SPECIAL ARTICLE Allan Krumholz, MD Samuel Wiebe, MD Gary S. Gronseth, MD David S. Gloss, MD Ana M. Sanchez, MD Arif A. Kabir, MD Aisha T. Liferidge, MD Justin P. Martello, MD Andres M. Kanner, MD Shlomo Shinnar, MD, PhD Jennifer L. Hopp, MD Jacqueline A. French, MD Correspondence to American Academy of Neurology: guidelines@aan.com Supplemental data at Neurology.org Evidence-based guideline: Management of an unprovoked first seizure in adults Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society ABSTRACT Objective: To provide evidence-based recommendations for treatment of adults with an unpro- voked first seizure. Methods: We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology’s classification of evidence criteria; we based recommen- dations on evidence level. Results and recommendations: Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%–45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (.3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians’ recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the sub- sequent 2 years. Neurology ® 2015;84:1705–1713 GLOSSARY AAN 5 American Academy of Neurology; AE 5 adverse event; AED 5 antiepileptic drug; CI 5 confidence interval; ILAE 5 International League Against Epilepsy; QOL 5 quality of life. An estimated 150,000 adults present annually with an unprovoked first seizure in the United States. 1 Even one seizure is a traumatic physical and psycho- logical event that poses difficult diagnostic and treat- ment questions, and has major social consequences (e.g., loss of driving privileges, limitations for employ- ment). 2,3 Recurrent seizures pose even more serious and costly problems. 2–4 Therefore, optimal evidence- based approaches for evaluating and managing adults after a first seizure and preventing recurrences with antiepileptic drug (AED) therapy are important. A 2007 practice guideline addresses the evaluation of an unprovoked first seizure in adults 3 ; the present practice guideline analyzes evidence regarding prog- nosis and therapy. We included studies of adults with an unprovoked first seizure and excluded those of patients with more than one seizure at the time of presentation. 3,5,6 Unprovoked seizures are classified in 1 of 2 broad categories: (1) a seizure of unknown etiology, or From the Department of Neurology, Maryland Epilepsy Center (A.K.), and Department of Neurology (A.M.S., A.A.K., J.P.M., J.L.H.), University of Maryland School of Medicine, Baltimore; US Department of Veterans Affairs (A.K.), Maryland Healthcare System, Epilepsy Center of Excellence, Baltimore, MD; Department of Clinical Neuroscience (S.W.), University of Calgary Faculty of Medicine, Canada; Department of Neurology (G.S.G.), University of Kansas School of Medicine, Kansas City, KS; Department of Neurology (D.S.G.), Geisinger Health System, Danville, PA; Department of Emergency Medicine (A.T.L.), George Washington University School of Medicine, Washington, DC; Department of Neurology (A.M.K.), International Center for Epilepsy, University of Miami Miller School of Medicine, FL; Departments of Neurology, Pediatrics, and Epidemiology & Population Health (S.S.), Albert Einstein College of Medicine, Yeshiva University, Bronx; and New York University Comprehensive Epilepsy Center (J.A.F.), New York, NY. Approved by the Guideline Development Subcommittee on November 16, 2013; by the Practice Committee on January 20, 2014; by the AES Board of Directors on February 13, 2014; and by the AANI Board of Directors on December 1, 2014. This guideline was endorsed by the World Federation of Neurology on May 20, 2014, and by the American Neurological Association on May 21, 2014. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2015 American Academy of Neurology 1705 ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.