According to current estimates, about 150,000 American adults present with an unprovoked first seizure each year. Studies show that even one seizure can be a traumatic physical and psychological event for patients. They can have major consequences for patients, including loss of driving privileges, employment limitations, a higher risk for falls, and fears of having another seizure in public. Recurrent seizures can be even more serious and costly.
Unprovoked first seizures are difficult to for clinicians to diagnose and treat. In 2007, practice guidelines were released to help clinicians evaluate an unprovoked first seizure in adults. In 2015, the American Academy of Neurology and the American Epilepsy Society issued evidence-based guidelines on prognosis and therapy for first seizures. This guideline, published in Neurology and available for free at http://www.neurology.org, clarifies when risk factors put individuals at greater risk for seizure recurrence. Prevention of seizure recurrence with antiepileptic drug (AED) therapy is also discussed.
“Evidence-based approaches are needed to evaluate and manage adults after a first seizure,” says Allan Krumholz, MD, who was lead author of the guideline. “This guideline is a valuable tool because it could change approaches to treating first seizures, enabling clinicians to possibly improve outcomes and quality of life in patients.”
Conveying Recurrence Risk
The guidelines offer recommendations regarding the risk of seizure recurrence among patients who have an unprovoked first seizure. “Adults who have an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years,” Dr. Krumholz says. Studies show that recurrence risks vary between 21% and 45%, depending on a variety of factors (Figure).
Several variables have been linked to increased risk of seizure recurrence. “These include a prior brain insult, an EEG with epileptiform abnormalities, a significant brain-imaging abnormality, and a nocturnal seizure,” explains Dr. Krumholz. The table below depicts the causes of seizures and their relative rate increases for seizure recurrence over time:
|Seizure cause||Rate increase||Years|
|Prior brain insult||2.55||1 to 5 years|
|EEGs with epileptiform abnormalities||2.16||1 to 5 years|
|Abnormal brain imaging||2.44||1 to 4 years|
|Nocturnal seizure||2.10||1 to 4 years|
Clinical variables that have not been consistently associated with an increased recurrence risk of seizures after an unprovoked first seizure in adults include age, sex, family history of seizures, seizure type, and presentation with status epilepticus or multiple discrete seizures within 24 hours with recovery between them.
Initiating AED Therapy
The guidelines note that immediate AED therapy is likely to reduce seizure recurrence risk within the first 2 years of a first seizure when compared with delaying treatment pending a second seizure. “AED therapy is important to reducing subsequent risks, but clinicians should caution patients that it may not improve their quality of life,” says Dr. Krumholz. “In addition, patients should be informed that immediate AED treatment is unlikely to improve prognoses beyond 3 years. They should also be advised that their risk of adverse events from AED use ranges from 7% to 31%, but these events are mild in nature and may be reversible in many cases.”
The decision on whether or not to initiate immediate AED treatment after a first seizure should be based on individualized assessments, according to the guidelines. “Initiating AED therapy is not a black-and-white treatment decision,” says Dr. Krumholz. “Individualized assessments should weigh the risk of recurrence against the adverse events of AED therapy. They should also consider patient preferences. Clinicians should advise their patients that immediate treatment will not improve the long-term prognosis for seizure remission, but will likely reduce seizure risks over the next 2 years.”
Dr. Krumholz notes that there is still much to learn regarding the optimal management of patients who suffer an unprovoked first seizure. The guidelines note that data are needed to determine when, how, and by whom patients would be best advised regarding driving, employment, and other social issues after a first seizure. More research is also needed on patient preferences, psychosocial factors, and quality-of-life measures. This information will then need to be incorporated into decision-making processes.
Studies are also lacking on the degree to which AED treatment may influence the risk of seizure recurrence based on the specific known clinical factors that increase risk (Table) taken individually or when considered in combination. Updated studies utilizing newer AEDs for initial therapy are also warranted and encouraged. “For now, clinicians should use these guidelines to assist them when making decisions on whether to immediately treat a first seizure,” says Dr. Krumholz. “This requires meaningful conversations between patients and doctors so that all of the variables can be accounted for and discussed.”
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 at: http://www.neurology.org/content/84/16/1705.full.
Hauser W, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia. 2008;49(suppl):8-12.
Krumholz A, Wiebe S, Gronseth G, et al. 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. Neurology. 2007;69:1996-2007.
Hesdorffer D, Benn E, Cascino G, Hauser W. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia. 2009;50:1102-1108.