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Treatment of first tonic–clonic seizure does not affect mortality: long-term follow-up of a randomised clinical trial
  1. Maurizio A Leone1,2,
  2. Roberto Vallalta2,
  3. Alessandra Solari3,
  4. Ettore Beghi2,
  5. for the FIRST Group
  1. 1SCDU Neurologia, AOU Maggiore della Carità, Novara, Italy
  2. 2Laboratorio di Malattie Neurologiche, Istituto Mario Negri, Milano, Italy
  3. 3Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
  1. Correspondence to Dr Maurizio A Leone, SCDU Neurologia, AOU ‘Maggiore della Carità,’ Mazzini 18, 28100 Novara, Italy; maurizio.leone{at}


Background Information on the effects of early treatment of seizures on mortality is scarce. The authors assessed the survival of patients with a first generalised tonic–clonic seizure, randomised to immediate treatment (treated) versus treatment only in the event of seizure recurrence (untreated), over a 20-year period.

Methods The authors followed 419 patients. The median follow-up was 19.7 years (range 0.2–21.5) for a total of 7867 person-years.

Results 40 persons (9.6%) died during follow-up, 19 (8.9%) treated and 21 (10.3.%) untreated. The probability of surviving was 100% at 1 year, 97% (95% CI 95% to 99%) at 5 years, 94% (91–97) at 10 years and 91% (87–95) at 20 years in treated patients and 100%, 98% (95–100), 97% (94–99) and 89% (85–94), respectively, in untreated patients (p=0.7). After adjustment for treatment of first seizure and putative risk factors (gender, age, seizure type, previous uncertain seizures, family history of seizures, pre-, peri- and postnatal risk factors, remote aetiological factors for epilepsy, abnormal neurological examination, CT or MRI abnormalities, EEG abnormalities and acute treatment), only the presence of aetiological factors for epilepsy predicted a higher mortality (HR 3.4, 95% CI 2.5 to 4.3%; p<0.01). Patients with remote aetiological factors and who did not achieve 5-year remission had the poorest survival.

Conclusion Starting antiepileptic treatment immediately after the first generalised tonic–clonic seizure or only after seizure recurrence did not affect survival over the following 20 years.

  • Epilepsy (tonic–clonic)
  • seizures
  • mortality
  • survival rate
  • risk factors
  • remission
  • epidemiology
  • epilepsy
  • neuroepidemiology

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  • See Editorial commentary, p 829

  • Linked article 244244.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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