Lennox-Gastaut Syndrome

Guidance for primary care clinicians diagnosing and managing children with Lennox-Gastaut syndrome

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE), which commonly begins in early childhood and is characterized by frequent seizures of multiple different types, particularly tonic (stiffening) and atonic (drop) seizures, neurodevelopmental delays, and characteristic electroencephalogram (EEG) abnormalities. LGS may evolve from other epilepsy syndromes, most commonly from infantile spasms.

Other Names

  • LGS

Key Points

Seizures and safety
There is increased risk of injury from falls during seizures, especially atonic (drop) seizures. Many individuals with LGS may benefit from a seizure helmet for head protection. See Safety Precautions for Children with Seizures.

Sudden unexpected death in epilepsy
There is an increased risk of sudden unexpected death in epilepsy (SUDEP). Adherence to antiseizure medications (ASMs) is essential for decreasing the risk of SUDEP, and the use of seizure alert devices may be beneficial. See SUDEP (Sudden Death with Epilepsy) and Danny Did Foundation.

Aspiration pneumonia

Aspiration pneumonia may result from unintentional inhalation of saliva during a seizure. This risk can be enhanced in individuals taking medications that cause excess salivation and/or sedation.

Mobility impairment
Individuals with LGS often have challenges with balance, muscle coordination, and mobility, which can include dysphagia (difficulty swallowing). Assistive mobility (walker, wheelchair) and eating devices (feeding tube, gastrostomy tube) may be indicated in some individuals. See Feeding Tubes & Gastrostomies in Children and Wheelchairs and Adapted Strollers.

Early screening
Development delay and learning and behavior problems are common. Early Developmental Screening and referral to developmental therapies are essential for pediatric patients with this syndrome. Also see Evaluation of Developmental Delay.

Early treatment
Treatment of epilepsy with antiseizure medications (ASMs) is the mainstay of LGS management. Seizures are typically refractory to multiple medications, and non-pharmacological interventions, including diet therapy, neurostimulation devices, and/or epilepsy surgery, may be indicated.

Early referral to pediatric neurology
Children with LGS should typically be under the care of a pediatric neurologist with expertise in seizures. If possible, a pediatric epileptologist is preferred. If LGS is suspected by a primary care provider, early referral to a pediatric neurologist is highly recommended.

Practice Guidelines

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;8:505. PubMed abstract / Full Text

Diagnosis

LGS usually appears in preschool-aged children. It typically takes time for all its features to emerge, making it challenging to accurately diagnose this syndrome in children under 3 years of age.

The diagnosis of LGS is based on a triad of clinical features: [Asadi-Pooya: 2018]

  • Multiple seizure types with seizure onset in early childhood
  • Characteristic EEG abnormalities
  • Developmental delay, intellectual disability

Presentations

The age of onset varies, with the peak occurring between 3-5 years. Approximately 30-50% of individuals have a history of other epilepsy syndrome, most commonly infantile epileptic spasms syndrome. [Cross: 2017]
Multiple seizure types are present, which can emerge at different ages. The most common to least common are: [Arzimanoglou: 2009]
  • Tonic seizures – body stiffening, often occur during sleep
  • Atypical absence seizures – staring, can have eyelid fluttering, chewing movements, longer duration than typical absence seizures
  • Atonic seizures – “drop” seizures, cause sudden loss of body tone, often result in falls
  • Myoclonic seizures – rapid jerking movements of one or more extremities, head/shoulders, can occur in isolation or clusters
  • Generalized tonic-clonic seizures – “convulsive” seizure, full body stiffening followed by rhythmic non-suppressible jerking movements, can be associated with irregular breathing, apnea, cyanosis
  • Focal seizures – can have variable presentation, eye/head deviation in 1 direction, 1 extremity and/or 1 side of body stiff, shaking, or both. Can have normal or impaired awareness.
Developmental delays are common, but development is highly variable, and early developmental milestones may be age-appropriate. Close monitoring of developmental progress is essential to ensure developmental therapies are expedited. See Developmental Screening and Evaluation of Developmental Delay.

Diagnostic Criteria and Classifications

LGS diagnosis is characterized by a triad of clinical features: [Asadi-Pooya: 2018] [Nelson: 2023]

  1. Multiple seizure types with seizure onset prior to 18 years, often occurring in early childhood
    • Onset of seizures peaks between 3-5 years of age and can evolve from different epilepsy syndromes, such as infantile epileptic spasms syndrome.
    • Primary seizure types include tonic (primarily occurring at night), atonic and atypical absence. Other seizure types may include generalized-tonic clonic, myoclonic, and focal impaired awareness.
  2. Abnormal EEG findings
    • Characteristic interictal (in between seizures) of diffuse slow spike-wave complexes ≤2.5 hz.
    • Additional EEG features may include generalized paroxysmal fast activity (GPFA) during non-REM sleep.
  3. Developmental delay, intellectual disability
    • These features may not necessarily be present at seizure onset and may develop over time.

Diagnostic Testing and Screening

Labs

No specific lab test is diagnostic for LGS. However, labs may help assess for potential etiologies (e.g., metabolic or infectious disorders).

Lab monitoring may be indicated in patients taking specific medications (i.e., valproic acid, cannabidiol, felbamate) to assess blood cell counts and liver function and ensure medication levels are within therapeutic range.

Imaging

  • Electroencephalogram (EEG) study that captures wakefulness and sleep
    • Slow spike-wave complexes ≤2.5hz
    • Generalized paroxysmal fast activity (GPFA) during non-REM sleep
  • Magnetic resonance imaging (MRI) – to assess for underlying structural abnormalities (cortical malformations, tumor, stigmata of certain disorders, such as tuberous sclerosis complex)

Genetic Testing

Emerging advances in next-generation sequencing have discovered LGS may be a heterogenous genetic disorder. [Zhou: 2018]

Genetic testing options include a targeted multigene epilepsy panel or whole exome sequencing. Early genetic testing should be considered in patients with LGS of unknown etiology.

Testing for Family Members

If a genetic cause of LGS is identified, testing parents may be indicated to determine if the genetic variant was inherited or arose spontaneously (de novo), as this may help inform seizure risk for family members and future family planning.

Genetics

Many genes have been implicated in LGS including ARX, ALG13, CHD2, DNM1, GABRB3, STXBP1, SCN2A, and many others. [Zhou: 2018] In most cases, genetic mutations occurred spontaneously (de novo) and were not inherited.

Incidence and Prevalence

Lennox-Gastaut syndrome accounts for approximately 1-2% of individuals with epilepsy and 2-5% of all childhood epilepsies. [Bourgeois: 2014] [Sullivan: 2024] [Bourgeois: 2014] The global prevalence of LGS is approximately 5.8 - 60.8 per 100,000.

Differential Diagnosis

  • Myoclonic atonic epilepsy (MAE) – also known as Doose syndrome
    • The predominant seizure types include myoclonic and atonic seizures. Tonic seizures are rare, which is a key feature that distinguishes this syndrome from LGS.
  • Dravet syndrome
    • Age of seizure onset is earlier than LGS, often <1 year of age.
    • Temperature-sensitive/febrile seizures are a characteristic feature. Seizures are often prolonged (status epilepticus) and involve one side of the body (hemiclonic).
    • The majority of patients with Dravet syndrome have a mutation in the SCN1A gene, which impacts sodium channel function in the brain.
  • Infantile epileptic spasms syndrome (IESS) – formerly known as West syndrome
    • Infantile spasms are clusters of sudden, repeated, uncontrolled movements that resemble body crunching, head bobbing, and/or exaggerated startle.
    • Onset peaks between 4-9 months of age but can occur anytime between 2-12 months of age.
    • The characteristic brain wave pattern is called hypsarrhythmia.
    • Many, but not all, individuals with infantile spasms will develop other seizure types, including LGS.

Comorbid Conditions

Etiology for LGS is identified in approximately 2/3rd of cases, with causes including hypoxic-ischemic brain injury, congenital brain malformations, central nervous system infections, Tuberous Sclerosis Complex (TSC), metabolic disease, and genetic causes. [Asadi-Pooya: 2018] Approximately 1/3rd of children will have no identifiable cause. Genetic causes likely account for a majority of unidentified cases.

Prognosis

LGS is a lifelong neurodevelopmental disorder with epilepsy that is often drug-resistant and requires multiple antiseizure medications. Individuals with LGS often live until their adult years but typically cannot live independently and require assistance with activities of daily living. Individuals with LGS can have varying degrees of intellectual and behavioral disabilities, which often range on the severe end of the spectrum.

Treatment and Management

Neurology

Children with LGS will typically be under the care of a pediatric neurologist [DH1] [SS2] with expertise in seizures. If possible, a pediatric epileptologist is preferred. There is no cure for LGS, and no disease-modifying therapies are currently available. The primary management goal is to reduce or eliminate seizures.

Antiseizure Medications

Multiple antiseizure medications (ASMs) are often needed due to the drug-resistant nature of epilepsy in LGS. Patient ASMs should be reviewed regularly to assess potential drug-drug interactions and perform monitoring labs as recommended.

A custom seizure action plan outlining when to administer seizure rescue medication should be addressed and updated annually. [Patel: 2022] [Gidal: 2022].

There are a number of FDA-approved ASMs specifically for the treatment of LGS. Most individuals will require multiple ASMs as well as non-pharmacologic epilepsy treatments during their lifespan.

Valproic acid (Depakote) is considered the first-line treatment for seizures in patients with LGS.

Additional FDA-approved ASMs for adjunct treatment for LGS include:

  • Cannabidiol (Epidiolex) (See CBD page.)
  • Clobazam (Onfi)
  • Felbamate (Felbatol)
  • Fenfluramine (Fintepla)
  • Lamotrigine (Lamictal)
  • Rufinamide (Bazel)
  • Topiramate (Topamax)
    • Although commonly used, the following agents are not FDA-approved for LGS:
  • Levetiracetam (Keppra)
  • Brivaracetam (Briviact)
  • Zonisamide (Zonegran)
  • Lacosamide (Vimpat)
  • Ethosuximide (Zarontin)
  • Perampanel (Fycompa)

Non-Pharmacological

Non-pharmacological treatment options for drug-resistant epilepsy (DRE), which is defined as failure to achieve sustained seizure freedom after adequate trials of 2 tolerated and appropriately chosen antiseizure medications, are often indicated. [Kwan: 2010]

  • Diet therapy
  • Neurostimulation devices [Thirunavu: 2021]
    • Vagus nerve stimulation (VNS)
    • Deep brain stimulation (DBS)
    • Responsive neurostimulation (RNS)
      • Implantable closed-loop neurostimulation device with electrodes targeting the bilateral centromedian nucleus of the thalamus
  • Palliative surgical intervention [Thirunavu: 2021]
    • Corpus callosotomy to disconnect the 2 hemispheres of the brain, can be specifically beneficial for treatment of atonic seizures

Family

Services and Referrals

Pediatric Neurology (see NW providers [0])
Children with LGS should typically be under the care of a pediatric neurologist with expertise in seizures. If possible, a pediatric epileptologist or epilepsy center is preferred. If LGS is suspected by a primary care provider, early referral to a pediatric neurologist is highly recommended.

Early Intervention for Children with Disabilities/Delays (see NW providers [3])
Refer early. Research shows that early discovery, diagnosis, and treatment of children with developmental delays or disabilities leads to better outcomes in developmental skills, academic performance, and social skills.

ICD-10 Coding

G40.814 Lennox-Gastaut syndrome, intractable, without status epilepticus

Resources

Information & Support

Related Portal Content
The Medical Home Portal provides information about some specific seizure syndromes and general diagnostic and management information, including:

Answers to questions that families may frequently ask can be found at: The Care Notebook may also be helpful for tracking seizure triggers, history, medical test results, and medical records.

Information & Support

For Parents and Patients

LGS Foundation
Causes, treatment, and support information for those affected by Lennox-Gastaut syndrome.

Lennox Gastaut Syndrome (Epilepsy Foundation)
Information about who develops this syndrome, what types of seizures it causes, how it affects families, and treatment.

Danny Did Foundation
Its mission is to prevent deaths caused by seizures and advancing public awareness of Sudden Unexpected Death in Epilepsy (SUDEP).

Practice Guidelines

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;8:505. PubMed abstract / Full Text

Services for Patients & Families Nationwide (NW)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Helpful Articles

PubMed search for articles on Lennox Gastaut Syndrome in children for the last 3 years.

Nelson JA, Knupp KG.
Lennox-Gastaut Syndrome: Current Treatments, Novel Therapeutics, and Future Directions.
Neurotherapeutics. 2023;20(5):1255-1262. PubMed abstract / Full Text

Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, Genton P, Guerrini R, Kluger G, Pellock JM, Perucca E, Wheless JW.
Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology.
Lancet Neurol. 2009;8(1):82-93. PubMed abstract

Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D.
Treatment of pediatric epilepsy: European expert opinion, 2007.
Epileptic Disord. 2007;9(4):353-412. PubMed abstract

Authors & Reviewers

Initial publication: June 2024
Current Authors and Reviewers:
Author: Shanna Swartwood, MD

Page Bibliography

Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, Genton P, Guerrini R, Kluger G, Pellock JM, Perucca E, Wheless JW.
Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology.
Lancet Neurol. 2009;8(1):82-93. PubMed abstract

Asadi-Pooya AA.
Lennox-Gastaut syndrome: a comprehensive review.
Neurol Sci. 2018;39(3):403-414. PubMed abstract

Bourgeois BF, Douglass LM, Sankar R.
Lennox-Gastaut syndrome: a consensus approach to differential diagnosis.
Epilepsia. 2014;55 Suppl 4:4-9. PubMed abstract

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;8:505. PubMed abstract / Full Text

Cross JH, Benítez A, Roth J, Andrews JS, Shah D, Butcher E, Jones A, Sullivan J.
A comprehensive systematic literature review of the burden of illness of Lennox-Gastaut syndrome on patients, caregivers, and society.
Epilepsia. 2024. PubMed abstract

Gidal B, Detyniecki K.
Rescue therapies for seizure clusters: Pharmacology and target of treatments.
Epilepsia. 2022;63 Suppl 1(Suppl 1):S34-S44. PubMed abstract / Full Text

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J.
Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.
Epilepsia. 2010;51(6):1069-77. PubMed abstract

Nelson JA, Knupp KG.
Lennox-Gastaut Syndrome: Current Treatments, Novel Therapeutics, and Future Directions.
Neurotherapeutics. 2023;20(5):1255-1262. PubMed abstract / Full Text

Patel AD, Becker DA.
Introduction to use of an acute seizure action plan for seizure clusters and guidance for implementation.
Epilepsia. 2022;63 Suppl 1:S25-S33. PubMed abstract

Sullivan J, Benítez A, Roth J, Andrews JS, Shah D, Butcher E, Jones A, Cross JH.
A systematic literature review on the global epidemiology of Dravet syndrome and Lennox-Gastaut syndrome: Prevalence, incidence, diagnosis, and mortality.
Epilepsia. 2024. PubMed abstract

Thirunavu V, Du R, Wu JY, Berg AT, Lam SK.
The role of surgery in the management of Lennox-Gastaut syndrome: A systematic review and meta-analysis of the clinical evidence.
Epilepsia. 2021;62(4):888-907. PubMed abstract

Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D.
Treatment of pediatric epilepsy: European expert opinion, 2007.
Epileptic Disord. 2007;9(4):353-412. PubMed abstract

Zhou P, He N, Zhang JW, Lin ZJ, Wang J, Yan LM, Meng H, Tang B, Li BM, Liu XR, Shi YW, Zhai QX, Yi YH, Liao WP.
Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies.
Genes Brain Behav. 2018;17(8):e12456. PubMed abstract