Sign Up for a Free Account
  • Updated 06.14.2023
  • Released 02.10.2014
  • Expires For CME 06.14.2026

First unprovoked seizure: workup and management



Seizures are dramatic and frightening occurrences for the patient and those who witness them. Clinicians should be familiar with and reassuring about 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, most of these patients will not go on to have recurrent seizures (ie, epilepsy).

• An electroencephalogram (EEG) is a standard of care in 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. Without 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 pharmacologic treatment reduces recurrence risk, it does not alter long-term prognosis. Therefore, reserving treatment until the 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 for treatment choices and 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" (15). 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" (15). The diagnosis of epilepsy requires the occurrence of at least one 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. Therefore, the clinician addressing the diagnosis and workup of a first seizure, whether in a child or in an adult, should 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 indicated by the clinical presentation (22; 02; 29).

Up to 30% of first seizures are defined as “acute symptomatic” or “provoked immediate” (01). These are seizures caused either by a direct trauma or insult to the brain or by some metabolic or toxic disturbance with an effect on the brain. These seizures, especially when caused by a reversible factor, lead to only a small risk of subsequent seizures or epilepsy and are not the focus of our discussion.

Approximately 10% of the population will have at least one unprovoked seizure during their lifetime, and as much as 4% of the population carries a diagnosis of epilepsy at some point (20; 29). 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 (22; 29). But for those who truly present with an isolated event, the approach to diagnosis and management has changed considerably over the past few decades.

For the past few decades, the assumption was that the vast majority of people who presented with a single seizure would go on to have more seizures unless treated with medication. 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 (19). Similar results were subsequently obtained in children and adolescents using the same methodology (41). Subsequently, several large landmark randomized clinical trials, including children and adults in Italy and the United Kingdom, showed that although treatment after an initial seizure reduces recurrence risk, it does not change long-term outcomes (08; 13; 36; 32). In general, our medications, although often called “antiepileptic drugs (AEDs),” are really anti-seizure medicines (ASMs), as they do not alter the natural history of epilepsy (42). Based on these studies, there was an evolving movement to not automatically initiate pharmacologic treatment after a first unprovoked seizure, but generally to wait until after a second (22; 32). 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) (18; 13; 32). A recent Cochrane review of available studies supported this practice, confirming less than 50% seizure recurrence rates as late as 2 years (37). This review will summarize the available data.

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660



ISSN: 2831-9125