title: Vigabatrin therapy implicates neocortical high frequency oscillations in an animal model of infantile spasms.
abstract: Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Frost
authors.affiliation: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Le
authors.affiliation: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Chong L
authors.initials: CL
authors.lastname: Lee
authors.affiliation: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ballester-Rosado
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX, USA; The Michael E. Debakey Veterans Affairs Medical Center, Houston, TX, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hrachovy
authors.affiliation: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA. Electronic address: jswann@bcm.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Swann
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001931:Brain Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography; D006801:Humans; D007223:Infant; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D013036:Spasms, Infantile / Q000188:drug therapy* / Q000503:physiopathology; D020888:Vigabatrin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin
keywords: Anticonvulsant; Epilepsy; HFOs; Hypsarrhythmia; West syndrome