Abstract
Objective
Our goal was to determine if animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term EEG recordings to evaluate the evolution of epileptiform activity in the same animals over time.
Methods
Objective Recognition Memory and Object Location Memory tests were undertaken, as well as a Matching to Place Water Maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified.
Results
Rats with a history of epileptic spasms showed impairment in the three behavioral tests, and their scores on the Objective Recognition Memory and Matching to Place Water Maze tests indicate neocortical involvement in the observed impaired cognition. Analysis of EEG recordings unexpectedly showed that the ictal events of spasms and their accompanying behaviors progressively increased in duration over a two-week period soon after onset, after which spasm duration plateaued. At the same time, spasm frequency remained unchanged. Soon after spasm onset, ictal events were variable in wave form but became more stereotyped as the syndrome evolved.
Significance
Our EEG findings are the first to demonstrate progressive ictogenesis for epileptic spasms. Further, in demonstrating cognitive deficits in the TTX model, we have met a criterion for an animal model of West syndrome. Animal models will allow in-depth studies of spasm progression’s potential role in cognitive regression and may elucidate why early treatment is considered essential for improved neurodevelopmental outcomes in children.
OCT