Treatment before Seizures: New Indications for Antiepileptic Therapy in Children with Tuberous Sclerosis Complex

To the Editors: In the latest issue of Epilepsia appeared a very comprehensive review on recent developments and future perspectives in epilepsy associated with tuberous sclerosis complex (TSC) (Holmes et al., 2007). The article prompted us to recognize a new challenge in the treatment of epilepsy in TSC, which emerged in clinical practice with rapid development of high resolution fetal echocardiography and magnetic resonance imaging and changed the approach to epilepsy treatment in TSC in our hospital. Epilepsy is present in 70–80% of patients with TSC. In most cases (70–75%) seizures appear in the first year of age and such an early onset of epilepsy is associated with high incidence of mental delay and autistic behavior (Jozwiak et al., 1998). In our cohort of 140 patients with TSC and epilepsy, 75% of subjects (105 out of 140) had epilepsy onset in the first year and in 82% of them (86 out of 105) mental retardation was diagnosed. In fact, epilepsy was the main cause of patient referral to a doctor. Introduction of routine fetal echocardiography in Poland in the 20th gestational week allowed early diagnosis of multiple cardiac tumors. Fetal brain MRI, postnatal skin evaluation for a search of depigmented spots or molecular genetic analysis are useful diagnostic tools in the first months of life (Jozwiak and Kotulska, 2006). Thus, in recent years, we may observe an increasing group of newborns and small infants in whom the diagnosis of TSC may be established before the onset of seizures. Our prospective EEG studies performed in these patients in the first months of life showed that in most cases initially normal EEG recordings changed into multifocal epileptic activity preceding the seizure onset. As shown in some recent articles, the epileptic discharges themselves may have detrimental effect on brain, resulting in cognition and behavior impairment (Rener-Primec et al., 2006). Now, having a chance to diagnose TSC very early, it seems reasonable to start antiepileptic treatment before the seizure onset. Humphrey et al. (2006) reported a child with TSC, which was treated with vigabatrin at the age of 6 months after an abnormal electroencephalogram but before the onset of seizures. EEG repeated at 7 months was normal, but treatment was discontinued at 13 months because of concerns about the risk of visual field defects and because the child remained seizure-free. At 21 months, the child developed infantile spasms and at 24 months of age he had developed features of autism and his cognitive development significantly regressed. This report is consistent with our prospective studies of young TSC patients. We currently introduce antiepileptic treatment with vigabatrin in patients below 2 years of age with spike and polyspike waves and a hypsarrhythmic pattern on EEG. Rapid EEG improvement is observed in the majority of patients. We expect that longitudinal prospective studies of these patients will confirm that such an approach may prevent the patients from drug-resistant epilepsy and mental retardation.