Lennox–Gastaut syndrome

Overview

Lennox–Gastaut syndrome (LGS) is a rare and severe form of childhood-onset epilepsy that is characterized by multiple types of seizures, intellectual and developmental disabilities, and distinctive findings on electroencephalograms (EEG). It typically begins between the ages of 1 and 7 years and is known for being difficult to treat. Children with LGS often experience frequent and varied seizure types, including drop attacks (atonic seizures), tonic seizures, and atypical absence seizures, which can significantly impair quality of life and increase the risk of injury.

Causes

Lennox–Gastaut syndrome can be caused by a variety of underlying conditions, but in some cases, no specific cause is identified (idiopathic). Known causes include:

• Brain malformations – congenital abnormalities such as cortical dysplasia or lissencephaly

• Perinatal brain injury – such as hypoxic-ischemic encephalopathy during birth

• Central nervous system infections – including meningitis or encephalitis

• Tuberous sclerosis complex

• Genetic mutations – some cases are associated with mutations in genes like CDKL5 or SCN1A

• Metabolic or degenerative diseases

Symptoms

Children with LGS typically exhibit a combination of seizures and developmental problems. Common signs and symptoms include:

• Multiple seizure types – including:

  • Tonic seizures – stiffening of the muscles, often during sleep

  • Atonic seizures – sudden loss of muscle tone, leading to falls (“drop attacks”)

  • Atypical absence seizures – brief periods of staring and unresponsiveness

  • Myoclonic and generalized tonic-clonic seizures

• Developmental delays or regression – affecting speech, cognition, and motor skills

• Behavioral problems – including hyperactivity, aggression, or autistic traits

• Abnormal EEG patterns – slow spike-and-wave discharges during wakefulness and bursts of fast activity during sleep

Diagnosis

Diagnosing Lennox–Gastaut syndrome involves a thorough clinical evaluation, neurological assessments, and diagnostic testing. Key components of the diagnostic process include:

• Detailed seizure history – evaluating the frequency, type, and onset of seizures

• Electroencephalogram (EEG) – showing characteristic slow spike-and-wave patterns (<2.5 Hz) and generalized paroxysmal fast activity during sleep

• Magnetic Resonance Imaging (MRI) – to detect structural brain abnormalities

• Genetic and metabolic testing – especially when no structural cause is found

• Neurodevelopmental assessment – to evaluate cognitive and motor development

Treatment

Treatment of Lennox–Gastaut syndrome is challenging due to its drug-resistant nature. A comprehensive, multidisciplinary approach is required, including:

• Antiseizure medications (ASMs) – such as valproic acid, lamotrigine, clobazam, rufinamide, or topiramate

• Cannabidiol (CBD) – FDA-approved for use in LGS (e.g., Epidiolex)

• Ketogenic diet – a high-fat, low-carbohydrate diet that can reduce seizure frequency in some patients

• Vagus nerve stimulation (VNS) – a device implanted to help reduce seizures through electrical impulses

• Corpus callosotomy – a surgical procedure for severe drop attacks when other treatments fail

• Supportive therapies – including physical therapy, occupational therapy, special education, and behavioral therapy

Prognosis

The prognosis for individuals with Lennox–Gastaut syndrome is generally guarded. Most patients continue to have seizures into adulthood, and developmental and intellectual disabilities often persist. While seizure control may improve with age or treatment, complete seizure freedom is rare. Early diagnosis, aggressive seizure management, and supportive care can improve quality of life. Lifelong care is usually required, and multidisciplinary support plays a critical role in maximizing developmental potential and functional independence.