Management and prognosis of Lennox-Gastaut syndrome

An epilepsy syndrome with an age of onset of 3-10 years characterised by multiple seizure types (including atonic, tonic, tonic-clonic and atypical absence seizures), cognitive impairment and specific EEG features of diffuse slow spike and wave (< 2 Hz) as well as paroxysmal fast activity (10 Hz or more) in sleep.

Typically the fits are resistant to treatment, and may require a combination of anti-epileptic drugs.

NICE state with respect to epilepsy management in Lennox-Gastaut syndrome (1):

• ensure that people with Lennox–Gastaut syndrome have an adult or paediatric neurologist with expertise in epilepsy involved in their care
• first-line treatment
  • sodium valproate should be considered as first-line treatment for people with Lennox–Gastaut syndrome
  • be aware that sodium valproate should be used with caution, but it is recommended as first-line treatment for Lennox–Gastaut syndrome because of the severity of the syndrome and the lack of evidence for other effective first-line treatment options.
• second-line treatment
  • lamotrigine should be considered as a second-line monotherapy or as an add-on treatment if first-line treatment is unsuccessful
• third-line treatment
  • if second-line treatment is unsuccessful, consider the following as third-line add-on treatment options for people with Lennox–Gastaut syndrome:
    • cannabidiol in combination with clobazam if the child is over 2 years, in line with NICE's technology appraisal guidance on cannabidiol with clobazam for treating seizures associated with Lennox–Gastaut syndrome
    • clobazam
    • rufinamide
    • topiramate (do not use topiramate in women and girls of childbearing potential unless the conditions of the Pregnancy Prevention Programme are fulfilled)
• further treatment options
  • seizures continue with third-line treatments for Lennox–Gastaut syndrome, consider a ketogenic diet as an add-on treatment under the supervision of a ketogenic diet team
  • if all other treatment options for Lennox–Gastaut syndrome are unsuccessful, consider felbamate as add-on treatment under the supervision of a neurologist with expertise in epilepsy

NICE suggest that fenfluramine is recommended as an option for treating seizures associated with Lennox–Gastaut syndrome (LGS), as an add-on to other antiseizure medicines, for people 2 years and over (2)

• is recommended only if:
  • the frequency of drop seizures is checked every 6 months, and fenfluramine is stopped if the frequency is not reduced by at least 30% compared with the 6 months before starting treatment
  • the NICE committee stated "..People with Lennox-Gastaut syndrome are offered a range of antiseizure medicines. If this does not control their seizures, other treatments can be introduced, including cannabidiol plus clobazam. People with LGS would have fenfluramine if their drop seizures are not controlled well enough after trying 2 or more antiepileptic drugs. For this appraisal, a rule was included for stopping fenfluramine if it has not lowered the drop seizure frequency enough. This is not in the licence for fenfluramine, but matches how cannabidiol plus clobazam is used in the NHS..."

Prognosis

• overall, the outcome remains poor for patients with Lennox-Gastaut syndrome (3)
  • mortality rate is between 3% and 7% in 8 to 10 years of follow-up
  • if there is a history of infantile spasms or West syndrome, the outcome is usually worse with seizure control as well as cognitive status while idiopathic Lennox Gastaut syndrome patients have less severe symptoms and resultant impairment

Reference:

1. NICE (January 2025). Epilepsies: diagnosis and management
2. NICE (March 2025). Fenfluramine for treating seizures associated with Lennox–Gastaut syndrome in people 2 years and over
3. Amrutkar CV, Riel-Romero RM. Lennox Gastaut Syndrome. Statpearls [Internet] 2023.