Population-level evidence for an autoimmune etiology of epilepsy.

IMPORTANCE Epilepsy is a debilitating condition, often with neither a known etiology nor an effective treatment. Autoimmune mechanisms have been increasingly identified. OBJECTIVE To conduct a population-level study investigating the relationship between epilepsy and several common autoimmune diseases. DESIGN, SETTING, AND PARTICIPANTS A retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. Participants were beneficiaries enrolled between 1999 and 2006 (N = 2 518 034). MAIN OUTCOMES AND MEASURES We examined the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease. RESULTS The risk of epilepsy was significantly heightened among patients with autoimmune diseases (odds ratio, 3.8; 95% CI, 3.6-4.0; P < .001) and was especially pronounced in children (5.2; 4.1-6.5; P < .001). Elevated risk was consistently observed across all 12 autoimmune diseases. CONCLUSIONS AND RELEVANCE Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other. The potential role of autoimmunity must be given due consideration in epilepsy so that we are not overlooking a treatable cause.

[1]  N. Jetté,et al.  Development and validation of a case definition for epilepsy for use with administrative health data , 2012, Epilepsy Research.

[2]  K. Chu,et al.  The immunosuppressant cyclosporin A inhibits recurrent seizures in an experimental model of temporal lobe epilepsy , 2012, Neuroscience Letters.

[3]  K. Lin,et al.  Antiglutamic acid decarboxylase antibodies in children with encephalitis and status epilepticus. , 2012, Pediatric neurology.

[4]  Hude Quan,et al.  Recommendations for optimal ICD codes to study neurologic conditions , 2012, Neurology.

[5]  G. Bergey Autoantibodies in the patient with drug-resistant epilepsy: are we missing a treatable etiology? , 2012, Archives of neurology.

[6]  J. Britton,et al.  Autoimmune epilepsy: clinical characteristics and response to immunotherapy. , 2012, Archives of neurology.

[7]  I. Bruce,et al.  Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study , 2012, Annals of the rheumatic diseases.

[8]  John S Duncan,et al.  The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study , 2011, The Lancet.

[9]  Eleonora Aronica,et al.  Inflammation in epilepsy: Clinical observations , 2011, Epilepsia.

[10]  D. Janigro,et al.  Efficacy of Anti-Inflammatory Therapy in a Model of Acute Seizures and in a Population of Pediatric Drug Resistant Epileptics , 2011, PloS one.

[11]  R. Balice-Gordon,et al.  Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis , 2011, The Lancet Neurology.

[12]  Itai Berger,et al.  Paediatric Hashimoto encephalopathy, refractory epilepsy and immunoglobulin treatment – unusual case report and review of the literature , 2010, Acta paediatrica.

[13]  Adrien Didelot,et al.  In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction , 2010, Orphanet journal of rare diseases.

[14]  J. Girardet,et al.  Natural history of Crohn's disease: Comparison between childhood‐ and adult‐onset disease , 2010, Inflammatory bowel diseases.

[15]  D. Kullmann,et al.  N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes , 2010, Brain : a journal of neurology.

[16]  M. Knip,et al.  Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy , 2010, Epilepsia.

[17]  Xiaoyu Peng,et al.  Cellular and Synaptic Mechanisms of Anti-NMDA Receptor Encephalitis , 2010, The Journal of Neuroscience.

[18]  S. Cha,et al.  Adult‐onset drug‐refractory seizure disorder associated with anti–voltage‐gated potassium‐channel antibody , 2010, Epilepsia.

[19]  Hude Quan,et al.  How accurate is ICD coding for epilepsy? , 2010, Epilepsia.

[20]  O. Dulac,et al.  Corticosteroids as treatment of epileptic syndromes with continuous spike‐waves during slow‐wave sleep , 2009, Epilepsia.

[21]  D. Vital-Durand,et al.  Influence of age at disease onset in the outcome of paediatric systemic lupus erythematosus. , 2009, Rheumatology.

[22]  Xiaoyu Peng,et al.  Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies , 2008, The Lancet Neurology.

[23]  Eleonora Aronica,et al.  Innate and adaptive immunity during epileptogenesis and spontaneous seizures: Evidence from experimental models and human temporal lobe epilepsy , 2008, Neurobiology of Disease.

[24]  A. Kornbluth,et al.  Adverse Events Associated With the Use of Cyclosporine in Patients With Inflammatory Bowel Disease , 2008, The American Journal of Gastroenterology.

[25]  J. Reveille,et al.  Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV) , 2007, Annals of the rheumatic diseases.

[26]  L. Pelizza,et al.  Drug-induced systemic lupus erythematosus after 7 years of treatment with carbamazepine. , 2006, Acta bio-medica : Atenei Parmensis.

[27]  J. Palace,et al.  Serum antibodies in epilepsy and seizure-associated disorders , 2005, Neurology.

[28]  L. Lagae,et al.  Steroids in intractable childhood epilepsy: Clinical experience and review of the literature , 2005, Seizure.

[29]  F. Cendes,et al.  Epileptic seizures in systemic lupus erythematosus , 2004, Neurology.

[30]  J. Piette,et al.  Features associated with epilepsy in the antiphospholipid syndrome. , 2004, The Journal of rheumatology.

[31]  Alon Friedman,et al.  Long-term seizure outcomes following amygdalohippocampectomy. , 2003, Journal of neurosurgery.

[32]  G. Rondouin,et al.  Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis , 2002, Brain Research.

[33]  J. Piette,et al.  Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. , 2002, Arthritis and rheumatism.

[34]  B. Abou-Khalil,et al.  Hashimoto’s encephalopathy: documentation of mesial temporal seizure origin by ictal EEG , 2001, Seizure.

[35]  J. Palace,et al.  Epilepsy: an autoimmune disease? , 2000, Journal of neurology, neurosurgery, and psychiatry.

[36]  I. Matoth,et al.  Inhibitory effect of carbamazepine on inflammatory mediators produced by stimulated glial cells , 2000, Neuroscience Research.

[37]  Takashi Ichiyama,et al.  Sodium valproate inhibits production of TNF-α and IL-6 and activation of NF-κB , 2000, Brain Research.

[38]  P. Kwan,et al.  Early identification of refractory epilepsy. , 2000, The New England journal of medicine.

[39]  N. Lapointe,et al.  Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus , 1999, Lupus.

[40]  J. Conde,et al.  Seizures induced by NSAID , 1999, Allergy.

[41]  A. Roberts,et al.  Corticosteroids enhance convulsion susceptibility via central mineralocorticoid receptors , 1995, Psychoneuroendocrinology.

[42]  P. Sacerdote,et al.  Carbamazepine exerts anti-inflammatory effects in the rat. , 1995, European journal of pharmacology.

[43]  J. Reveille,et al.  Clinical, serologic, and immunogenetic studies in childhood-onset systemic lupus erythematosus. , 1993, Arthritis and rheumatism.

[44]  K. Jain Systemic Lupus Erythematosus (SLE)-Like Syndromes Associated with Carbamazepine Therapy , 1991, Drug safety.

[45]  M. Wallenstein Attenuation of epileptogenesis by nonsteroidal anti-inflammatory drugs in the rat , 1991, Neuropharmacology.