Saturday, March 25, 2017

Risk of seizure recurrence after a first seizure

Syed Rizvi, Lady Diana Ladino, Lizbeth Hernandez-Ronquillo and José F. Téllez-Zenteno. Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure .  Seizure.  In press.


• Early antiepileptic drug treatment reduces seizure recurrence risk in the short-term.
• Early antiepileptic drug treatment does not affect the prognosis for the development of epilepsy.
• Focal or nocturnal seizure and prior brain injury increased the risk of seizure recurrence.
• Epileptiform discharges on EEG and neuroimaging abnormalities increased risk of recurrence.
• A Single Seizure Clinic model reduces wait-times and impacts clinical care decisions.


A single unprovoked seizure is a frequent phenomenon in the general population and the rate of seizure recurrence can vary widely. Individual risk prognostication is crucial in predicting patient outcomes and guiding treatment decisions. In this article, we review the most important risk factors associated with an increased likelihood of seizure recurrence after a single unprovoked seizure. In summary, the presence of focal seizure, nocturnal seizure, history of prior brain injury, family history of epilepsy, abnormal neurological exam, epileptiform discharges on electroencephalography and neuroimaging abnormalities, portend increased risk of seizure recurrence. Elucidation of these risk factors in patient assessment will augment clinical decision-making and may help determine the appropriateness of instituting anti-epilepsy treatment. We also discuss the Canadian model of single seizure clinics and the potential use to assess these patients.

From the article:

The overall risk of recurrence after a first generalized tonic–clonic seizure is approximately 30% at 5 years, assuming that subtle prior seizures or known ongoing risk factors are absent .  If the seizure is idiopathic, only 17% had a recurrence at 20 months. If the seizure was idiopathic and the patient had a sibling with seizures, the risk of seizure recurrence increased to 29%, and if the seizure was idiopathic with spike-wave discharges on electroencephalogram (EEG), the risk of seizure recurrence increased to 50%. The recurrence rate is higher in individuals who have a symptomatic etiology compared to those with an idiopathic or cryptogenic etiology. For children with first seizures that are idiopathic/cryptogenic, the recurrence risk is 40% by 2 years, while for symptomatic seizures the estimate of recurrence risk is above 50%.   

Patients with head trauma have a high recurrence risk (46% at 20 months). Overall, a history of a previous neurologic injury is associated with a 2.5-fold increased risk of recurrence. Prolonged seizures, status epilepticus, prior acute symptomatic seizures, and a Todd paralysis also increase the risk of recurrence in patients with remote symptomatic seizures. A population-based study in Italy reported that among ischemic strokes, seizure recurrence risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within intracerebral hemorrhages, the only risk factor for seizure recurrence was the presence of a previous early seizure (p = 0.017).

In children, the 5-year recurrence risk after a first seizure hovers around 42%  [41]  . Shinnar et al.  [53]  observed that the risk of seizure recurrence in a child with a first seizure in the presence of epileptiform abnormalities on EEG is comparable to the recurrence risk after a second seizure (>50% likelihood of seizure recurrence). In their quantitative review of 1930 patients, Berg and Shinnar  [1]  determined that an abnormal neurological exam or EEG, and partial epilepsy emerged as the strongest predictors of a second seizure. The lowest seizure recurrence risk was in the idiopathic group with normal EEGs (24%, 95% CI = 19%, 29%) and the highest risk was carried by the group with remote symptomatic seizures and abnormal EEGs (65%, 95% CI = 55%, 76%).

Recently a meta-analysis examining patients who underwent routine EEG after a first unprovoked seizure and were followed for seizure recurrence for at least 12 months, was published. They reported differences between adults and children. An adult with epileptiform discharges on routine EEG after a first unprovoked seizure has a 77% probability of having a second seizure, whilst a child with similar findings has a 66% probability. Another study evaluated the yield of 24-h video-EEG in assessing recurrence risk after a first unprovoked seizure. Chen and colleagues reported a risk of recurrence of 73.2% in the epileptiform discharges abnormality group. Overall, epileptiform abnormalities were associated with an increased risk of seizure recurrence (RR 2.84, 95% CI 1.67–4.82, p < 0.001)  [55]  . Finally there is a study by Dash et al. assessed the yield of portable EEG in adult population. In this study the portable EEG was used in a subgroup of patients with clear single unprovoked seizures. Epileptiform activity was identified in all of them. These patients were started on medication. This study suggests that the identification of epileptiform activity in patients with single unprovoked seizures using prolonged recording could help to avoid seizure recurrence.

A self-propagating mechanism of kindling – seizures promoting the occurrence of more seizures, causing intractable epilepsy – has been cited as a reason to start early AED treatment after a first seizure. However, despite evidence of kindling and secondary epileptogenesis in animal models, there is no firm evidence of this phenomenon occurring in humans. The decision to initiate AED treatment is relatively straightforward in patients who experience two or more unprovoked seizures, and hence have a diagnosis of epilepsy. The decision to treat a patient in the wake of a solitary unprovoked seizure is more complex and requires a thorough consideration of various demographic and personal risk factors such as socioeconomic impact, stigma, sick role, medical comorbidities, patient age, employment, need to drive, insurance concerns, personal preference, and AED side-effect profile and teratogenicity. The adverse effects range from mild symptoms to life threatening reactions and up to 30% of patients discontinue their first prescribed AED due to adverse effects. In the National General Practice Study of Epilepsy, only 15% of patients received AED treatment after a first seizure. AED treatment was justified when there was a high risk of seizure recurrence or potential for serious injury…

Before any treatment decisions are approached, it is critical to determine whether the event is truly a seizure and whether it is in fact the first seizure event. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic therapy. As in adults, early treatment with AED reduces the risk of early seizure recurrence, but does not prevent the development of epilepsy. Additionally, AED therapy in children has potential side effects such as somnolence, headache, anorexia, nausea or abdominal pain, increased irritability, rash, hirsutism, weight gain (7–58%), and significant cognitive, behavioral and psychosocial side effects, particularly affecting brain development during infancy.

Clinicians must involve the patient and caregivers in the shared decision making process. In general, clinicians should advise patients with an unprovoked non-febrile first seizure that the risk of recurrence is highest in the two years following the seizure. Family should also be informed of factors that place a child increase risk, as well as initiation detailed discussion of the side-effect profiles of relevant AED agents. Ultimately, the decision to withhold or initiate AED treatment is based on assessment of individualized risk and benefit as determined by the clinician.

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