Epilepsia, 46(Suppl. 11):40–42, 2005 Blackwell Publishing, Inc. C  International League Against Epilepsy Mortality in Special Groups Mortality in Patients with a First Unprovoked Seizure ∗ †Ettore Beghi, ‡§Maurizio Leone, and ¶Alessandra Solari ∗ Centro per l’Epilessia, Universit` a di Milano-Bicocca, Ospedale “San Gerardo,” Monza, Italy; †Laboratorio di Malattie Neurologiche, Istituto “Mario Negri,” Milano, Italy; ‡Clinica Neurologica, Ospedale “Maggiore della Carit` a,” Novara, Italy; §Laboratorio di Malattie Neurologiche, Istituto “Mario Negri,” Milano, Italy; ¶ Laboratorio di Neuroepidemiologia, Istituto Neurologico “C.Besta,” Milano, Italy Summary: Purpose: The mortality after a first epileptic seizure is affected by the source of cases, the intensity of the diagnostic work-up, the type and the presumed etiology of the seizure, the length of follow-up, and the modalities of data collection (ret- rospective vs. prospective). We review the four studies of this topic. Methods: Four studies have been identified which focused on the mortality of the first unprovoked seizures or the first afebrile (provoked or unprovoked) seizure. These included two population-based surveys, one clinic-based community survey, and a randomized clinical trial on the treatment of the first un- provoked generalized tonic–clonic seizure. Results: A standardized mortality ratio (SMR) of 2.3 (95% confidence interval, CI 1.5–3.3) for unprovoked first seizures was found in a retrospective cohort study in the population of Rochester, Minnesota. The SMR was higher during the first year after the seizures to progressively decrease thereafter. Acute symptomatic seizures carried the higher risk, followed by re- mote symptomatic seizures, while idiopathic and cryptogenic seizures carried no risk. The increased SMR found in women and in patients aged 0–19 years enrolled in the randomized trial differs from that seen in other mortality studies in epilepsy (SMR being highest in the youngest age groups) and may be a chance finding. Conclusions: Mortality is increased in patients with a first unprovoked seizure, particularly during the first year after the seizure. This increased mortality is associated with known etiol- ogy of the seizure, and is not present when etiology is unknown. Key Words: Mortality—First unprovoked seizure. As indicated elsewhere in this volume, the mortality rate in epilepsy is increased compared to that of the gen- eral population. However, mortality in epilepsy tends to vary significantly according to the source population (e.g., incident cases of epilepsy in the community vs. prevalent cases of epilepsy seen in a epilepsy clinic). Most patients with a first epileptic seizure will not develop epilepsy; consequently, their mortality may differ from that of pa- tients with epilepsy. The question of interest is whether their mortality differs significantly from that of the gen- eral population. REVIEW OF METHODOLOGICAL ISSUES The mortality after a first epileptic seizure can be sig- nificantly affected by the source population from which the cases are drawn, the intensity of the medical work-up, Address correspondence and reprint requests to Dr. Ettore Beghi at Is- tituto di Ricerche Farmacologiche “Mario Negri,” Via Eritrea 62, 20157 Milano, Italy. E-mail: beghi@marionegri.it The commission wishes to acknowledge the support of UCB Pharma for logistical support in the organization of this workshop. the presumed etiology of the seizure, seizure type, length of the follow-up, and whether data are collected retrospec- tively or prospectively. Population- and clinic-based studies tend to provide different estimates of the mortality rates on the basis of the different characteristics of the sample. Compared to first seizure cases drawn from a community sample, first seizure cases drawn from a clinic may be characterized by the presence of cases with a higher proportion of re- mote symptomatic first seizures and consequently higher mortality rates. Definitions exist for determining whether a first seizure is unprovoked or acute symptomatic (1), however, docu- mentation of etiology of unprovoked seizures reflects the intensity of the diagnostic work-up, which may vary in completeness according to the expertise and sophistica- tion of the local medical facility. Some seizure types are more likely than others to be associated with traumatic death. An accidental fall pre- sumably caused by a myoclonic, atonic, or tonic–clonic seizure has been implicated as the cause of traumatic death in patients with epilepsy (2). Status epilepticus, which has 40