Sleep in Lennox-Gastaut Syndrome: A Scoping Review

Background and Objective: Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple seizure types, distinctive electroencephalography (EEG) abnormalities, and cognitive impairment. Sleep disturbances are highly prevalent in LGS and contribute substantially to reduced quality of life. However, no comprehensive analysis has yet been conducted to systematically examine key aspects of sleep-including architecture, microstructure, sleep-disordered breathing, and circadian regulation-leaving critical knowledge gaps. To address this, we conducted a scoping review to map the current evidence on sleep abnormalities in LGS and to identify priorities for future research. Method: A scoping review was conducted following PRISMA-ScR guidelines. PubMed, Embase, Ovid, and ClinicalTrials.gov from inception to October 2025 for studies evaluating sleep parameters in individuals with LGS or mixed epilepsy cohorts with ≥50% LGS cases. Eligible designs included observational and interventional studies using polysomnography, video-EEG, actigraphy, or sleep questionnaires. Data were synthesized narratively due to heterogeneity, and methodological quality was assessed using relevant Joanna Briggs Institute (JBI) checklists. Results: After screening 1242 articles, eleven studies met inclusion criteria, spanning 1986-2025 and conducted across four continents. Most were small single-center observational studies (5-16 LGS participants) using polysomnography as the primary assessment, with others employing wearable monitoring, surface and intracranial EEG, or circadian biomarker analyses. Across studies, individuals with LGS demonstrated markedly disrupted sleep architecture-notably reduced or absent rapid eye movement (REM) sleep, fragmented non-rapid eye movement (NREM) sleep, and attenuated spindles. Microstructural analysis showed elevated cyclic alternating pattern (CAP) rates, with epileptiform discharges clustering in CAP phase A. Sleep-disordered breathing (SDB) was common, particularly in adults, and associated with tonic seizures and central apneas. Circadian rhythm dysregulation, including altered melatonin and cortisol profiles, was also reported. A feasibility study demonstrated that home-based wearable devices and sleep apnea monitors were both acceptable and practical for use in children with LGS. No interventional studies have evaluated whether addressing sleep abnormalities modifies seizure or cognitive outcomes. Interpretation: Sleep in LGS is profoundly disrupted at both macrostructural and microstructural levels. These abnormalities may exacerbate seizure burden, cognitive impairment, and SUDEP risk, representing a potentially modifiable contributor to disease severity. Larger, prospective studies integrating polysomnography, wearable monitoring, and interventional approaches are needed to clarify causal mechanisms and therapeutic potential.