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

被引：39

作者：

Bebin, Elizabeth Martina ^{[1
]}

Peters, Jurriaan M. ^{[2
]}

Porter, Brenda E. ^{[3
]}

McPherson, Tarrant O. ^{[4
]}

O'Kelley, Sarah ^{[5
]}

Sahin, Mustafa ^{[2
,6
]}

Taub, Katherine S. ^{[7
]}

Rajaraman, Rajsekar ^{[8
]}

Randle, Stephanie C. ^{[9
]}

McClintock, William M. ^{[10
]}

Koenig, Mary Kay ^{[11
,12
]}

Frost, Mike D. ^{[13
]}

Northrup, Hope A. ^{[11
,12
]}

Werner, Klaus ^{[14
]}

Nolan, Danielle A. ^{[15
]}

Wong, Michael ^{[16
]}

Krefting, Jessica L. ^{[1
]}

Biasini, Fred ^{[5
]}

Peri, Kalyani ^{[17
]}

Cutter, Gary ^{[17
]}

Krueger, Darcy A. ^{[18
]}

机构：

[1] Univ Alabama Birmingham, Dept Neurol, 719 6th Ave South CIRC 312, Birmingham, AL 35294 USA

[2] Harvard Med Sch, Boston Childrens Hosp, Dept Neurol, Boston, MA USA

[3] Stanford Univ, Dept Psychol, Stanford, CA USA

[4] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA USA

[5] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA

[6] Harvard Med Sch, Rosamund Stone Zander Translat Neurosci Ctr, Boston Childrens Hosp, Boston, MA USA

[7] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA

[8] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA

[9] Seattle Childrens Hosp, Dept Pediat, Div Pediat Neurol & Epilepsy, Seattle, WA USA

[10] Childrens Natl Med Ctr, Dept Pediat, Div Neurol, Washington, DC USA

[11] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Pediat, Houston, TX USA

[12] Childrens Mem Hermann Hosp, Houston, TX USA

[13] Minnesota Epilepsy Grp PA, Minnesota Epilepsy Grp, Roseville, MN USA

[14] Duke Univ, Dept Pediat, Durham, NC USA

[15] Beaumont Hosp, Beaumont Florence & Richard McBrien Pediat Neurosc, Royal Oak, MI USA

[16] Washington Univ, Dept Neurosci, St Louis, MO USA

[17] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA

[18] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA

来源：

ANNALS OF NEUROLOGY | 2024年 / 95卷 / 01期

关键词：

EPILEPSY; INFANTS; ONSET;

D O I：

10.1002/ana.26778

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：15 / 26

页数：12

共 24 条

[11] Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial [J].

Kotulska, Katarzyna ;

Kwiatkowski, David J. ;

Curatolo, Paolo ;

Weschke, Bernhard ;

Riney, Kate ;

Jansen, Floor ;

Feucht, Martha ;

Krsek, Pavel ;

Nabbout, Rima ;

Jansen, Anna C. ;

Wojdan, Konrad ;

Sijko, Kamil ;

Glowacka-Walas, Jagoda ;

Borkowska, Julita ;

Sadowski, Krzysztof ;

Domanska-Pakiela, Dorota ;

Moavero, Romina ;

Hertzberg, Christoph ;

Hulshof, Hanna ;

Scholl, Theresa ;

Benova, Barbora ;

Aronica, Eleonora ;

de Ridder, Jessie ;

Lagae, Lieven ;

Jozwiak, Sergiusz .

ANNALS OF NEUROLOGY, 2021, 89 (02) :304-314

[12] Epilepsy in newborns with tuberous sclerosis complex [J].

Kotulska, Katarzyna ;

Jurkiewicz, Elzbieta ;

Domanska-Pakiela, Dorota ;

Grajkowska, Wieslawa ;

Mandera, Marek ;

Borkowska, Julita ;

Jozwiak, Sergiusz .

EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, 2014, 18 (06) :714-721

[13] Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [J].

Kwan, Patrick ;

Arzimanoglou, Alexis ;

Berg, Anne T. ;

Brodie, Martin J. ;

Hauser, W. Allen ;

Mathern, Gary ;

Moshe, Solomon L. ;

Perucca, Emilio ;

Wiebe, Samuel ;

French, Jacqueline .

EPILEPSIA, 2010, 51 (06) :1069-1077

[14] Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways [J].

Kwiatkowski, DJ ;

Manning, BD .

HUMAN MOLECULAR GENETICS, 2005, 14 :R251-R258

[15] The Neurology of mTOR [J].

Lipton, Jonathan O. ;

Sahin, Mustafa .

NEURON, 2014, 84 (02) :275-291

[16] Risk Factors Associated with Refractory Epilepsy in Patients with Tuberous Sclerosis Complex: A Systematic Review [J].

Miszewska, Dominika ;

Sugalska, Monika ;

Jozwiak, Sergiusz .

JOURNAL OF CLINICAL MEDICINE, 2021, 10 (23)

[17] Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex? [J].

Moavero, Romina ;

Kotulska, Katarzyna ;

Lagae, Lieven ;

Benvenuto, Arianna ;

Gialloreti, Leonardo Emberti ;

Weschke, Bernhard ;

Riney, Kate ;

Feucht, Martha ;

Krsek, Pavel ;

Nabbout, Rima ;

Jansen, Anna C. ;

Wojdan, Konrad ;

Borkowska, Julita ;

Sadowski, Krzysztof ;

Hertzberg, Christoph ;

Van Schooneveld, Monique M. ;

Samueli, Sharon ;

Maulisova, Alice ;

Aronica, Eleonora ;

Kwiatkowski, David J. ;

Jansen, Floor E. ;

Jozwiak, Sergiusz ;

Curatolo, Paolo .

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2020, 7 (08) :1371-1381

[18] Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations [J].

Northrup, Hope ;

Aronow, Mary E. ;

Bebin, E. Martina ;

Bissler, John ;

Darling, Thomas N. ;

de Vries, Petrus J. ;

Frost, Michael D. ;

Fuchs, Zoe ;

Gosnell, Elizabeth S. ;

Gupta, Nishant ;

Jansen, Anna C. ;

Jozwiak, Sergiusz ;

Kingswood, J. Chris ;

Knilans, Timothy K. ;

McCormack, Francis X. ;

Pounders, Ashley ;

Roberds, Steven L. ;

Rodriguez-Buritica, David F. ;

Roth, Jonathan ;

Sampson, Julian R. ;

Sparagana, Steven ;

Thiele, Elizabeth Anne ;

Weiner, Howard L. ;

Wheless, James W. ;

Towbin, Alexander J. ;

Krueger, Darcy A. .

PEDIATRIC NEUROLOGY, 2021, 123 :50-66

[19] Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex [J].

Salussolia, Catherine L. ;

Klonowska, Katarzyna ;

Kwiatkowski, David J. ;

Sahin, Mustafa .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 20, 2019, 2019, 20 :217-240

[20] Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? [J].

Slowinska, Monika ;

Jozwiak, Sergiusz ;

Peron, Angela ;

Borkowska, Julita ;

Chmielewski, Dariusz ;

Sadowski, Krzysztof ;

Jurkiewicz, Elzbieta ;

Vignoli, Aglaia ;

La Briola, Francesca ;

Canevini, Maria Paola ;

Kotulska-Jozwiak, Katarzyna .

ORPHANET JOURNAL OF RARE DISEASES, 2018, 13

← 1 2 3 →