|This article has been reviewed by the NeuroWiki Editorial Board|
Lennox-Gastaut syndrome (LGS), also known as Lennox syndrome, is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life, and is characterized by frequent seizures and different seizure types; it is often accompanied by mental retardation and behavior problems.
As a general rule, the age of seizure onset in LGS patients is between the ages of two and six; however, this does not exclude the possibility that seizures can begin before age two, or after age eight. The syndrome shows clear parallels to West syndrome, enough to suggest a connection.
Daily multiple seizures are typical in LGS. Also typical is the broad range of seizures that can occur, larger than that of any other epileptic syndrome. The most frequently occurring seizure types are: tonic, which are often nocturnal (90%); the second most frequent are myoclonic seizures, which often occur when the patient is over-tired.1
Atonic, atypical absence, complex partial, focalized and tonic-clonic seizures are also common. Additionally, about half of patients will suffer from status epilepticus, usually the nonconvulsive type, which is characterized by dizziness, apathy, and unresponsiveness. The seizures can cause sudden falling (or spasms in tonic, atonic and myoclonic episodes) and/or loss of balance, which is why patients often wear a helmet to prevent head injury.
In addition to daily multiple seizures of various types, children with LGS frequently have arrested/slowed psychomotor development and behavior disorders.
Incidence and prevalence
Approximately 5% of children with epilepsy have LGS, and is more common in males than females. Whereas some children seem perfectly normal prior to the development of seizures, others already had some form of epilepsy, such as West syndrome, which is seen in 20% of patients before (symptomatic) LGS. West syndrome is characterized by Blitz Nick Salaam seizures, and typically evolves into LGS in the second year of life.
According to a 1997 community-based retrospective study in the Helsinki metropolitan area and the province of Uusimaa, the annual incidence of both Lennox-Gastaut was 2 in 100,000 (0.002%) from 1975-1985.2
0.026% of all children in the Atlanta, Georgia metropolitan area were estimated to have LGS in 1997, which was defined as, "onset of multiple seizure types before age 11 years, with at least one seizure type resulting in falls, and an EEG demonstrating slow spike-wave complexes (<2.5 Hz)." The study concluded that LGS accounts for 4% of childhood epilepsies.3
Mortality and morbidity
The mortality rate ranges from 3% to 7%.4
There is no uniform cause: in 20% of the concerned, the LGS develops from the West syndrome. The medical history frequently includes infantile spasms or focalized and generalized seizures.
The most common type of LGS (70-78%). This does not mean that LGS patients in other categories have no symptoms whatsoever; rather, it means that there is an identifiable underlying pathology responsible. This includes encephalopathy (brain damage) or another disease and/or developmental disorder. Frequent causes include tuberous sclerosis, hereditary metabolic diseases, inflammatory brain disease such as encephalitis, meningitis, and toxoplasmosis; hypoxia-ischemia injury and other birth injuries; and lesions of the frontal lobe. These patients tend to have a worse prognosis than the idiopathic ones.
In up to one-third of cases no cause can be found. These cases are referred as cryptogenic and/or idiopathic Lennox-Gastaut syndrome. Patients are considered to have idiopathic LGS if they were developing normally prior to the seizures, and cryptogenic if a cause is suspected by unknown. Not all investigators mention the second category.
Generally speaking, LGS can often only be defined as a syndrome and/or distinguished from other syndromes because there are various overlaps with other syndromes. Currently, the fact that there is no uniform cause complicates things.
- CT scans, usually in the case of suspected injury resulting from an atonic and/or tonic seizure.
LGS seizures are often treatment resistant, but this does not mean that treatment is futile. Options include anticonvulsants, anesthetics, steroids such as prednisone, immunoglobulins, and various other pharmacological agents that have been reported to work in individual patients.
- valproates (valproic acid, sodium valproate and valproate semisodium)
- benzodiazepines, specifically clonazepam, nitrazepam, and clobazam
Nitrazepam and Clobazam are not approved in the USA.
In 1999, Dr. Sachdeo and colleagues at the University of Medicine and Dentistry of New Jersey and the Robert Wood Johnson Medical School in New Brunswick reported that 33% of the patients in the topiramate group experienced a minimum 50% reduction in seizures (specifically drop attacks and tonic-clonics), compared with 8% in the placebo group.5 It was also found to be effective as an adjunctive therapy in a review published by Drs. Edith Alva Moncayo and Antonio Ruiz Ruiz in March of 2003.6
Dr. Motte and colleagues at the American Memorial Hospital at Reims, France reported in 1997 that lamotrigine was effective in the treatment of LGS, with the most common side effect in the treatment group relative to placebo being colds or viral illnesses.7 Two years later, it was approved by Health Canada for adjunctive therapy in Lennox Gastaut in adults and children.8 The United States Food and Drug Administration approved it for that in August of 1998.9
Unapproved, off-label, and investigational drugs
Vigabatrin was found by Feucht et al to be an effective add-on in patients whose seizures were not satisfactorily controlled by valproate. Out of 20 children, only 1 experienced a serious side effect (dyskinesia).13
Zonisamide showed promise in an overview of controlled and uncontrolled trials conducted in Japan.14 However, in a physician survey conducted December of 2004, only 28% of Lennox-Gastaut and West syndrome patients improved on zonisamide.15
A ketogenic diet is a diet that causes ketosis, a state in which there is an excessive amount of ketones in the body. It is becoming increasingly popular for treating intractable epilepsy.
Intravenous immunoglobulin therapy
Intravenous immunoglobulin therapy has been used in Lennox-Gastaut syndrome as early as 1986, when van Rijckevorsel-Harmant and colleagues used it in seven patients with ostensibly idiopathic LGS and saw EEG improvement and decreased seizure frequency in six of them.16
Hippotherapy is a form of physical, occupational, or speech therapy that utilizes the movement of a horse. It can be an effective treatment for some of the symptoms of Lennox-Gastaut syndrome, including developmental delays and communication problems. Hippotherapy has proven effective in increasing the walking speed and other gross motor functions in children with Lennox-Gastaut syndrome.
- Childhood seizures - epilepsy and convulsions in children. Retrieved on August 16, 2005.
- Heiskala H. (1997). "Community-based study of Lennox-Gastaut syndrome". Epilepsia 38 (5): 526-31. PubMed.
- Trevathan E, Murphy CC, Yeargin-Allsopp M. (1997). "Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children". Epilepsia 38 (12): 1283-8. PubMed.
- Glauser, Tracy A. and Morita, Diego A. (2002). Introduction. Lennox-Gastaut Syndrome. eMedicine.com, Inc.. Retrieved on 8 July 2005.
- Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G (1999). "A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group". Neurology 10 (52): 1882-7. PubMed.
- Alva-Moncayo E, Ruiz-Ruiz A (2003). "The value of topiramate used with conventional schemes as an adjunctive therapy in the treatment of Lennox-Gastaut syndrome]". Revista de Neurologia 36 (5): 453-7. PubMed.
- Motte J, Trevathan E, Arvidsson JF, Barrera MN, Mullens EL, Manasco P (1997). "Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group". New England Journal of Medicine 337 (25): 1807-12. PubMed.
- Epilepsy Ontario (1999). Lamotrigine Approved in Canada for Lennox-Gastaut Syndrome. 'Sharing' News. Retrieved on 13 November 2005.
- Glaxo Wellcome Inc (1998). Final Printed Labeling -- Part 1. Lamictal Tablets & Chewable Dispersible Tablets (Lamotrigine) Drug Approval Page. United States Food and Drug Administration Center for Drug Evaluation and Research. Retrieved on 13 November 2005.
- Ritter, Frank J.; Ilo E. Leppik, Fritz E. Dreifuss, Ihor Rak, Nancy Santilli, Roberta Homzie, W. Edwin Dodson, Tracy A. Glauser, J. Chris Sackellares, Larry Olson, Elizabeth A. Garafolo, W. Donald Shields, Jacqueline French, Michael Sperling, Lynn D. Kramer, Marc Kamin, Alberto Rosenberg, Robert Shumaker, James L. Perhach, and Robert Dix (1993). "Efficacy of Felbamate in Childhood Epileptic Encephalopathy (Lennox-Gastaut Syndrome)". New England Journal of Medicine 328 (1): 29-33. PubMed.
- Devinsky, Orrin; R. Edward Faught, B. Joseph Wilder, Andres M. Kanner, Marc Kamin, L. D. Kramer and A. Rosenberg (1995). "Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures". Epilepsy Research 20 (3): 241-6. PMID 7796796.
- O'Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S (1996). "Felbamate-associated fatal acute hepatic necrosis". Neurology 46 (5): 1457-1459. PubMed.
- Feucht M, Brantner-Inthaler S (1994). "Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study". Epilepsia 35 (5): 993-8. PMID 7925171.
- Yagi K (2004). "Overview of Japanese experience-controlled and uncontrolled trials". Seizure 13 (Supplement 1): S11-5; discussion S16. PMID 15511680.
- Yamauchi, Toshio; Aikawa Hiroshi (December 2004). "Efficacy of zonisamide: our experience". Seizure 13 (Suppl 1): S41-8 discussion S49. DOI:10.1016/j.seizure.2004.04.021.
- van_Rijckevorsel-Harmant, K.; M. Delire and M. Rucquoy-Ponsar (1986). "Treatment of idiopathic West and Lennox-Gastaut syndromes by intravenous administration of human polyvalent immunoglobulins". European Archives of Psychiatry and Neurological Sciences 236 (2): 119-22. PubMed.