Neurobehavioral Deficits and a Progressive Ictogenesis in the Tetrodotoxin Model of Epileptic Spasms

Authors

John T Le
Carlos J Ballester-Rosado
James D Frost
John W Swann

Language

English

Publication Date

12-1-2022

Journal

Epilepsia

DOI

10.1111/epi.17428

PMID

36179064

PMCID

PMC9742150

PubMedCentral® Posted Date

12-1-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.

Methods: Object 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 on the three behavioral tests, and their scores on the object recognition memory and matching to place water maze tests indicated 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 2-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. Furthermore, in demonstrating cognitive deficits in the tetrodotoxin 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.

Keywords

Rats, Animals, Spasms, Infantile, Retrospective Studies, West syndrome, infantile spasms, ictal events, learning and memory, EEG

Published Open-Access

yes

Recommended Citation

Le, John T; Ballester-Rosado, Carlos J; Frost, James D; et al., "Neurobehavioral Deficits and a Progressive Ictogenesis in the Tetrodotoxin Model of Epileptic Spasms" (2022). Duncan NRI Faculty and Staff Publications. 190.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/190