Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut syndrome (LGS) is a severe type of epilepsy syndrome in children marked by a variety of seizure types, including tonic, atonic, generalized tonic-clonic, and atypical absence seizures, and progressive cognitive impairment. The disease also shows characteristic findings on electroencephalography (EEG) of generalized slow (2.5 Hz) spike-wave discharges. 

Lennox-Gastaut syndrome is more common in male individuals and predominantly develops between the ages of 3 and 5 years. Approximately 10% of all cases of childhood epilepsy are caused by LGS. The majority of patients continue to experience daily seizures, as the seizures of nearly 80% of patients are resistant to treatment with many antiepileptic drugs. This significantly worsens patients’ quality of life and causes significant morbidity.¹ 

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The 2 recognized forms of LGS are based on etiology: secondary LGS and idiopathic LGS. Secondary LGS occurs when an identifiable underlying pathology is responsible. Most children (75%) have LGS of the secondary form, and it is usually due to diffuse cerebral injury. Causes include tuberous sclerosis, infectious or inflammatory conditions such as encephalitis and meningitis, birth injury or trauma, hypoxic-ischemic insult, metabolic disorders, and developmental cortical malformations. Approximately 30% of children with LGS have a previous history of West syndrome or infantile spasms.^1,2

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Histological Findings in Lennox-Gastaut Syndrome

Data on histology findings in LGS are scarce. Histological findings were evaluated in a study of 18 patients with LGS who underwent single-lobe/lesionectomy or multilobe resection along with multiple subpial transection and/or callosotomy. Histopathological examination showed specific findings in 8 patients, such as focal cortical dysplasia, hippocampal sclerosis with nonspecific gliosis, and vascular malformation, while 10 patients showed findings of nonspecific gliosis.³ 

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Cortical architectural abnormalities caused by alterations in cortical development characterize focal cortical dysplasia. Histomorphological features of areas of focal cortical dysplasia include radial dyslamination of the neocortex, cortical dyslamination, tangential dyslamination of the neocortex, and dysmorphic neurons with or without balloon cells.⁴ 

Some patients with LGS may have cardiac abnormalities like cardiomyopathy, which could increase the risk of sudden unexpected death in epilepsy (SUDEP). SUDEP is described as a death that occurs suddenly, unexpectedly, nontraumatically, and without drowning in a person with epilepsy, either witnessed or unwitnessed. However, postmortem examination does not identify an anatomical or toxicologic cause of death.⁵ 

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References

1. Al-Banji MH, Zahr DK, Jan MM. Lennox-Gastaut syndrome: management update. Neurosciences (Riyadh). 2015;20(3):207-212. doi:10.17712/nsj.2015.3.20140677
2. Amrutkar C, Riel-Romero RM. Lennox Gastaut syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated August 1, 2022. Accessed February 27, 2023.
3. Liu SY, An N, Fang X, et al. Surgical treatment of patients with Lennox-Gastaut syndrome phenotype. ScientificWorldJournal. 2012;2012:614263. doi:10.1100/2012/614263
4. Prayson BE, Prayson R. Focal cortical dysplasia (epilepsy related malformations). PathologyOutlines.com. Updated November 16, 2022. Accessed February 27, 2023.
5. Nouri S. Sudden unexpected death in epilepsy. Medscape. Updated February 24, 2020. Accessed February 27, 2023.

Reviewed by Hasan Avcu, MD, on 2/28/2023.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.