Lennox-Gastaut syndrome

Synonyms

1

Overview

Lennox–Gastaut syndrome (LGS) is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life. LGS is characterized by a triad of signs including frequent seizures of multiple types, an abnormal EEG pattern of less than 2.5 Hz slow spike wave activity, and moderate to severe intellectual impairment.

Symptoms

Children with LGS have frequent and severe seizures. And they often have different kinds of seizures, including:

• Atonic seizures: Also called "drop attacks," because the person loses muscle tone and can fall to the ground. Their muscles may jerk. These seizures are brief, usually lasting a few seconds.
• Tonic seizures: These seizures cause the person's body to stiffen and can last for a few seconds to a minute. They usually happen when the person is asleep. If they happen when the person is awake, they can cause falls. Like atonic seizures, they are also called drop attacks.
• Absence seizures: During these seizures, a person may have a blank stare or nod their head or blink quickly.

In some children, the first sign of LGS is an ongoing seizure that lasts 30 minutes, or continuous seizures without full recovery between them. This is called status epilepticus, and it is a medical emergency. 
Other signs may be:

• Lower reaction time
• Learning deficiency
• Behavioral problems

Causes

There is no uniform cause: in 20% of those concerned, the LGS develops from West syndrome. The medical history frequently includes infantile spasms or focal and generalized seizures.

The most common type of LGS (70–78%) is symptomatic (secondary) - that is an identifiable underlying pathology. This includes encephalopathy (brain damage) or another disease and/or developmental disorder. Frequent causes include tuberous sclerosis, hereditary metabolic diseases, inflammatory brain disease such as encephalitis, meningitis, and toxoplasmosis; hypoxia–ischemia injury and other birth injuries; and lesions of the frontal lobe. These patients tend to have a worse prognosis than those with idiopathic LGS.

Progress in genome and exome sequencing is revealing that some individuals diagnosed with Lennox Gastaut Syndrome have de novo mutations in a variety of genes, including CHD2, GABRB3, ALG13 and SCN2A The Epi4K study consortium (2013) observed de novo mutations in at least 15% of a study cohort of 165 patients with LGS and Infantile Spasms using whole exome sequencing. A 2013 study by Lund and colleagues found a high frequency of rare Copy Number Variants (CNV's) in adult patients with LGS or LGS-like epilepsy.

In up to one-third of cases no cause can be found.

Lennox–Gastaut syndrome and drug resistant/drug refractory epilepsy have been recorded with neurovisceral porphyrias including acute intermittent porphyria, hereditary coproporphyria and variegate porphyria. Care must be taken to avoid porphyrinogenic anti-seizure drugs in these cases. Diagnosis may be difficult in children who require enzyme or DNA testing.

Prevention

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Diagnosis

The diagnosis or suspicion of LGS is often a question of probability rather than certainty. This is because the varied presentations of LGS share features with other disorders, many of which may be said to have overlapping characteristics.

The diagnosis is more obvious when the epilepsy has frequent and manifold attacks, with the classic pattern on the electro-encephalogram (EEG); the latter is a slowed rhythm with Spike-wave-pattern, or with a multifocal and generalizing Sharp-slow-wave-discharges at 1.5–2.5 Hz. During sleep, frequently, tonic patterns can be seen. But variations of these patterns are known in patients with no diagnosis other than LGS, and they can differ bilaterally, and from time to time, within the same patient.

General medical investigation usually reveals developmental delay and cognitive deficiencies in children with true LGS. These may precede development of seizures, or require up to two years after the seizures begin, in order to become apparent.

Exclusion of organic or structural brain lesions is also important in establishing a correct diagnosis of LGS; this may require magnetic resonance imaging (MRI) or computerized tomography (CT). An important differential diagnosis is 'Pseudo-Lennox-Syndrome', which differs from LGS, in that there are no tonic seizures; sleeping EEG provides the best basis for distinguishing between the two.

Prognosis

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

People with Lennox-Gastaut syndrome have an increased risk of death compared to their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures and injuries from falls.

Treatment

Doctors may prescribe a variety of drugs to treat seizures from LGS. The goal is to reduce the number of seizures with medication that causes the fewest side effects. There is usually no single antiepileptic medication that will control seizures. Children who improve initially may later show tolerance to a drug or have uncontrollable seizures. 

Antiepiletic Drugs (AEDs) approved by the FDA as adjunctive treatment in patients with siezures associated with Lennox-Gastaut syndrome:

• Clobazam (Onfi)
• Felbamate (Felbatol)
• Rufinamide (Banzel)
• Topiramate (Topamax)
• Lamotrigine (Lamictal)

Usually, no single medication controls seizures completely. The doctor will monitor your child's medication closely, especially if your child takes more than one at a time.

Other treatments:
Surgical:

• vagus nerve stimulation
• corpus callosotomy

Ketogenic diet:

Resources

Refer to Resource Publications.