Lennox-Gastaut syndrome is a severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.

In people with Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures typically occur during sleep; they may also occur during wakefulness. Also common are atonic seizures, which are caused by a sudden loss of muscle tone. Tonic and atonic seizures can cause sudden falls that can result in serious or life-threatening injuries. Additionally, many affected individuals have atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome. Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.

Although each seizure episode associated with Lennox-Gastaut syndrome is usually brief, more than two-thirds of affected individuals experience prolonged periods of seizure activity (known as status epilepticus) or episodes of many seizures that occur in a cluster.

About one-third of people with Lennox-Gastaut syndrome have normal intellectual development before seizures begin. The remainder have intellectual disability or learning problems even before seizures arise. Intellectual problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many are also slow to develop motor skills such as sitting and crawling. As a result of their seizures and intellectual disability, most people with Lennox-Gastaut syndrome require help with daily activities. However, a small percentage of affected adults can live independently.

People with Lennox-Gastaut syndrome have a higher risk of death than their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures, pneumonia resulting from inhaling saliva (aspiration pneumonia) during a seizure, and injuries from falls. In addition, individuals with Lennox-Gastaut syndrome are at risk of sudden unexpected death in epilepsy (SUDEP), which describes sudden death with no known cause in someone with epilepsy; it is not the direct result of a seizure.

What is Lennox-Gastaut syndrome?

Lennox-Gastaut syndrome is a severe form of epilepsy. Seizures begin in early childhood, usually before the age of 4 years.

Children, adolescents, and adults with Lennox-Gastaut syndrome have multiple types of seizures that vary among individuals. Common seizure types include:

• Tonic seizures (stiffening of the body, upward eye gaze, dilated pupils, and altered breathing patterns)
• Atypical absences (staring spells)
• Atonic seizures (brief loss of muscle tone, which could cause abrupt falls)
• Myoclonic seizures (sudden muscle jerks)
• Generalized tonic-clonic seizures (muscle stiffness and rhythmic jerking)

There may be periods of frequent seizures mixed with relatively seizure-free periods. Although not always present at the onset of seizures, most people living with Lennox-Gastaut syndrome experience some degree of impaired intellectual functioning or information processing, along with developmental delays and behavioral disturbances. A particular pattern of brain electric activity can be seen using electroencephalogram (EEG).

Lennox-Gastaut syndrome can be caused by a variety of conditions, including:

• Brain malformations
• Tuberous sclerosis
• Perinatal asphyxia
• Severe head injury

• Central nervous system infection
• Inherited genetic and inherited degenerative or metabolic conditions

No cause can be found in 30 to 35 percent of individuals and Lennox-Gastaut syndrome can be very difficult to treat. A combination of seizure medications and other treatments may be used to improve seizure control and other associated conditions.

The medication valproate is generally considered a first-line therapy for various seizure types. Other anticonvulsant medications may include clobazam, felbamate, lamotrigine, rufinamide, topiramate, and cannabidiol. The U.S. Food and Drug Administration (FDA) approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Lennox-Gastaut syndrome in individuals ages 2 and older. The drug contains only small amount of the psychoactive element in marijuana and does not induce euphoria associated with the drug.

Other treatment options include:

• Dietary therapy with the ketogenic diet
• Vagus nerve stimulation
• Epilepsy surgery (typically a corpus callostomy, which involves severing the band of nerve fibers that connect the two halves of the brain to prevent seizures from spreading)

Medication may be combined with the other treatments to optimize seizure control. Children who improve initially may later show tolerance to a drug or have uncontrollable seizures.

The prognosis for individuals with Lennox-Gastaut syndrome varies. There is no cure for the disorder. Complete recovery, including freedom from seizures, is very rare.

Lennox-Gastaut syndrome can have many different causes. The disorder likely has a genetic component, although the specific genetic factors are not well understood.

Most cases of Lennox-Gastaut syndrome develop from an existing neurological abnormality. These cases maybe be caused by brain injuries that occur before or during birth, problems with blood flow in the developing brain, brain infections, or other disorders affecting the nervous system. The condition can also arise from brain malformations such as forms of cortical dysplasia, which are abnormalities in the outer surface of the brain (cerebral cortex). Many people with Lennox-Gastaut syndrome have a history of epilepsy beginning in infancy (infantile spasms) or a related condition called West syndrome before developing the features of Lennox-Gastaut syndrome. It is not clear why these neurological abnormalities evolve into Lennox-Gastaut syndrome.

In addition, variants (also called mutations) in several genes have been associated with Lennox-Gastaut syndrome, each in a small number of affected individuals. These genes are involved in the function of nerve cells in the brain, but it is unclear how changes in them contribute to the development of Lennox-Gastaut syndrome. The condition can also occur as part of a genetic disorder, such as tuberous sclerosis complex.

Most cases of Lennox-Gastaut syndrome are sporadic, which means they occur in people with no history of the disorder in their family. When Lennox-Gastaut syndrome is associated with a genetic change, the variant is usually not inherited but occurs as a random (de novo) event during the formation of reproductive cells (eggs or sperm) in an affected person's parent or during early embryonic development. However, 3 to 30 percent of people with this condition have a family history of some type of epilepsy, indicating that inherited genetic factors may play a role in some cases of Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome affects an estimated 1 to 2 per million people worldwide. This condition accounts for 3 to 4 percent of cases of epilepsy in children and 1 to 2 percent of cases in adults. For unknown reasons, it appears to be more common in males than in females.