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Lennox–Gastaut syndrome
Classification and external resources
ICD-10 G40.4
ICD-9 345.0
DiseasesDB 29493
eMedicine neuro/186

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.

Contents

Characteristics

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 six. 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 psycho-motor development and behavior disorders.

The syndrome is also characterized by an interictal (between-seizures) EEG featuring slow spike-wave complexes.

Incidence and prevalence

Approximately 5% of children with epilepsy have LGS, and it 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.

Finland

According to a 1997 community-based retrospective study in the Helsinki metropolitan area and the province of Uusimaa, the annual incidence of Lennox–Gastaut was 2 in 100,000 (0.002%) from 1975–1985.[2]

United States

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]

Causes

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; hypoxiaischemia 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.

Lennox–Gastaut syndrome, drug resistant/drug refractory epilepsy have been recorded with neurovisceral porphyrias including acute intermittent porphyria, hereditary coproporphyria and variegate porphyria. Care must be taken to avoid porphyrinogenic anti-seizure drugs in these cases. Diagnosis may be difficult in children who require enzyme or DNA testing.

Diagnosis

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.

The diagnosis or suspicion of LGS is often a question of probability rather than certainty. This is because the varied presentations of LGS share features with other disorders, many of which may be said to have overlapping characteristics.

The diagnosis is more obvious when the epilepsy has frequent and manifold attacks, with the classic pattern on the electro-encephalogram (EEG); the latter is a slowed rhythm with Spike-wave-pattern, or with a multifocal and generalizing Sharp-slow-wave-discharges at 1.5–2.5 Hz. During sleep, frequently, tonic patterns can be seen. But variations of these patterns are known in patients with no diagnosis other than LGS, and they can differ bilaterally, and from time to time, within the same patient.

General medical investigation usually reveals developmental delay and cognitive deficiencies in children with true LGS. These may precede development of seizures, or require up to two years after the seizures begin, in order to become apparent.

Exclusion of organic or structural brain lesions is also important in establishing a correct diagnosis of LGS; this may require magnetic resonance imaging (MRI) or computerized tomography (CT). An important differential diagnosis is 'Pseudo-Lennox-Syndrome', which differs from LGS, in that there are no tonic seizures; sleeping EEG provides the best basis for distinguishing between the two.

Treatment

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.

Pharmacological

No scientific study has shown any drug to be highly efficacious for treatment of LGS, and its best treatment remains uncertain. Rufinamide(Banzel), lamotrigine, topiramate and felbamate may help as add-on therapy.[5]

Approved

First-line drugs

Nitrazepam and Clobazam are not approved in the USA.

Second-line drugs

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.[6] 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 2003.[7]

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.[8] Two years later, it was approved by Health Canada for adjunctive therapy in Lennox Gastaut in adults and children.[9] The United States Food and Drug Administration approved it for that in August 1998.[10]

Felbamate is indicated in the use of LGS in the event that everything else fails,[11] and was found to be superior to placebo in controlling treatment resistant partial seizures and atonic seizures.[12][13] However, it has been known to cause aplastic anemia and liver toxicity.[14]

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).[15]

Zonisamide showed promise in an overview of controlled and uncontrolled trials conducted in Japan.[16] However, in a physician survey conducted December 2004, only 28% of Lennox–Gastaut and West syndrome patients improved on zonisamide.[17]

Surgical

Other

Ketogenic diet

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.[18 ]

History

LGS was named for neurologists William G. Lennox (Boston, USA) and Henri Gastaut (Marseille, France).

References

  1. ^ "Childhood seizures – epilepsy and convulsions in children". http://hcd2.bupa.co.uk/fact_sheets/html/childhood_seizures.html. Retrieved August 16, 2005.  
  2. ^ Heiskala, H (1997). "Community-based study of Lennox-Gastaut syndrome". Epilepsia 38 (5): 526–31. doi:10.1111/j.1528-1157.1997.tb01136.x. PMID 9184597.  
  3. ^ Trevathan, E; Murphy, CC; Yeargin-Allsopp, M (1997). "Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children". Epilepsia 38 (12): 1283–8. doi:10.1111/j.1528-1157.1997.tb00065.x. PMID 9578523.  
  4. ^ Glauser, Tracy A. and Morita, Diego A. (2002). "Introduction". Lennox–Gastaut Syndrome. eMedicine.com, Inc.. http://www.emedicine.com/neuro/topic186.htm. Retrieved 8 July 2005.  
  5. ^ Hancock, EC; Cross, HH (2009). "Treatment of Lennox-Gastaut syndrome". Cochrane database of systematic reviews (Online) (3): CD003277. doi:10.1002/14651858.CD003277.pub2. PMID 19588340.  
  6. ^ Sachdeo, R. C. (1999). "A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome". Neurology 52 (9): 1882. PMID 10371538. http://www.neurology.org/cgi/content/abstract/52/9/1882.  
  7. ^ Alva-Moncayo, E; Ruiz-Ruiz, A (2003). "Utilidad del topiramato como terapia añadida a esquemas convencionales para el síndrome de Lennox-Gastaut [The value of topiramate used with conventional schemes as an adjunctive therapy in the treatment of Lennox-Gastaut syndrome]" (in Spanish). Revista de neurologia 36 (5): 453–7. PMID 12640599. http://www.revneurol.com/sec/resumen.php?or=pubmed&id=2002014.  
  8. ^ 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". The New England journal of medicine 337 (25): 1807–12. doi:10.1056/NEJM199712183372504. PMID 9400037.  
  9. ^ Epilepsy Ontario (1999). "Lamotrigine Approved in Canada for Lennox–Gastaut Syndrome". 'Sharing' News. http://epilepsyontario.org/client/EO/EOWeb.nsf/web/Lamotrigine+Approved+in+Canada+for+Lennox-Gastaut+Syndrome. Retrieved 13 November 2005.  
  10. ^ 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. http://www.fda.gov/cder/foi/nda/98/020241s003.htm. Retrieved 13 November 2005.  
  11. ^ "Felbatol (felbamate)". p. 3. http://www.rxlist.com/cgi/generic/felbamate_ids.htm. Retrieved 2007-09-19.  
  12. ^ The Felbamate Study Group In Lennox-gastaut Syndrome (1993). "Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). The Felbamate Study Group in Lennox-Gastaut Syndrome". The New England journal of medicine 328 (1): 29–33. doi:10.1056/NEJM199301073280105. PMID 8347179.  
  13. ^ Devinsky, O; Faught, RE; Wilder, BJ; Kanner, AM; Kamin, M; Kramer, LD; Rosenberg, A (1995). "Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures". Epilepsy research 20 (3): 241–6. doi:10.1016/0920-1211(94)00084-A. PMID 7796796.  
  14. ^ O'neil, MG; Perdun, CS; Wilson, MB; Mcgown, ST; Patel, S (1996). "Felbamate-associated fatal acute hepatic necrosis". Neurology 46 (5): 1457–9. PMID 8628501.  
  15. ^ 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. doi:10.1111/j.1528-1157.1994.tb02544.x. PMID 7925171.  
  16. ^ Yagi, K (2004). "Overview of Japanese experience-controlled and uncontrolled trials". Seizure : the journal of the British Epilepsy Association 13 Suppl 1: S11–5; discussion S16. doi:10.1016/j.seizure.2004.04.018. PMID 15511680.  
  17. ^ Yamauchi, T; Aikawa, H (2004). "Efficacy of zonisamide: our experience". Seizure : the journal of the British Epilepsy Association 13 Suppl 1: S41–8; discussion S49. doi:10.1016/j.seizure.2004.04.021. PMID 15511689.  
  18. ^ Van Rijckevorsel-Harmant, K; Delire, M; Rucquoy-Ponsar, M (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. doi:10.1007/BF00454021. PMID 3792407.  

See also








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