Lennox-Gastaut Syndrome

Synonyms: childhood epileptic encephalopathy

The syndrome is characterized by multiple types of seizures, mental retardation or regression, and an abnormal EEG with generalized slow spike-and-wave discharges.

• The most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalized tonic-clonic, and partial seizures may also occur.¹
• Seizures are often resistant to treatment.
• Lennox-Gastaut syndrome can be classified as either idiopathic (25% of the total) or symptomatic (75%). In idiopathic, normal psychomotor development occurs prior to the onset of symptoms and no neurological or neuro- radiological abnormalities are found.
• Symptomatic cases are due to diverse cerebral conditions, which are usually bilateral, diffuse, or multifocal, involving cerebral grey matter.²
• Examples of underlying disorders responsible for symptomatic Lennox-Gastaut include encephalitis, meningitis, tuberous sclerosis, brain malformations, birth injury, frontal lobe lesions and trauma.

• Prevalence is about 2 per 10,000 in Europe
• The number of children affected is not known with certainty but it may account for about 3% of all childhood epilepsies³
• Males are affected five times more often than females

• Twenty percent of all patients with Lennox-Gastaut syndrome have prior infantile spasms with hypsarrythmia.²
• The mean age of epilepsy onset is 2 years.
• Young children may show mood instability, personality disturbances, or slowing of psychomotor development.
• Older children experience personality problems, acute psychotic episodes, or chronic psychosis with aggressiveness, irritability, or social isolation.
• Mental deterioration leads to apathy and memory disorders.
• Physical examination can be important in helping to identify specific aetiologies although there are no pathognomonic physical findings.

• Epilepsy with mental retardation
• Infantile spasms
• Juvenile myoclonic epilepsy
• Myoclonic-astatic epilepsy

• Electroencephalogram:
  • Interictal EEG is characterized by a slow background that can be either constant or transient.
  • The characteristic interictal EEG pattern is 1.5 to 2.5 Hz slow spike wave activity, which is bilaterally synchronous, dominant over the frontocentral regions, and usually symmetrical.²
  • The characteristic diffuse slow spike wave pattern gradually disappears with age and is replaced by focal epileptic discharges.
• MRI is important in order to search for an underlying aetiology.
• Positron emission tomography or single-photon emission computed tomography may be useful during evaluation for epilepsy surgery.

A ketogenic diet appears useful in a minority of patients. Potential serious adverse effects include dehydration, metabolic acidosis when the diet is initiated, renal stones, cardiac abnormalities and an abnormal lipid profile.

Drugs

• Anticonvulsants are the mainstay of therapy but the optimum treatment for Lennox-Gastaut syndrome remains uncertain.⁴ A combination of drugs is usually required.
• Sodium valproate, felbamate, lamotrigine (with or without sodium valproate) and topiramate may be effective;⁴ ethosuximide is also worth trying for atypical absences.³
• Benzodiazepines can be effective in the remainder of seizure types but unfortunately the effect is often transient.³
• Tonic seizures may persist and be more difficult to control over time, while myoclonic and atypical absences appear easier to control.

Surgical

• Corpus callosotomy is effective in reducing drop attacks but typically is not helpful for other seizure types and is considered palliative rather than curative.
• Seizure freedom following corpus callosotomy is rare but can occur.
• Vagus nerve stimulation has been reported to reduce seizure frequency but the results are anecdotal.³

• Injuries or death resulting from a seizure.
• Renal, cardiac, or metabolic complications resulting from a ketogenic diet.

• Long-term prognosis overall is unfavourable but variable.⁵
• A minority of patients can eventually work normally, but many still have typical characteristics (mental retardation, treatment resistant seizures) many years after the onset.
• A worse prognosis is associated with symptomatic Lennox-Gastaut, early onset of seizures, prior history of infantile spasms, higher frequency of seizures, or constant slow EEG background activity.