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

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.

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

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

• 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.

Diagnostic Criteria and Classifications

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

Genetics

Incidence and Prevalence

Differential Diagnosis

Comorbid Conditions

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.

Neurology

Family

Pediatric Neurology (see NM providers [5])
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 NM providers [34])
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.

• Safety Precautions for Children with Seizures
• Seizure Disorders (FAQ)
• Lennox-Gastaut Syndrome (KidsHealth)

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