Conference Coverage

EEG surveillance, preseizure treatment prevents TSC epilepsy, cognitive loss



– Monitoring children who have tuberous sclerosis with EEG and treating them with vigabatrin (Sabril) at the first sign of preseizure abnormalities, rather than the usual practice of no surveillance and waiting until they have seizures, prevents epilepsy and cognitive decline, according to European investigators.

Dr. Sergiusz Jozwiak, head of pediatric neurology at Warsaw Medical University M. Alexander Otto/MDedge News

Dr. Sergiusz Jozwiak

Early surveillance is recommended and standard practice in Europe. That’s not the case in the United States, but might be someday pending the results of the PREVENT trial (Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex), an ongoing, National Institute of Neurological Disorders and Stroke–funded study to confirm the European findings.

“We are trying to convince doctors” in the United States and other “countries to do this. If you are not convinced to do early treatment,” at least “do surveillance with EEG. You will diagnose epilepsy earlier, and treat earlier, and children will do much better,” said Sergiusz Jozwiak, MD, PhD, head of pediatric neurology at Warsaw Medical University and recipient of an award from the U.S. Tuberous Sclerosis Alliance for his pioneering work.

Some U.S. physicians are already doing preventive treatment, but it’s hit and miss. “We are talking about monitoring children below the age of 2 years,” when seizures are associated with cognitive decline, he noted at the annual meeting of the American Epilepsy Society.

Dr. Jozwiak presented a follow-up at the meeting to his 2011 investigation, the first prevention study in tuberous sclerosis. Fourteen infants diagnosed within 2 months of birth underwent video-EEG monitoring every 4-6 weeks until age 2 years and were treated with vigabatrin 100-150 mg/kg per day when multifocal epileptiform discharges – a sign of impending seizures – were detected. Outcomes were compared with infants treated traditionally, with no EEG monitoring and vigabatrin only after they seized.

The children are about 9 years old now; the median IQ in the prevention arm is 94 versus 46 in the control group (P less than .03). Seven of the 14 prevention children (50%) never had a clinical seizure, while all but 1 of 25 (96%) in the control arm did (P = .001). Six of 11 prevention children (55%) versus 4 of 24 in the control group (17%), were able to come off antiepileptic drugs altogether, with no seizures (P less than .03). The work was published shortly before the epilepsy meeting.

The original 2011 report, which had similarly favorable outcomes when the children were 2 years old, led directly to the EpiStop trial, conducted at 16 mostly European centers and also reported at the meeting. Dr. Jozwiak was the senior investigator.

The design was different; all of the infants had EEG monitoring every 4 weeks until month 6, then every 6 weeks until age 12 months, then every 2 months until age 2 years. At the first detection of multifocal epileptiform discharges, infants were randomized 1:1 to vigabatrin or to the control group, with further monitoring followed by vigabatrin at the first seizure on EEG or first clinical seizure. An additional group of children – the open-label arm – also had EEG monitoring, but when to start vigabatrin was left up to the study site.

Dr. Katarzyna Kotulska-Jozwiak, head of neurology, Children's Memorial Health Institute, Warsaw M. Alexander Otto/MDedge News

Dr. Katarzyna Kotulska-Jozwiak

Only 50 of the original 94 children completed the trial to the full 2 years; tuberous sclerosis comorbidities drove many of them out, said lead investigator Katarzyna Kotulska-Jozwiak, MD, PhD, head of neurology at Children’s Memorial Health Institute, Warsaw.

Even so, the 25 children treated preventively in the randomized and open-label cohorts were more than three times as likely to be seizure free at 2 years (P = .01), and 74% less likely to develop drug-resistant epilepsy (P = .013). None of the prevention children developed infantile spasms versus 10 controls (40%) treated at first clinical or EEG seizure.

The incidence of neurodevelopmental delay was 34%, and autism 33%, at 24 months, and did not differ between prevention and control subjects. It’s probably because even children in the control group benefited from EEG surveillance and early treatment, the investigators said.

Historically, the rate of intellectual disability with usual treatment is around 60%, Dr. Kotulska-Jozwiak noted.

Overall, Dr. Jozwiak said that European physicians are more comfortable using vigabatrin than U.S. doctors, where the drug hasn’t been on the market as long and carries a Food and Drug Administration boxed warning of visual impairment. Its indications in the United States include infantile spasms in children 1-24 months old.

Levetiracetam (Keppra) is another option, but it’s not as effective in tuberous sclerosis. The PREVENT trial is using vigabatrin, and some U.S. doctors “are changing their minds, but it takes time,” Dr. Jozwiak said.

He noted that TSC is increasingly being diagnosed in utero, which gives a leg up on early diagnosis and prevention. The giveaways are heart tumors on ECG and cortical tubers on fetal MRI.

Dr. Jozwiak thinks the prevention approach might also help in other early seizure disorders, such as Sturge-Weber syndrome.

The work was funded by the European Commission and Polish government. Dr. Jozwiak and Dr. Kotulska-Jozwiak didn’t have any disclosures.

SOURCES: Jozwiak S et al. AES 2019, Abstract 1.218; Kotulska-Jozwiak K et al. AES 2019, Abstract 2.121.

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