Bart P. Keogh MD, PhD, Presenter: Nothing to Disclose

Phillip Schwartzkroin PhD, Abstract Co-Author: Nothing to Disclose

Larissa Stanberry, Abstract Co-Author: Nothing to Disclose

Dietmar Cordes PhD, Abstract Co-Author: Nothing to Disclose

Carol Robbins, Abstract Co-Author: Nothing to Disclose

Brad Figler, Abstract Co-Author: Nothing to Disclose

Kelvin Wu, Abstract Co-Author: Nothing to Disclose

Adriana Emmi, Abstract Co-Author: Nothing to Disclose

Thomas Lewis, Abstract Co-Author: Nothing to Disclose

Kenneth R. Maravilla MD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Childhood epilepsy associated with brain malformations is often severe and resistant to conventional anticonvulsant drugs. A fundamental question in the study of epilepsy is the anatomic location of seizure origination and how neural activation propagates through the brain. We have developed a model system and statistical tools that allow this complex biological question to be addressed.

Rats exposed to methylazoxymethanol acetate (MAM) in utero have nodular heterotopia in both neocortex and hippocampus with a reduced seizure threshold. Cortical heterotopia were demonstrated by both MRI and histology. BOLD fMRI data was acquired following the intravenous systemic administration of Pentylenetetrazol (PTZ) at a dose which induces generalized seizures in rats. Animals were anesthetized, paralyzed and fully physiologically supported. Seizure initiation was identified by simultaneous EEG acquired during imaging. EEG signal was denoised by FFT and removal of magnet specific frequency components. Activation, anatomic location and the time course of activation was determined by a novel Hierarchical Cluster Analysis method combined with prior t-test selection of activating voxels

Structural imaging and histology of in utero MAM treated rats demonstrates areas of cortical heterotopia within the hippocampus and hydrocephalus. Simultaneous EEG and fMRI of MAM treated animals after PTZ administration shows rapid seizure associated hippocampal and cortical activation. Hierarchical Cluster Analysis yields a group of rapidly and synchronously activating voxels corresponding to the areas of heterotopia. In contrast, activation in control animals occurs heterogenously, initiating primarily in cortex, caudo-putamen and thalamus. Moreover, it appears that the MAM treated rats have a lower seizure threshold as measured by time to seizure onset – by both imaging and EEG measures.

Our preliminary data suggests that, in this model of cortical malformation, areas of heterotopia act as the point of seizure initiation after inhibition of GABA-ergic receptors. This is the first example of fMRI used to demonstrate that a structural abnormality acts as the nidus for seizure initiation.

Keogh, B, Schwartzkroin, P, Stanberry, L, Cordes, D, Robbins, C, Figler, B, Wu, K, Emmi, A, Lewis, T, Maravilla, K, et al, , Heterotopia-associated Initiation of Seizure Activity in a Rat Model of Cortical Dysplasia Demonstrated by Simultaneous EEG and FMRI Using Hierarchical Cluster Analysis.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4407432.html