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Lennox-Gastaut Syndrome

Description

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that usually begins before a child is 4 years old, with most cases beginning when the child is about 2 years old. [NINDS: 2007]. Characteristics include:
  • The presence of multiple seizure types before age 11 years, with at least 1 seizure type resulting in falls (drop attacks) including:
    • Drop attacks (atonic seizures)
    • Tonic seizures
    • Atypical absence seizures
    • Myoclonic seizures
    • Generalized tonic-clonic seizures
    • Partial seizures
  • Atonic (drop) seizures seem to account for many of the injuries associated with LGS, and many patients with intractable seizures must wear helmets for head protection.
  • Children often have increased seizures during transitions to and from sleep.
  • Slow spike-wave complexes are seen on EEG (<2.5 Hz).
  • Forty percent have a history of infantile spasms.
  • Although not a diagnostic criterion, 91% of children with LGS have/will develop intellectual disability.
  • One half to two-thirds have focal neurologic abnormalities, most commonly motor signs such as spastic diplegia and hemiparesis.
  • Tonic-clonic convulsions become more frequent in older children and adolescents.
  • With genetic testing, the etiology can be understood in more individuals with LGS.
[Shbarou: 2016].

Etiology

Etiologies for LGS include perinatal asphyxia, hypoxic-ischemic brain injury, congenital brain malformations, CNS infections, tuberous sclerosis, metabolic/degenerative disease, and genetic causes. Approximately 1/3 of children will be normal intellectually and neurologically at presentation, but greater than 90% will eventually exhibit intellectual disability. See the module Intellectual Disabilityfor more information. This is particularly true if the onset of LGS is when the child is younger and if there is an obvious etiology. [Oguni: 1996]. There is speculation but no proof that control of the seizures would result in better cognitive outcome.

Prevalence

Prevalence is low; lifetime prevalence at 10 years is 0.26/1000 and 4% of all pediatric epilepsy. [Trevathan: 1997]) Patients with LGS account for a large proportion of epilepsy clinic visits and phone calls.

Clinical Assessment

Diagnosis is based on the multiple seizure types and an EEG that shows slow spike wave complexes. The history and physical exam and further testing, such as MRI imaging and genetic testing, are aimed at identifying the cause of the LGS. Look for growth problems, including head circumference, skin abnormalities (signs of tuberous sclerosis; a Woods lamp exam should be performed), and neurological abnormalities.

Treatment

Typically, children with LGS will be under the care of a pediatric neurologist with expertise in seizures, and, if possible, a pediatric epileptologist. The management plan for each patient should be reviewed in detail at least yearly. Generally, no single seizure medication will control seizures in these children and there is no cure. Multiple anti-epileptic medications are often used, but even then, control is difficult.
Valproic acid, lamotrigine, and topiramate are considered initial drugs of choice. [Wheless: 2005] Felbamate has potentially serious side effects that include liver toxicity and life-threatening bone marrow failure, and it is only used when other treatment options are exhausted. Zonisamide and levetiracetam may be reasonable alternatives, but experience with these agents is limited. Benzodiazepines are sometimes effective, but tolerance is not uncommon, and escalating doses (with accompanying side effects) are required to achieve efficacy. Seizures tend to wax and wane, even when some degree of control has been achieved. The Ketogenic Diet, vagal nerve stimulation (Vagus Nerve Stimulator (VNS)), and Epilepsy Surgery are also used after pharmacological treatment has failed.
Cannabidiol, which is marketed as Epidiolex, has shown some progress in decreasing seizures, especially drop or atonic seizures which have been resistant to treatment in the past. [Ružić: 2018] [Lattanzi: 2018] [Thiele: 2018] [Gaston: 2018] Complete seizure control may not be possible in all individuals with LGS. See CBD for Neurologic Conditions in Children.

Resources

Information & Support

For Parents and Patients

LGS Foundation
Causes, treatment, and support information for those affected by Lennox-Gastaut syndrome.

Lennox Gastaut Syndrome (Epilepsy Foundation)
Information about who develops this syndrome, what types of seizures it causes, how it affects families, and treatment.

Practice Guidelines

Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A.
Expert Opinion on the Management of Lennox-Gastaut Syndrome: Treatment Algorithms and Practical Considerations.
Front Neurol. 2017;8:505. PubMed abstract / Full Text

Helpful Articles

PubMed search for articles on Lennox Gastaut Syndrome in children for the last 3 years.

Ferrie CD, Patel A.
Treatment of Lennox-Gastaut Syndrome (LGS).
Eur J Paediatr Neurol. 2009. PubMed abstract

Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, Genton P, Guerrini R, Kluger G, Pellock JM, Perucca E, Wheless JW.
Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology.
Lancet Neurol. 2009;8(1):82-93. PubMed abstract

Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D.
Treatment of pediatric epilepsy: European expert opinion, 2007.
Epileptic Disord. 2007;9(4):353-412. PubMed abstract

Authors & Reviewers

Initial publication: September 2008; last update/revision: January 2019
Current Authors and Reviewers:
Author: Lynne M. Kerr, MD, PhD
Authoring history
2013: first version: Lynne M. Kerr, MD, PhDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Gaston TE, Szaflarski JP.
Cannabis for the Treatment of Epilepsy: an Update.
Curr Neurol Neurosci Rep. 2018;18(11):73. PubMed abstract

Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M.
Efficacy and Safety of Adjunctive Cannabidiol in Patients with Lennox-Gastaut Syndrome: A Systematic Review and Meta-Analysis.
CNS Drugs. 2018. PubMed abstract

NINDS.
Lennox-Gastaut Syndrome Information Page.
Epilepsy Foundation; (2007)

Oguni H, Hayashi K, Osawa M.
Long-term prognosis of Lennox-Gastaut syndrome.
Epilepsia. 1996;37 Suppl 3:44-7. PubMed abstract

Ružić Zečević D, Folić M, Tantoush Z, Radovanović M, Babić G, Janković SM.
Investigational cannabinoids in seizure disorders, what have we learned thus far?.
Expert Opin Investig Drugs. 2018;27(6):535-541. PubMed abstract

Shbarou R, Mikati MA.
The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.
Semin Pediatr Neurol. 2016;23(2):134-42. PubMed abstract

Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K.
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet. 2018;391(10125):1085-1096. PubMed abstract

Trevathan E, Murphy CC, Yeargin-Allsopp M.
Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children.
Epilepsia. 1997;38(12):1283-8. PubMed abstract

Wheless JW, Clarke DF, Carpenter D.
Treatment of pediatric epilepsy: expert opinion, 2005.
J Child Neurol. 2005;20 Suppl 1:S1-56; quiz S59-60. PubMed abstract