Lennox-Gastaut syndrome

Other Names: Encephalopathy of childhood; Epileptic encephalopathy Lennox-Gastaut type

Lennox-Gastaut syndrome is a severe condition characterized by recurrent seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, a particular pattern of brain activity (called slow spike-and-wave) measured by a test called an electroencephalogram (EEG), and impaired mental abilities.

In Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures.

Additionally, many affected individuals have episodes called drop attacks, which cause sudden falls that can result in serious or life-threatening injuries.

Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.

Most children with Lennox-Gastaut syndrome have intellectual disability or learning problems even before seizures begin. These problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems.

Cause

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 are caused by an existing neurological abnormality. These cases can be associated with 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 result 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.

In addition, 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.

In about 10 percent of affected individuals, the cause of Lennox-Gastaut syndrome is unknown. These individuals have no history of seizures, neurological problems, or delayed development.

Inheritance

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 mutation 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 in 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.

Diagnosis

The diagnosis of LGS should be suspected in children less than 8 years old with seizures of multiple types that cannot be treated with antiseizure medications. Because of high risk of irreversible brain damage in early stages of syndrome (particularly in infants and young children), early diagnosis is essential. It may take 1–2 years after first initial seizure for all criteria for diagnosis to emerge, so LGS should be considered if there are suggestive signs and symptoms without presence of complete triad.

To confirm diagnosis, awake and asleep EEG and magnetic resonance imaging (MRI) are performed. MRI is used to detect focal brain lesions.

Treatment

There are several treatment options, including medications, surgery, and diet

Surgery

Two studies on LGS patients series who underwent curative surgery in Korea showed very good results, up to seizure freedom for 80% of these patients below 5 years old, and 40% above 5 years old. Like all epilepsy curative surgeries, seizures may recur in the years following surgery, but surgery allows the child to have better brain development during the seizure free period. There are several procedures that have shown efficacy:

• vagus nerve stimulation, which involves implantation of battery-operated generator of intermittent electrical stimuli to an electrode wrapped around left vagus nerve. Some studies have been shown it to have greater than 50% reduction in seizures reported in more than half of patients.
• corpus callosotomy, which has shown to be effective with atonic seizures. This procedure is considered in cases in which vagus nerve stimulation has failed
• transcranial direct current stimulation
• resection

Diet

A ketogenic diet is a diet that causes ketosis, a state in which there is an increased amount of ketones in the body. Adopting and maintaining rigid diet may be difficult for some families. Short-term ketogenic diet might be associated with nonsignificant decreases in frequency of parent-reported seizures in children with LGS.

Medications

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Rufinamide (Brand name: Banzel) Adjunctive therapy of seizures associated with Lennox-Gastaut syndrome
• Cannabidiol (Brand name: Epidiolex) cannabidiol (Epidiolex) was approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older.
• Felbamate (Brand name: Felbatol®)As adjunctive therapy in the treatment of partial and generalized seizures associated with the Lennox-Gastaut syndrome in children.

perampanel (Brand name: Fycompa)Treatment of Lennox-Gastaut Syndrome. Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older and as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

• Lamotrigine (Brand name: Lamictal®)Adjunctive treatment of Lennox-Gastaut syndrome in pediatric and adult patients.
• Topiramate (Brand name: Topamax®)As adjunctive therapy in patients two years and older with siezures associated with Lennox-Gastaut syndrome.

Prognosis

The mortality rate ranges from 3–7% in a mean follow up period of 8.5 to 9.7 years. Death is often related to accidents.

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