. 2023 Aug 28:10.1002/ana.26778.

doi: 10.1002/ana.26778. Online ahead of print.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

Elizabeth Martina Bebin¹, Jurriaan M Peters², Brenda E Porter³, Tarrant O McPherson⁴, Sarah O'Kelley⁵, Mustafa Sahin^{2

6}, Katherine S Taub⁷, Rajsekar Rajaraman⁸, Stephanie C Randle⁹, William M McClintock¹⁰, Mary Kay Koenig¹¹, Mike D Frost¹², Hope A Northrup¹¹, Klaus Werner¹³, Danielle A Nolan¹⁴, Michael Wong¹⁵, Jessica L Krefting¹, Fred Biasini⁵, Kalyani Peri¹⁶, Gary Cutter¹⁶, Darcy A Krueger¹⁷; PREVeNT Study Group

Affiliations

¹ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
² Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Neurology, Stanford University, Stanford, CA, USA.
⁴ Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
⁵ Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, MA, USA.
⁷ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁸ Department of Pediatrics and Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Department of Pediatrics, Division Pediatric Neurology and Epilepsy, Seattle Children's Hospital, Seattle, WA, USA.
¹⁰ Department of Pediatrics, Division of Neurology, Children's National Medical Center, Washington, DC, USA.
¹¹ Department of Pediatrics, McGovern Medical School at University of Texas Health Science Center at Houston and Children's Memorial Hermann Hospital, Houston, TX, USA.
¹² Minnesota Epilepsy Group, P.A., Minnesota Epilepsy Group, Roseville, MN, USA.
¹³ Department of Pediatrics, Duke University, Durham, NC, USA.
¹⁴ Beaumont Florence and Richard McBrien Pediatric Neuroscience Center, Beaumont Hospital, Royal Oak, MI, USA.
¹⁵ Department of Neuroscience, Washington University in Saint Louis, Saint Louis, MO, USA.
¹⁶ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁷ Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.

PMID: 37638552
PMCID: PMC10899525
DOI: 10.1002/ana.26778

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

Elizabeth Martina Bebin et al. Ann Neurol. 2023.

. 2023 Aug 28:10.1002/ana.26778.

doi: 10.1002/ana.26778. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
² Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Neurology, Stanford University, Stanford, CA, USA.
⁴ Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
⁵ Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, MA, USA.
⁷ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁸ Department of Pediatrics and Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Department of Pediatrics, Division Pediatric Neurology and Epilepsy, Seattle Children's Hospital, Seattle, WA, USA.
¹⁰ Department of Pediatrics, Division of Neurology, Children's National Medical Center, Washington, DC, USA.
¹¹ Department of Pediatrics, McGovern Medical School at University of Texas Health Science Center at Houston and Children's Memorial Hermann Hospital, Houston, TX, USA.
¹² Minnesota Epilepsy Group, P.A., Minnesota Epilepsy Group, Roseville, MN, USA.
¹³ Department of Pediatrics, Duke University, Durham, NC, USA.
¹⁴ Beaumont Florence and Richard McBrien Pediatric Neuroscience Center, Beaumont Hospital, Royal Oak, MI, USA.
¹⁵ Department of Neuroscience, Washington University in Saint Louis, Saint Louis, MO, USA.
¹⁶ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁷ Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.

PMID: 37638552
PMCID: PMC10899525
DOI: 10.1002/ana.26778

Abstract

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.

Interpretation: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

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Conflict of interest statement

POTENTIAL CONFLICTS OF INTEREST

Nothing to report

Figures

**Figure 2.**
CONSORT Diagram: PREVeNT participants across study arms

**Figure 3.**
Time from randomization to first (A) any type of seizure, (B) focal seizure, (C) infantile spasms

**Figure 4.**
(A) Developmental outcome scores for the Bayley-III cognitive composite standard scores and (B) Vineland-II standard scores

See this image and copyright information in PMC

Comment in

Vigabatrin in Epilepsy Related to TSC: Does it PREVeNT AND OR (EPI) STOP Seizures OR… Do We Need Some More STEPS as VI RAP?
Joshi C. Joshi C. Epilepsy Curr. 2024 Jan 10;24(2):87-89. doi: 10.1177/15357597231225097. eCollection 2024 Mar-Apr. Epilepsy Curr. 2024. PMID: 39280055 Free PMC article. No abstract available.

References

1. Northrup H, Aronow ME, Bebin EM, et al. International Tuberous Sclerosis Complex Consensus Group. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol 2021;123:50–66 - PubMed
1. Kwiatkowski DJ, Manning BD. Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 2005;14:R251–R258 - PubMed
1. Lipton J, Sahin M. The neurology of mTOR. Neuron 2014;84(2):275–291 - PMC - PubMed
1. Ihnen SKZ, Capal JK, Horn PS, et al. Epilepsy is heterogeneous in early-life tuberous sclerosis complex. Pediatr Neurol 2021;123:1–9 - PMC - PubMed
1. Chu-Shore CJ, Major P, Camposano S, et al. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 2010;51:1236–1241 - PMC - PubMed

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Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

Affiliations

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Grants and funding

LinkOut - more resources

Full Text Sources

Medical