Abstract: Features Associated with Epilepsy in the Antiphospholipid Syndrome

Features Associated with Epilepsy in the Antiphospholipid Syndrome

YEHUDA SHOENFELD, SHAUL LEV, ILAN BLATT, MIRI BLANK, JOSEPH FONT, PHILIPP von LANDENBERG, NIRIT LEV, JOSEPH ZAECH, RICARD CERVERA, JEAN-CHARLES PIETTE, MUNTHER A. KHAMASHTA, MARIA L. BERTOLACCINI, GRAHAM R.V. HUGHES, PIERRE YOUINOU, PIERRE LUIGI MERONI, VITTORIO PENGO, J. DELGADO ALVES, ANGELA TINCANI, GYULA SZEGEDI, GABRIELLA LAKOS, GUNNAR STURFELT, ANDREAS JÖNSEN, TAKAO KOIKE, MARIELLE SANMARCO, AMELIA RUFFATTI, ZDENKA ULCOVA-GALLOVA, SONJA PRAPROTNIK, BLAZ ROZMAN, MARGALIT LORBER, JOAB CHAPMAN, PETER J.C. van-BREDA-VRIEZMAN, and JAN DAMOISEAUX

ABSTRACT.

Objective. To assess the frequency of epilepsy in primary and secondary antiphospholipid syndrome (APS); to analyze the clinical and laboratory features characterizing those with epilepsy in a cohort of 538 patients with APS; and to find associated features that would suggest risk factors for epilepsy in APS.

Methods. We analyzed the clinical features of patients with APS who had epilepsy and compared them to the clinical features of non-epileptic APS patients.

Results. Of 538 APS patients, 46 (8.6%) had epilepsy. Epilepsy was more prevalent among APS secondary to systemic lupus erythematosus (SLE) compared to primary APS (13.7% vs 6%; p < 0.05). The patients with epilepsy had a higher prevalence of central nervous system (CNS) manifestations including focal ischemic events (strokes or transient ischemic events, 54.3% vs 24.6%; p < 0.0001) and amaurosis fugax (15.2% vs 4.9%; p < 0.05). APS patients with epilepsy had a higher frequency of valvular pathology (30.4% vs 14.6%; p < 0.01), thrombocytopenia (43.5% vs 25%; p < 0.05), and livedo reticularis (26.1% vs 11.5%; p < 0.01). The multivariate logistic regression analysis found CNS thromboembolic events as the most significant factor associated with epilepsy, with an odds ratio (OR) of 4.05 (95% confidence interval, CI: 2.05–8), followed by SLE (OR 1.4, 95% CI 1.2–4.7), and valvular vegetations (OR 2.87, 95% CI 1–8.27).

Conclusion. Epilepsy is common in APS and most of the risk seems to be linked to vascular disease as manifested by extensive CNS involvement, valvulopathy, and livedo reticularis and to the presence of SLE. These factors, however, explain only part of the increased occurrence of epilepsy in APS and other causes such as direct immune interaction in the brain should be investigated. (J Rheumatol 2004;31:1344-8)

Key Indexing Terms:

EPILEPSY
ANTIPHOSPHOLIPID SYNDROME
VALVULAR HEART DISEASE
THROMBOCYTOPENIA
LIVEDO RETICULARIS
ANTIPHOSPHOLIPID ANTIBODIES

From the Departments of Medicine "B," Neurology and Research Center for Autoimmune Diseases, Sheba Medical Center (affiliated to the Sackler Faculty of Medicine, Tel-Aviv University), Tel-Hashomer, Israel; Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany; Systemic Autoimmune Diseases Unit, Institut Clínic d'Infeccions i Immunologia (ICII), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Hôpital Pitié-Salpêtrière, Paris, France; Lupus Unit, Rayne Institute, St. Thomas' Hospital, London, UK; Laboratoire d'Immunologie, Centre Hospitalier Universitaire, Brest, France; Allergy and Clinical Immunology Unit, Dipartimento di Medicina Interna, IRCCS Istituto Auxologico, Università di Milano, Milan; Clinica Cardiologica—Centro Trombosi Universita di Padova, Padova, Italy; Autoimmune Diseases Unit, Curry Cabral Hospital, Lisbon, Portugal; Servizio di Immunologia Clinica e Allergologia, Spedali Civili, Azienda Ospedaliera, Brescia, Italy; Third Department of Medicine, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary; Department of Rheumatology, Lund University Hospital, Lund, Sweden; Medicine II, Hokkaido University School of Medicine, Sapporo, Japan; Laboratoire d'Immunologie, Hopital de La Conception, CHU Marseille, Marseille, France; Division of Rheumatology, University of Padova, Padova, Italy; Department of Gynecology and Obstetrics, Medical Faculty Hospital Charles University, Pilsen, Czech Republic; Department of Rheumatology, University Medical Center Ljubljana, Slovenia; Institute of Allergy, Clinical Immunology and AIDS, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa, Israel; Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany; and University of Maastricht, Maastricht, The Netherlands.

Part of the Euro APS Study.

Y. Shoenfeld, MD; S. Lev, MD; I. Blatt, MD; N. Lev, MD; M. Blank, PhD; J. Chapman, MD, PhD, Departments of Medicine "B," Neurology and Research Center for Autoimmune Diseases, Sheba Medical Center; J. Font, MD; R. Cervera, MD, Systemic Autoimmune Diseases Unit, Institut Clínic d'Infeccions i Immunologia (ICII), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer; P. von Landenberg, MD; J. Zaech, MD, Departments of Medicine "B," Neurology and Research Center for Autoimmune Diseases, Sheba Medical Center and Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University of Mainz; J-C. Piette, MD, Hôpital Pitié-Salpêtrière; M.A. Khamashta, MD; M.L. Bertolaccini, MD; G.R.V. Hughes, MD, Rayne Institute, St. Thomas' Hospital; P. Youinou, MD, PhD, Laboratoire d'Immunologie, Centre Hospitalier Universitaire; P.L. Meroni, MD, Allergy and Clinical Immunology Unit, Dipartimento di Medicina Interna, IRCCS Istituto Auxologico, Università di Milano; V. Pengo, MD, Clinica Cardiologica–Centro Trombosi, Universita di Padova; J.D. Alves, MD, Autoimmune Diseases Unit, Curry Cabral Hospital; A. Tincani, MD, Servizio di Immunologia Clinica e Allergologia, Spedali Civili, Azienda Ospedaliera; G. Szegedi, MD; G. Lakos, MD, Third Department of Medicine, University of Debrecen; G. Sturfelt, MD; A. Jönsen, MD, Department of Rheumatology, Lund University Hospital; T. Koike, MD, Hokkaido University School of Medicine; M. Sanmarco, PhD, Laboratoire d'Immunologie, Hopital de La Conception; A. Ruffatti, MD, Division of Rheumatology, University of Padova; Z. Ulcova-Gallova, MD, Department of Gynecology and Obstetrics, Med. Fac. and Fac. Hospital Charles University; S. Praprotnik, MD; B. Rozman, MD, Department of Rheumatology, University Medical Center Ljubljana; M. Lorber, MD, Institute of Allergy, Clinical Immunology and AIDS, Rambam Medical Center and Rappaport Faculty of Medicine; P.J.C. van-Breda-Vriezman, MD, University of Maastricht; J. Damoiseaux, PhD, Laboratory of Clinical Immunology, Department of Clinical and Experimental Immunology, University Hospital Maastricht.

Address reprint requests to Dr. Y. Shoenfeld, Department of Medicine B, Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail: Shoenfel@post.tau.ac.il

Submitted November 8, 2002; revision accepted January 14, 2004.