Evaluation of the patient with a first seizure is focused on determining (1) the risk of recurrence and whether antiepileptic drug (AED) therapy is warranted to reduce this risk, and (2) whether there is sufficient concern for an underlying cause to warrant further specific diagnostic testing. About 8%–10% of the population will experience a seizure in their lifetime. On average, patients with a single seizure have a risk of recurrence of 32% in the first year, reaching 46% over 5 years. This risk is substantially lower in patients with provoked seizures (e.g., following acute infection or metabolic derangement) and substantially higher in patients with structural brain injury or an abnormal electroencephalogram (EEG). Further, if there have been two unprovoked seizures occurring on different days (meeting the criteria for a diagnosis of epilepsy), the chance of recurrent seizures is at least 60%. In general, those with a risk of seizure recurrence of 60% of greater should be treated with an AED.
Patients should be asked about prior known seizures and about possible previously unidentified subtle seizure activity, such as auras, that may immediately suggest a diagnosis of epilepsy. If prior seizures are confirmed or seem likely, an AED should be started, and magnetic resonance imaging (MRI) of the brain with contrast to identify structural lesions that might serve as a seizure focus and EEG should be done. The latter is important for estimating risk of recurrence, but also to help determine whether generalized or focal epilepsy is present, which affects AED choice.
If there is an identified reversible provoking factor, the risk of seizure recurrence is likely to be substantially lower than otherwise, and AED therapy is generally not indicated. Brain imaging and EEG can be considered in select cases to help better estimate this risk, but are not uniformly necessary.
Nocturnal seizure (occurring from sleep), history of prior brain injury including stroke, severe traumatic brain injury, or central nervous system infection, and neurologic examination findings consistent with focal cortical injury (e.g., as seen in cerebral palsy or prior stroke) are all associated with an increased risk of seizure recurrence. Epileptiform activity is seen on EEG in approximately 30% of patients with epilepsy and approximately doubles the chance of seizure recurrence. Note that a normal EEG does not exclude the diagnosis of epilepsy. Brain MRI has a higher yield than computed tomography (CT) and should be obtained, most often as an outpatient. A structural abnormality felt to constitute a seizure focus is found in ~ 10% of patients with an unprovoked first seizure, and increases recurrence risk by ~ 2.5-fold. Other testing, such as toxicology screen, and analysis of electrolytes and cerebrospinal fluid may be useful in the appropriate setting, although these are not universally needed. In cases where the diagnosis of seizure is uncertain, an elevated lactic acid level and anion gap may help to distinguish seizures from syncopal or psychogenic events, but has not been shown to predict the chance of seizure recurrence.
Patients with an increased risk of recurrence are typically treated with an AED. However, the decision to treat or not should be based on an individual assessment. Patients with a prolonged aura, or without loss of consciousness, may opt not to treat even in the setting of a high probability of recurrence; other patients may have experienced multiple events of uncertain etiology, where seizure is not clearly proven, and may prefer to confirm the diagnosis prior to treatment. Conversely, patients with high-stress jobs, a need to resume driving as soon as possible, or whose single seizure episode included a cluster of generalized convulsions may opt to treat even in the absence of a clear epilepsy diagnosis.
The benefits of starting AED treatment presumptively after a first seizure in a potentially lower-risk patient include decreasing the chance of recurrence within the first two years by ~ 35%, possible earlier return of driving privileges, possible decreased severity of future seizures, and peace of mind. However, early AED treatment, as compared to waiting, does not affect quality of life, and is not believed to affect the long-term prognosis for seizure recurrence. Any benefits should be weighed against medication side effects, pregnancy concerns, convenience, and cost. In general, AED therapy is not started in this scenario.