Background
Symptomatic generalized epilepsy (SGE) encompasses a group of challenging epilepsy syndromes. As a group, SGE has 3 main features: (1) multiple seizure types, especially generalized tonic and atonic seizures; (2) brain dysfunction other than the seizures, in the intellectual domain (mental retardation or developmental delay) and in the motor domain (cerebral palsy); and (3) EEG evidence of diffuse brain abnormality.
The following are examples of epilepsy syndromes that are included in the category of SGE:
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Early myoclonic encephalopathy
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Early infantine epileptic encephalopathy with suppression bursts or Ohtahara syndrome
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West syndrome
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Epilepsy with myoclonic atonic seizures
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Epilepsy with myoclonic absence
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Lennox-Gastaut syndrome
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Progressive myoclonic epilepsies
See the following Medscape Reference epilepsy topics for more information on these conditions:
Pathophysiology
Overall, seizures are a paroxysm of high-frequency or synchronous low-frequency high-voltage electrical discharges that cause a sudden alteration in the CNS. Three conditions are involved: (1) population of pathologically excitable neurons, (2) an increase in excitatory glutaminergic activity, and (3) reduction of inhibitory GABAergic projections. [1] In symptomatic generalized epilepsy, an underlying structural or metabolic derangement is also present. EEG findings reflect age-related changes as the brain matures. [2]
Epidemiology
Frequency
Assessing the frequency of symptomatic generalized epilepsy (SGE) is difficult because the definition varies and can be more or less inclusive.
In a study by Ohtahara and Yamatogi, 12 of 16 patients with Ohtahara syndrome developed into West syndrome or infantile spasms between ages 3 and 6 months as defined by EEG findings. [3] Infantile spasms affect 1 in 2000 infants. [4] Lennox-Gastaut syndrome has an incidence of 1.9-2.1 cases per 100,000 children and accounts for 6-7% of intractable pediatric epilepsy; however, this depends of the definition used for Lennox-Gastaut syndrome.
Mortality/Morbidity
A study of social outcomes in a Nova Scotia study found that 20 years after diagnosis of childhood-onset symptomatic generalized epilepsy (SGE), 25% die. All survivors have mental retardation and depend on parents and institutions in terms of living and finances. [5] Most patients with SGE grow up to have intractable epilepsy, with a small percentage who are seizure free with no antiepileptic drugs. [5] In a follow-up study of 14 patients with Ohtahara syndrome, 4 died early and the remaining 10 were severely handicapped. [6]
Age
These refer to age at onset. In adulthood, most patients with symptomatic generalized epilepsy (SGE) have a less well-defined syndrome that still has the characteristics of SGE and is closest to a Lennox-Gastaut syndrome (intractable multiple seizure types, mental retardation, and cerebral palsy). Note the following progression:
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Neonates - Early myoclonic encephalopathy, early infantine epileptic encephalopathy with suppression bursts, or Ohtahara syndrome
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Infancy - West syndrome
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Childhood - Epilepsy with myoclonic atonic seizures, epilepsy with myoclonic absence, Lennox-Gastaut syndrome
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Adolescence-adults - Progressive myoclonic epilepsies
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Atonic seizure. Abrupt loss of muscle tone is followed by clonic rhythmic movements. This type of seizure is typical for the symptomatic generalized epilepsies of the Lennox-Gastaut type.
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Electroencephalogram demonstrating hypsarrhythmia in infantile spasms. Note the chaotic high-amplitude background.
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Electroencephalogram demonstrating hypsarrhythmia. Note the electrodecremental response that is associated with a spasm in infantile spasms (ie, West syndrome).
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Slow (< 2.5 Hz) electroencephalographic spike and wave discharges associated with atypical absence seizures (ie, Lennox-Gastaut syndrome).
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Slow (< 2.5 Hz) electroencephalographic spike and wave discharges in atypical absence epilepsy (ie, Lennox-Gastaut syndrome).
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Spike, generalized. Significant spikes usually are followed by a slow wave, as shown here. This example also illustrates that generalized spikes are typically maximal frontally. This is typical of primary (ie, idiopathic, genetic) epilepsies. If burst lasted 3 seconds or more, it could be classified as spike-wave complexes.
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Slow spike-wave complexes. In addition to being slower, they are also less monomorphic than 3-Hz spike-wave complexes. With other findings, this often is seen in symptomatic/cryptogenic epilepsies of Lennox-Gastaut type.
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Slow spike-wave complexes. In addition to being slower, they are also less monomorphic than 3-Hz spike-wave complexes. With other findings, this often is seen in symptomatic/cryptogenic epilepsies of Lennox-Gastaut type.
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Hypsarrhythmia. High-amplitude slowing with no organized background and multifocal spikes (left and right frontal in this sample). This is phenotype of first year of life and is associated with West syndrome (ie, infantile spasms).
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Hypsarrhythmia. High-amplitude slowing (note scale) with no organized background and multifocal spikes (right frontal and left occipital in this sample). This is phenotype of first year of life and is associated with West syndrome (ie, infantile spasms).
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Generalized paroxysmal fast activity and electrodecrement. This pattern is characteristic of symptomatic/cryptogenic epilepsies of Lennox-Gastaut type and may be subclinical or associated with tonic or atonic seizures.
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Typical generalized tonic seizure in an adult patient with a "symptomatic" (now termed structural-metabolic) generalized epilepsy of the Lennox-Gastaut type.
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Typical generalized tonic seizure in a patient with a "symptomatic" (now termed structural-metabolic) generalized epilepsy of the Lennox-Gastaut type and severe static encephalopathy with cerebral palsy.
