Vigabatrin Treatment Prior To Seizures Decreased the Proportion of EEGs with Epileptiform Activity in Infants with Tuberous Sclerosis Complex During the PREVeNT Trial
Abstract number :
1.381
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
894
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Tarrant McPherson, PhD – Emory University
Martina Bebin, MD, MPA – The University of Alabama at Birmingham
Sarah O'Kelley, PhD – The University of Alabama at Birmingham
Mustafa Sahin, MD, PhD – Boston Children's Hospital, Harvard
Katherine Taub, MD – Children's Hospital of Philadelphia
Rajsekar Rajaraman, MD – David Geffen School of Medicine; UCLA Mattel Children’s Hospital
Stephanie Randle, MD – Seattle Children's Hospital
William McClintock, MD – Children's National Medical Center
Mary Koenig, MD – The University of Texas Health Science Center at Houston
Michael Frost, MD – University of Minnesota
Hope Northrup, MD – Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Klaus Werner, MD, PhD – Duke University
Danielle Nolan, MD – Beaumont Hospital
Michael Wong, MD, PhD – Washington University in Saint Louis
Jessica krefting, RN, BSN – The University of Alabama at Birmingham
Kalyani Peri, MS – The University of Alabama at Birmingham
Gary Cutter, PhD – The University of Alabama at Birmingham
Darcy Krueger, MD,PhD – Cincinnati Children's Hospital
Peter Davis, MD – Boston Children's Hospital
Jurriaan Peters, MD PhD – Boston Children's Hospital
Brenda Porter, MD, PhD – Stanford
Rationale: The PREVeNT trial enrolled 84 infants with tuberous sclerosis complex (TSC), using the presence of epileptiform activity on a one-hour EEG over the course of the first 24 months to randomize into a blinded arm of the trial comparing placebo to early vigabatrin at 100 milligrams/kilogram per day. Once patients developed clinical or electrographic seizures, they were treated with vigabatrin as standard of care. Of interest was whether early administration of vigabatrin would delay the onset of seizures or mitigate neurocognitive delay. Initial study results have been published: the early vigabatrin group had an overall lower incidence and later onset of infantile spasms; however, no differences were found in neurodevelopmental outcomes or the incidence of focal seizures at 24 months. Here we evaluate the effect of early vigabatrin on EEG epileptiform activity.
Methods: A total of 793 EEGs were collected over the course of the study: subjects underwent an EEG every 6 weeks/1st year of life, every 3 months/ 2nd year of life and a single EEG at 36 months of age. All EEGs were reviewed by at least two electrophysiologists blinded to treatment group for the presence or absence of epileptiform activity; if they disagreed then a third reviewer adjudicated.
Results: Of the 793 EEGs, 33.5% had epileptiform activity. 12 patients had 115 consistently normal EEGs throughout the study; they were not randomized and never developed seizures. There was a higher percentage of EEGs with epileptiform activity in the placebo arm of the study (n=27, 45.9 % of 296 EEGs) compared to those in the early vigabatrin group (n=29, 34.3% of 332 EEGs) Wilcoxon Rank-sum p=0.0290 . The difference in epileptiform activity by treatment group was stable over the study duration. The early vigabatrin group that never developed infantile spasms were the driver of the reduced number of EEGs with epileptiform activity. Placebo n=15/27 without spasms, 41.3% of EEGs had epileptiform activity; versus early vigabatrin n= 23/29 without spasms, 27.7% of the EEGSs had epileptiform activity, Wilcoxon Rank-sum p=0.0383. In contrast the placebo group with spasms n= 12/27 had 51.9% of their EEGs with epileptiform activity versus early vigabatrin n=6/29 with spasms had 60.3% of their EEGs with epileptiform activity, Wilcoxon Rank-sum p=0.4817. Regardless of treatment assignment, patients with epileptic spasms n=18, 54.8% of their EEGs had epileptic activity versus patients without spasms n=38, 32.9% of their EEGs had epileptic activity, Wilcoxon Rank-sum p=0.0009.
Conclusions: Treatment with vigabatrin at first detection of epileptiform activity on an EEG decreased by ~10% the overall proportion of EEGs with epileptiform activity up to 3 years of age. Patients in the early vigabatrin treatment group without epileptic spasm drove the reduction in the frequency of epileptiform EEGs . Early vigabatrin did not impact the number of epileptiform EEGs in subjects eventually developing epileptic spasms. History of epileptic spasms in either treatment group was associated with the highest percentage of epileptiform EEGs across the duration of the study.
Funding: U01 NS092595/NS/NINDS NIH HHS/United States
Anti-seizure Medications