Childhood febrile convulsions—which factors determine the subsequent epilepsy syndrome? A retrospective study
Introduction
Febrile convulsions (FC) occur in 2–4% of children between the ages 3 months and 5 years (Schumann and Miller, 1966, Van den Berg and Yerushalmy, 1969, Hauser and Kurland, 1975, Nelson and Ellenberg, 1978, Ross et al., 1980, Verity et al., 1985). Although FC are apparently a benign syndrome (Knudsen, 2000), different studies have identified an increased risk in these children for future development of epilepsy depending on the length of follow up (Van den Berg and Yerushalmy, 1969, Nelson and Ellenberg, 1978, Nelson and Ellenberg, 1976, Annegers et al., 1979, Annegers et al., 1987, Lee et al., 1998). The risk varies according to certain clinical features of the FC and prior neurological development (Wallace, 1977, Tsuboi and Endo, 1977, Annegers et al., 1987, Maher and McLachlan, 1995, Hamati-Haddad and Abou-Khalil, 1998). A long duration (greater than 15 min), focal or lateralized convulsive activity, or repeated occurrence in a 24-h interval were defined as ‘complex’ features and are predictors of subsequent epilepsy (Annegers et al., 1987). The risk ranged from 2.4% among children with simple FC to 49% among children with all three complex features of FC (Annegers et al., 1987). In addition different prognostic factors were present among patients with focal epilepsies and patients with generalized epilepsies (GE). Annegers and co-workers found a greater number of FC, a family history of epilepsy, and age >3 years at the time of first FC were associated with GE, whereas complex features of FC were strongly associated with partial epilepsy (Annegers et al., 1987). However, in their seminal study on 687 children, only 32 developed epilepsy. Therefore, the numbers were too small to calculate the risk for a specific epilepsy syndrome.
The relative contribution of childhood FC to the subsequent development of epilepsy is still a matter of debate. The aim of this study was to analyze the relative contribution of previously described risk factors for epilepsy in patients who had childhood FC with respect to the epilepsy syndrome and to examine whether or not clinical features of FC would enable to discriminate patients who develop temporal lobe epilepsy (TLE) from those who develop GE.
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Methods
Patients with epilepsy and a previous history of FC as defined by the National Institute of Health Consensus Conference on febrile seizures (Freeman, 1980, Commission on Classification, 1989) were identified from a database of a large epilepsy outpatient clinic in a University Hospital serving a population of 1.1 million. A total of 4127 patients were screened. Patients with uncertain epilepsy diagnosis, convulsions in the setting of CNS infections or severe metabolic abnormalities during the
Patients and epilepsy syndromes
We analyzed 113 patients (48 men, 65 women). Mean age at investigation was 41.5 years (S.D. 15.7, range 1–78, median 14). Seventy two patients had focal epilepsies and 41 patients had GEs (Table 1). Forty five of 72 patients with focal seizure onset had TLE, whereas 27 patients had an extratemporal epileptogenic focus. Forty one patients had GE syndromes: childhood absence epilepsy (n=3), juvenile absence epilepsy (n=1), juvenile myoclonic epilepsy (n=4), epilepsy with grand mal on awakening (n
Discussion
This study of adult patients with epilepsy preceded by FC revealed that analysis of the clinical pattern of FC allows discrimination of patients who later develop TLE versus GE in a stepwise discriminant analysis model. Patients with later TLE tend to have more often febrile status epileptics and focal FC than patients with GE. These results remained stable after cross-validation procedure with a correct group classification of 100% of GE and 84.2% of TLE patients.
Conclusions
Epilepsy syndromes, which follow childhood FC generally, fall into two major groups: idiopathic GEs, which have a strong genetic background and TLE. The results of our study support the view that prolonged and lateralized FC are associated with TLE, whereas brief and generalized FC are probably an age dependent expression of generalized seizure susceptibility. Children with prolonged and lateralised FC should be prospectively investigated with repeated MRI studies into adulthood to describe the
Acknowledgements
We are gratefully indebted to the dedicated work of Dr. Haffner, who cared for many of the young patients in this study. He died during the preparation of the manuscript. Results of this study were presented at the 24th International Epilepsy Congress Buenos Aires, Argentinia, May 13–18, 2001 (Trinka et al., 2001).
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