First seizure in an adult: To treat or not

By Jennie Smith

credit: 18percentgrey/Getty Images

In 2014, the International League Against Epilepsy redefined who could be considered to have epilepsy. An adult with only a single seizure – previously the threshold was two seizures at least 24 hours apart – could be considered to have epilepsy if the seizure lacked an immediate triggering cause such as trauma or metabolic disturbance, and the clinician deemed the person at risk of further seizures based on imaging or EEG results, or clinical factors. Patients at 60% or greater risk for a second seizure over the next 10 years could be considered to have epilepsy.

In redefining the clinical definition of epilepsy, ILAE also unpegged disease and treatment: the presence of disease does not mandate treatment and the absence of disease does not preclude treatment, the organization said (Epilepsia 2014 55(4):475-82. doi: 10.1111/epi.12550).

That opened the door to many more people being treated with anti-epileptic drugs. In 2015, the American Academy of Neurology and American Epilepsy Society issued a guideline focused on adults with first seizures, citing evidence that initiating AEDs immediately – without waiting for a second seizure to occur – reduced the person’s risk of new seizures by about 35% in the two years that followed, a period when risk of recurrence is highest (Neurology April 2015; 84[16]).

But the decision on whether to start the drugs had to be made carefully, the guidelines stressed, in collaboration with the patient, who would need to be advised that AED treatment could compromise quality of life, and that long-term prognosis would not necessarily be improved as a result of AED treatment.

In one sense, the guidelines’ main point was a simple one to assimilate: consider talking with the patient about starting AED treatment if the patient might be at risk of another seizure. Two of the guidelines’ authors say that in this sense, they do appear to be having an impact on clinical practice.

The authors also acknowledge that a host of ancillary questions could not be addressed in the guidelines. These include many practical issues faced in day-to-day practice, leaving neurologists and patients to fill in the gaps until more research can be brought to bear.

Dr. Allan Krumholz

“There are many things that this evidence-based guideline could not address, and some things that we thought were important to consider in future studies,” said Allan Krumholz of the University of Maryland in Baltimore, MD, the guidelines’ lead author, in an interview.

Among the issues outside the scope of the guideline is which AEDs to use after a first seizure, and who should initiate them. “Another question we did not address is: How long should you continue this medicine? There’s really no good data on that,” Dr. Krumholz said.



Jacqueline A. French, MD, of NYU Langone Health in New York, NY, a co-author on the 2015 guidelines, said she thinks that they have been effective in their most important objective: getting clinicians to discuss treatment with a patient after a first seizure.

“I think that the word is definitely getting out, to consider treating after a first seizure if the risk is high,” Dr. French said in an interview. And the recommendations seem to be having an impact not just among neurologists but emergency and general practice physicians, she said.

“I have seen more and more that people will get started on an antiepileptic drug in the emergency department, and then be referred to neurology,” she said. Usually, Dr. French said, the drug started in the ED is levetiracetam, because it does not need to be titrated, “so it’s easy to start and send people out. I’m not saying that it’s always the right drug, but it is the drug that in 2019 is likely to get started. Many times when patients are followed up in the office, I will switch people off of it if they report side effects that bother them.”

But not all patients with epilepsy get to see a neurologist, especially in areas where neurologists are scarce, Dr. French noted, and therefore may be treated long-term with the drug they were started on be a non-specialist. Dr. French and her colleagues are now following a cohort of 450 people with new-onset epilepsy to learn, among other things, how people with first seizure are evaluated and treated.

Dr. Jacqueline A. French

credit: Copyright © 2019, American Epilepsy Society link: 

Dr. Krumholz said that the concept of “immediate” treatment with an AED remains somewhat poorly defined. It could mean right in the ED following a seizure, he said, or could mean weeks or even months later during a dedicated workup with a neurologist. “It depends on the patient and the circumstances,” Dr. Krumholz said. “Ideally, in my mind at least, it’s best to have a specialist involved. But if an emergency room physician or primary care physician feels compelled to start a medication, it’s hard to criticize that.”

Dr. Krumholz cited legal considerations as potentially affecting the decision to prescribe an AED. “People are afraid of sending somebody out of the emergency room without a medication, and in the United States anyway, there may be more of a propensity to start medications right away for that reason.” The 2015 AAN/AES guideline does not address where, or by whom, the decision to start an AED should be made.

Dr. French said her approach to drug selection after a first seizure depends largely on patient preference. “Since we have a large number of relatively safe drugs to choose from, we will select the one that we think matches that person’s needs,” she said. “Maybe someone can only take a drug once daily, or cannot afford to gain weight, or has a psychiatric history that could be exacerbated by a certain drug. But I like to advise people, particularly when treating them after a single seizure, that when you start a drug, you’re not marrying it, you’re just dating it. And if it’s not a match there are alternatives, one of which is non-treatment.”

When to cease treatment is another issue that remains to be defined – and here, too, patient preference takes on a key role.

“There are data that suggest that if somebody has been seizure-free for a period of two to four years, then one can consider stopping or taking them off medication,” Dr. Krumholz said. “But they have as much as a 30% chance of having a recurrent seizure. So it’s a discussion that you have to have with a patient. Some patients will say, ‘Well, 30%, I’ll take the chance.’ Others won’t want to. Each patient is a little different. What’s important with any of these decisions – whether choosing, starting or stopping an AED — is that patients are well informed and can make a decision based on accurate information.”


    The 2015 guidelines’ proactive approach was supported by the findings of one 2018 modeling study, which considered three first-seizure cases to take into account quality of life measures, seizure risk, and AED side effects. The authors of that study, led by M. Brandon Westover, MD, PhD, of Massachusetts General Hospital in Boston, Mass., determined that immediately treating a patient with a single unprovoked seizure would result in improved quality of life compared with delayed treatment, even if the patient did not meet the ILAE definition of epilepsy. In all three cases, modeling favored intervention with AEDs (Neurology Oct 2018, 91 (15) e1429-e1439). In an editorial accompanying the modeling study, Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, of Brigham & Women’s Hospital in Cambridge, Mass., noted that in practice, most clinicians are likely basing treatment decisions on the ILAE’s 60% risk threshold for further seizures, resulting in deferred treatment for most patients with first unprovoked seizure.

    But the results of the modeling study, while not able to capture the cost of medications or the “vast variability in patient perceptions and preferences” about AEDs and the consequences of seizures, nonetheless should “shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” Dr. Jacobs and Dr. Lee concluded (Neurology Oct 2018, 91 (15) 684-685).

    Another 2018 study, by R. Edward Hogan, MD, of Washington University in St Louis, Mo., used a Q-PULSE decision-making questionnaire to evaluate how clinicians might incorporate the 2015 AAN/AES guideline in their practice. Dr. Hogan presented two case histories of first unprovoked seizure and asked physicians how they would decide whether to prescribe an AED, and what information they would seek to inform that decision (Epil Curr 2018; 18: 6, 363-364).

    The first case described a 25-year-old man with a nocturnal generalized tonic-clonic seizure whose imaging in the emergency department was negative. Only 6% of the study’s respondents said they would initiate an AED in this setting, with the rest evenly divided between “no” and “it depends” — on EEG findings and the patient’s own preference.

    A second case described a 17-year-old girl who presented for evaluation 2 weeks after an apparent focal seizure, with a normal EEG and MRI. Only 12% of respondents said they would start an AED based on this information alone, with 55% saying they would not, and 33% saying “it depends” – again on results from more EEG studies and on the patient’s preference.

    The survey and its cautious responses, Dr. Hogan concluded, highlight “the complexity of the clinical situation, where sufficient evidence may or may not exist to guide decisions, highlighting the importance of patient preference in the decision to start an AED after an unprovoked first seizure.”

    credit: © 2019 International League Against Epilepsy

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