title: Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex.
abstract: Cognitive development in patients with tuberous sclerosis complex is highly variable. Predictors in the infant years would be valuable to counsel parents and to support development. The aim of this study was to confirm factors that have been reported to be independently correlated with cognitive development. 102 patients included in this study were treated at the ENCORE-TSC expertise center of the Erasmus Medical Center-Sophia Children's Hospital. Data from the first 24 months of life were used, including details on epilepsy, motor development and mutation status. Outcome was defined as cognitive development (intellectual equivalent, IE) as measured using tests appropriate to the patients age and cognitive abilities (median age at testing 8.2 years, IQR 4.7-12.0). Univariable and multivariable regression analyses were used. In a univariable analysis, predictors of lower IE were: the presence of infantile spasms (β = -18.3, p = 0.000), a larger number of antiepileptic drugs used (β = -6.3, p = 0.000), vigabatrin not used as first drug (β = -14.6, p = 0.020), corticosteroid treatment (β = -33.2, p = 0.005), and a later age at which the child could walk independently (β = -2.1, p = 0.000). An older age at seizure onset predicted higher IE (β = 1.7, p = 0.000). In a multivariable analysis, only age at seizure onset was significantly correlated to IE (β = 1.2, p = 0.005), contributing to 28% of the variation in IE. In our cohort, age at seizure onset was the only variable that independently predicted IE. Factors predicting cognitive development could aid parents and physicians in finding the appropriate support and schooling for these patients.
authors.affiliation: Department of Neurology, Erasmus University Medical Centre, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: I E
authors.identifier: http://orcid.org/0000-0001-8990-5049
authors.initials: IE
authors.lastname: Overwater
authors.affiliation: Department of Neurology, Erasmus University Medical Centre, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: B J H
authors.initials: BJ
authors.lastname: Verhaar
authors.affiliation: Department of Public Health, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: H F
authors.initials: HF
authors.lastname: Lingsma
authors.affiliation: Department of Pediatrics, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: G C B
authors.initials: GC
authors.lastname: Bindels-de Heus
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: A M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nellist
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: L W
authors.initials: LW
authors.lastname: Ten Hoopen
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Elgersma
authors.affiliation: Department of Pediatrics, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Moll
authors.affiliation: Department of Neurology, Erasmus University Medical Centre, PO Box 2060, 3000 CB, Rotterdam, The Netherlands. m.c.y.dewit@erasmusmc.nl.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, PO Box 2060, 3000 CB, Rotterdam, The Netherlands. m.c.y.dewit@erasmusmc.nl.
authors.forename: M C Y
authors.initials: MC
authors.lastname: de Wit
mesh_terms: D017668:Age of Onset; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D004827:Epilepsy / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D002666:Psychology, Child; D012044:Regression Analysis; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology* / Q000628:therapy
keywords: Epilepsy; Intellectual disability; Intelligence; Tuberous sclerosis complex