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Lennox-Gastaut Syndrome: Symptoms, Causes, and Treatments

Updated on April 13, 2020

Article written by
Laurie Berger

  • Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy with multiple seizure types.
  • Of children with epilepsy, 3 percent to 4 percent have LGS.
  • LGS is resistant to most anti-epileptic medications and difficult to treat.
  • Epidiolex (Cannabidiol) is a new drug that has helped control seizures in children with LGS.

What Is Lennox-Gastaut Syndrome?

Lennox-Gastaut syndrome (LGS) is a rare and severe type of epilepsy that begins in early childhood. LGS is characterized by multiple types of recurrent seizures, an abnormal electroencephalograph (EEG), and mental disability.1 Brain disease, injury, or abnormal development is known to cause LGS in 70 percent to 80 percent of people with the condition.2

An estimated 3 percent to 4 percent of children with epilepsy develop LGS, according to the Lennox-Gastaut Syndrome Foundation.3 LGS typically begins between ages 3 and 5, and it occurs more frequently in males.4 Seizures can continue into adolescence and adulthood.5

LGS belongs to a group of disorders called epileptic encephalopathies, which lead to progressive cognitive impairment, developmental delays, and behavioral problems.2,5 Ninety-one percent of people with LGS develop intellectual disabilities.6 Most children experience developmental or intellectual problems before LGS is diagnosed.5

LSG can be difficult to treat because it’s resistant (refractory) to many types of anti-epileptic medications.2 Some people with LGS are able to live independently. However, many experience a poorer quality of life, and some require round-the-clock care.1

Complete recovery from LGS is rare, and there is no cure.7 People with LGS have an estimated mortality rate of 5 percent. In cases where death is associated with LGS, it’s usually due to accidents from falls, or dangerously long seizures known as status epilepticus.8

Lennox-Gastaut Syndrome Symptoms and Seizure Types

People with LGS experience multiple types of epileptic seizures. The most common include:

Tonic seizures

Up to 92 percent of individuals experience tonic seizures.8 Tonic seizures typically cause muscles to stiffen and contract uncontrollably.5 They last less than 20 seconds and occur primarily during sleep. Seizures of this type that occur while awake can cause sudden falls.2

Atonic seizures

At least 50 percent of children and adults with LGS have atonic seizures, also known as drop attacks.9 During an atonic seizure, a person loses muscle tone, causing their body to go limp and fall to the ground. Helmets or other head protection are needed to protect from injury.5

Atypical absence seizures

Atypical absence seizures affect up to 65 percent of people with LGS, generally before age 6.5,8 Most children with this type of seizure have cognitive and developmental problems.5 Atypical absence seizures are brief (under 30 seconds) and cause a short period of “blanking out” or staring into space. Falling is more common during an atypical absence seizure than in a typical absence seizure.5

Focal seizures

Focal seizures, which typically affect one side of the brain, are another common seizure in adults and children with LGS. A person may be aware (or partially aware) of their surroundings, but can’t move or respond.10 Automatic movements, such as lip smacking, wandering, or hand fumbling, may occur.5

Other seizure types with Lennox-Gastaut syndrome include:

Myoclonic seizures

Myoclonic seizures are less common, but sometimes seen with LGS. These are brief, shock-like jerks of a muscle or a group of muscles.5

Tonic-clonic seizures

These seizures combine characteristics of tonic (stiffening) and clonic (rhythmical jerking). During tonic-clonic seizures, which last one to three minutes, a person can lose consciousness and fall to the floor.5

Infantile spasms

Some children with LGS may be initially affected by infantile spasms. Also known as West syndrome, they involve sudden, involuntary contractions of the head, neck, and torso or uncontrolled extension of legs and arms.2 An estimated 30 percent to 50 percent of children with infantile spasms will develop LGS later on.3

Status epilepticus (SE)

Seizures lasting longer than five minutes, or occurring too close together for the person to recover, can be life-threatening and require emergency medical intervention.5 Two types of status epilepticus seizures — convulsive and nonconvulsive — can affect awareness and body movements, and promote or worsen cognitive decline.5,11 More than two-thirds of people with LGS experience SE.1

Dangers Associated With Seizures

The most disabling seizures for people with LGS are falls from drop attacks, which can result in recurrent injuries and debilitation.11 Uncontrolled seizures also increase the risk of sudden unexpected death in epilepsy (SUDEP).3

The best way to prevent injury or death due to status epilepticus and SUDEP is to control seizures as much as possible. Your medical team can find the best treatment plan with medication, dietary treatments, or alternative treatments.

Children and adults with LSG may need 24-hour care. For daily management, many families use protective helmets, seizure alarms, and video monitoring. They also adapt living quarters to accommodate a wheelchair and include safety measures, such as shower bars in the bathroom.3

Developmental and Behavioral Issues With Lennox-Gastaut Syndrome

Most children with LGS have intellectual disabilities or learning problems even before seizures begin. These issues may worsen over time, particularly if seizures are frequent or severe.2 In a 17-year assessment of children with LGS, up to 99 percent exhibited mental retardation.9 Many had delayed development of motor skills, such as sitting and crawling.2 Behavioral problems, such as hyperactivity, aggression, and autistic traits, occurred in half of the cases.9

As a result of such developmental and behavioral issues, most people with LGS require help with the activities of daily living.2

Lennox-Gastaut Syndrome in Teens and Adults

About 80 percent to 90 percent of children with LGS will continue to have seizures into adulthood, but they may occur with less severity and frequency.3 Daytime tonic and atonic seizures may decrease or disappear over the years, resulting in lower fall risk. People with later LGS onset have a more favorable prognosis.3 Their brains have progressed beyond critical developmental stages, so seizures may have a less detrimental impact.3

Diagnosing Lennox-Gastaut Syndrome

To be diagnosed with LGS, a person must exhibit all of the following symptoms:

  • Multiple seizure types
  • Abnormal EEG with a specific brain wave pattern
  • Cognitive and/or behavioral challenges12

A diagnosis is usually made — together with a multidisciplinary team — after a thorough physical exam, medical history, and neurological evaluation.13 You will likely undergo an electroencephalogram (EEG) to analyze the brain’s electrical activity and seizures.5 Magnetic resonance imaging (MRI) may also be ordered to help physicians examine brain structure and locate the cause of the seizure activity.2,14 More than two-thirds of people with LGS have abnormal MRIs.9

Routine lab tests may be used to rule out other medical conditions that might cause seizures, such as metabolic disorders, infections, kidney or liver malfunction, or toxins.12

It can take several years to correctly diagnose LGS because the disease has significant overlap with other types of epilepsy, and it may not show its unique features when seizures begin.9

Causes of Lennox-Gastaut Syndrome

An estimated 70 percent to 80 percent of people experience symptomatic LGS — when the disease has an identifiable cause.2 Here are some of the causes of LGS:

Brain Injury or Developmental Problems

When part of the brain has developed abnormally (also called brain malformation) or is injured, it becomes more prone to seizures.5 Brain injuries can include lack of adequate oxygen or blood flow, stroke, bleeding, infections such as meningitis or encephalitis, or head injury.5

Genetic Disorders

In most LGS cases, there’s no family history of the disorder. When LGS is caused by a genetic mutation, it typically occurs as a new (de novo) event during reproduction, not an inherited trait.5 Genetic mutations with family history have been observed in up to 30 percent of people with LGS.6

Mutations of the TSC1 or TSC2 gene can cause a disease called tuberous sclerosis complex — the growth of noncancerous (benign) tumors throughout the body and brain.15,16,17 TSC in the brain can cause seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems.5

Other Causes

LGS can also develop from other epilepsy syndromes, such as West syndrome (infantile spasms), Ohtahara syndrome, or epilepsy in infancy with migrating focal seizures.18,19,20

When the cause is unknown, LGS is classified as cryptogenic.2 In 1 in 4 people with LGS, no cause can be found.5 Scientists believe genetics may be the primary driver of cryptogenic LGS, but more research is needed.3

Treating Lennox-Gastaut Syndrome

LGS can be difficult to treat. Treatment options for LGS are limited because of the disease’s resistance to anti-epileptic drugs (AED). Side effects of AEDs may also affect quality of life.3 A combination of seizure medications and other treatments are typically used to control LGS-related seizures.7

First-Line Treatment

The anti-seizure medication Depakene (Valproic acid) is considered the first-line monotherapy for LGS in children and adults because it’s effective against a wide spectrum of seizures.2,21 Klonopin (Clonazepam) is another effective first-line AED, but side effects can limit usefulness over time.22

Second-Line Treatment

If valproic acid fails to control seizures, other drugs — such as Onfi (Clobazam), Lamictal (Lamotrigine), Topamax (Topiramate), and Banzel (Rufinamide) — may be prescribed.23 These AEDs are approved by the U.S. Food and Drug Administration (FDA) as add-on therapies to treat seizures associated with Lennox-Gastaut syndrome.2 Keppra (Levetiracetam), which is approved for partial seizures, may also be used as an add-on therapy for LGS.

Third-Line Treatment

The anti-convulsant drug Felbatol (Felbamate) is also approved for treating seizures in children with LGS. Felbamate has been found to be safe and effective, but rare, serious side effects make it a third- or fourth-line LGS drug.2

Anti-epileptic drugs may be associated with significant side effects, especially in people on multidrug, high-dose regimens. These drugs can also become less effective over time. Taking multiple medications can sometimes worsen seizure control.2

Treatment regimens will change throughout a person’s life — as types and frequency of seizures change and effectiveness of a particular therapy decreases.2 It’s important for family members and caretakers to work closely with physicians to manage prescribed medications and keep a list of drugs that may worsen seizures or have other serious side effects.

Other treatments for Lennox-Gastaut syndrome include:

Epidiolex (Cannabidiol)

An oral form of cannabidiol (CBD), Epidiolex is the first FDA-approved drug to control LGS-related seizures. In a phase 3 clinical trial published in The Lancet in 2018, adding CBD to prescribed medications in people with LGS resulted in a 44 percent reduction of drop seizures compared to a 22 percent decrease with placebo.24 Rare side effects from Epidiolex - as well as interactions with the drugs valproic acid and clobazam - were noted in the study.6,24

Fintepla (Fenfluramine)25

Currently being tested for treating LGS in phase 3 clinical trials, Fintelpa belongs to a class of drugs called selective serotonin releasing agonists.5 When added as an off-label therapy to other standard AEDs for LGS, fenfluramine has been shown in trials to reduce seizure frequency and could be a potential treatment add-on for children ages 2 to 17 and adults.26

Dietary Therapies for Lennox-Gastaut Syndrome

Ketogenic Diet

A ketogenic diet and its variations, including a modified Atkins diet, are often used to treat children with LGS who have not responded well to AEDs.27 Studies have shown that the high-fat, low-carb diet — in combination with at least one epilepsy medication — helped more than 50 percent of children with epilepsy reduce seizures by half. As many as 15 percent of children became seizure-free on the ketogenic diet.28

Low Glycemic Index Diet

The low glycemic index treatment (LGIT) is a less-restrictive alternative for people with drug-resistant LGS. Lower in fat than the ketogenic diet, LGIT includes carbohydrates that are low-glycemic (a measurement of how much a food raises your blood sugar level after eating). Seizures were reduced in a majority of people on a LGIT. Some became seizure-free, and others were able to reduce use of anticonvulsant medications.29

Other Therapies for Lennox-Gastaut Syndrome

Vagus Nerve Stimulation (VNS)

VNS is an effective treatment for people with LGS who do not respond to medication.30 A device surgically implanted in the chest sends mild electrical signals to the brain, via the vagus nerve, to treat focal or partial seizures.30 A VNS study of 50 people with LGS found a 42 percent to 58 percent reduction in seizures within six months. The study concluded that VNS is well tolerated, safe, and may improve quality of life.30

Corpus Callosotomy

In some people with LGS, a focal area of the brain can be removed to help control seizures.5 Several studies have found this type of brain surgery to be helpful in decreasing the frequency of drop attacks.31 Corpus callosotomy is considered an option to control — but not cure — these potentially dangerous seizures.5,31

Resective Surgery

This common epilepsy surgery (also known as temporal lobe resection) removes areas of the brain that cause seizures, with the goal of stopping them altogether. In a 2018 study of long-term outcome of resective surgery for refractory LGS, 50 percent of people were seizure-free after six years.32 Others experienced a high degree of seizure control, as well as improved behavior and social competence.32

Rescue Medications for Lennox-Gastaut Syndrome

Rescue medicines can prevent and treat life-threatening seizures. The most commonly prescribed rescue medicines are fast-acting benzodiazepines: Valium (Diazepam), Ativan (Lorazepam), and Versed (Midazolam).33,34,35,36 These rescue medications are given orally, under the tongue (sublingual), between the cheek and gum (buccally), or sprayed into a nostril (nasal spray). Diastat, the rectal form of diazepam, is most often prescribed for children.5,37

Developing a seizure response plan is important in helping prevent or manage emergency situations.38 The Epilepsy Foundation offers information and tools for creating a seizure response plan. Keeping a seizure diary is a self-tracking tool that can help you be proactive about seizure type and frequency — and allow your medical team to detect interactions between seizures and medications.39

On MyEpilepsyTeam, a free social network for people living with epilepsy, more than 81,000 members offer each other support and advice. MyEpilepsyTeam members who are living with or taking care of someone with Lennox-Gastaut syndrome often discuss their experiences.

Here are some conversations on MyEpilepsyTeam about Lennox-Gastaut syndrome:

Here is a question-and-answer thread about Lennox-Gastaut syndrome:

References

  1. Lennox-Gastaut syndrome — Genetics Home Reference — NIH. (n.d.). Retrieved March 17, 2020, from https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome
  2. Lennox-Gastaut Syndrome. (n.d.). Retrieved March 17, 2020, from https://rarediseases.org/rare-diseases/lennox-gastaut-syndrome/
  3. About Lennox-Gastaut Syndrome. (n.d.). Retrieved March 17, 2020, from https://www.lgsfoundation.org/aboutlgs
  4. Hancock EC, Cross JH. Treatment of Lennox-Gastaut syndrome. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003277. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003277.pub3/full
  5. Shafer, P. O. (n.d.). Lennox-Gastaut Syndrome (LGS). Retrieved March 17, 2020, from https://www.epilepsy.com/learn/types-epilepsy-syndromes/lennox-gastaut-syndrome-lgs
  6. Jacob, E. C. (2019, January 18). Emerging Treatments for Dravet and Lennox-Gastaut Syndromes. Retrieved March 17, 2020, from https://www.uspharmacist.com/article/emerging-treatments-for-dravet-and-lennoxgastaut-syndromes
  7. Lennox-Gastaut Syndrome Information Page. (n.d.). Retrieved March 17, 2020, from https://www.ninds.nih.gov/disorders/all-disorders/lennox-gastaut-syndrome-information-page
  8. Inserm. (n.d.). Orphanet: Lennox Gastaut syndrome. Retrieved March 17, 2020, from https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=885&Disease_Disease_Search_diseaseGroup=Lennox-Gastaut&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Lennox-Gastaut-syndrome&title=Lennox-Gastaut%20syndrome&search=Disease_Search_Simple
  9. Bourgeois, B.F.D., Douglass, L.M. and Sankar, R. (2014), Lennox‐Gastaut syndrome: A consensus approach to differential diagnosis. Epilepsia, 55: 4-9. doi:10.1111/epi.12567
  10. Focal seizures — Epilepsy Action (n.d.). Retrieved March 17, 2020, from https://www.epilepsy.org.uk/info/seizures/focal-seizures
  11. van Rijckevorsel, K. (2008, December). Treatment of Lennox-Gastaut syndrome: overview and recent findings. Retrieved March 17, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646636/
  12. Lennox-Gastaut Syndrome. (n.d.). Retrieved March 17, 2020, from https://www.cedars-sinai.edu/Patients/Health-Conditions/Lennox-Gastaut-Syndrome.aspx
  13. Shafer, P. O. (n.d.). My Health Care Team. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/managing-your-epilepsy/managing-my-seizures-101/my-health-care-team
  14. Magnetic Resonance Imaging (MRI) of the Spine and Brain. (n.d.). Retrieved March 17, 2020, from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/magnetic-resonance-imaging-mri-of-the-spine-and-brain
  15. TSC1 gene — Genetics Home Reference — NIH. (n.d.). Retrieved March 17, 2020, from https://ghr.nlm.nih.gov/gene/TSC1
  16. TSC2 gene — Genetics Home Reference — NIH. (n.d.). Retrieved March 17, 2020, from https://ghr.nlm.nih.gov/gene/TSC2
  17. Hernandez, M. S. P. M. D. A. (n.d.). Tuberous Sclerosis Complex (TSC). Retrieved March 17, 2020, from https://www.epilepsy.com/learn/epilepsy-due-specific-causes/neurocutaneous-syndromes/tuberous-sclerosis-complex-tsc
  18. Wirrell, A. H. M. D. E. (n.d.). Infantile Spasms (West Syndrome). Retrieved March 17, 2020, from https://www.epilepsy.com/learn/types-epilepsy-syndromes/infantile-spasms-west-syndrome
  19. Kiriakopoulos, E. (n.d.). Ohtahara Syndrome. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/types-epilepsy-syndromes/ohtahara-syndrome
  20. Hernandez, A. (n.d.). Epilepsy in Infancy with Migrating Focal Seizures. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/types-epilepsy-syndromes/epilepsy-infancy-migrating-focal-seizures
  21. Schachter, S. C. (n.d.). Seizure and Epilepsy Medicines. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/seizure-and-epilepsy-medicines
  22. Lennox-Gastaut Syndrome Medication: Anticonvulsants, Benzodiazepines. (2019, November 10). Retrieved March 17, 2020, from https://emedicine.medscape.com/article/1176735-medication#2
  23. Onfi Uses, Dosage, Side Effects & Warnings. (n.d.). Retrieved March 17, 2020, from https://www.drugs.com/onfi.html
  24. Thiele, E. A., Marsh, E. D., French, J. A., Mazurkiewicz-Beldzinska, M., Benbadis, S. R., Joshi, C., … GWPCARE4 Study Group. (2018, March 17). Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Retrieved March 17, 2020, from https://www.ncbi.nlm.nih.gov/pubmed/29395273
  25. Fintepla (fenfluramine) FDA Approval Status. (n.d.). Retrieved March 17, 2020, from https://www.drugs.com/history/fintepla.html
  26. Fenfluramine hydrochloride for treatment of seizures associated with Lennox-Gastaut syndrome. (n.d.). Retrieved March 17, 2020, from http://www.io.nihr.ac.uk/wp-content/uploads/2019/06/15020-Fenfluramine-for-Seizures-Associated-with-Lennox-Gastaut-Syndrome-V1.0-MAY2019-NON-CONF.pdf
  27. Schachter, S. C. (2015, November 19). Modified Atkins Diet. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/dietary-therapies/modified-atkins-diet
  28. Caraballo, R. H., Fortini, S., Fresler, S., Armeno, M., Ariela, A., Cresta, A., … Escobal, N. (2014). Ketogenic diet in patients with Lennox–Gastaut syndrome. Seizure, 23(9), 751–755. https://www.ncbi.nlm.nih.gov/pubmed/25011392
  29. Pfeifer, H. H. (2013, August 22). Low Glycemic Index Treatment. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/dietary-therapies/low-glycemic-index-treatment
  30. Frost, M., Gates, J., Helmers, S. L., Wheless, J. W., Levisohn, P., Tardo, C., & Conry, J. A. (2002, January 12). Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox–Gastaut Syndrome. Retrieved March 17, 2020, from https://onlinelibrary.wiley.com/doi/full/10.1046/j.1528-1157.2001.23900.x
  31. Douglass, L.M. and Salpekar, J. (2014), Surgical options for patients with Lennox‐Gastaut syndrome. Epilepsia, 55: 21-28. doi:10.1111/epi.12742
  32. Joon Won Kang, Soyong Eom, William Hong, Hye Eun Kwon, Soyoung Park, Ara Ko, Hoon-Chul Kang, Joon Soo Lee, Young-Mock Lee, Dong Seok Kim, Heung Dong Kim, Pediatrics Oct 2018, 142 (4) e20180449; https://pediatrics.aappublications.org/content/early/2018/09/05/peds.2018-0449/tab-article-info?versioned=true
  33. Shafer, P. O. (n.d.). Using Rescue Medications. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/seizure-first-aid-and-safety/responding-seizures/using-rescue-medications
  34. Diagnosis & Treatment. (n.d.). Retrieved March 17, 2020, from https://www.epilepsy.com/learn/professionals/diagnosis-treatment/psychotropic-effects-dehttps://www.epilepsy.com/learn/professionals/diagnosis-treatment/psychotropic-effects-developmental-disabilities/specific-9velopmental-disabilities/specific-9
  35. Ativan: Uses, Dosage, Side Effects & Warnings. (n.d.). Retrieved March 17, 2020, from https://www.drugs.com/ativan.html
  36. Versed Uses, Side Effects & Warnings. (n.d.). Retrieved March 17, 2020, from https://www.drugs.com/mtm/versed.html
  37. Diastat: Indications, Side Effects, Warnings. (n.d.). Retrieved March 17, 2020, from https://www.drugs.com/cdi/diastat.html
  38. Schachter, S. C. (n.d.). Seizure Emergencies. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/challenges-epilepsy/seizure-emergencies
  39. Schachter, S. C. (n.d.). Seizure Response Plans 101. Retrieved March 17, 2020, from https://www.epilepsy.com/learn/managing-your-epilepsy/seizure-response-plans-101

Laurie has been a health care writer, reporter, and editor for the past 14 years. Learn more about her here.

A MyEpilepsyTeam Member said:

My neurologist convinced my insurance to cover the cost of the Epidiolex since her plan is to take me off a medication or 2 since I'm taking too much… read more

posted about 1 month ago

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