Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut syndrome (LGS) is a rare type of severe epileptic encephalopathy that usually manifests in patients aged 2 to 5 years.¹ It is characterized by 3 distinct clinical features: multiple seizure types, cognitive impairment (which may or may not appear before seizure onset), and a specific slow spike-and-wave pattern of brain waves on electroencephalography (EEG).¹ 

Comorbidities frequently found in individuals with LGS include cognitive impairment, behavioral disorders, mobility dysfunction, sleep disturbances, and cardiac abnormalities — some of which are also diagnostic features of the disorder.^2,3 

Cognitive Impairment 

Cognitive impairment in LGS is usually moderate to severe. In many children with LGS (20% to 60%), it precedes seizure onset, but not all patients with LGS exhibit cognitive impairment at the time of diagnosis.^2,4 However, severe intellectual disability develops in 75% to 95% of children who have LGS within 5 years after seizure onset, possibly due to the repetitive and refractory nature of the seizures and/or etiological brain injury.²

LGS is characterized by changes in specific thalamocortical networks involved in a wide variety of cognitive functions.^2,5 One theory behind the development of cognitive impairment in children with early-onset LGS is that frequent epileptic activity during sensitive periods of neurodevelopment interfere with the maturation of cognitive networks. In contrast, cognitive function is better preserved in those with later-onset LGS.^2,6-8

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Behavioral Disorders

Behavioral problems are frequent in patients with LGS, including hyperactivity, inattention, anxiety, depression, agitation, aggression, and sometimes autism. However, autism is more common in patients with Dravet syndrome.^2,9

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Mobility Restriction or Disability

Often, mobility problems in patients with LGS are a direct result of frequent atonic seizures. These drop attacks can be physically exhausting and cause severe physical trauma. To prevent injury due to frequent drop attacks, wheelchair use is often recommended.^2,3

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Sleep Disturbances

Sleep disturbances caused by seizure activity at night, especially tonic seizures, may contribute to cognitive, behavioral, and psychological impairment.²

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Cardiac Abnormalities

The incidence of sudden unexpected death in epilepsy (SUDEP) is 24- to 28-fold higher in patients with epilepsy than sudden death in the general population.^2,10 One possible explanation for this life-threatening complication in epilepsy is a common genetic channelopathy that contributes to both epilepsy and cardiac disease and increases the incidence of death via lethal cardiac arrhythmias.^2,11,12 

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Long-Term Management of Comorbidities

The symptoms and comorbidities of LGS persist from childhood through adolescence into adulthood. Because LGS a chronic condition, a smooth transition of care from pediatric specialists to adult health care is required for the optimal management of LGS and its related comorbidities.^13,14

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References

1. Lennox-Gastaut syndrome. MedlinePlus. Accessed February 26, 2023.
2. Marchese F, Cappelletti S, Filippini M, et al. Comorbidities in Dravet syndrome and Lennox–Gastaut syndrome. SN Compr Clin Med. 2021;3(10):2167-2179. doi:10.1007/s42399-021-00989-y
3. Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A. Expert opinion on the management of Lennox–Gastaut syndrome: treatment algorithms and practical considerations Front Neurol. 2017;8. doi:10.3389/fneur.2017.00505
4. Lennox Gastaut syndrome. LGS Foundation. Accessed February 26, 2023.
5. Warren AEL, Abbott DF, Jackson GD, Archer JS. Thalamocortical functional connectivity in Lennox–Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks. Epilepsia. 2017;58(12):2085-2097. doi:10.1111/epi.13932
6. Chourasia N, Maheshwari A, Kalamangalam G. Cognitive and functional status in late-onset Lennox–Gastaut syndrome: variation on a classic phenotype. Epilepsy Behav. 2020;102. doi:10.1016/j.yebeh.2019.106660
7. Warren AEL, Abbott DF, Vaughan DN, Jackson GD, Archer JS. Abnormal cognitive network interactions in Lennox-Gastaut syndrome: a potential mechanism of epileptic encephalopathy. Epilepsia. 2016;57(5):812-822. doi:10.1111/epi.13342
8. Goldsmith IL, Zupanc ML, Buchhalter JR. Long-term seizure outcome in 74 patients with Lennox–Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup. Epilepsia. 2000;41(4):395-399. doi:10.1111/j.1528-1157.2000.tb00179.x
9. He N, Li BM, Li ZX, et al. Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome. J Neurodevelop Disord. 2018;10(1):10. doi:10.1186/s11689-018-9229-x
10. Tomson T, Surges R, Delamont R, Haywood S, Hesdorffer DC. Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs. Epilepsia. 2016;57(S1):4-16. doi:10.1111/epi.13234
11. Partemi S, Vidal MC, Striano P, et al. Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series. Int J Legal Med. 2015;129(3):495-504. doi:10.1007/s00414-014-1063-4
12. Coll M, Striano P, Ferrer-Costa C, et al. Targeted next-generation sequencing provides novel clues for associated epilepsy and cardiac conduction disorder/SUDEP. PLoS ONE. 2017;12(12):e0189618. doi:10.1371/journal.pone.0189618
13. Reaven NL, Funk SE, Montouris GD, Saurer TB, Story TJ. Burden of illness in patients with possible Lennox–Gastaut syndrome: a retrospective claims-based study. Epilepsy Behav. 2018;88:66-73. doi:10.1016/j.yebeh.2018.08.032
14. Samanta D. Management of Lennox-Gastaut syndrome beyond childhood: a comprehensive review. Epilepsy Behav. 2021;114. doi:10.1016/j.yebeh.2020.107612

Reviewed by Kyle Habet, MD, on 2/27/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.