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From the Istituto di Tecnologie Biomediche Avanzate (Dr. Musicco), Consiglio Nazionale delle Ricerche, Milan, and the Istituto Mediterraneo di Neuroscienze NEUROMED, Pozzilli (IS); the Istituto di Ricerche Farmacologiche"Mario Negri" (Dr. Beghi), Milan; the Department of Epidemiology (Dr. Solari), Istituto Nazionale Neurologico "C. Besta," Milan; and the Clinica Pediatrica"G. e D. De Marchi" (Dr. Viani), Milan, Italy.
Address correspondence and reprint requests to Dr. Massimo Musicco, Istituto di Technologie Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Via Filli Cervi 93, 20090 Segrate (MI), Italy.
It is widely agreed that after two or more seizures patients should be given antiepileptic treatment, but there is still controversy about the treatment of patients after a first unprovoked seizure. In a multicenter, randomized, open trial, patients with a first tonic-clonic seizure were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment only after another seizure. Fifty-two(24%) of the 215 patients randomized to immediate treatment and 85 (42%) of the 204 randomized to delayed treatment experienced seizure recurrence during follow-up. Age, acute treatment of the seizure with benzodiazepines, remote etiologic factors, and EEG abnormalities were significant predictors of relapse. Of the immediately treated patients, 87% had no seizures for a year and 68% had no seizures for 2 years, whereas only slightly fewer initially untreated patients (83% and 60%) achieved these endpoints. Patients treated after the first seizure and those treated after seizure relapse had the same time-dependent probability of achieving 1 and 2 seizure-free years. None of the variables that were prognostic predictors of relapse was significantly associated with the probability of having 1 or 2 years of seizure control. Anticonvulsants in patients presenting a first tonic-clonic seizure reduce the risk of relapse; however, 50% of patients who are not treated will never experience a second seizure. Moreover, the probability of long-term remission is not influenced by treatment of the first seizure.
* See the Appendix on page 997 for the institutions and investigators participating in the FIRST Group.
Supported in part by Ciba-Geigy, Italy.
Presented in part at the 43rd and 46th annual meetings of the American Academy of Neurology, Boston, MA, April 1991 and Washington, DC, May, 1994.
Received October 23, 1996. Accepted in final form April 25, 1997.
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