First unprovoked seizure: workup and management

Susan Duberstein MD (Dr. Duberstein of the Montefiore Medical Center and Albert Einstein College of Medicine has no relevant financial relationships to disclose.)
Shlomo Shinnar MD PhD (Dr. Shinnar of the Montefiore Medical Center and Albert Einstein College of Medicine has no relevant financial relationships to disclose.)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released February 10, 2014; last updated May 3, 2018; expires May 3, 2021


In this article, the authors address the workup and approach to management for a pediatric or adult patient presenting with a first seizure.

Key points


• First seizure (single or multiple events within 24 hours) represents a frequent presentation of new-onset seizures, accounting for up to a third of such presentations. However, the majority of these patients will not go on to have recurrent seizures (ie, epilepsy).


• An EEG is a standard of care in both children and adults. MRI is indicated except in those cases with an EEG diagnostic of a known self-limited pediatric syndrome such as benign epilepsy of childhood with centrotemporal spikes or primary generalized epilepsy. A toxicology screen is useful in the emergency department, but not in the office setting. In the absence of a relevant history (eg, vomiting and diarrhea), other blood work is generally not helpful. A careful history will guide both investigation and treatment options.


• Although treatment reduces recurrence risk, it does not alter long-term prognosis. Therefore, reserving treatment until occurrence of the second seizure is appropriate in most cases, especially in children and adolescents.


• Education and counseling for patients with a first seizure is important both for treatment choices and for safety considerations.

Historical note and terminology

Seizure (or epileptic seizure) is defined as "a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain" (Fisher et al 2005). The manifestation of a seizure can range from physical thrashing in a tonic-clonic event to the brief loss of awareness seen in a typical absence seizure. Epilepsy is "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures" (Fisher et al 2005). The diagnosis of epilepsy requires the occurrence of at least 1 epileptic seizure, and even a single seizure is frightening to the patient and family. However, the psychosocial and practical ramifications of the diagnosis of epilepsy are significant, making the diagnosis of epilepsy a momentous step.

Seizures and epilepsy have long shared a hidden and stigmatized history. From ancient times, the "falling sickness" was recognized, but often associated with evil and supernatural causes such as demonic possession. As recently as the 20th century, patients with seizures were routinely segregated and treated alongside those with psychiatric disturbances and neurodegenerative disorders such as neurosyphilis. To this day, the diagnosis of seizure is fraught with emotional, financial, and social ramifications; the diagnosis of epilepsy even more so. The clinician addressing the diagnosis and workup of a first seizure, whether in a child or in an adult, should therefore address the task with a comprehensive and directed approach. The primary requirement is a complete history and physical and neurologic examination. Further testing should be guided by the information thus obtained, and limited to those tests that are indicated by the clinical presentation (Hirtz et al 2000; Beghi et al 2006; Krumholz et al 2007).

Approximately 10% of the population will have at least 1 unprovoked seizure during their lifetime, and as much as 4% of the population carries a diagnosis of epilepsy at some point (Hauser et al 1990; Krumholz et al 2007). Up to 50% of patients presenting with an apparent first seizure prove, on careful history, to have had previous events suspicious enough for seizure to warrant the diagnosis of epilepsy (Hirtz et al 2000; Jallon et al 2001; Krumholz et al 2007). But for those who truly present with an isolated event, the approach to diagnosis and management has changed considerably over the past 30 years.

Until 30 years ago, the assumption was that the vast majority of people who presented with a single seizure would go on to have more seizures unless treated. This view changed with the landmark paper by Hauser and colleagues, which demonstrated that only a minority of adolescents and adults with a single seizure would experience a seizure recurrence (Hauser et al 1982). Similar results were obtained in children and adolescents 20 years ago, using the same methodology (Shinnar et al 1990). Subsequently, several large landmark randomized clinical trials, including children and adults in Italy and the UK, showed that although treatment after an initial seizure reduces recurrence risk, it does not change long-term outcomes (Camfield et al 1989; First Seizure Trial Group 1993; Musicco et al 1997; Marson et al 2007). In general, our medications, although called “antiepileptic drugs,” are really anti-seizure medicines and do not alter the natural history of epilepsy (Shinnar et al 1996). Based on these studies, there was an evolving movement to not automatically initiate treatment after a first unprovoked seizure, but generally to wait until after a second (Hirtz et al 2000; Marson et al 2007). This practice was first applied in children, in whom the risk-benefit ratio in favor of not treating was more clear-cut, but has since evolved to include adults (with some exceptions) (Shinnar et al 1994; Grinspan and Shinnar 2013; FIRST Group 1993; Marson et al 2007). This review will summarize the available data.

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