What are the other Names for this Condition? (Also known as/Synonyms)

• Epilepsy with Myoclonic Absences due to Lennox-Gastaut Syndrome
• Infantile Spasms due to Lennox-Gastaut Syndrome
• LGS (Lennox-Gastaut Syndrome)

What is Lennox-Gastaut Syndrome? (Definition/Background Information)

• Lennox-Gastaut Syndrome (LGS) is a rare and severe form of epilepsy that mostly affects individuals during infancy or early childhood
• Epilepsy is a term to describe a group of neurological disorders characterized by seizures, loss of consciousness, convulsions, and spasms. There are various types of seizures associated with LGS, including tonic, atonic, atypical absence, and more
• Symptoms of Lennox-Gastaut Syndrome typically begin to appear between ages of 3 and 6 years, and as children become older, the seizures experienced can become different. In addition to seizures, children with LGS can also suffer from impaired intellectual functioning, delays in development, and behavioral problems
• Although the underlying mechanism of how Lennox-Gastaut Syndrome is able to cause seizures is not known, common causes of LGS include developmental malformations in the brain, lack of oxygen during birth, or infection of the central nervous system. In majority of the cases, the cause of LGS is known; however, for about 20-30% of the patients, the exact cause cannot be identified
• The treatment of Lennox-Gastaut Syndrome needs a team of healthcare professionals. It is undertaken through the use of anti-epileptic drugs (AEDs), ketogenic diet, and surgery, which may include vagus nerve stimulation therapy or corpus callosotomy
• The prognosis depends on multiple factors and the response of LGS to treatment. The prognosis of Lennox-Gastaut Syndrome is generally guarded

Who gets Lennox-Gastaut Syndrome? (Age and Sex Distribution)

• The number of Lennox-Gastaut Syndrome cases per year is estimated to be 2 per 100,000 children
• LGS is responsible for approximately 2-4% of all childhood epilepsy cases. In addition, peak age of onset in children is typically between 3 and 6 years
• Although the symptoms of the disorder first appear during infancy or early childhood, the condition can persist through childhood, adolescence, and adulthood
• LGS is found slightly more often in male children than female children

What are the Risk Factors for Lennox-Gastaut Syndrome? (Predisposing Factors)

The risk factors of Lennox-Gastaut Syndrome may be described as follows:

• One risk factor associated with Lennox-Gastaut Syndrome is having a history of infantile spasms. Approximately 17-30% of individuals with LGS have had a prior history of infantile spasms. Infantile spasms are seizures characterized by sudden jerky movements in the head and neck, uncontrollable movements in the arms and legs, and stiffening of the muscles
• About 20-30% of children with LGS, however, do not show any neurological deficits or developmental problems, before or at the time of onset. The symptoms associated with LGS become apparent as the disorder evolves

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Lennox-Gastaut Syndrome? (Etiology)

In about 70-80% of cases, the cause of Lennox-Gastaut Syndrome is known. Common causes include:

• Brain malformations
• Congenital infections
• Stroke
• Trauma
• Reduced oxygen supply before birth (perinatal hypoxia)
• Infections of the central nervous system (encephalitis, meningitis)
• Tuberous sclerosis (a genetic disorder)

In about 20-30% of the cases, the origin of the disorder cannot be identified.

• In addition, approximately 17-30% of Lennox-Gastaut Syndrome patients have a prior history of infantile spasms. Individuals with a history of infantile spasms often have a more severe prognosis with LGS
• Currently, the mechanisms responsible for triggering the various types of seizures in LGS patients are not known
• Moreover, there has not been any discovery of genes linked to LGS and its symptoms

What are the Signs and Symptoms of Lennox-Gastaut Syndrome?

There are different seizure types associated with Lennox-Gastaut Syndrome; affected children typically begin experiencing these symptoms, when they are between 3 and 6 years old. Most LGS-affected children suffer from more than one type of seizure, multiple times per day.

Tonic seizures:

• These are the most common type of Lennox-Gastaut Syndrome -linked seizures and are characterized by a continuous increase in muscle contractions
• Often lasting anywhere between a few seconds to minutes, these sustained contractions lead to muscle stiffness, symptoms of which include a bend in the body and short interruptions in one’s breathing
• Muscles spasms in the face leading to grimacing and problems with the flexion or extension of the arms and legs are also experienced by individuals with LGS
• Tonic seizures typically occur at night during one’s sleep. Sometimes, they can go unnoticed because they last for a short period of time
• However, this type of seizure can also happen during the day; typically, a short loss of consciousness can accompany the seizure causing patients to fall (drop attacks) 

Atonic seizures:

• These are also experienced by the affected individuals
• These bring about loss of muscle tone and limpness. If walking, individuals can suddenly fall down, or if seated, atonic seizures can lead children to fall forward or backwards. Limpness can sometimes occur only in the head, causing the head to drop or nod
• Also called drop attacks, atonic seizures typically last a few seconds but can result in injuries to the head and face due to the sudden falls

Atypical absence seizures:

• Another type of seizure associated with LGS is atypical absence seizures, which are characterized by a short loss of consciousness and a period of unresponsive staring
• Lasting several seconds, these seizures can sometimes go unnoticed, especially if the child is already experiencing a delayed development

With Lennox-Gastaut Syndrome, there are several other, less frequently occurring types of seizures.

• In partial-onset seizures, children with LGS gradually lose muscle tone and awareness. These can last anywhere between 30 and 60 seconds, and can lead to myoclonic seizures. Myoclonic seizures consist of sporadic, jerky movements
• Tonic-clonic seizures, lasting a couple minutes, are represented by stiffened limbs, as seen with tonic seizures, followed by a clonic phase involving the jerking of the arms and legs
• Non-convulsive status epilepticus is a form of seizure that involves an individual undergoing a series of seizures for at least 30 minutes. It can involve a combination of seizure types, including tonic and atypical
• Status epilepticus requires medical intervention, as children can take days or weeks to recover

Other symptoms of Lennox-Gastaut Syndrome include:

• Impaired intellectual functioning
• Developmental delays, including not being able to walk, sit, or crawl
• Behavioral problems
• Loss of previously learned skills

Although Lennox-Gastaut Syndrome initially appears during infancy or early childhood, it persists as children grow older and the nature and frequency of seizures may be altered. Impaired intellectual functioning persists, as does behavioral changes, such as irritability, aggressiveness, psychotic episodes, psychosis, personality changes, and social isolation. 

How is Lennox-Gastaut Syndrome Diagnosed?

Lennox-Gastaut Syndrome is generally diagnosed upon the presence of 3 particular factors. These factors are:

• The presence of multiples seizures of various types
• A specific electroencephalography (EEG) pattern called the slow spike-and-wave
• Intellectual impairment or developmental delays

However, diagnosing LGS is a difficult task because not all of these factors may be present at the very start of the disorder. Moreover, tonic seizures, which often occur at night, may not always be identified.

• A diagnosis of Lennox-Gastaut Syndrome requires a physical examination, a close evaluation of the patient history and seizure activity, as well as a complete neurological evaluation
• Magnetic resonance imaging (MRI) and electroencephalography (EEG) are both tools that can be used in diagnosing LGS
• A MRI can produce a three-dimensional image of the brain to study its structure and the activities occurring within it
• An EEG is useful in studying the electrical activity in the brain to detect any abnormalities. In individuals with LGS, a specific slow spike-and-wave pattern will be revealed

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Lennox-Gastaut Syndrome?

The possible complications associated with Lennox-Gastaut Syndrome include:

• Injuries due to sudden falls during seizures
• About 90% of children with LGS have some form of mental retardation
• Approximately 50% have cerebral palsy
• Medication side effects

How is Lennox-Gastaut Syndrome Treated?

Lennox-Gastaut Syndrome is a difficult condition to treat, as it is resistant to various anti-seizure medications. However, there are 3 forms of treatment that can be used, which include:

• Anti-epileptic drugs (AEDs)
• Ketogenic diet
• Surgery that includes vagus nerve stimulation therapy or corpus callosotomy

Anti-epileptic drugs (AEDs):

• Because LGS patients experience several different types of seizures, more than one anti-epileptic drug (AED) may be prescribed
• The purpose of these medications is to control the seizures that occur
• AEDs are categorized as monotherapy and adjunctive (add-on) medications
• Monotherapy drugs can be given alone, while adjunctive medications need to be administered along with other drug

There are different side effects for different drugs, and not all affected individuals respond in the same way. The potential side effects become especially important, if an individual is taking multiple types of AEDs. Moreover, some AEDs can become less effective over time.

Ketogenic diet:

• The ketogenic diet is another treatment option, especially when affected children no longer respond to medication therapy
• It consists of a high-fat, low-protein, and low-carbohydrate diet that force the body to burn fat, instead of sugar for energy
• This diet has been shown to help reduce the number of seizures and appears to be most effective against atonic, atypical absence, and myoclonic seizures
• However, this treatment method has side effects, including dehydration, renal stones, metabolic acidosis, and cardiac abnormalities
• The success of the ketogenic diet strongly depends on the home environment and the strict commitment of families, as children can only eat what is specified for the ketogenic diet
• The ketogenic diet may be successful for some individuals, but not others. If successful, the ketogenic diet is continued for two years or more if needed

Surgery: Surgical therapies are another potential treatment option for children with Lennox-Gastaut Syndrome. There are two common surgical options: Vagus nerve stimulation (VNS) therapy and corpus callosotomy

Vagus nerve stimulation (VNS) therapy:

• VNS involves inserting a device called a pulse generator into the chest of an individual
• This pulse generator is able to send electrical impulses to the brain by way of the vagus nerve, which is a large nerve located in the neck
• This procedure, taking about 50-90 minutes long, helps prevent seizures from occurring
• The timing and intensity of the electrical impulses can be adjusted
• Side effects of VNS include hoarseness in the voice, tickling in the throat, and coughing during stimulation

Corpus callosotomy:

• It is a procedure done to cut the corpus callosum connecting the two hemispheres of the brain. The corpus callosum is a bundle of nerves between the two halves of the brain that allow each to share information with the other
• The purpose of corpus callosotomy is to help reduce generalized seizures and is most effective against atonic (drop attack) seizures
• This procedure will still result in seizure activity in one or both sides of the brain, but the overall severity of the seizures is reduced

It is important for families of affected children to collaborate with healthcare professionals, including pediatricians, neurologists, surgeons, and pediatric neurologists.

• Lennox-Gastaut Syndrome patients need a treatment plan that takes into account seizure emergencies and what should be done if a dosage of medication is missed
• Because the types and frequency of seizure activity can change throughout an affected individual’s life, the treatment plan will most likely be changed often
• Furthermore, revision of the treatment plan is also dependent on the child’s response to certain treatments as well as the presence or absence of side effects

How can Lennox-Gastaut Syndrome be Prevented?

There are no identified methods to prevent the onset of Lennox-Gastaut Syndrome, because the mechanism of how LGS triggers seizures is not yet known.

What is the Prognosis of Lennox-Gastaut Syndrome? (Outcomes/Resolutions)

• The prognosis for Lennox-Gastaut Syndrome varies from case to case. Nevertheless, for individuals affected with LGS, being seizure-free and having a normal development is very unusual
• Currently, there is no cure for LGS, but there are several treatment options available, including anti-epileptic drugs (AEDs), the ketogenic diet, vagus nerve stimulation therapy, and corpus callosotomy
• Affected individuals with a past history of infantile spasms have a much more severe prognosis for LGS, than compared to those who did not have infantile spasms

Additional and Relevant Useful Information for Lennox-Gastaut Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/