Management of seizures in Lennox-Gastaut syndrome

Abstract

Lennox-Gastaut syndrome is an epilepsy syndrome that begins in childhood (between 1 and 8 years of age), worsens during latency and persists frequently into adulthood, is refractory to antiepileptic medications, and results in cognitive decline and behavioral problems in affected individuals. Seizure types consist primarily of axial tonic, atonic, and atypical absence; nocturnal tonic seizures are the most common seizure pattern in this population, but often are not one of the initial seizure patterns. Some patients also have myoclonic seizures; this seizure pattern is less frequent than the three preceding types. Although there are some cases that are cryptogenic, most are symptomatic, arising during prenatal and perinatal periods from intrauterine infections, and vascular insults to the brain. Examples of causes of Lennox-Gastaut syndrome include migrational abnormalities of the brain, late effects of CNS infections, certain genetic disorders such as tuberous sclerosis, and inherited metabolic disorders. The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset. EEG is a helpful diagnostic tool in the diagnosis of Lennox-Gastaut syndrome, usually demonstrating high voltage, bifrontal 1.5-2.5 Hz spike and wave complexes interictally, and attenuation with paroxysmal fast activity (10-13 Hz) during the ictal phase. Treatment options for Lennox-Gastaut syndrome have been less than optimal. In recent years, several drugs have been tested and approved for the treatment of this syndrome; these include felbamate, lamotrigine, topiramate, and rufinamide. The long-term outcome does not appear to be any better with the newer antiepileptic drugs than when using earlier prescribed antiepileptic drugs or polytherapy. Treatment options other than antiepileptic drugs include a ketogenic diet, vagus nerve stimulation, and corpus callosotomy. Long-term outcome of these patients relative to seizure control and cognition is poor. Most develop moderate intellectual disability within a few years of onset of the syndrome. Many develop behavioral problems with inattention, hyperactivity, and aggression.