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__NOTOC__
{{Infobox_Disease |
{{Infobox_Disease |
   Name        = Lennox-Gastaut syndrome |
   Name        = Lennox-Gastaut syndrome |
   ICD10      = {{ICD10|G|40|4|g|40}} |
   ICD10      = {{ICD10|G|40|4|g|40}} |
   ICD9        = {{ICD9|345.0}} |
   ICD9        = {{ICD9|345.0}} |
  eMedicineSubj  = neuro |
  eMedicineTopic = 186 |
   DiseasesDB    = 29493 |
   DiseasesDB    = 29493 |
}}
}}
{{SI}}
{{SI}}
{{CMG}}


{{EH}}
{{SK}} Lennox syndrome, LGS


'''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.
==Overview==
'''Lennox-Gastaut syndrome''' is a difficult-to-treat form of childhood-onset [[epilepsy]]. It is often accompanied by [[mental retardation]] and behavior problems.
==Historical Perspective==
LGS was named for [[neurology|neurologist]] [[William G. Lennox]] (Boston, USA) and [[Henri Gastaut]] (Marseille, France).


==Characteristics==
==Pathophysiology==
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.
The most frequently occurring seizure types are: [[tonic seizure|tonic]], which are often nocturnal (90%); the second most frequent are [[myoclonic seizure]]s, which often occur when the patient is over-tired.<ref name=tired_bad>{{cite web | title=Childhood seizures - epilepsy and convulsions in children | url=http://hcd2.bupa.co.uk/fact_sheets/html/childhood_seizures.html | accessdate= August 16 | accessyear= 2005 }}</ref>
 
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 seizure|tonic]], which are often nocturnal (90%); the second most frequent are [[myoclonic seizure]]s, which often occur when the patient is over-tired.<ref name=tired_bad>{{cite web | title=Childhood seizures - epilepsy and convulsions in children | url=http://hcd2.bupa.co.uk/fact_sheets/html/childhood_seizures.html | accessdate= August 16 | accessyear= 2005 }}</ref>


[[Atonic seizure|Atonic]], [[atypical absence seizure|atypical absence]], [[complex partial seizure|complex partial]], [[focal seizure|focalized]] and [[tonic-clonic seizure]]s 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. <!--Insbesondere die atypischen Absencen können mit statusartiger Häufung vorkommen.--> The seizures can cause sudden falling (or [[spasm]]s in tonic, atonic and myoclonic episodes) and/or loss of balance, which is why patients often wear a helmet to prevent head injury.
[[Atonic seizure|Atonic]], [[atypical absence seizure|atypical absence]], [[complex partial seizure|complex partial]], [[focal seizure|focalized]] and [[tonic-clonic seizure]]s 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. <!--Insbesondere die atypischen Absencen können mit statusartiger Häufung vorkommen.--> The seizures can cause sudden falling (or [[spasm]]s in tonic, atonic and myoclonic episodes) and/or loss of balance, which is why patients often wear a helmet to prevent head injury.
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In addition to daily multiple seizures of various types, children with LGS frequently have arrested/slowed [[psychomotor development]] and behavior disorders.
In addition to daily multiple seizures of various types, children with LGS frequently have arrested/slowed [[psychomotor development]] and behavior disorders.


The syndrome is also characterized by an [[Wiktionary:interictal|interictal]] (between-seizures) [[electroencephalogram|EEG]] featuring slow [[spike-wave complexe]]s.
==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)  
* [[Developmental disorder]]
* [[Tuberous sclerosis]]
* Hereditary metabolic diseases
* [[Encephalitis]]
* [[Meningitis]]
* [[Toxoplasmosis]]
* [[Hypoxia (medical)|hypoxia]]-[[ischemia]] injury
* [[Birth injuries]]
* [[Lesion]]s of the [[frontal lobe]]- these patients tend to have a worse prognosis than the idiopathic ones.
* [[Porphyrias]] - neurovisceral porphyrias
 
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.
 
==Epidemiology and Demographics==


==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.
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.
 
===Age===
It is most common in between second and sixth year of life.
===Gender===
It is more common in males than females.
===Finland===
===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.<ref name=Finland>{{cite journal | author = Heiskala H. | title = Community-based study of Lennox-Gastaut syndrome | journal = Epilepsia | volume = 38 | issue = 5 | year = 1997 | pages = 526-31 | id = {{PMID|9184597}} | url = http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9184597.ui}}</ref>
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.<ref name=Finland>{{cite journal | author = Heiskala H. | title = Community-based study of Lennox-Gastaut syndrome | journal = Epilepsia | volume = 38 | issue = 5 | year = 1997 | pages = 526-31 | id = {{PMID|9184597}} | url = http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9184597.ui}}</ref>


===United States===
===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.<ref name=trevathanetal1997>{{cite journal | author=Trevathan E, Murphy CC, Yeargin-Allsopp M. | title=Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children | journal=Epilepsia | volume=38 | issue=12 | year=1997 | pages=1283-8 | id={{PMID|9578523}} | url = [http://gateway.ut.ovid.com/gw1/ovidweb.cgi?T=JS&PAGE=fulltext&D=ovft&AN=00003606-199712000-00005&NEWS=N&CSC=Y&CHANNEL=PubMed}}</ref>
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.<ref name=trevathanetal1997>{{cite journal | author=Trevathan E, Murphy CC, Yeargin-Allsopp M. | title=Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children | journal=Epilepsia | volume=38 | issue=12 | year=1997 | pages=1283-8 | id={{PMID|9578523}} | url = [http://gateway.ut.ovid.com/gw1/ovidweb.cgi?T=JS&PAGE=fulltext&D=ovft&AN=00003606-199712000-00005&NEWS=N&CSC=Y&CHANNEL=PubMed}}</ref>


==Mortality and morbidity==
===Mortality and morbidity===
The mortality rate ranges from 3% to 7%.<ref name=7percent>{{cite web | author=Glauser, Tracy A. and Morita, Diego A. | year=2002 | title=Introduction | url=http://www.emedicine.com/neuro/topic186.htm | work=Lennox-Gastaut Syndrome | publisher=eMedicine.com, Inc. | accessdate=8 July | accessyear=2005 }}</ref>
The mortality rate ranges from 3% to 7%.<ref name=7percent>{{cite web | author=Glauser, Tracy A. and Morita, Diego A. | year=2002 | title=Introduction | url=http://www.emedicine.com/neuro/topic186.htm | work=Lennox-Gastaut Syndrome | publisher=eMedicine.com, Inc. | accessdate=8 July | accessyear=2005 }}</ref>
==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]]; [[Hypoxia (medical)|hypoxia]]-[[ischemia]] injury and other birth injuries; and [[lesion]]s of the [[frontal lobe]]. These patients tend to have a worse prognosis than the idiopathic ones.
==Natural History, Complications, Prognosis==
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.


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.
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.
==Diagnosis==
===Symptoms===
* Daily multiple seizures
* Dizziness


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.
===Physical Examination===
====Neurologic====
* Unresponsive
* [[Status epilepticus]]
* Loss of balance


==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.
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.
<!--This stays up until someone can better translate it.
<!--This stays up until someone can better translate it.
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Bei der allgemeinmedizinischen Untersuchung fallen bei den meisten Kindern mit LGS im physischen Bereich Besonderheiten auf, insbesondere ist eine deutliche Entwicklungsverzögerung zu erkennen. Darüber hinaus zeigen sich vielfach kognitive Schwächen, eine entsprechende Einschränkung der  Leistungsfähigkeit und Verhaltenauffälligkeiten. Die Besonderheiten können schon vor dem erstmaligen Auftreten der epileptischen Anfälle in Erscheinung getreten sein, aber auch erst nach bis zu zwei Jahren nach der Manifestation des LGS auftreten und sind vielfach auf die Grunderkrankung zurückzuführen, dass zu den Anfällen geführt hat.-->
Bei der allgemeinmedizinischen Untersuchung fallen bei den meisten Kindern mit LGS im physischen Bereich Besonderheiten auf, insbesondere ist eine deutliche Entwicklungsverzögerung zu erkennen. Darüber hinaus zeigen sich vielfach kognitive Schwächen, eine entsprechende Einschränkung der  Leistungsfähigkeit und Verhaltenauffälligkeiten. Die Besonderheiten können schon vor dem erstmaligen Auftreten der epileptischen Anfälle in Erscheinung getreten sein, aber auch erst nach bis zu zwei Jahren nach der Manifestation des LGS auftreten und sind vielfach auf die Grunderkrankung zurückzuführen, dass zu den Anfällen geführt hat.-->
* [[EEG]]
===[[EEG]]===
* [[MRI]]
The syndrome is also characterized by an [[Wiktionary:interictal|interictal]] (between-seizures) [[electroencephalogram|EEG]] featuring slow [[spike-wave complexe]]s.
* [[CT scan]]s, usually in the case of suspected injury resulting from an atonic and/or tonic seizure.
===[[CT]]===
* Useful in evaluating the underlying cause of seizures
===[[MRI]]===
* Useful in evaluating the minor lesions as in hypoxic ischemic encephalopahy


==Treatment==
==Treatment==
LGS seizures are often treatment resistant, but this does not mean that treatment is futile. Options include anticonvulsants, anesthetics, steroids such as [[prednisone]], [[immunoglobulin]]s, and various other pharmacological agents that have been reported to work in individual patients.
LGS seizures are often treatment resistant, but this does not mean that treatment is futile. Options include anticonvulsants, anesthetics, steroids such as [[prednisone]], [[immunoglobulin]]s, and various other pharmacological agents that have been reported to work in individual patients.  Care must be taken to avoid porphyrinogenic anti-seizure drugs.


=====First-line drugs=====
=====First-line drugs=====
Line 107: Line 138:


Viele Betroffene sind auch nach erfolgreicher Einstellung der Anfälle körperlich und kognitiv deutlich beeinträchtigt, wobei dies in der Regel nicht in erster Linie auf die epileptischen Anfälle sondern auf deren Ursache (hirnorganische Besonderheit bzw. dessen Schweregrad) zurückgeführt werden kann. Häufig zeigen sich auch im Erwachsenenalter Lernstörungen, Sprachstörungen und Bewegungsstörungen sowie eine Einschränkung der kognitiven Leistungsfähigkeit und [[Cerebralparese]]n.-->
Viele Betroffene sind auch nach erfolgreicher Einstellung der Anfälle körperlich und kognitiv deutlich beeinträchtigt, wobei dies in der Regel nicht in erster Linie auf die epileptischen Anfälle sondern auf deren Ursache (hirnorganische Besonderheit bzw. dessen Schweregrad) zurückgeführt werden kann. Häufig zeigen sich auch im Erwachsenenalter Lernstörungen, Sprachstörungen und Bewegungsstörungen sowie eine Einschränkung der kognitiven Leistungsfähigkeit und [[Cerebralparese]]n.-->
==History==
LGS was named for [[neurology|neurologist]] [[William G. Lennox]] (Boston, USA) and [[Henri Gastaut]] (Marseille, France).<!--
die diese Form der Epilepsie in den 1950er Jahren (ab [[1945]]) erstmals eingehend unter wissenschaftlichen Gesichtspunkten beschrieben und sich intensiv mit ihrer Erforschung und Abgrenzung zu anderen Formen der Epilepsie befassten.-->


==References==
==References==
Line 125: Line 151:


{{Diseases of the nervous system}}
{{Diseases of the nervous system}}
{{SIB}}
 
[[Category:Neurology]]
[[Category:Neurology]]
[[Category:Epilepsy]]
[[Category:Epilepsy]]
[[Category:Disease]]


[[de:Lennox-Gastaut-Syndrom]]
[[fr:Syndrome de Lennox-Gastaut]]
[[nl:Lennox-syndroom]]
[[pl:Zespół Lennoxa-Gastauta]]
[[pt:Síndrome de Lennox-Gastaut]]
[[fi:Lennox-Gastaut'n oireyhtymä]]
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Latest revision as of 19:38, 10 August 2012

Lennox-Gastaut syndrome
ICD-10 G40.4
ICD-9 345.0
DiseasesDB 29493

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Lennox syndrome, LGS

Overview

Lennox-Gastaut syndrome is a difficult-to-treat form of childhood-onset epilepsy. It is often accompanied by mental retardation and behavior problems.

Historical Perspective

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

Pathophysiology

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.

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

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.

Epidemiology and Demographics

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.

Age

It is most common in between second and sixth year of life.

Gender

It is more common in males than females.

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]

Natural History, Complications, Prognosis

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.

Diagnosis

Symptoms

  • Daily multiple seizures
  • Dizziness

Physical Examination

Neurologic

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.

EEG

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

CT

  • Useful in evaluating the underlying cause of seizures

MRI

  • Useful in evaluating the minor lesions as in hypoxic ischemic encephalopahy

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. Care must be taken to avoid porphyrinogenic anti-seizure drugs.

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.[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]

Felbamate is indicated in the use of LGS in the event that everything else fails,[10] and was found to be superior to placebo in controlling treatment resistant partial seizures and atonic seizures.[11][12] However, it has been known to cause aplastic anemia and liver toxicity.[13]

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).[14]

Zonisamide showed promise in an overview of controlled and uncontrolled trials conducted in Japan.[15] However, in a physician survey conducted December of 2004, only 28% of Lennox-Gastaut and West syndrome patients improved on zonisamide.[16]

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.[17]


References

  1. "Childhood seizures - epilepsy and convulsions in children". Retrieved August 16. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  2. Heiskala H. (1997). "Community-based study of Lennox-Gastaut syndrome". Epilepsia. 38 (5): 526–31. PMID 9184597.
  3. Trevathan E, Murphy CC, Yeargin-Allsopp M. (1997). ["Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children" Check |url= value (help). Epilepsia. 38 (12): 1283–8. PMID 9578523.
  4. Glauser, Tracy A. and Morita, Diego A. (2002). "Introduction". Lennox-Gastaut Syndrome. eMedicine.com, Inc. Retrieved 8 July. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  5. 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" Check |url= value (help). Neurology. 10 (52): 1882–7. PMID 10371538.
  6. 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. PMID 12640599.
  7. 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. PMID 9400037.
  8. Epilepsy Ontario (1999). "Lamotrigine Approved in Canada for Lennox-Gastaut Syndrome". 'Sharing' News. Retrieved 13 November. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  9. 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 13 November. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  10. "Felbatol (felbamate)". p. 3. Retrieved 2007-09-19.
  11. Ritter, Frank J. (1993). "Efficacy of Felbamate in Childhood Epileptic Encephalopathy (Lennox-Gastaut Syndrome)". New England Journal of Medicine. 328 (1): 29–33. PMID 8347179. Unknown parameter |coauthors= ignored (help)
  12. Devinsky, Orrin (1995). "Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures". Epilepsy Research. 20 (3): 241–6. PMID 7796796. Unknown parameter |coauthors= ignored (help)
  13. O'Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S (1996). "Felbamate-associated fatal acute hepatic necrosis". Neurology. 46 (5): 1457–1459. PMID 8628501.
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See also


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