TY - JOUR
T1 - Association of Early MRI Characteristics with Subsequent Epilepsy and Neurodevelopmental Outcomes in Children with Tuberous Sclerosis Complex
AU - Hulshof, Hanna M.
AU - Kuijf, Hugo J.
AU - Kotulska, Katarzyna
AU - Curatolo, Paolo
AU - Weschke, Bernhard
AU - Riney, Kate
AU - Krsek, Pavel
AU - Feucht, Martha
AU - Nabbout, Rima
AU - Lagae, Lieven
AU - Jansen, Anna
AU - Otte, Wim M.
AU - Lequin, Maarten H.
AU - Sijko, Kamil
AU - Benvenuto, Arianna
AU - Hertzberg, Christoph
AU - Benova, Barbora
AU - Scholl, Theresa
AU - de Ridder, Jessie
AU - Aronica, Eleonora M. A.
AU - Kwiatkowski, David J.
AU - Jozwiak, Sergiusz
AU - Jurkiewicz, Elzbieta
AU - Braun, Kees
AU - Jansen, Floor E.
AU - on behalf of the EPISTOP Consortium
AU - Ing, J. Anink
AU - Blazejczyk, M.
AU - Bongaarts, A. J. Borkowska
AU - Breuillard, D.
AU - Chmielewski, D.
AU - Dabrowska, M.
AU - Domańskapakieła, D.
AU - Gialloreti, L. Emberti
AU - Giannikou, K.
AU - Głowacka-Walas, J.
AU - Hamieh, L.
AU - Iyer, A.
AU - Janssen, B.
AU - Jaworski, J.
AU - Kaczorowska-Frontczak, M.
AU - Lehmann, K.
AU - Maćkowiak, N.
AU - Mills, J. D.
AU - Moavero, R.
AU - Muelebner, A.
AU - de Ridder, J.
AU - Sadowski, K.
AU - Scheldeman, C.
AU - Scholl, T.
AU - van Scheppingen, J.
AU - Sciuto, A.
N1 - Funding Information: This study was supported by the Framework Programme FP7/2007–2013 under the project EPISTOP (grant agreement 602391). S. Jozwiak, K. Kotulska, and K. Sijko were partly financed by the EPIMARKER grant of the Polish National Center for Research and Development (STRATEGMED3/306,306/4/2016). Publisher Copyright: © American Academy of Neurology.
PY - 2022/3/22
Y1 - 2022/3/22
N2 - Background and ObjectivesMultiple 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.MethodsWe 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.ResultsLesions 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.DiscussionIn 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 EvidenceThis 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.
AB - Background and ObjectivesMultiple 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.MethodsWe 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.ResultsLesions 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.DiscussionIn 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 EvidenceThis 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.
UR - http://www.scopus.com/inward/record.url?scp=85127730003&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000200027
DO - https://doi.org/10.1212/WNL.0000000000200027
M3 - Article
C2 - 35101906
SN - 0028-3878
VL - 98
SP - E1216-E1225
JO - Neurology
JF - Neurology
IS - 12
ER -