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 developmental delay and psychological and behavioral problems.

Characteristics [edit]

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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 type is tonic seizures, which are often nocturnal (90%); the second most frequent are myoclonic seizures, which often occur when the person is over-tired.^[1]

Atonic, atypical absence, tonic, complex partial, focalized and tonic–clonic seizures are also common. Additionally, about half of patients will have 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 [edit]

Approximately 5% of children with epilepsy have LGS,^{[citation needed]} and it is more common in males than females.^{[citation needed]} 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.^{[citation needed]} West syndrome is characterized by Blitz Nick Salaam seizures, and typically evolves into LGS in the second year of life.^{[citation needed]}

Finland [edit]

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 to 1985.^[2]

United States [edit]

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 [edit]

The mortality rate ranges from 3-7% in a mean follow up period of 8.5 to 9.7 years. Death is often related to accidents.^[4]

Causes [edit]

There is no uniform cause: in 20% of the concerned, the LGS develops from the West syndrome.^{[citation needed]} The medical history frequently includes infantile spasms or focalized and generalized seizures.

The most common type of LGS (70–78%) is symptomatic (secondary) - that is an identifiable underlying pathology is responsible.^{[citation needed]} 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.^{[citation needed]}

In up to one-third of cases no cause can be found.^{[citation needed]} These cases are referred as cryptogenic if a cause is suspected, but 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 [edit]

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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 [edit]

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 [edit]

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 [edit]

First-line drugs [edit]

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

Nitrazepam is not approved in the USA.

Clobazam has been recently approved by the FDA on 10/24/11.

Second-line drugs [edit]

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 [edit]

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 [edit]

• vagus nerve stimulation
• corpus callosotomy

Other [edit]

Ketogenic diet [edit]

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 [edit]

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 [edit]

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

In 2010 the first documentary highlighting this disorder was produced by Eisai Inc. in cooperation with the LGS Foundation.

http://www.livingwithlgs.com/lgs-documentary.aspx

Support [edit]

Caregivers of individuals living with Lennox-Gastaut Syndrome may seek support and information from a variety of resources including the LGS Foundation and the Epilepsy Foundation of America. The LGS Foundation offers regional support groups across the United States and numerous programs and services.

Resources [edit]

LGS Foundation [1]
Epilepsy.com [2]
Epilepsy Foundation [3]

References [edit]

See also [edit]

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