Editor’s Note: The ACEP Clinical Policies Committee regularly reviews guidelines published by other organizations and professional societies. Periodically, new guidelines are identified on topics with particular relevance to the clinical practice of emergency medicine. This article highlights recommendations for management of an unprovoked first seizure in adults developed by the American Academy of Neurology and the American Epilepsy Society in 2015.

Seizures are no stranger in the emergency department: There are more than 1 million ED visits annually for seizures in the United States, and up to 150,000 of those visits are because of unprovoked, first-time seizures.^1,2

There are many questions that arise when caring for these patients—most importantly, should antiepileptic drug (AED) therapy be started? How likely is a recurrent seizure? Would starting AED therapy improve outcomes? What harms are associated with AEDs? The American Academy of Neurology and American Epilepsy Society recently developed an updated guideline on the management of unprovoked first seizure in adults that addresses these important questions.³

The guideline developers conducted a systematic literature review to answer four clinical questions; 47 articles provided the evidence for the recommendations. The strength of each recommendation was graded as A (well-established), B (probably effective), C (possibly effective), or U (data inadequate or conflicting).

Question 1: For the adult who presents with an unprovoked first seizure, what are the risks for seizure recurrence?
Conclusions: The risk of recurrence is highest within the first two years (21 to 45 percent), and especially in the first year (Level A). Recurrence risk is higher (increased relative risk greater than 2.0) in patients with a prior brain lesion or insult causing the seizure (stroke (Level A), trauma (Level A), CNS infection, cerebral palsy, cognitive developmental disability), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B).
The broad range of early seizure recurrence (21 to 45 percent) included all comers; in patients without any of the high-risk features, recurrence was only 10 percent, 24 percent, and 29 percent at one, three, and five years, respectively. This data may help frame providers’ discussions with patients as to the pros and cons of initiating AED therapy, as many patients encountered in the emergency department fall into this “low-risk” category.

Question 2: For the adult presenting with an unprovoked first seizure, does immediate treatment with an AED change the short-term (two-year) prognosis for seizure recurrence?
Conclusion: For adults presenting with an unprovoked first seizure, immediate AED therapy is likely to reduce the absolute risk of recurrence by about 35 percent within the subsequent two years (Level B) when compared with no treatment. Initiation of AED therapy hasn’t been shown to affect quality of life (Level C).
While seizure risk may be reduced by 35 percent, time to initiation of AED therapy ranged from one to 12 weeks after the first-time seizure occurred. Outpatient management and the decision to start AED therapy may be deferred to a neurologist or primary care physician if adequate outpatient follow-up is arranged. Only one small study addressed quality-of-life outcomes, and it showed no significant difference between treated and untreated patients.

Question 3: For the adult presenting with an unprovoked first seizure, does immediate treatment with an AED compared with delay pending a seizure recurrence influence prognosis, such as the potential for seizure remission over the longer term (greater than three years)?
Conclusion: For adults presenting with an unprovoked first seizure, immediate AED treatment after a second seizure occurs is unlikely to achieve sustained seizure remission over the longer term (greater than three years) (Level B) compared with delayed treatment.
This is helpful when discussing patient expectations regarding long-term risks and benefits; early AED treatment may not increase the probability of being seizure-free over the long term.

Question 4: For the adult who presents with an unprovoked first seizure, what are the nature and frequency of adverse events (AEs) with AED treatment?
Conclusion: For adults with an unprovoked first seizure immediately treated with AEDs, studies indicated a wide range of predominantly mild and reversible AEs that occur in 7 to 31 percent of patients (Level B).
AEs should be considered when starting any new therapy; AEDs aren’t without risk, and these potential adverse effects should always be discussed with the patient. Although the specific AEs weren’t described in detail in the guideline, no deaths or life-threatening allergic reactions were reported. Included medications were phenytoin, phenobarbital, carbamazepine, valproic acid, and lamotrigine. Newer agents weren’t included in these data.

While this guideline doesn’t make a specific recommendation on whether or not to initiate AED therapy, it offers information to help initiate a discussion with patients and their families regarding the risks and benefits of AED therapy for a first-time seizure. It also helps frame what patients may expect in the years ahead regarding the possibility of recurrence and how AED therapy may have only a small impact over the long term. In summary, the physician and patient must make a shared decision on how to manage a first-time seizure.

Dr. Ingalsbe is a third-year emergency medicine resident physician at the Denver Health Residency in Emergency Medicine in Colorado.

References

1. Pallin DJ, Goldstein JN, Moussally JS, et al. Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med. 2008;1:97-105.
2. Hauser WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia. 2008;49(suppl 1):8-12.
3. Krumholz A, Wiebe S, Gronseth G, et al. 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. Neurology. 2015;84:1705-1713. Available online at: http://www.neurology.org/content/84/16/1705.full. Accessed May 6, 2016.
4. Huff J, Melnick E, Tomaszewski C, et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2014;63:437-447.