Objective: Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE). However, so far, relatively few and small size-based studies have been conducted. We aimed to investigate the link between seizure and SLE utilizing a large sample of subjects and extensive data analysis. Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of epilepsy in a cross-sectional study. Chi-square and t tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. Results: The study included 5,018 patients with SLE and 25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using logistic regression, adjusting for multiple confounding factors, older age (≥70 years) resulted as negative predictor (OR 0.42 [95% CI 0.27–0.62], p <0.001), whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI 3.94–5.82], p < 0.001). Interaction between SLE and elderly age resulted in high OR of 5.47 for epilepsy (95% CI 2.53–11.9). Conclusion: Our study confirms the higher prevalence of epilepsy in SLE patients. Physicians should be aware of such findings and have a lower threshold for suspecting epileptic seizures in these patients. Further studies are needed to better elucidate the mechanisms by which SLE favors the insurgence of seizures.

Beghi E: Addressing the burden of epilepsy: many unmet needs. Pharmacol Res 2016; 107: 79–84.
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators: Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388: 1545–1602.
Adelow C, Andersson T, Ahlbom A, Tomson T: Unprovoked seizures in multiple sclerosis and systemic lupus erythematosus: a population-based case-control study. Epilepsy Res 2012; 101: 284–287.
Gorter JA, van Vliet EA, Aronica E: Status epilepticus, blood-brain barrier disruption, inflammation, and epileptogenesis. Epilepsy Behav 2015; 49: 13–16.
Vezzani A, Friedman A: Brain inflammation as a biomarker in epilepsy. Biomark Med 2011; 5: 607–614.
Mikdashi J, Krumholz A, Handwerger B: Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus. Neurology 2005; 64: 2102–2107.
Ramsey-Goldman R, Alarcon GS, McGwin G, Petri M, Vila LM, Edberg JC, Reveille JD, Kimberly RP: Time to seizure occurrence and damage in PROFILE, a multi-ethnic systemic lupus erythematosus cohort. Lupus 2008; 17: 177–184.
Rezgui A, Ghannouchi N, Gabbouj A, Anoun J, Karmani M, Mzabi A, Ben Fredj F, Bahri F, Laouani C: [Seizures in patients with systemic lupus erythematosus]. Rev Med Liege 2017; 72: 101–105.
Chiewthanakul P, Sawanyawisuth K, Foocharoen C, Tiamkao S: Clinical features and predictive factors in neuropsychiatric lupus. Asian Pac J Allergy Immunol 2012; 30: 55–60.
Mayes B, Brey RL: Evaluation and treatment of seizures in patients with systemic lupus erythematosus. J Clin Rheumatol 1996; 2: 336–345.
Devinsky O, Schein A, Najjar S: Epilepsy associated with systemic autoimmune disorders. Epilepsy Curr 2013; 13: 62–68.
Postal M, Costallat LT, Appenzeller S: Neuropsychiatric manifestations in systemic lupus erythematosus: epidemiology, pathophysiology and management. CNS Drugs 2011; 25: 721–736.
Kampylafka EI, Alexopoulos H, Fouka P, Moutsopoulos HM, Dalakas MC, Tzioufas AG: Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations. Lupus 2016; 25: 1260–1265.
Bautista JF, Kelly JA, Harley JB, Gray-McGuire C: Addressing genetic heterogeneity in complex disease: finding seizure genes in systemic lupus erythematosus. Epilepsia 2008; 49: 527–530.
Yang Y, Yuan C, Shen SQ, Wang XE, Mei QH, Jiang WQ, Huang Q: Autoantibodies to NR2A peptide of the glutamate/NMDA receptor in patients with seizure disorders in neuropsychiatric systemic lupus erythematosus. Mediators Inflamm 2017; 2017: 5047898.
Devinsky O, Dilley C, Ozery-Flato M, Aharonov R, Goldschmidt Y, Rosen-Zvi M, Clark C, Fritz P: Changing the approach to treatment choice in epilepsy using big data. Epilepsy Behav 2016; 56: 32–37.
Grammer AC, Ryals MM, Heuer SE, Robl RD, Madamanchi S, Davis LS, Lauwerys B, Catalina MD, Lipsky PE: Drug repositioning in SLE: crowd-sourcing, literature-mining and Big Data analysis. Lupus 2016; 25: 1150–1170.
Sciascia S, Radin M: What can google and wikipedia can tell us about a disease? Big Data trends analysis in systemic lupus erythematosus. Int J Med Inform 2017; 107: 65–69.
Bragazzi NL, Bacigaluppi S, Robba C, Nardone R, Trinka E, Brigo F: Infodemiology of status epilepticus: A systematic validation of the google trends-based search queries. Epilepsy Behav 2016; 55: 120–123.
Watad A, Tiosano S, Grysman N, Comaneshter D, Cohen AD, Shoenfeld Y, Amital H: The association between systemic lupus erythematosus and valvular heart disease: an extensive data analysis. Eur J Clin Invest 2017; 47: 366–371.
Watad A, Bragazzi NL, Adawi M, Aljadeff G, Amital H, Comaneshter D, Cohen AD, Amital D: Anxiety disorder among rheumatoid arthritis patients: insights from real-life data. J Affect Disord 2017; 213: 30–34.
Yavne Y, Tiosano S, Watad A, Comaneshter D, Cohen AD, Amital H: Investigating the link between ischemic heart disease and Behcet’s disease: a cross-sectional analysis. Int J Cardiol 2017; 241: 41–45.
Tiosano S, Farhi A, Watad A, Grysman N, Stryjer R, Amital H, Comaneshter D, Cohen AD, Amital D: Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study. Epidemiol Psychiatr Sci 2017; 26: 424–429.
Watad A, Tiosano S, Azrielant S, Whitby A, Comaneshter D, Cohen AD, Shoenfeld Y, Amital H: Low levels of calcium or vitamin D – which is more important in systemic lupus erythematosus patients? An extensive data analysis. Clin Exp Rheumatol 2017; 35: 108–112.
Burck L, Tsibel N: Characterization and Classification of Geographical Units by the Socio-Economic Level of the Population. Central Bureau of Statistics, Israel, 2013.
Bertsias GK, Boumpas DT: Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol 2010; 6: 358–367.
Govoni M, Bortoluzzi A, Padovan M, Silvagni E, Borrelli M, Donelli F, Ceruti S, Trotta F: The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun 2016; 74: 41–72.
Perricone C, Pendolino M, Olivieri M, Conti F, Valesini G, Alessandri C: Neuropsychiatric manifestations associated with anti-endothelial cell antibodies in systemic lupus erythematosus. Isr Med Assoc J 2015; 17: 171–178.
Vincent A, Crino PB: Systemic and neurologic autoimmune disorders associated with seizures or epilepsy. Epilepsia 2011; 52(suppl 3):12–17.
Najjar S, Bernbaum M, Lai G, Devinsky O: Immunology and epilepsy. Rev Neurol Dis 2008; 5: 109–116.
Hu C, Li M, Liu J, Qian J, Xu D, Zhang S, Li P, Zhao J, Tian X, Zeng X: Anti-SmD1 antibodies are associated with renal disorder, seizures, and pulmonary arterial hypertension in Chinese patients with active SLE. Sci Rep 2017; 7: 7617.
Cieslinski JZ, Skare TL, Nisihara R, De Messias-Reason IJ, Utiyama SRR: Mannose-binding lectin serum levels in patients with systemic lupus erythematosus: association with thrombocytopaenia and seizure. Lupus 2017, Epub ahead of print.
Huang X, Magder LS, Petri M: Predictors of incident seizure in systemic lupus erythematosus. J Rheumatol 2016; 43: 565–575.
Anghel D, Tanasescu R, Campeanu A, Lupescu I, Podda G, Bajenaru O: Neurotoxicity of immunosuppressive therapies in organ transplantation. Maedica 2013; 8: 170–175.
Tsai JD, Lin CL, Lin CC, Sung FC, Lue KH: Risk of epilepsy in patients with systemic lupus erythematosus – a retrospective cohort study. Neuropsychiatr Dis Treat 2014; 10: 1635–1643.
Appenzeller S, Cendes F, Costallat LT: Epileptic seizures in systemic lupus erythematosus. Neurology 2004; 63: 1808–1812.
Hanly JG, Urowitz MB, Su L, Gordon C, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Wallace DJ, Clarke AE, Ginzler E, Merrill JT, Isenberg DA, Rahman A, Petri M, Fortin PR, Gladman D, Bruce IN, Steinsson K, Dooley M, Khamashta MA, Alarcón GS, Fessler BJ, Ramsey-Goldman R, Manzi S, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven R, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Theriault C, Thompson K, Farewell V: Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study. Ann Rheum Dis 2012; 71: 1502–1509.
Padovan M, Castellino G, Bortoluzzi A, Caniatti L, Trotta F, Govoni M: Factors and comorbidities associated with central nervous system involvement in systemic lupus erythematosus: a retrospective cross-sectional case-control study from a single center. Rheumatol Int 2012; 32: 129–135.
Ong MS, Kohane IS, Cai T, Gorman MP, Mandl KD: Population-level evidence for an autoimmune etiology of epilepsy. JAMA Neurol 2014; 71: 569–574.
Lin Z, Si Q, Xiaoyi Z: Association between epilepsy and systemic autoimmune diseases: a meta-analysis. Seizure 2016; 41: 160–166.
Unterman A, Nolte JE, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G: Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41: 1–11.
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