Abstract
Background: Epilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population. Methods: Children aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups. Results: Epilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months. Conclusions: Although epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Pediatric neurology |
| Volume | 123 |
| DOIs | |
| State | Published - Oct 2021 |
Funding
We are sincerely indebted to the generosity of the families and patients in TSC clinics across the United States who contributed their time and effort to this study. We also thank the Tuberous Sclerosis Complex Alliance for their continued support of TSC research. We are grateful to the following individuals for help and suggestions related to this manuscript: Ravindra Arya, Kristn Currans, Jurriaan Peters, and Jun Wei. Disclosures of conflicts of interest: Dr. Bebin reports grants from Greenwich Biosciences, REGENXBIO, Neurelis and MEDSCAPE outside the submitted work. Dr. Capal reports grants from Roche, outside the submitted work. Dr. Krueger reports grants from National Institutes of Health (NINDS) during the conduct of the study, personal fees from Novartis Pharmaceuticals, personal fees from Greenwich Bioscience, grants from Marinus Pharmaceuticals, personal fees from Nobelpharma America, personal fees from REGENXBIO, and grants and nonfinancial support from Tuberous Sclerosis Complex Alliance, outside the submitted work. Dr. Northrup has no conflicts of interest related to the submitted work. Dr. Sahin reports grant support from Novartis, Roche, Biogen, Astellas, Aeovian, Bridgebio, Aucta, and Quadrant Biosciences. He has served on scientific advisory boards for Novartis, Roche, Celgene, Regenxbio, Alkermes, and Takeda. Dr. Wu reports grants and other from Greenwich Biosciences, other from Novartis, outside the submitted work. The remaining authors have nothing to disclose. Funding sources: National Institutes of Health U01-NS082320 (D.A.K. and M.S.), P20-NS080199 (E.M.B.), and U54-NS092090 (M.S.). The Developmental Synaptopathies Consortium (U54-NS092090) is part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) and is supported by the RDCRN Data Management and Coordinating Center (DMCC) (U2CTR002818). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, funded through a collaboration between NCATS and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NINDS), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), and National Institute of Mental Health (NIMH). The project also utilized resources supported by NCATS under Award Number 2UL1TR001425. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). Funding sources: National Institutes of Health U01-NS082320 (D.A.K. and M.S.), P20-NS080199 (E.M.B.), and U54-NS092090 (M.S.). The Developmental Synaptopathies Consortium (U54-NS092090) is part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) and is supported by the RDCRN Data Management and Coordinating Center (DMCC) (U2CTR002818). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, funded through a collaboration between NCATS and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NINDS), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), and National Institute of Mental Health (NIMH). The project also utilized resources supported by NCATS under Award Number 2UL1TR001425. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH).
Keywords
- Epilepsy in infancy
- Epilepsy phenotype
- Epileptic spasms
- Focal seizures
- Seizure burden
- Seizure diary
- Tubers
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Developmental Neuroscience
- Pediatrics, Perinatology, and Child Health