Mexico, 8Cedars-Sinai/UCLA, Los Angeles, CA, 9Research Institute of the McGill Univ. Health, Montreal, QC, 10McGill UHC/RVH, Montreal, QC, 11SUNY-Downstate Medical Center, Brooklyn, NY, 12Oklahoma Medical Research Foundation, Oklahoma City, OK, 13University College London, London, United Kingdom, 14Johns Hopkins University School of Medicine, Baltimore, MD, 15Toronto Western Hospital, Toronto, ON, 16Toronto Western Hospital, University of Toronto, Toronto, ON, 17A, Manchester, United Kingdom, 18Landspital Univ Hospital, Reykjavik, Iceland, 19University of North Carolina at Chapel Hill, Chapel Hill, NC, 20Lupus Research Unit, The Rayne Institute, Kings College London School of Medicine, London, United Kingdom, 21University of Alabama at Birmingham, Birmingham, AL, 22Northwestern University Feinberg School of Medicine, Chicago, IL, 23Allegheny Singer Research Institute, Pittsburgh, PA
Presentation Number: 592

Background/Purpose: Neuropsychiatric (NP) manifestations of SLE include seizure disorders. Our objective was to determine which clinical and laboratory variables were associated with seizures in a long-term prospective study of SLE patients.

Method:A multi-center, international, research network enrolled patients within 15 months of fulfilling ACR criteria for SLE and performed annual assessments for up to 10 years. Seizures and other NP manifestations were recorded using the ACR case definitions. Decision rules determined the attribution of seizures to SLE and non-SLE causes. Clinical variables included demographic characteristics, disease duration, educational status, medication utilization, global SLE disease activity (SLEDAI-2K) and cumulative organ damage (SLICC/ACR Damage Index (SDI)) computed with and without NP variables. Plasma/serum samples were available at enrollment for the determination of the following autoantibodies: lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies. The association between clinical and serological variables and the risk of the first occurrence of seizures was examined by univariate and multivariate Cox regression analysis. 

Result:The 1631 enrolled patients were predominantly female (89.4%) with a mean (± SD) age of 35.0 ± 13.4 years and mean disease duration of 5.6 ± 4.8 months. The mean followup was 3.5 ± 2.9 years. Over this period 75/1631 (4.6%) patients had ≥ 1 seizure with a total of 91 seizures of which 78/91 (86%) were attributed to SLE. Multivariate analysis indicated a significantly higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07-3.63); p=0.02) and lack of post-secondary education (1.97 (1.21-3.19); p<0.01) after adjustment for age at diagnosis and gender. In order to examine the effect of prior organ damage and medication use, the analysis was restricted to those seizures occurring after the enrollment visit (n=20). In these patients higher SDI scores calculated without NP variables were associated with an increased risk of subsequent seizures (SDI=1: 3.71(1.38-9.95); SDI=2or3: 1.33(0.27-6.46); SDI≥4: 6.44(0.72-57.2); p=0.04). After adjustment for prior medication, this risk was less significant (p=0.07) demonstrating some confounding between disease severity and medication. Prior use of anti-malarial drugs in the absence of immunosuppressive agents was the most notable treatment effect on seizures (0.07 (0.01-0.66); p=0.02). There was no association with SLEDAI scores or between any of the autoantibodies detected at enrollment with subsequent seizures.

Conclusion:The risk of seizures in SLE patients is higher in patients of African race/ethnicity, lower educational status and organ damage outside of the nervous system. The association with lupus related therapies is complex but anti-malarial drugs may have a protective effect.

Keywords: neuropsychiatric disorders

Disclosure: J. G. Hanly, None; M. B. Urowitz, None; L. Su, None; C. Gordon, None; S. C. Bae, None; J. Sanchez-Guerrero, None; J. Romero-Diaz, None; D. Wallace, None; A. E. Clarke, None; S. Bernatsky, None; E. M. Ginzler, Human Genome Sciences, Inc., 2, Human Genome Sciences, Inc., 5 ; J. T. Merrill, None; D. A. Isenberg, None; A. Rahman, None; M. Petri, None; P. R. Fortin, None; D. D. Gladman, None; I. N. Bruce, None; K. Steinsson, None; M. A. Dooley, Human Genome Sciences, UCB, Genentech, Cephalon, Bristol-Myers Squibb, Eli Lilly, 2, Human Genome Sciences, GlaxoSmithKline, Vifor Pharma, Lupus Foundation of America Medical Scientific and Advisory Board, 5 ; M. A. Khamashta, None; G. S. Alarcon, None; B. J. Fessler, None; R. Ramsey-Goldman, None; S. Manzi, Bristol-Myers Squibb, 2, Cephalon, 2, Human Genome Sciences, Inc., 2, Immunomedics, Inc., 2, NIH, 2, Cypress Biosciences, Inc., 5, Bristol-Myers Squibb, Human Genome Sciences, Inc., Cephalon, Anthera, Medammune, Inc. .