New Evidence-Based Guideline on the Management of the First Unprovoked Seizure in Adults


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Wednesday, May 20, 2015

The American Epilepsy Society and American Academy of Neurology have issued a new evidence-based guideline on the management of a first unprovoked seizures in adults. These guidelines are designed to serve as a tool to help medical providers with clinical decision making.

In practice, the decision to initiate antiepileptic drug (AED) therapy should involve careful consideration of the likelihood of future seizures, the risks associated with recurrent seizures including seizure related injury and impact on lifestyle such as working and driving, as well as the negative aspects of medication. To this should be added individual circumstances including age, occupation, childbearing status, and personal preference and risk aversion.

The optimum treatment goal is seizure freedom without lifestyle limitations due to uncontrolled seizures, but also without significant adverse medication side effects. Because medical therapy is not without potential pitfalls, it is important to avoid use in cases where seizures are unlikely to recur in the absence of treatment.

Epilepsy, defined as an enduring predisposition to recurrent seizures, has traditionally been clinically diagnosed after two unprovoked seizures. This is based on studies demonstrating that a person who has experienced two unprovoked seizures has a 60 to 90% chance of another in the following 4 years (Hauser WA et al 1991). Because of the high recurrence risk, initiation of antiepileptic therapy is usually recommended in this case. For an adult presenting after a single unprovoked seizure, the decision to start medication is less straightforward. For some, this will be an isolated event requiring no treatment. However, others are known to be at high risk for future seizures. Thus, the 2014 International League Against Epilepsy (ILAE) epilepsy definition expanded to included one unprovoked seizure with high risk (greater than 60% at 10 years) of recurrence (Fisher RS et al, 2014).

The New Guideline

The new treatment guideline summarizes the current evidence on risk of seizure recurrence, effectiveness of early antiepileptic drug therapy in preventing future seizures, as well as the risks of treatment in the adult population.

Regarding the risk of a future (second) seizure, the guideline notes:

  • The risk of seizure recurrence is 32% at 1 year, 36% at 2 years, and 46% at 5 years.
  • The majority of recurrent seizures occur in the first 2 years.
  • The risk of seizure recurrence is increased by the presence of a brain injury or lesion that is the cause of the seizure, an abnormal EEG demonstrating epileptiform abnormalities, and for nocturnal seizures.
    • Specifically, compared to people with a single seizure of unknown cause those with a seizure attributed to a prior brain injury or insult are at 2.55 times greater risk for recurrence.
    • Those with an abnormal head imaging study demonstrating a potentially epileptogenic lesion are at 2.44 times greater risk for a second seizure than those with a normal head imaging.
    • An abnormal EEG increases the risk of recurrence by 2.16 times.
    • After a nocturnal seizure, this risk is 2.1 times greater than after a seizure during wakefulness.

Regarding the potential benefits and risks of starting medication after the first seizure, the guidelines notes:

  • Early treatment reduces the risk of a second seizure in the following 2 years by 35%.
  • Starting medication after the first seizure versus waiting to treat after a second seizure did not change the likelihood of subsequently becoming seizure free.
  • There is no known difference in quality of life between people who were treated after the first seizure compared to those who delayed treatment; however the evidence for this is relatively weak.
  • 7% to 31% of people treated after their first seizure developed adverse medication side effects. Most side effects were mild and reversible.

Ultimately, treatment decisions for the adult with a first time seizure must still be individualized. Providers and patients should discuss these points when developing a treatment plan to meet the person's specific needs.


Krumholz A, Wieber S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology 2015, 84: 1705-1713.

Hauser WA, Anderson VE, Loewenson RB, McRoberts SM. Seizure recurrence after a first unprovoked seizure. N Engl J Med 1982, 307: 522-528.

Fisher RS, Acevedo C, Arzimanoglou A, et al. A practical clinical definition of epilepsy. Epilepsia 2014 , 55: 475-482.

Authored by: Katherine Noe MD, PhD on 5/2015

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