Beyond seizures: the hidden burden of developmental epileptic encephalopathies
8 affiliations
- 1Department of Developmental Disabilities, IRCCS San Raffaele Roma
- 2Department of Medicine and Surgery, Saint Camillus International University of Health Sciences
- 3Department of Pediatrics, University of Perugia
- 4Department of Biotechnological and Applied Clinical Sciences, Academic Unit of Pediatrics, University of L'Aquila
- 5Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London
- 6Unit of Pediatrics, Campus Bio-Medico University
- 7Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa
- 8Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto “Giannina Gaslini”
Abstract
Developmental and epileptic encephalopathies (DEEs) are a group of severe childhood-onset disorders characterized by drug-resistant epilepsy and a broad spectrum of neurodevelopmental, behavioral, psychiatric, and systemic manifestations. Although seizure control has traditionally been the primary therapeutic goal, growing evidence indicates that non-seizure manifestations often represent the main determinants of long-term disability, quality of life, and caregiver burden. This review highlights the hidden burden of DEEs by focusing on three paradigmatic syndromes: Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). DS and LGS represent prototypical DEEs, whereas TSC is a multisystem genetic disorder that is frequently, although not invariably, associated with early-onset drug-resistant epilepsy and DEE-like neurodevelopmental trajectories. Across these conditions, the severity and progression of clinical manifestations are influenced by complex interactions between genetic, structural, developmental, and epileptic mechanisms, supporting the concept that epilepsy and associated manifestations represent interconnected features of a broader neurodevelopmental disorder. The review also emphasizes the substantial psychosocial, physical, and economic burden experienced by families and caregivers, which often exceeds the impact of seizures alone. Current management strategies should therefore extend beyond seizure reduction and adopt a multidisciplinary, life-course approach integrating early genetic diagnosis, syndrome-specific surveillance, developmental interventions, rehabilitation, behavioral support, and coordinated multidisciplinary care. Future research should prioritize disease-modifying therapies and personalized strategies aimed at addressing both epileptic and non-epileptic manifestations, ultimately improving functional outcomes and quality of life for individuals with DEEs and their families.
Related
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BibTeX
@article{dellisola2026beyond,
title = {{Beyond seizures: the hidden burden of developmental epileptic encephalopathies}},
author = {Giovanni Battista Dell’Isola and Michele Sorrentino and Sara Massara and Gianluca Dini and Vincenzo Salpietro and Pietro Ferrara and Pasquale Striano and Federico Vigevano and Alberto Verrotti},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1960314},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1960314/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond seizures: the hidden burden of developmental epileptic encephalopathies
AU - Giovanni Battista Dell’Isola
AU - Michele Sorrentino
AU - Sara Massara
AU - Gianluca Dini
AU - Vincenzo Salpietro
AU - Pietro Ferrara
AU - Pasquale Striano
AU - Federico Vigevano
AU - Alberto Verrotti
PY - 2026
DA - 2026/10/14
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1960314
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1960314/full
AB - Developmental and epileptic encephalopathies (DEEs) are a group of severe childhood-onset disorders characterized by drug-resistant epilepsy and a broad spectrum of neurodevelopmental, behavioral, psychiatric, and systemic manifestations. Although seizure control has traditionally been the primary therapeutic goal, growing evidence indicates that non-seizure manifestations often represent the main determinants of long-term disability, quality of life, and caregiver burden. This review highlights the hidden burden of DEEs by focusing on three paradigmatic syndromes: Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). DS and LGS represent prototypical DEEs, whereas TSC is a multisystem genetic disorder that is frequently, although not invariably, associated with early-onset drug-resistant epilepsy and DEE-like neurodevelopmental trajectories. Across these conditions, the severity and progression of clinical manifestations are influenced by complex interactions between genetic, structural, developmental, and epileptic mechanisms, supporting the concept that epilepsy and associated manifestations represent interconnected features of a broader neurodevelopmental disorder. The review also emphasizes the substantial psychosocial, physical, and economic burden experienced by families and caregivers, which often exceeds the impact of seizures alone. Current management strategies should therefore extend beyond seizure reduction and adopt a multidisciplinary, life-course approach integrating early genetic diagnosis, syndrome-specific surveillance, developmental interventions, rehabilitation, behavioral support, and coordinated multidisciplinary care. Future research should prioritize disease-modifying therapies and personalized strategies aimed at addressing both epileptic and non-epileptic manifestations, ultimately improving functional outcomes and quality of life for individuals with DEEs and their families.
SN - 1664-2295
ER -