March 22, 2022; 98 (12) Research Article
Association of Early MRI Characteristics With Subsequent Epilepsy and Neurodevelopmental Outcomes in Children With Tuberous Sclerosis Complex
View ORCID ProfileHanna M. Hulshof, View ORCID ProfileHugo J. Kuijf, View ORCID ProfileKatarzyna Kotulska, View ORCID ProfilePaolo Curatolo, View ORCID ProfileBernhard Weschke, View ORCID ProfileKate Riney, View ORCID ProfilePavel Krsek, View ORCID ProfileMartha Feucht, View ORCID ProfileRima Nabbout, View ORCID ProfileLieven Lagae, View ORCID ProfileAnna Jansen, View ORCID ProfileWim M. Otte, View ORCID ProfileMaarten H. Lequin, View ORCID ProfileKamil Sijko, View ORCID ProfileArianna Benvenuto, View ORCID ProfileChristoph Hertzberg, View ORCID ProfileBarbora Benova, View ORCID ProfileTheresa Scholl, View ORCID ProfileJessie De Ridder, View ORCID ProfileEleonora M.A. Aronica, View ORCID ProfileDavid J. Kwiatkowski, View ORCID ProfileSergiusz Jozwiak, View ORCID ProfileElzbieta Jurkiewicz, View ORCID ProfileKees Braun, View ORCID ProfileFloor E. Jansen, on behalf of the EPISTOP consortium
First published January 31, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200027
Hanna M. Hulshof
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Hugo J. Kuijf
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Katarzyna Kotulska
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Paolo Curatolo
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Bernhard Weschke
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Kate Riney
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Pavel Krsek
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Martha Feucht
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Rima Nabbout
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Lieven Lagae
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Anna Jansen
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Wim M. Otte
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Maarten H. Lequin
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Kamil Sijko
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Arianna Benvenuto
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Christoph Hertzberg
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Barbora Benova
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Theresa Scholl
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Jessie De Ridder
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Eleonora M.A. Aronica
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
David J. Kwiatkowski
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Sergiusz Jozwiak
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Elzbieta Jurkiewicz
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Kees Braun
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Floor E. Jansen
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
From the Department of Pediatric Neurology, Brain Center (H.M.H., W.M.O., K.B., F.E.J.),* Image Sciences Institute (H.J.K.), Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences (W.M.O.), and Department of Radiology (M.H.L.), University Medical Center Utrecht, the Netherlands; Instytut Pomnik-Centrum Zdrowia Dziecka (K.K., K.S., S.J., E.J.), The Children's Memorial Health Institute,* Warsaw, Poland; Department of Pediatric Neuropsychiatry (P.C., A.B.), Tor Vergata University, Rome, Italy; Department of Neuropediatrics (B.W. C.H.), Charite–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universitat zu Berlin, Berlin Institute of Health (BIH), Germany; Neurosciences Unit (K.R.), Queensland Children's Hospital, Brisbane Australia and University of Queensland, Brisbane, Australia; Department of Pediatric Neurology (P.K., B.B.), Motol University Hospital, Prague, Czech Republic; Medizinische Universitaet Wien (M.F., T.S.),* Vienna, Austria; Department of Pediatric Neurology (R.N.), Necker Enfants Maladies Hospital,* Paris, France; Katholieke Universiteit (L.L., J.D.R.),* Leuven; Pediatric Neurology Unit (A.J.), Department of Pediatrics, UZ Brussel, Brussels, Belgium; Utrecht University (W.M.O.), the Netherlands; Transition Technologies (K.S.), Warsaw, Poland; Department of (Neuro)Pathology (E.M.A.A.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience; Stichting Epilepsie Instellingen Nederland (SEIN) (E.M.A.A.), Hoofddorp, the Netherlands; Brigham and Women's Hospital (D.J.K.), Harvard Medical School, Boston, MA; and Department of Child Neurology (S.J.), Medical University of Warsaw, Poland.
Association of Early MRI Characteristics With Subsequent Epilepsy and Neurodevelopmental Outcomes in Children With Tuberous Sclerosis Complex
Hanna M. Hulshof, Hugo J. Kuijf, Katarzyna Kotulska, Paolo Curatolo, Bernhard Weschke, Kate Riney, Pavel Krsek, Martha Feucht, Rima Nabbout, Lieven Lagae, Anna Jansen, Wim M. Otte, Maarten H. Lequin, Kamil Sijko, Arianna Benvenuto, Christoph Hertzberg, Barbora Benova, Theresa Scholl, Jessie De Ridder, Eleonora M.A. Aronica, David J. Kwiatkowski, Sergiusz Jozwiak, Elzbieta Jurkiewicz, Kees Braun, Floor E. Jansen, on behalf of the EPISTOP consortium
Neurology Mar 2022, 98 (12) e1216-e1225; DOI: 10.1212/WNL.0000000000200027
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Abstract
Background and Objectives Multiple factors have been found to contribute to the high risk of epilepsy in infants with tuberous sclerosis complex (TSC), including evolution of EEG abnormalities, TSC gene variant, and MRI characteristics. The aim of this prospective multicenter study was to identify early MRI biomarkers of epilepsy in infants with TSC aged <6 months and before seizure onset, and associate these MRI biomarkers with neurodevelopmental outcomes at 2 years of age. The study was part of the EPISTOP project.
Methods We evaluated brain MRIs performed in infants younger than 6 months with TSC. We used harmonized MRI protocols across centers and children were monitored closely with neuropsychological evaluation and serial video EEG. MRI characteristics, defined as tubers, radial migration lines, white matter abnormalities, cysts, calcifications, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA), were visually evaluated and lesions were detected semiautomatically. Lesion to brain volume ratios were calculated and associated with epilepsy and neurodevelopmental outcomes at 2 years.
Results Lesions were assessed on MRIs from 77 infants with TSC; 62 MRIs were sufficient for volume analysis. The presence of tubers and higher tuber-brain ratios were associated with the development of clinical seizures, independently of TSC gene variation and preventive treatment. Furthermore, higher tuber-brain ratios were associated with lower cognitive and motor development quotients at 2 years, independently of TSC gene variation and presence of epilepsy.
Discussion In infants with TSC, there is a significant association between characteristic TSC lesions detected on early brain MRI and development of clinical seizures, as well as neurodevelopmental outcomes in the first 2 years of life. According to our results, early brain MRI findings may guide clinical care for young children with TSC.
Classification of Evidence This study provides Class I evidence that in infants with TSC, there is a significant association between characteristic TSC lesions on early brain MRI and the development of clinical seizures and neurodevelopmental outcomes in the first 2 years of life.
Glossary
- ADOS=
- Autistic Diagnostic Observation Schedule;
- ASD=
- autism spectrum disorder;
- BSID-III=
- Bayley Scales of Infant Development–III;
- DSM-5=
- Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
- FLAIR=
- fluid-attenuated inversion recovery;
- mTOR=
- mammalian target of rapamycin;
- RCT=
- randomized clinical trial;
- RML=
- radial migration lines;
- SEGA=
- subependymal giant-cell astrocytoma;
- SEN=
- subependymal nodules;
- TE=
- echo time;
- TR=
- repetition time;
- TSC=
- tuberous sclerosis complex;
- TSE=
- turbo spin echo;
- WMA=
- white matter abnormalities
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The EPISTOP consortium coinvestigators are listed at links.lww.com/WNL/B795.
*Member of the European Reference Network EpiCARE.
Class of Evidence: NPub.org/coe
CME Course: NPub.org/cmelist
- Received May 22, 2021.
- Accepted in final form January 3, 2022.
- © 2022 American Academy of Neurology
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