Preventive Treatment Delays First Seizure Onset in Tuberous Sclerosis Complex

Erik Greb

October 22, 2020

In patients with tuberous sclerosis complex (TSC), preventive treatment with vigabatrin is safe and changes the natural history of seizures, according to research presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. This treatment strategy reduces the risk and severity of epilepsy, said the investigators.

As much as 90% of patients with TSC have epilepsy. Seizures generally start during infancy and are often resistant to medication. Clinicians are increasingly able to diagnose TSC prenatally, thus creating an opportunity for pursuing preventive strategies.

In the multicenter EPISTOP trial, Katarzyna Kotulska, MD, head of neurology and epileptology at Children's Memorial Health Institute in Warsaw, and colleagues compared the efficacy and safety of preventive vigabatrin treatment with those of conventional vigabatrin treatment in infants with TSC. The researchers followed 94 infants with TSC and without a history of seizures with monthly video EEG. Conventional treatment was initiated after the first electrographic or clinical seizure, and preventive treatment was administered when epileptiform discharges were visible on EEG but before the first seizure.

Six sites randomly assigned patients to treatment in a equal groups in a randomized, controlled trial. At four other sites, treatment allocation was fixed in an open-label trial. All patients were followed until age 2 years. The study's primary endpoint was the time to first clinical seizure.

A total of 53 patients participated in the randomized, controlled trial, and 41 participated in the open-label study; 79 patients completed the study. Of this group, 25 received preventive treatment, 25 received conventional treatment, and 22 patients had seizures before epileptiform activity was detected on EEG. Seven patients had neither seizures nor abnormal EEG.

The time to first clinical seizure was significantly longer in patients who received preventive treatment, compared with those who received conventional treatment. In the randomized, controlled trial, time to first seizure was 364 days in the preventive treatment group and 124 days in the conventional treatment group. In the open-label trial, time to first seizure was 426 days in the preventive treatment group and 106 days in the conventional treatment group.

A pooled analysis indicated that, at 24 months, preventive treatment significantly reduced the risk of clinical seizures (odds ratio, 0.21), drug-resistant epilepsy (OR, 0.23), and infantile spasms (OR, 0). The investigators did not record any adverse events related to preventive treatment.

The study was funded by the 7th Framework Program of the European Union. Kotulska did not report any disclosures.

SOURCE: Kotulska K et al. CNS-ICNA 2020, Abstract PL13.

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