Lennox-Gastaut syndrome

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

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.

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 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.cite web | title=Childhood seizures - epilepsy and convulsions in children | url=http://hcd2.bupa.co.uk/fact_sheets/html/childhood_seizures.html | accessmonthday= August 16 | accessyear= 2005 ]

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.

The syndrome is also characterized by an (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.cite journal | author = Heiskala H. | title = Community-based study of Lennox-Gastaut syndrome | journal = Epilepsia | volume = 38 | issue = 5 | year = 1997 | pages = 526–31 | pmid = 9184597 | url = http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9184597.ui | doi = 10.1111/j.1528-1157.1997.tb01136.x]

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.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 | 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| doi=10.1111/j.1528-1157.1997.tb00065.x]

Mortality and morbidity

The mortality rate ranges from 3% to 7%.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. | accessdaymonth=8 July | accessyear=2005 ]

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-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.

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.

"A temporary machine translation of the above German text is:"::Generally is to be said that the LGS often only heavily can be limited as a syndrome and/or lets delimit clearly of other syndromes because there are various and in part fluent transitions to similar Syndromen. How already carried out is no uniform cause for example given, that that Diagnostics simplify would become.

::Is openly visible this form of the epilepsy through frequent and manifold attacks. In the measurement of the brain waves by means of a EEGs, an as a rule slowed down reason rhythm with of Spike-wave-pattern slow always or multifokalen and generalizing Sharp-slow-wave-discharges, that can be registered with a frequency between 1.5 and 2.5 once per second, appears. Variations of the patterns are indicating possible that it can come to side difference and stove-shaped peculiarities in the derivation. In the sleep, frequently tonic patterns can, therefore series of quick tip, registers become.

::Especially the Differentialdiagnose to the " ‚Pseudo-Lennox-Syndrom' " must be clarified, which differs through it by the LGS, that no tonic attacks appear. Based on whose the diagnosis must result through EEG in the sleep (sleep EEG) because the attacks typical tonic for the LGS appear usually in the sleep

::For the examination of the existence of a brain organic peculiarity, an imaging investigation of the brain is by means of Magnetresonanztomographie (MRT) or Computertomographie (CT) possible. If the movement patterns appear side emphasizes in especially the tonic attacks, this lets assume for example a brain damage of the corresponding side, that should investigated become.

::In the general medical investigation, peculiarities be noticeable is to be recognized at most children with LGS in the physical area, especially a clear development delay. In addition multiply cognitive weakness, a corresponding restriction of the efficiency and behavior striking features appear. The peculiarities can have appeared already before the initial appearance of the epileptic attacks, but appear and are also first after up to two years after the manifestation of the LGS to lead back multiply to the reason disease that to the attacks led has.
* EEG
* MRI
* CT scans, usually in the case of suspected injury resulting from an atonic and/or tonic seizure.

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

Approved

First-line drugs

* valproates (valproic acid, sodium valproate and valproate semisodium)
* benzodiazepines, specifically clonazepam, nitrazepam, and clobazam

Nitrazepam and Clobazam are not approved in the USA.

econd-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.cite journal | author=Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G | title=A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group | journal=Neurology | volume=10 | issue=52 | year=1999 | pages=1882–7 | pmid=10371538 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=10371538&dopt=ExternalLink] 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.cite journal | author=Alva-Moncayo E, Ruiz-Ruiz A | title= [The value of topiramate used with conventional schemes as an adjunctive therapy in the treatment of Lennox-Gastaut syndrome] | journal= Revista de Neurologia | volume=36 | issue=5 | year=2003 | pages=453–7 | pmid=12640599 | url = http://www.revneurol.com/LinkOut/formMedLine.asp?Refer=2002014&Revista=Revneurol]

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.cite journal | author=Motte J, Trevathan E, Arvidsson JF, Barrera MN, Mullens EL, Manasco P | title=Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group | journal=New England Journal of Medicine | volume=337 | issue=25 | year=1997 | pages=1807–12 | pmid=9400037 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9400037&dopt=ExternalLink | doi=10.1056/NEJM199712183372504] Two years later, it was approved by Health Canada for adjunctive therapy in Lennox Gastaut in adults and children.cite web | author = Epilepsy Ontario | year = 1999 | url = http://epilepsyontario.org/client/EO/EOWeb.nsf/web/Lamotrigine+Approved+in+Canada+for+Lennox-Gastaut+Syndrome | title = Lamotrigine Approved in Canada for Lennox-Gastaut Syndrome | work = 'Sharing' News | accessdaymonth = 13 November | accessyear = 2005] The United States Food and Drug Administration approved it for that in August 1998.cite web | author = Glaxo Wellcome Inc | year = 1998 | url = http://www.fda.gov/cder/foi/nda/98/020241s003.htm | title = Final Printed Labeling -- Part 1 | work = Lamictal Tablets & Chewable Dispersible Tablets (Lamotrigine) Drug Approval Page | publisher = United States Food and Drug Administration Center for Drug Evaluation and Research | accessdaymonth = 13 November | accessyear = 2005]

Felbamate is indicated in the use of LGS in the event that everything else fails,cite web | url = http://www.rxlist.com/cgi/generic/felbamate_ids.htm | title = Felbatol (felbamate) | accessdate = 2007-09-19 | page = 3 ] and was found to be superior to placebo in controlling treatment resistant partial seizures and atonic seizures.cite journal | first = Frank J. | last = Ritter | coauthors = 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 | title=Efficacy of Felbamate in Childhood Epileptic Encephalopathy (Lennox-Gastaut Syndrome) | journal=New England Journal of Medicine | volume=328 | issue=1 | year=1993 | pages=29–33 | pmid=8347179 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=8347179&dopt=ExternalLink | doi=10.1056/NEJM199301073280105] cite journal | first = Orrin | last = Devinsky | coauthors = R. Edward Faught, B. Joseph Wilder, Andres M. Kanner, Marc Kamin, L. D. Kramer and A. Rosenberg | title=Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures | journal=Epilepsy Research | volume=20 | issue=3 | year=1995 | pages=241–6 | pmid=7796796 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=7796796&dopt=ExternalLink | doi=10.1016/0920-1211(94)00084-A] However, it has been known to cause aplastic anemia and liver toxicity.cite journal | author=O'Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S | title=Felbamate-associated fatal acute hepatic necrosis | journal=Neurology | volume=46 | issue=5 | year=1996 | pages=1457–1459 | pmid=8628501 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=8628501&dopt=ExternalLink]

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).cite journal | author=Feucht M, Brantner-Inthaler S | title=Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study | journal=Epilepsia | volume=35 | issue=5 | year=1994 | pages=993–8 | pmid=7925171 | doi=10.1111/j.1528-1157.1994.tb02544.x]

Zonisamide showed promise in an overview of controlled and uncontrolled trials conducted in Japan.cite journal | author=Yagi K | title=Overview of Japanese experience-controlled and uncontrolled trials | journal=Seizure | volume=13 | issue=Supplement 1 | year=2004 | pages=S11–5; discussion S16 | id=PMID [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15511680&query_hl=14&itool=pubmed_docsum 15511680] | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15511680&dopt=ExternalLink | doi=10.1016/j.seizure.2004.04.018] However, in a physician survey conducted December 2004, only 28% of Lennox-Gastaut and West syndrome patients improved on zonisamide.cite journal | first = Toshio | last = Yamauchi | coauthors = Aikawa Hiroshi | year = 2004 | month = December | title = Efficacy of zonisamide: our experience | journal = Seizure | volume = 13 | issue = Suppl 1 | pages = S41–8 discussion S49 | doi = 10.1016/j.seizure.2004.04.021 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15511689&dopt=ExternalLink]

urgical

* vagus nerve stimulation
* corpus callosotomy

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.cite journal | first = K. | last = van Rijckevorsel-Harmant | coauthors = M. Delire and M. Rucquoy-Ponsar | year = 1986 | title = Treatment of idiopathic West and Lennox-Gastaut syndromes by intravenous administration of human polyvalent immunoglobulins | journal = European Archives of Psychiatry and Neurological Sciences | volume = 236 | issue = 2 | pages = 119–22 | pmid = 3792407 | doi = 10.1007/BF00454021]

History

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

References

ee also

* Epilepsy
* West syndrome
* Ohtahara syndrome
* Syndromes
* Epilepsy Phenome/Genome Project