Medical Care for SGE
Symptomatic generalized epilepsy (SGE) is often intractable to antiepileptic medications, and no consensus has been reached on how it should be treated. Usually, many drug trials are needed to achieve reasonable seizure control. When neonates and infants as old as 1 year initially present with intractable seizures, a trial of intravenous (IV) pyridoxine should be administered in case the neonate has a pyridine-dependent seizure. When seizures remain uncontrolled with antiepileptic drugs, nonpharmacologic options should be considered, such as ketogenic diet, vagus nerve stimulation, and surgical options.
Antiepileptic medication
Myoclonic encephalopathy is found to respond to pyridoxine and benzoate. Ohtahara syndrome is found to respond to phenobarbital and zonisamide. Case reports have shown that corticotropin (ACTH) has not been useful in decreasing seizure frequency.
Traditionally, infantile spasm/West syndrome is treated with ACTH, corticosteroids, or benzodiazepines (Clonazepam). A Cochrane Database Systematic Review found strong evidence that high-dose hormonal treatments of prednisolone alleviates spasms faster and improves long-term developmental delay compared with vigabatrin for infantile spasms of no underlying cause. [17, 18] West syndrome associated with tuberous sclerosis responds best to vigabatrin, [4] and, in this setting, vigabatrin has become the drug of choice in many countries.
Lennox-Gastaut syndrome treatment involves valproate, lamotrigine, topiramate, rufinamide, and felbamate. [2] Risk factors associated with felbamate include aplastic anemia and hepatoxicity. Antiepileptic drugs to avoid include carbamazepine, oxcarbazepine, phenytoin, and vigabatrin.
Myoclonic atonic treatment involves valproic acid, lamotrigine, and benzodiazepine. [2] Seizures are worsened by carbamazepine, oxcarbazepine, phenytoin, vigabatrin, and phenobarbital. [2]
Myoclonic absence treatment involves a combination of ethosuximide and valproate.
Progressive myoclonic epilepsy treatment involves a combination of valproic acid, ethosuximide, benzodiazepines, phenobarbital, zonisamide, and lamotrigine. [19] Antiepileptic drugs to avoid because they may exacerbate myoclonus include phenytoin, carbamazepine, vigabatrin, and tiagabine. Lamotrigine should be used with caution as it can exacerbate myoclonus. Zonisamide as add-on therapy was been found to be useful in a study by Kyllerman and Ben-Menachem in which 7 patients with progressive myoclonic epilepsy who had intractable seizures on a regimen of valproic acid and benzodiazepine had reduction of seizures after the addition of zonisamide. [20]
Go to Antiepileptic Drugs for more information.
Ketogenic diet
The ketogenic diet is used in children aged 1-10 years and consists of 90% of daily calories coming from fat. Typically, the diet is initiated in a hospital setting because the child must undergo 1-2 days of starvation to induce the ketosis. Then, the ketogenic diet is started. Approximately 10% of children who undergo the ketogenic diet have complications of nephrolithiasis; the risk is higher in children on topiramate. Several reviews have concluded there are benefits with the ketogenic diet as treatment for intractable pediatric epilepsy, which is often symptomatic generalized epilepsy (SGE). [21]
A review by Lefevre and Aronson found a reduction of seizure frequency in two thirds of the children, which subsequently permitted a reduction in their seizure medication. [22] In a study examining the long-term effects after cessation of the ketogenic diet on pediatric patients with epilepsy, 60% with SGE, the most common adverse effect was less than tenth percentile for height. [4] A ketogenic diet was the most effective treatment in decreasing seizures in a pediatric group of 23 myoclonic astatic epilepsy patients. [23]
Vagus nerve stimulation
The vagal nerve stimulator is a pacemakerlike device implanted in the chest with stimulating electrodes that connect to the vagus nerve at the left carotid bifurcation. The stimulator is found to decrease as much as 25% of seizures in intractable partial or secondarily generalized seizures. [1]
The mechanism of action is unknown, and its use is still considered experimental. In a retrospective trial of 46 patients with Lennox-Gastaut syndrome, vagus nerve stimulation resulted in 43 patients having a 58.2% median seizure reduction in 3 months. [24] The most common adverse effect reported was coughing during the stimulation and voice alteration.
Go to Vagus Nerve Stimulation for more information.
Surgical Care for SGE
Corpus callosotomy is a surgical option for patients with drop attacks and atonic and tonic seizures and has also reduced the rates of generalized tonic-clonic seizures. [25] In patients with Lennox-Gastaut syndrome, patients with atonic or tonic seizures as the primary seizure type have the option of resection of the complete corpus callosum or just the anterior portion. If the patient has mental retardation, the recommendation is a 90-100% (complete) corpus callosotomy. If the patient has no mental retardation, then an anterior 75% corpus callosotomy is recommended. Vagus nerve stimulation should be attempted before surgery.
Consultations
Consultation with a neurosurgeon may be needed.
Diet
See Ketogenic diet in Medical Care.
Further Outpatient Care
Pediatric patients who present with seizures require close follow-up because epilepsy syndromes transform into other syndromes as the patient grows older.
Complications
Patients with symptomatic generalized epilepsy (SGE) often have long-term complications from antiepileptic drug adverse effects; thus, maximizing all treatment options such as ketogenic diet and vagus nerve stimulation are encouraged.
Prognosis
The seizures in symptomatic generalized epilepsy (SGE) are often intractable, and patients require continued supportive management of their underlying brain lesions.
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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.
