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SPECIAL ARTICLE Practice Parameter: Evaluating an apparent unprovoked first seizure in adults (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society A. Krumholz, MD ABSTRACT S. Wiebe, MD Objective: The Quality Standards Subcommittee of the American Academy of Neurology develops G. Gronseth, MD practice parameters as strategies for patient care based on analysis of evidence. For this practice S. Shinnar, MD, PhD parameter the authors reviewed available evidence relevant to evaluating adults presenting with an P. Levisohn, MD apparent unprovoked first seizure. T. Ting, MD Methods: Relevant questions were defined and addressed by multiple searches of medical literature. J. Hopp, MD Each article was then reviewed, abstracted, and classified using an established evidence scoring P. Shafer, RN system. Conclusions and recommendations were based on a standard three-tiered scheme of evi- H. Morris, MD dence classification. L. Seiden, MD G. Barkley, MD Results: For adults presenting with a first seizure, a routine EEG revealed epileptiform abnormalities J. French, MD in approximately 23% of patients, and these were predictive of seizure recurrence. A brain imaging study (CT or MRI) was significantly abnormal in 10% of patients, indicating a possible seizure etiology. Laboratory tests such as blood counts, blood glucose, and electrolyte panels were abnormal in up to 15% of individuals, but abnormalities were minor and did not cause the seizure. Overt clinical signs of Address correspondence and reprint requests to the infection such as fever typically predicted significant CSF abnormalities on lumbar puncture. Toxicol- American Academy of ogy screening studies were limited, but report some positive tests. Neurology, 1080 Montreal Avenue, St. Paul, MN 55116 Recommendations: EEG should be considered as part of the routine neurodiagnostic evaluation of [email protected] adults presenting with an apparent unprovoked first seizure (Level B). Brain imaging with CT or MRI should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Laboratory tests, such as blood counts, blood glucose, and electrolyte panels (particularly sodium), lumbar puncture, and toxicology screening may be helpful as determined by the specific clinical circumstances based on the history, physical, and neurologic examination, but there are insufficient data to support or refute recommending any of these tests for the routine evaluation of adults presenting with an apparent first unpro- voked seizure (Level U). Neurology® 2007;69:1996–2007 INTRODUCTION provoked seizures.1,2 The lifetime cumulative Seizures are RETIREDamong the most common seri- risk of developing recurrent unprovoked sei- ous neurologic disorders cared for by neurol- zures or epilepsy by the age of 80 years ranges ogists. Annually approximately 150,000 from 1.4% to 3.3%.1 Since even one seizure is adults will present with a first seizure in the a frightening, traumatic event with serious United States.1 It is estimated that 40 to 50% potential consequences, such as loss of driv- of these incident seizures recur to be classi- ing privileges, limitations for employment, fied as epilepsy, a condition of recurrent un- and bodily injury; information about opti- Supplemental data at From the University of Maryland School of Medicine (A.K., T.T., J.H.), Baltimore; University of Calgary Foothills Medical Centre (S.W.), www.neurology.org Calgary, Alberta, Canada; University of Kansas Medical Center (G.G.), Kansas City, KS; Departments of Neurology and Pediatrics (S.S.), Comprehensive Epilepsy Management Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Children’s Hospital (P.L.), Denver, CO; Beth Israel Deaconess Medical Center (P.S.), Boston, MA; Fletcher Allen Health Care/University of Vermont College of Medicine (H.M.), Burlington; Peachtree Neurological Clinic (L.S.), Atlanta, GA; Henry Ford Medical Hospital (G.B.), Detroit, MI; and Department of Neurology (J.F.), New York University School of Medicine, New York. Approved by the Quality Standards Subcommittee on October 28, 2006; by the Practice Committee on July 16, 2007; and by the AAN Board of Directors on July 19, 2007. Disclosure: The authors report no conflicts of interest. 1996 Copyright © 2007 by AAN Enterprises, Inc. mal, evidence-based approaches for evaluat- defined the first seizure using the Interna- ing and treating adults presenting with a tional League Against Epilepsy criteria, as seizure is important. This practice parameter did the pediatric guideline,10 to include a addresses evidence regarding methods for single or multiple seizures within 24 hours evaluating a first seizure in adults. with recovery of consciousness between One major study estimates the annual the seizures.6 We have, therefore, excluded cost of epilepsy in the United States at patients who would be diagnosed with epi- $12.5 billion in 1995, with the majority of lepsy at the time of initial presentation. direct cost attributed to diagnostic tests, However, we recognize that seizures and epi- medical care, and drugs prescribed at the lepsy syndromes overlap, may be difficult to time of the initial evaluation for a seizure separate, and pose similar diagnostic issues, disorder or epilepsy.3 Misdiagnosis may particularly at initial presentation. Studies of lead to ineffective management choices4,5 individuals presenting with presumed new and excessive and unnecessary costs.3 Er- onset seizures report that about 50% of these rors are not only expensive but may also individuals, after careful history and ques- result in harm to the patient. tioning, actually have had previous seizures Errors in diagnosis, seizure classifica- and merit a diagnosis of epilepsy.11 Although tion, and prognosis are known to lead to the recurrence rates differ in individuals after inappropriate decisions on the use or a first seizure as opposed to a new diagnosis choice of antiepileptic drugs and to other of epilepsy, both patient groups are at signif- serious patient management errors.4,5 A icant risk for seizure recurrence.2 We also ex- single seizure can be the first manifestation cluded adults presenting with a seizure as a of epilepsy, which is characterized by re- known consequence of an acute condition current unprovoked seizures (two or more) such as immediate cerebral trauma or or may be a symptom of a brain tumor, a stroke.6 In addition, we considered only pa- systemic disorder, an infection, or a syn- tients who had returned to their normal base- drome that deserves special attention and line level of function in order to avoid treatment.6-8 including patients with an acute symptom- In this analysis, we focus on the methods atic or provoked seizure. We limited our and procedures that complement the stan- analysis in this manner because these disor- dard initial history, physical, and neuro- ders are diagnostically and therapeutically logic examination. In particular, we assess different, but this substantially reduced the the yield and value of various diagnostic number of relevant studies. procedures such as EEG, CT, or MRI, and specific laboratoryRETIRED or diagnostic tests, in- DESCRIPTION OF THE ANALYTICAL PROCESS cluding blood counts, blood glucose, elec- This is an evidence-based appraisal of currently available trolytes, lumbar puncture, and toxicology clinical measures pertinent to the initial evaluation of a pre- sumed new unprovoked seizure in adults who have returned 7,9 screening. to their previous baseline functional levels. The appraisal For the purposes of this practice param- consists of a systematic review of the literature published in eter, we considered studies of adults (ap- English based on established standards.12 pendix 4), defined here as individuals over Our literature search was conducted by the University of Minnesota using methodology and filters that increase the 18 years of age. Another recent practice pa- yield of evidence-based articles. Our search used MedLine, rameter has already addressed evaluation 1966 to November 2004, and also included CINAHL and of a first nonfebrile seizure in children.10 The Cochrane Trials Register. All citations and abstracts were printed and screened by We attempted to include only patients two reviewers for any mention of patients with a first sei- with an apparent unprovoked first seizure, zure, a first presentation, or a new diagnosis of seizure or of any type, and we specifically excluded epilepsy using established criteria (appendix 5). To be in- patients with epilepsy per se. The defini- cluded in the review, studies had to report results of any diagnostic or monitoring intervention pertinent to a first or tion of epilepsy we used requires recurrent new seizure in adults or adolescents (Ͼ18 years of age), with (two or more) unprovoked seizures.6 We at least 10 patients as total sample size. Studies with mixed Neurology 69 November 20, 2007 1997 age populations were reviewed for data pertaining to pa- chogenic seizures.5 No single test, clinical finding, tients Ͼ18 years of age when possible. or symptom is reliable in discriminating between Literature search results. In our search, we found 793 an initial seizure and such nonepileptic events. In articles and obtained all in abstract form. Each abstract was addition, the reliability of witnesses to the event is reviewed by two committee members. We identified 157 ar- variable, and witnesses are not always available. ticles for review of the full text article (an article was in- The next goal of assessment is to determine a cluded for review if selected by at least one committee cause for the seizure. For some patients, the history, member based on criteria in appendix 4). physical, and neurologic examination prove ade- These 157 full text articles were obtained and reviewed by two committee members using established criteria. Arti- quate to discern a probable cause or provide infor- cles were accepted or rejected when agreed on by both re- mation to guide the physician to consider other viewers using inclusion and exclusion criteria in appendix 4.

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