Abstracts

Rationale: Up to 80% of patients with tuberous sclerosis complex (TSC) experience epilepsy in the first year of age. Early onset of epilepsy is associated with development of drug-resistant epilepsy and mental retardation in more than 80% of patients. Some authors showed that paroxysmal epileptic activity precedes the onset of infantile spasms for up to 26 days. Moreover, damage to the brain made by constant epileptic activity not only results in neuronal loss and disturbed myelination and maturation, but also may induce the expression of multidrug resistance gene thus leading to the development of drug-resistant epilepsy. We hypothesized that preventative antiepileptic treatment of infants with multifocal activity on EEG may lower the incidence of drug-resistant epilepsy.Methods: Two groups of infants with prenatal or perinatal diagnosis of TSC, established according to criteria of Tuberous Sclerosis Consensus Conference took part in the study. In standard (S) group antiepileptic treatment was launched early, but after the onset of seizures. In preventative (P) group, medication was commenced when active epileptic discharges were seen on EEG, but before the onset of clinical seizures. Thirty one patients (17 girls and 14 boys) were enrolled to S group and 14 patients (8 girls and 6 boys) were enrolled to P group. All the patients were followed-up at least till the end of 24 month of life. Results: Seizures developed in 22 (71.0%) patients in S group and in 6 (42.9%) patients in P group (p=0.072) In P group, seizures developed only in patients with previous EEG deterioration. All these patients had vigabatrin started before the onset of seizures. In patients with normal EEG, no seizures were recorded. In P group epilepsy was much better controlled. At the end of the study, in P group only 1 of 6 patients with epilepsy (16.7%) presented with active epilepsy, while in S group, 20 out of 22 children (91%) were still experiencing seizures (p=0.0003). In P group, 3 patients required two or more antiepileptic drugs to control seizures, while in S group, polytherapy was necessary in 17 children (p=0.039). Drug resistant epilepsy was also more frequently observed in S group: 13 patients (41.9%) in this group vs 1 child (7.1%) in P group (p=0.021). Preventative approach was associated with significantly higher number of patients whose EEG turned to normal at the age of 2 years (p=0.0001 comparing only treated patients within P and S group). Conclusions: Preventative antiepileptic treatment of infants with paroxysmal epileptic activity and TSC markedly reduces the incidence of drug-resistant seizures and number of patients requiring polytherapy