Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy. Epilepsy is a seizure disorder. LGS usually begins in the preschool years. However, it can start later in childhood.
LGS is a developmental and epileptic encephalopathy, or DEE. This means two things:
- Persons with LGS have developmental and behavioral problems as well as epilepsy
- These problems are often worsened by seizures and seizure activity
Persons with LGS have several seizure types.
A diagnosis of LGS can be supported by an electroencephalogram, or EEG.
LGS can be due to a wide range of causes.
LGS may develop in children without a history of epilepsy. It may also evolve from another type of epilepsy.
Anything that affects the brain at a critical time in its development can result in learning problems and seizures. In some cases, the exact cause of LGS is unknown.
The core features of LGS include:
- Multiple seizure types
- Seizures continue despite medication
- Particular EEG pattern
- Intellectual disability
Severity differs to some degree between patients. However, LGS is considered very severe.
LGS is a lifelong form of epilepsy. Therapies may help. However, they do not completely stop seizures. Persons with LGS have varying degrees of intellectual disability and behavioral issues. Some struggle with aggression. Some meet autism spectrum disorder criteria.
Many with LGS survive into late adulthood. However, there is an increased risk of early death known as Sudden Unexpected Death in Epilepsy (SUDEP). This is due to seizure complications. In addition, those with severe neurological disability may have limited mobility and have difficulty swallowing. This increases risk of infection, such as aspiration pneumonia. The limited mobility can also result in falls and injuries with seizures
SIGNS AND SYMPTOMS
Age of Onset
LGS usually develops in the preschool years.
In about one in four cases, it evolves from another type of epilepsy. In these cases, it usually evolves from an epilepsy that starts very early in life. LGS most commonly evolves from infantile spasms or West syndrome.
It usually takes time for all features of LGS to appear. Therefore, it can be challenging to accurately diagnose the disease early in childhood.
Seizure Types Seen in LGS
Persons with LGS have several types of seizures. These can include:
- Tonic seizure. This is the most common type in LGS. They consist of neck, and sometimes arm and leg, stiffening. They often involve eye opening and upward eye rolling. They often occur in sleep. They can be subtle and easily missed. An overnight-video laboratory test can reliably detect them. If they occur in the day, while a child is upright, they can result in a fall.
- Atypical absence seizure. This type consists of brief blank-outs where a child is less aware.
- Atonic seizure. In atonic seizure, a child abruptly loses body tone and slumps. If these occur while sitting, they can look like a quick head nod. If they occur while upright, they can lead to abrupt falls and injury.
- Myoclonic seizure. These consist of isolated, brief body jerks.
- Focal impaired awareness seizure. These typically begin with staring and altered awareness. This lasts up to several minutes and are followed by a period of confusion. These seizures can progress into generalized tonic-clonic seizures.
- Generalized tonic-clonic seizure. These consist of generalized stiffening and rhythmic shaking.
Other Symptoms of LGS
Persons with LGS nearly always have intellectual disability. It may be mild in earlier childhood. However, those with LGS often gain developmental skills more slowly. They may have moderate to severe intellectual disability by adolescence. Behavioral differences are also common. They become more of a problem with age. Behavioral issues include:
- Autism spectrum disorder
Motor and Mobility Difficulties
Most children with LGS also have motor difficulties. These include:
- Problems with balance and coordination. This is a common motor difficulty.
- Problems with feeding and swallowing. A small number require a feeding tube.
Limited mobility and frequent seizures can also mean a higher risk of infections such as pneumonia.
Sleep problems are common in those with LGS.
Risk of Death
Children with LGS are at higher risk of death. This is for several reasons:
- Sudden Unexpected Death in Epilepsy (SUDEP). This is a major concern in LGS. The exact cause of SUDEP is not well understood. However, it may be related to post-seizure heart and breathing issues. Those with frequent convulsive seizures are at the highest risk.
- Infection. Lower mobility can lead to infection. Pneumonia is an example.
- Accidental injury. Seizures, particularly atonic or tonic seizures, may cause falling and injury.
In LGS, the brain is affected at a critical time in its development. Learning problems and seizures result. There are many causes of LGS. LGS is not anyone’s fault. It is highly unlikely anyone can prevent the condition.
In most but not all cases, a cause can be found. Finding it can take extensive testing. In some cases, more than one cause is found.
Structural Brain Differences
An altered brain structure is the most common cause of LGS. MRI, or magnetic resonance imaging, can detect altered brain structure. Brain structure can be affected by:
Abnormal development. This occurs when the baby is still in the womb. Often, the cause of it is unknown. However, it can result from:
- Infection during pregnancy
- Genetic abnormality
Brain injury early in life. Various types of brain injury early in life can result in LGS:
- Low oxygen or blood flow to the brain
- Brain infection
- Traumatic brain injury
- Early brain radiation
Genetic differences are important causes of early-childhood epilepsy. Some types of genetic changes result in abnormal brain development that can be seen on MRI.
In other cases, genetic causes result in changes that occur at a microscopic level. This can change how the brain functions. In these cases, the brain MRI is usually normal.
Several lab tests can look for genetic causes. However, genetic testing can have implications for relatives. Therefore, families should receive counseling prior to genetic testing.
Metabolic causes of LGS are rare. Still, they are important to consider. There are many types of metabolic disorders. They usually relate to difficulty breaking down nutrients in the body. They cause symptoms due to:
- A lack of an essential nutrients to keep brain cells healthy
- A toxic buildup that results in brain cell dysfunction
Some of these conditions have specific treatments. Early recognition can prevent further brain injury. Metabolic disorders can be diagnosed with lab tests. These usually include blood, urine, and spinal fluid tests. Some can be detected in genetic tests.
Infections are a rare cause of LGS.
- Prenatal infection. Viruses can infect the fetus during pregnancy. Blood tests and eye exams can usually detect prenatal infection.
- Brain infection early in life. Brain infections can lead to brain injury and a severe seizure disorder like LGS.
Some epilepsies result from the body creating abnormal proteins or antibodies. They can cause injury to the brain. This is an exceedingly rare cause of LGS. When seizures begin suddenly following illness or vaccination, this can be considered. It is detected in blood and spinal fluid tests.
There are several useful ways to investigate LGS:
EEG and Diagnosing LGS
An electroencephalogram, or EEG, is a type of medical test. It measures the electrical activity of the brain. Those with LGS will have an abnormal EEG result. Several typical electrical patterns are seen in most children with LGS.
The top two are known as:
- Generalized paroxysmal fast activity
- Generalized slow-spike and wave discharge
MRI, or magnetic resonance imaging, can find structural causes of LGS. This may guide treatment decisions. MRI can detect:
- Cortical malformations
- Tuberous sclerosis
- Acquired brain injury
There is no characteristic MRI pattern for LGS. The MRI may be normal.
MRI scans are not all the same. An epilepsy-protocol MRI read by an experienced epilepsy neuroradiologist increases the likelihood of detecting an abnormality if one is present.
Sometimes, an MRI does not provide a cause. In these cases, a genetic test is recommended. These include:
- Epilepsy gene panel. This is one of the most common genetic tests for epilepsy. It looks for many different genes associated with epilepsy.
- Chromosomal microarray. This evaluates extra or missing pieces of a chromosome.
- Whole exome sequencing. This can be ordered by a genetics specialist. It evaluates the entire DNA code. It looks for changes in genes associated with epilepsy. Usually, it requires a child and both parents to be tested.
Other Lab Testing
Other tests can look for metabolic, infectious, and autoimmune causes of LGS:
- Blood tests
- Urine tests
- Spinal fluid tests
Repeating testing or imaging in older LGS patients can be useful. It can help when an underlying cause has not been determined. It can identify previously missed causes. However, it is not necessary in all cases. Sometimes, genetic testing can be reviewed rather than repeated as knowledge about genetics grows.
Insurance generally covers most tests listed above.
Genetic testing coverage varies by state and insurance provider.
There are several ways to treat LGS.
Medications can treat LGS. They can significantly reduce the seizure frequency. However, they do not lead to freedom from seizures.
Valproic acid is a first-line medication. There are many other medications shown effective. There are several antiseizure medications that are effective in the treatment of LGS, including felbamate, rufinamide, lamotrigine, topiramate, clobazam, cannabidiol, and others.
All seizure medications can be associated with fatigue and sedation. Other side effects are specific to certain medications and treatments. Speak to your doctor about side effects before deciding on treatment.
Speak to your doctor about medication options and their side effects.
The ketogenic diet can be effective in LGS. It can reduce seizures by 50% in more than half of children. The diet is:
- High fat
- Adequate protein
- Low carbohydrate
There are various types of ketogenic diet. The classical diet is the strictest. It is used mostly in infants and toddlers. Milder versions include the modified-Atkins or low-glycemic-index diets. These are better options for school-aged children, teens, and adults. Dietary therapy should be prescribed and monitored by an experienced dietician.
Corpus callosotomy surgery can help with atonic seizures in most LGS patients. This involves separating the brain tissue on the two sides of the brain. It may be used if atonic seizures persist despite medicine and diet therapies.
In rare cases, LGS is caused by a localized brain abnormality. In these cases, surgery on that tissue can lead to fewer or no seizures.
Vagus nerve stimulation (VNS) involves placing a device in the chest. The device sends mild pulses of electricity to the brain via the vagus nerve. Several studies show VNS can reduce seizures. It can reduce them by 50% in more than half of patients.
Other management issues
Children with LGS can often benefit from ongoing physical, occupational and speech therapy. In school they usually require an Individualized Education Plan (IEP). IEP’s allow the school curriculum to be targeted to their specific needs.
Given the high medical needs of persons with LGS, families often require some type of respite care. Working with a knowledgeable social worker is important to identify resources to support families.
A 2015 report showed that average yearly medical costs are about $64,000 for LGS. This number depends on insurance status. Hospitalizations and home health services are a big expense. Many medication options are generic. They are relatively inexpensive. Newer medications, such as cannabidiol, are more expensive. However, they are generally covered by insurance.
Sometimes, a therapy is denied insurance coverage at first. However, working with a healthcare provider to appeal the decision can help.
LGS always persists into adulthood. Certain types of seizures are more common in adult with LGS than others. Over time, those with LGS experience developmental slowing, plateauing or regression. This culminates in moderate to severe intellectual disability in more than 90% of patients. Behavior disorders are common in childhood and adolescence.
Untreated seizures can lead to head injury. Those with some kinds of seizures are also at higher risk of sudden death. LGS requires lifelong antiseizure treatment.
These disorders can sometimes be mistaken for LGS:
- Infantile spasms syndrome. This may progress to LGS. It can be hard to tell them apart. LGS seizures look different from spasms, however.
- Myoclonic-atonic epilepsy (or Doose syndrome). In this disorder, seizures are preceded by normal development. Persons with Doose syndrome typically have a unique seizure type called a myoclonic-atonic seizure, with a brief jerk or vocalization that precedes the fall. It is often outgrown in early childhood.
- Dravet syndrome. Dravet syndrome typically presents with recurrent prolonged seizures in the first year of life. It has its own brain and seizure pattern.
- Other early-onset DEEs. Like LGS, other DEEs include multiple types of seizures.
- Frontal lobe epilepsy. This has its own brain and seizure pattern. The seizures often have asymmetrical features.
The Brain Recovery Project: Childhood Epilepsy Surgery Foundation
The Brain Recovery Project (BRP) provides research-based, reliable information to help parents and caregivers understand when a child’s seizures are drug-resistant. The BRP team explains the risks and dangers of seizures and helps families weigh the pros and cons of the various brain surgeries to stop them. Caring BRP team members also help parents understand the medical, cognitive, and behavioral challenges a child may have through life, as well as guide parents through financial and life care issues, and the IEP process. If desired, parents can connect with other families for support. The Brain Recovery Project also hosts a private Facebook group, Education After Pediatric Epilepsy Surgery with over 200 members.
In addition, BRP has resources for medical professionals to assist in helping clinicians help the parents of their patients find the resources they need after surgery. Educators and therapists will also find helpful resources and information including videos, guides, and relevant research. Patients who have undergone surgery are encouraged to register with the Global Pediatric Epilepsy Surgery Registry to help in setting future research priorities.
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