Lennox-Gastaut syndrome
| Lennox-Gastaut syndrome | |
| ICD-10 | G40.4 |
|---|---|
| ICD-9 | 345.0 |
| DiseasesDB | 29493 |
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
- Encephalopathy (brain damage)
- Developmental disorder
- Tuberous sclerosis
- Hereditary metabolic diseases
- Encephalitis
- Meningitis
- Toxoplasmosis
- hypoxia-ischemia injury
- Birth injuries
- Lesions 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
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
- Unresponsive
- Status epilepticus
- Loss of balance
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
- valproates (valproic acid, sodium valproate and valproate semisodium)
- benzodiazepines, specifically clonazepam, nitrazepam, and clobazam
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
- ↑ "Childhood seizures - epilepsy and convulsions in children". Retrieved August 16. Unknown parameter
|accessyear=ignored (|access-date=suggested) (help); Check date values in:|accessdate=(help) - ↑ Heiskala H. (1997). "Community-based study of Lennox-Gastaut syndrome". Epilepsia. 38 (5): 526–31. PMID 9184597.
- ↑ 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. - ↑ 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) - ↑ 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. - ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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) - ↑ "Felbatol (felbamate)". p. 3. Retrieved 2007-09-19.
- ↑ 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) - ↑ 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) - ↑ 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.
- ↑ 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 (2004). "Efficacy of zonisamide: our experience". Seizure. 13 (Suppl 1): S41-8 discussion S49. doi:10.1016/j.seizure.2004.04.021. Unknown parameter
|coauthors=ignored (help); Unknown parameter|month=ignored (help) - ↑ van Rijckevorsel-Harmant, K. (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. PMID 3792407. Unknown parameter
|coauthors=ignored (help)