Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome is a severe form of childhood epilepsy that causes multiple types of seizures, developmental delays, and lasting disabilities. While there is no cure, various treatments can help control symptoms and improve quality of life.

Table of contents

• What is Lennox-Gastaut syndrome?
• What causes this condition?
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• What to expect over time

What is Lennox-Gastaut syndrome?

Lennox-Gastaut syndrome is a severe form of epilepsy, which is a condition that causes seizures. Epilepsy happens when the brain cells that send signals to each other stop working properly^[1]. Seizures begin in early childhood, usually before the age of 4 years, with most cases starting between ages 3 and 5^[1][2].

This syndrome is rare, affecting an estimated 1 to 2 people per million worldwide^[3]. It accounts for about 3 to 4 percent of all cases of epilepsy in children and 1 to 2 percent in adults^[3]. For reasons that are not fully understood, the condition appears to be slightly more common in males than in females^[2][3].

The condition was named after two doctors, William G. Lennox from Boston and Henri Gastaut from France, who each described it independently^[6].

What causes this condition?

Lennox-Gastaut syndrome can have many different causes. The disorder likely has a genetic component, although the specific genetic factors are not well understood^[3]. In about 70 percent of cases, doctors can identify a specific cause^[5].

Most cases develop from an existing problem in the brain. These problems can include injuries that occur before or during birth, problems with blood flow in the developing brain, brain infections, or other disorders affecting the nervous system^[3].

Common causes include^[1]:

• Brain malformations or differences in how the brain formed
• Tuberous sclerosis, a genetic condition that causes noncancerous tumors to grow in the body
• Severe lack of oxygen during birth (perinatal asphyxia)
• Severe head injury
• Central nervous system infection
• Inherited genetic and metabolic conditions

Many people with Lennox-Gastaut syndrome have a history of epilepsy beginning in infancy, such as infantile spasms or West syndrome, before developing the features of Lennox-Gastaut syndrome^[3][6]. It is not clear why these conditions sometimes evolve into Lennox-Gastaut syndrome^[3].

In 30 to 35 percent of cases, no cause can be found^[1].

Signs and symptoms

Children, adolescents, and adults with Lennox-Gastaut syndrome have multiple types of seizures that vary among individuals. The condition is identified by three main features: multiple seizure types, specific patterns seen on a brain wave test called an electroencephalogram (EEG), and problems with learning and development^[1][4].

Types of seizures

People with this syndrome experience several different types of seizures. Common seizure types include^[1][2]:

• Tonic seizures cause stiffening of the body, upward eye gaze, enlarged pupils, and changes in breathing patterns. These are the most common type and occur in nearly everyone with this condition. They happen most often during sleep^[6].
• Atypical absence seizures appear as staring spells where the person seems to lose awareness of their surroundings
• Atonic seizures cause a brief loss of muscle tone, which can lead to sudden falls. These are sometimes called “drop attacks”
• Myoclonic seizures cause sudden muscle jerks
• Generalized tonic-clonic seizures involve muscle stiffness followed by rhythmic jerking movements

Seizures can cause sudden falling, often leading to injury. These drop attacks are typically the first sign of Lennox-Gastaut syndrome^[6]. Many children must wear protective helmets to prevent head injuries^[4].

There may be periods of frequent seizures mixed with relatively seizure-free periods^[1]. About half of patients experience nonconvulsive status epilepticus, which means having very long seizures or many seizures in a row without fully recovering between them^[6].

Developmental and behavioral challenges

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^[1]. About one-third of people have normal intellectual development before seizures begin, but the remainder have intellectual disability or learning problems even before seizures arise^[3].

Intellectual problems may worsen over time, particularly if seizures are very frequent or severe^[3]. Some affected children develop additional problems with movement and balance, as well as behavioral issues^[3]. Many are also slow to develop motor skills such as sitting and crawling^[3].

Children with this condition usually struggle with learning, making friends, and communicating with others. They may also have trouble controlling emotions^[2].

How is it diagnosed?

The appearance of multiple types of seizures in early childhood is a key sign of Lennox-Gastaut syndrome. Diagnosis is based on three features: multiple seizure types beginning in childhood, specific brain wave patterns, and developmental delays or intellectual disability^[4][5].

Brain wave testing

A particular pattern of brain electrical activity can be seen using an electroencephalogram (EEG)^[1]. The EEG can record unusual spikes or waves in electrical activity patterns^[8]. Findings that strongly suggest this syndrome include abnormal, slow spike-wave patterns (less than 3 waves per second) on awake EEG^[6]. The EEG also shows a specific pattern called generalized paroxysmal fast activity during sleep^[4].

Other tests

Doctors may use brain imaging tests such as magnetic resonance imaging (MRI) to look for structural problems in the brain^[8]. Blood tests may be used to rule out other medical conditions that might be causing the seizures, such as infections, abnormal chemical levels in the blood, or genetic conditions^[8].

Genetic testing may be helpful in some cases to identify inherited causes^[5].

Treatment options

Lennox-Gastaut syndrome can be very difficult to treat. The seizures often resist treatment with medications^[1][2]. A combination of seizure medications and other treatments may be used to improve seizure control and other associated conditions^[1].

Medications

The medication valproate is generally considered a first-line therapy for various seizure types^[1]. Other medications that may be used include clobazam, felbamate, lamotrigine, rufinamide, topiramate, and cannabidiol^[1].

The U.S. Food and Drug Administration approved cannabidiol (Epidiolex, derived from marijuana) for the treatment of seizures associated with Lennox-Gastaut syndrome in individuals ages 2 and older. The drug contains only a small amount of the psychoactive element in marijuana and does not cause the feeling of being “high” associated with the drug^[1].

It is common that multiple medications are necessary, and while they can help this condition, it is rare that medications alone can completely stop seizures^[2]. Children who improve initially may later show tolerance to a drug or continue to have uncontrollable seizures^[1].

Dietary therapy

The ketogenic diet is a high-fat, low-carbohydrate diet that can reduce seizures in some people with epilepsy^[1]. This special diet may be useful in patients whose seizures do not respond to medical treatment^[4].

Device-based treatments

Vagus nerve stimulation is a treatment where a small device is implanted under the skin that sends electrical signals to the brain through a nerve in the neck^[1].

Surgery

Epilepsy surgery may be an option for some people. A corpus callostomy is the most common surgical procedure for this condition. It involves severing the band of nerve fibers that connect the two halves of the brain to prevent seizures from spreading^[1]. In some cases, other types of surgery may be considered if there is a specific area of the brain causing the seizures^[4].

Medication may be combined with these other treatments to optimize seizure control^[1].

What to expect over time

The prognosis for individuals with Lennox-Gastaut syndrome varies^[1]. As a result of their seizures and intellectual disability, most people with this condition require help with daily activities. However, a small percentage of affected adults can live independently^[3].

Around 80 to 90 percent of children continue to have seizures into adulthood^[4]. The condition typically continues throughout life, though the types of seizures may change over time^[7].

People with Lennox-Gastaut syndrome have a higher risk of death than others of the same age^[3]. The overall mortality rate is around 5 percent, though it is partly due to poorly controlled seizures, pneumonia resulting from inhaling saliva during a seizure (aspiration pneumonia), and injuries from falls^[3]. In addition, individuals with this 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^[3].

Despite these challenges, there are more treatment options available today than in the past. New medications and therapies are providing people with this condition more options and hope for better seizure control and quality of life^[4].