What is Lennox-Gastaut Syndrome?
Lennox-Gastaut syndrome (LGS) is a form of epilepsy that usually affects infants or young children between three and five years. The disorder is characterized by recurrent seizures of multiple types and a distinctive pattern of brain-wave activity. Sometimes a child with LGS will develop normally before the onset of symptoms, but the condition usually causes developmental delays and cognitive impairments.
Symptoms of Lennox-Gastaut Syndrome
LGS does not have a definitive set of symptoms, but doctors look for three specific signs to diagnosis the condition. These signs include:
- Recurrent seizures of multiple types
- A distinctive pattern of brain-wave activity called a slow spike-and-wave pattern
- Cognitive impairments
The most common types of seizures associated with LGS include:
- Tonic seizures. These seizures are characterized by stiffening of muscles, the extension of the arms or legs, spasms in facial muscles, breathing disruption, or brief loss of consciousness.
- Atonic seizures. These seizures cause an abrupt loss of muscle tone or limpness. They may also cause falls, or a sudden collapse called a drop attack.
- Myoclonic seizures that cause sudden jerking of muscles.
- Tonic-clonic seizures that cause both muscle stiffness and jerking
- Atypical absence seizures that cause brief periods of unresponsiveness.
Other symptoms of LGS can include:
- Delays in developing motor skills such as sitting or walking
- Loss of skills that have been previously acquired
- Cognitive and intellectual delays and impairments
- Behavioral symptoms such as hyperactivity or irritability
What Causes Lennox-Gastaut Syndrome?
In most cases, LGS has an identifiable cause, usually a pre-existing problem or abnormality in the brain. Common causes of LGS include:
- Malformations in the outer part of the brain called cortical dysplasia
- Infections such as meningitis or encephalitis
- Disruption of blood flow to the brain before or during birth (perinatal hypoxia)
- Brain injury
- Tuberous sclerosis
In many cases, LGS develops after a child has experienced a different type of epilepsy, such as West syndrome or infantile spasms.
In some cases, LGS has no readily identifiable cause, and the precise way that the disorder causes seizures is still unknown.
Is Lennox-Gastaut Syndrome Hereditary?
Researchers have not identified any genes that are definitely associated with LGS, and most cases occur in children with no family history of the disorder. In cases where LGS is associated with an abnormal change (mutation) in a gene, the mutation appears to occur at some point in the development of the fetus and is not inherited.
In a minority of cases, children with LGS have a family history of epilepsy, suggesting an inherited component to the disorder. However, scientists have not yet identified a specific genetic factor that may be to blame.
How Is Lennox-Gastaut Syndrome Detected?
Early detection of LGS is essential because early intervention and treatment may help lessen the severity of cognitive impairments and other complications. Children who experience severe, frequent seizures during early neurological development are most vulnerable to serious, long-term complications.
LGS is typically diagnosed by the distinctive features of the disorder, but some symptoms may begin before those features are detectable. In its early stages, LGS may look like other forms of epilepsy. Consequently, doctors are encouraged to pursue treatment even if a diagnosis is not yet possible.
How Is Lennox-Gastaut Syndrome Diagnosed?
LGS can be diagnosed when the three key features of the disorder (multiple seizure types, brain-wave pattern, cognitive impairment) are present. The diagnostic process will include exams to look for these features.
Diagnostic steps often include:
- Evaluation of the child’s medical history
- Physical and neurological exams
- Electroencephalogram, a non-invasive exam to measure brain-wave activity
- Magnetic resonance imaging (MRI) to look for structural brain abnormalities
- Genetic testing
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Lennox-Gastaut Syndrome Treated?
LGS seizures are often resistant to standard courses of treatment for epilepsy, and individual children may respond differently than others to specific types of treatment. Doctors are likely to try different treatments to find the course that the child responds to best.
Common treatment options include:
- Anti-seizure medications such as valproic acid, clobazam, felbamate, lamotrigine, rufinamide, topiramate, and cannabidiol
- Ketogenic diet
- Vagus nerve stimulation
- Surgery is usually only considered in cases where seizures have not responded to other treatments.
How Does Lennox-Gastaut Syndrome Progress?
The progression of LGS varies widely depending on many factors, including; the severity of symptoms, the underlying cause, and the effectiveness of treatments. In rare cases, seizure activity may improve over time, and cognitive impairments may be mild. However, in severe cases, intellectual disabilities may worsen over time. Other behavioral problems may also develop.
People with LGS have a higher than average mortality rate than unaffected people of the same age, but the reason for this higher rate is not known.
Some adults with LGS can live independently, but most will require assistance from caregivers.
How Is Lennox-Gastaut Syndrome Prevented?
There is no known way to prevent LGS. Prevention of the infections and events that may cause the disorder may lower the risk of developing LGS. Risk factors include:
- Brain injury or obstruction of blood flow before or during birth
- Brain injury in infancy or early childhood
Lennox-Gastaut Syndrome Caregiver Tips
- Educate yourself about LGS. The disorder has many potential causes, and it uniquely affects each child. Learn all you can about the condition and your child’s specific experience with it so you can be an informed, effective part of the treatment process.
- Carefully watch for signs of the disorder. Early treatment can make a difference in long-term outcomes; spotting the condition at an early stage is crucial. Consult your doctor right away when you see any of the disorder’s warning signs.
- Find support from people who know what you’re going through. The Epilepsy Foundation operates a 24/7 helpline through which you can find information and links to support resources.
Lennox-Gastaut Syndrome Brain Science
Although the underlying condition that causes LGS is often apparent, scientists don’t understand precisely what mechanism in the brain causes the disorder’s seizures. One area of research interest is that many children with LGS have developed the condition after progressing through other infantile and early-onset forms of epilepsy, such as Ohtahara syndrome and West syndrome. Some scientists believe that the three disorders constitute a spectrum of age-dependent epilepsies that evolve in a predictable sequence as the child ages.
Lennox-Gastaut Syndrome Research
Title: Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
Study chair: Ry R. Forseth, PhD
SK Life Science, Inc.
This is an open-label, multi-center study of carisbamate in adult and pediatric subjects with LGS, with single- and multiple-dose PK assessments from Days 1 through 73. There will be a Screening Period of up to 28 days and a Treatment Period of 87 days.
A total of 24 subjects are planned: 6 subjects in each of 4 cohorts: Cohort I (≥18 years), Cohort II (12 to <18 years), Cohort III (6 to <12 years), and Cohort IV (2 to <6 years).
For Cohorts I and II, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations, will be conducted on Days 1, 2 and 3 of the single-dose period at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort III, PK assessments of carisbamate, S-enantiomer and its R-enantiomer plasma concentrations will be conducted on Days 1, 2 and 3 of the single-dose period at pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours after dosing and on Day 17 of the multiple-dose period at pre-dose and 2 hours after dosing; trough samples will be collected on Days 45 and 73 of the dose-adjustment period.
For Cohort IV, a sparse PK sampling approach will be used, and the time of PK sampling time will be based on the PK results from the other cohorts. A maximum of 2 to 4 time points on each day (1 and 17) will be collected.
Safety assessments include adverse event (AE) and concomitant medication reporting, clinical laboratory testing, vital sign measurements, 12 lead electrocardiograms (ECGs), physical examinations, and neurologic examinations.
Title: Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
Woodcliff Lake, NJ
This study is being conducted to demonstrate that perampanel given as adjunctive anti-epileptic treatment is superior to placebo in reducing the number of drop seizures in participants with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (LGS).
This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of perampanel as adjunctive therapy in participants with inadequately controlled seizures associated with LGS. The study will consist of 3 phases: Prerandomization (4 to 8 weeks), Randomization (18 weeks), and an Extension A (52 weeks). An additional Extension B with open-label treatment will be available for optional participation to participants who reside in Japan and in countries where an expanded access program (EAP) cannot be implemented or has not yet been implemented.
Title: Long-term Cardiac Monitoring in Epilepsy (LOOP)
Contact: Martha Karran
New York, NY
Most cardiac studies have investigated patients with intractable focal epilepsy who have a high risk for co-morbidities, accidents, injury, and SUDEP. This is confounded by the major antiepileptic drug burden in this population. Very little, however, is known about the risk of cardiac arrhythmias in patients with a lower seizure burden, i.e., patients with infrequent focal seizures and/or those without secondarily generalized convulsions. Furthermore, no chronic cardiac data is available in patients with epileptic encephalopathies, especially given that some of these patients are known to carry mutations that increase the risk for cardiac arrhythmias. In addition, periods of reduced cerebral blood flow during tachy or brady arrhythmias may exacerbate seizure severity and duration. Diagnosing and treating these arrhythmias may not only prevent adverse cardiac events, but also reduce seizure burden. This study primarily aims to compare the frequency of cardiac rhythm abnormalities in patients with epilepsy of different severity, assess the long-term cardiac risk and evaluate the possible preventive role of anti-arrhythmic agents and/or cardiac pacemaker/defibrillator needs.