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Appendix A: Summary of Evidence-Based Guideline for Clinicians: Management of an Unprovoked First Seizure in Adults.
Published 2016 ·
Continuum
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Abstract
Objective: To provide evidence-based recommendations for treatment of adults with an unprovoked 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 recommendations 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 subsequent 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. Even one seizure is a traumatic physical and psychological event that poses difficult diagnostic and treatment questions, and has major social consequences (e.g., loss of driving privileges, limitations for employment). Recurrent seizures pose even more serious and costly problems. Therefore, optimal evidencebased 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; the present practice guideline analyzes evidence regarding prognosis 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. 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. (2) a seizure in relation to a demonstrated preexisting brain lesion or progressive CNS disorder (so-called “remote symptomatic” seizure). We excluded studies of provoked seizures, which are defined as seizures due to an acute symptomatic condition (e.g., a metabolic or toxic disturbance, cerebral trauma, stroke) and differ in prognosis from unprovoked seizures. This practice guideline considers the evidence for prognosis and treatment of adults with an unprovoked first seizure; a 2003 guideline addresses this for children. We posed 3 questions: (1) What are the risks for seizure recurrence after a first seizure? (2) Does immediate treatment with an AED reduce or change (a) short-term risks for a seizure recurrence or (b) longterm prognosis for seizure freedom or remission? (3) For those patients prescribed AEDs immediately, what are the risks for adverse events (AEs)? DESCRIPTION OF THE ANALYTIC PROCESS This is an evidence-based appraisal from a systematic review of the literature published in English and based on established 2004 process standards from the American Academy of Neurology (AAN) Guideline Development Subcommittee (see appendices e-1 and e-2 on the Neurology® Web site at Neurology.org). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases (1966 to March 2013), and reviewed the literature for relevant publications using established criteria. See appendix e-3 for complete search strategy and appendix e-4 for inclusion and exclusion criteria. We identified 2,613 articles, obtained all in abstract form, and selected 281 for full-text review. Of the selected articles, 47 were judged relevant and acceptable. We systematically reviewed and rated the 47 articles according to the AAN classification of evidence scheme for prognostic or therapeutic articles (appendix e-5). We linked recommendations to evidence strength based primarily on studies rated Class I or II (appendix e-6). Appendix e-7 presents all rated articles. Tables e-1 through e-4 show the data. ANALYSIS OF EVIDENCE Risk of seizure recurrence. Question. For the adult who presents with an unprovoked first seizure, what are the risks for seizure recurrence? Evidence. We identified 2 prognostic Class I and 8 prognostic Class II studies addressing the probability that an adult with an unprovoked first seizure would have recurrent seizures, and estimated the recurrence risk from these pooled data, which included studies wherein AED treatment was not randomized or controlled (table 1, figure 1). Generalized tonic–clonic convulsive seizures comprise the major seizure type, with some studies including only patients with such seizures. These studies, including both AED-treated and untreated subjects, demonstrate that the cumulative incidence of seizure recurrence increases over time, with the great majority of recurrences occurring within the first 1 to 2 years after the initial seizure and the greatest risk in the first year (i.e., 32% at 1 year, compared with just 46% by 5 years) (table 1, figures 1 and 2). Patient ascertainment and treatment differences among studies may account for some of the wide variation in recurrence rates observed. If recruitment into trials is delayed by weeks or months, patients may experience a recurrence and become ineligible. Also, seizure recurrence was lower for patients treated with AEDs in most of these studies, but treatment often was not randomized. These 2 factors would lead to variability and underestimation of recurrence risk. Table 1 Risk of seizure recurrence after an unprovoked first seizure in adults (Class I and II studies) Ref. Class Age, y No. Seizure recurrences at various times, n (%) Treated 1 mo 3 mo 6 mo 1 y 2 y 3 y 5 y .5 y 10, 11 I 70% .19 238 164 (69) — — — 38 (16) 50 (21) 60 (29) 70 (34) 81 (39) 12, 13 I 72% .16 397 204 (51) 24 (6) 58 (15) 75 (19) 98 (25) 111 (28) — — — 17 II $16 147 62 (42) — — 39 (27) 50 (34) 60 (41) 61 (41) — — 18 II Mean .20 76 36 (47) 2 (3) 18 (24) 20 (26) 22 (29) — — — — 16 II $16 306 41 (13) 55 (18) 79 (26) 111 (36) 136 (44) 144 (47) — — 19 II 75% .15 424 ? 38 (9) 89 (21) 127 (30) 153 (36) 191 (45) 204 (48) 237 (56) 244 (58) 20 II 14–91 497 127 (26) — — 191 (38) — — — — 15 II 60% .20 812 404 (50) — 179 (22) — 288 (35) — 378 (46) 398 (49) 21 II $16 228 113 (50) — — — 68 (30) — — — — 22 II 18–50 87 45 (52) — — 30 (34) 37 (43) 39 (45) — — Total 3,212 1,196 (43) 64 (7) 220 (18) 519 (24) 761 (32) 873 (36) 508 (42) 685 (46) 723 (49) Abbreviation: Ref. 5 reference. 1706 Neurology 84 April 21, 2015 a 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. We also identified clinical variables found in studies to be associated with an increased risk of seizure recurrence. The most consistently noted factors associated with an increased risk of seizure recurrence following an unprovoked first seizure include a prior brain lesion or insult causing the seizure, an EEG with epileptiform abnormalities (characterized by spikes or sharp waves), a significant brain-imaging abnormality (judged the cause of the seizure), and a nocturnal seizure. Of 2 Class I and 2 Class II studies, most confirm that individuals with a seizure related to a prior brain lesion (including those due to stroke, trauma, CNS infection, cerebral palsy, and cognitive developmental disability), a so-called “remote symptomatic” seizure, demonstrate an approximately 2-fold
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