Approximately 80 percent of TSC patients develop seizures between birth and age 3. The new EEG biomarker, the first of its kind in TSC patients, presents as an abnormality in the EEG called an epileptiform discharge. In the study, all infants with the biomarker developed seizures within two to three months.
"The earlier seizures are recognized and treated, the better the developmental outcomes for children with TS," said E. Martina Bebin, M.D., professor in the Department of Neurology at UAB and the study's senior author. "The development of this predictive biomarker may provide a critical window of opportunity for families and medical providers to initiate treatment at seizure onset, with potentially a positive impact on the infant's developmental outcome."
The study, conducted at five medical centers across the United States, examined 40 children with a diagnosis of TSC.
The presence of the biomarker means families will need to learn the identifying signs of seizures and begin to involve a neurologist in their child's care prior to actual seizure onset. Bebin says the study reinforces the idea that EEG should be done at time of diagnosis for TSC, and repeated on a regular basis. The study conducted EEG every six weeks.
"The results of this study not only support the importance of that initial EEG but also the importance of subsequent EEGs in monitoring the development of seizuresand epileptiform discharges," Bebin said. "Our study demonstrates the feasibility and importance of close EEG surveillance in infants with TSC for predicting those who will subsequently develop epilepsy."
Bebin says further studies are needed to better understand the relationship between various therapeutic agents and the biomarker, along with determination of the optimal timeframe in which to begin therapy.
Joyce Y. Wu, Jurriaan M. Peters, Monisha Goyal, Darcy Krueger, Mustafa Sahin, Hope Northrup, Kit Sing Au, Gary Cutter, E. Martina Bebin. Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants. Pediatric Neurology. Published online: September 23 2015
We assessed the clinical utility of routine electroencephalography (EEG) in the prediction of epilepsy onset in asymptomatic infants with tuberous sclerosis complex.
This multicenter prospective observational study recruited infants younger than 7 months, seizure-free and on no antiepileptic drugs at enrollment, who all underwent serial physical examinations and video EEGs throughout the study. Parental education on seizure recognition was completed at the time of initial enrollment. Once seizure onset occurred, standard of care was applied, and subjects were followed up until 24 months.
Forty patients were enrolled, 28 older than 12 months with completed EEG evaluation at the time of this interim analysis. Of those, 19 (67.8%) developed seizures. Epileptic spasms occurred in 10 (52.6%), focal seizures in five (26.3%), generalized tonic-clonic seizure in one (5.3%), and a combination of epileptic spasms and focal seizures in three (15.7%). Fourteen infants (73.6%) had the first emergence of epileptiform abnormalities on EEG at an average age 4.2 months, preceding seizure onset by a median of 1.9 months. Hypsarrhythmia or modified hypsarrhythmia was not found in any infant before onset of epileptic spasms. All children with epileptiform discharges subsequently developed epilepsy (100% positive predictive value), and the negative predictive value for not developing epilepsy after a normal EEG was 64%.
Serial routine EEGs in infants with tuberous sclerosis complex is a feasible strategy to identify individuals at high risk for epilepsy. The most frequent clinical presentation was epileptic spasms followed by focal seizures, and then a combination of both seizure types.