Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut syndrome (LGS) is a rare, chronic neurological condition characterized by the onset of severe, recurrent seizures in childhood.¹ Although disease onset can occur at variable ages in childhood, most cases of LGS begin within the first 3 years of life.^2,3 Several sources report that seizures most frequently begin in children between 2 and 5 years of age.^1-4 

LGS accounts for approximately 3% to 4% of all cases of pediatric epilepsy. Between 10% and 30% of children with LGS have a history of an epilepsy syndrome with an earlier onset, such as West syndrome or Ohtahara syndrome, which then evolves to LGS.⁴

Read more about LGS etiology 

Neurological Features

Multiple Seizure Types

One classic criterion that is required for an official diagnosis of LGS is the presence of multiple types of seizures, including tonic, atonic, myoclonic, atypical absence, and generalized tonic-clonic seizures.⁴ 

Common seizure-related complications of LGS include nonconvulsive status epilepticus (in more than half of individuals with LGS), injuries or accidents that occur during seizures, and sudden unexpected death in epilepsy (SUDEP).^2,5  

Read more about LGS complications

Electroencephalographic Clinical Findings

Diffuse slow spike-and-wave and generalized paroxysmal fast activity brain wave patterns are hallmark abnormalities of LGS visualized on electroencephalography (EEG). These brain wave patterns are observed between seizure episodes and contribute to the progression of developmental, cognitive, and behavioral problems and the exacerbation of seizures.² In up to approximately 70% of individuals with LGS, slow spike-and-wave complexes are no longer seen on EEG in adulthood.⁶

Read more about LGS testing

Neurological and Motor Deficits

Neurological examination may reveal any of the following clinical features^3,5,7:

• Sensory or motor deficits
• Limited mobility
• Impaired reflexes
• Cerebellar abnormalities
• Dysphagia
• Gait disturbance (which may be due to brain injury from a seizure or a side effect of antiseizure medications)

Motor deficits following recurrent seizures may progress to a point at which a patient with LGS has difficulty walking unassisted and requires the use of a wheelchair, walker, or other device. ^7,8 A wheelchair may also be used to prevent severe injury in patients with seizures types that occur frequently (eg, atonic seizures).^7-9 

Read more about LGS comorbidities

Developmental Features 

LGS is a type of epileptic encephalopathy in which frequent seizures and abnormal EEG activity directly contribute to worsening cognitive and behavioral problems.^4,10 Approximately 70% to 80% of children with LGS present with cognitive impairment or developmental delay before the onset of seizures.¹⁰ 

Initially, the attainment of motor skills, such as sitting and crawling, is delayed in many children who become diagnosed with LGS.¹ Nearly all individuals with LGS exhibit developmental delay within 5 years of their initial seizure.² Intellectual and learning abilities then decline progressively after the onset of increasing and varying types of seizures.¹¹

Children with LGS may survive into adulthood. Because of cognitive disabilities and seizures that are often difficult to control, most adults with LGS require a caregiver or personal assistant, but a small percentage of individuals can live and work independently.¹

Read more about LGS life expectancy

Behavioral Abnormalities

Hyperactivity, aggression, agitation, irritability, autism, and psychosis are commonly reported behavioral problems in individuals with LGS.^10,11 

Treatment Resistance

Seizures experienced by patients with LGS are often difficult to manage with antiseizure medications (ASMs). Combination therapy, composed of different AEDs indicated for LGS, is often required for partial control, in addition to rescue medications to stop or shorten seizure episodes.⁴ Medication-induced complications may result when one medication adequately controls one type of seizure while at the same time worsening another type.¹¹ 

Multiple medications have been approved by the Food and Drug Administration (FDA) and indicated for usage in LGS, including Banzel® (rufinamide), Felbatol® (felbamate), Epidiolex® (cannabidiol), Topamax® (topiramate), Lamictal® (lamotrigine), Klonopin® (clonazepam), Onfi® (clobazam), and Fintepla (fenfluramine) Although not FDA indicated for LGS, Depakote (Valproate) is also considered a first-line therapy for LGS.¹¹

Read more about LGS treatment

References

1. Lennox-Gastaut syndrome. MedlinePlus. Accessed February 15, 2023.
2. What is Lennox-Gastaut syndrome? LGS Foundation. Accessed February 15, 2023.
3. Cherian KA. Lennox-Gastaut syndrome: practice essentials. Medscape. Updated August 6, 2020. Accessed February 15, 2023.
4. Lennox-Gastaut syndrome. Children’s Hospital of Philadelphia. Accessed February 15, 2023.
5. Ajinka J, Wirrell E. Lennox-Gastaut syndrome. Child Neurology Foundation. Reviewed April 2021. Accessed February 15, 2023.
6. Lennox Gastaut syndrome. LGS Foundation. Accessed February 15, 2023.
7. 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
8. Gibson PA. Lennox-Gastaut syndrome: impact on the caregivers and families of patients. J Multidiscip Healthc. 2014;7:441-448. doi:10.2147/JMDH.S69300
9. Piña-Garza JE, Chung S, Montouris GD, Radtke RA, Resnick T, Wechsler RT. Challenges in identifying Lennox–Gastaut syndrome in adults: a case series illustrating its changing nature. Epilepsy Behav Case Rep. 2016;5:38-43. doi:10.1016/j.ebcr.2016.01.004
10. Lennox Gastaut syndrome LGS. Epilepsy Foundation. Accessed February 15, 2023.
11. Amrutkar C, Riel-Romero RM. Lennox Gastaut syndrome. StatPearls [Internet]. Updated August 1, 2022. Accessed February 15, 2023. 

Reviewed by Debjyoti Talukdar, MD, on 3/1/2023.

---

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.