Epilepsia, 49(Suppl. 1):8–12, 2008 doi: 10.1111/j.1528-1167.2008.01443.x SUPPLEMENT - MANAGEMENT OF A FIRST SEIZURE First seizure definitions and worldwide incidence and mortality * W. Allen Hauser and †‡Ettore Beghi * Sergievsky Center, Columbia University, New York, New York, U.S.A.; †Laboratory of Neurological Disorders, Institute for Pharmacological Research “Mario Negri,” Milano, Italy; and ‡Epilepsy Center, University of Milano-Bicocca, Monza, Italy SUMMARY While all patients with epilepsy experience seizures, not all individuals with seizures have epilepsy. Seizures may be acute symptomatic or unprovoked. Acute symptomatic seizures are seizures occurring at the time of a systemic in- sult or in close temporal association with a doc- umented brain insult. Unprovoked seizures are seizures occurring in the absence of precipitat- ing factors and may be caused by a static in- jury (remote symptomatic seizures) or a pro- gressing injury (progressive symptomatic seizures). Unprovoked seizures may be single or recurrent (epilepsy). The incidence of acute symptomatic seizures is 29–39 per 100,000 per year. These pre- dominate in men, in the youngest age class, and in the elderly. Traumatic brain injury, cerebrovascular disease, drug withdrawal, infarction, and metabolic insults are the commonest causes. The incidence of single unprovoked seizures is 23–61 per 100,000 person-years. As with epilepsy, single unprovoked seizures predominate in men and in patients less than 12 months and older than 65 years. Studies on the mortality of acute symptomatic seizures are lacking. A standardized mortality ratio (SMR) of 2.3 has been reported in patients experienc- ing a single unprovoked seizure. The SMR in pa- tients with a newly diagnosed unprovoked seizure ranges from 2.5 to 4.1 according to the study population and design. The SMR is highest in the youngest patients and in those with symptomatic seizures. KEY WORDS: First seizure, Definition, Inci- dence, Mortality. While all patients with epilepsy experience seizures, not all individuals with seizures have epilepsy. One or more epileptic seizures may occur in the context of a brain insult (systemic, toxic, or metabolic). These events (de- fined acute symptomatic seizures, provoked seizures, or situation-related seizures) are presumed to be an acute manifestation of the insult and may not recur when the underlying cause has been removed or the acute phase has elapsed. Acute symptomatic seizure is a term used for seizures occurring at the time of a systemic insult or in close temporal association with a documented brain in- sult (Commission, 1993). Acute symptomatic seizures dif- fer from epilepsy in several important aspects. First, unlike epilepsy, the proximate cause of these seizures is clearly Address correspondence to Dr. Ettore Beghi, Istituto di Ricerche Far- macologiche “Mario Negri” Via Eritrea 62, 20157 – Milano, Italy. E-mail: beghi@marionegri.it Blackwell Publishing, Inc. C  International League Against Epilepsy identifiable. The close temporal sequence makes causality likely for conditions such as uremia, head injury, anoxia, or stroke, which all immediately precede or are concurrent with the seizure. Biologic plausibility also supports causal- ity when there is an acute disruption of brain integrity or of metabolic homeostasis in association with the insult. In many cases, there is also a dose effect with more severe injury leading to a higher risk of seizures. Second, unlike epilepsy, acute symptomatic seizures are not necessarily characterized by a tendency for recurrence unless there is recurrence of the underlying acute causal condition (Hes- dorffer et al., 1998). Third, although acute symptomatic seizures are an undisputable risk factor for epilepsy, they cannot be included in the definition of epilepsy, which is intended as the occurrence of two or more unprovoked seizures (Commission, 1993). An unprovoked seizure is a seizure or a cluster of seizures occurring within 24 h in a person older than 1 month of age, occurring in the absence of precipitating factors. Unprovoked seizures are defined as convulsive episodes occurring in the absence 8