Some mice were treated with ethosuximide until they reached five months of age, when treatment was stopped. During the following 90 days, these mice had considerably fewer bursts of spike and wave than at baseline. “The suggestion is that the tendency to manifest spike-and-wave discharges has been reduced in a durable way, even after ethosuximide treatment is discontinued,” said Dr. Cole. Mice who received ethosuximide continuously fared slightly better than mice for which ethosuximide was stopped.
Ethosuximide, a calcium-channel active agent, appears to change the function of the epileptic network and could potentially modify the expression of what in the mice is a genetically determined disease. Research by Berg et al suggests that the rodent data could be relevant for humans, “but that’s clearly not definitive yet,” said Dr. Cole.
Modification of Epileptic Encephalopathies
Much attention is focused on disease modification of epileptic encephalopathies, but the literature contains “precious little evidence, although there are some encouraging trends,” said Dr. Cole. A review article by Chapman et al provides a summary of the data on this topic. The data clearly establish that early treatment and response to treatment is associated with a better cognitive outcome in most of the patient populations, including people with Dravet syndrome, tuberous sclerosis complex, and Lennox–Gastaut syndrome. The findings seem to be independent of the treatment used.
“The weight of the evidence from the majority of the studies [indicates] that symptomatic etiologies are more resistant to treatment and have poorer outcome,” said Dr. Cole. “But the bottom line with this whole area is that it’s difficult, and I would suggest, almost impossible, to conduct any kind of a randomized or blinded study to make a determination. Of course, the major intellectual pitfall here is confusing association with causation,” he concluded.
—Erik Greb