The overall goal of this research proposal (now being submitted competitively for its 3 cycle of funding) is to increase understanding of structural and functional changes as epilepsy evolves in order to improve the localization of epileptic foci for surgical treatment of medically-refractory epilepsy. Towards this goal, we have pioneered the use of 2-deoxy-2[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) positron emission tomography (PET) for better localization of the epileptic focus in children with epilepsy. Despite improvements in seizure focus localization using various technologies and improved surgical outcome, however, patients with extratemporal lobe epilepsy still do not achieve a 90% seizure-free outcome as is possible with temporal lobe epilepsy surgery. Surgical failures may be partly accounted for by two major findings from the previous funding period: (1) the site of seizure onset depicted by intracranial EEC is often not coincident with the site of significantly decreased FMZ binding, but is typically adjacent to it, and (2) there are often additional sites of decreased FMZ binding in cortex remote from, but in areas that are synaptically connected to, the primary seizure focus. We believe that we are beginning to identify, for the first time using a neuroimaging modality, the presence of secondary epileptic foci, which are known to exist and to account for surgical failures but have been difficult to identify preoperatively. The present proposal seeks to understand in great detail the formation, localization and connectivity of secondary epileptic foci by combining longitudinal measures of FMZ binding and diffusion tensor imaging in a cohort of children with newly-diagnosed partial epilepsy. In addition, we will undertake a cross-sectional study, which will relate FMZ binding and diffusion tensor imaging abnormalities of primary and secondary epileptic foci to intracranial electrophysiological measures in a subset of children undergoing epilepsy surgery.
The aims being proposed in this application are a logical extension of the research and accomplishments of the previous funding period, and will contribute to further definition and clarification of primary and secondary epileptogenic brain regions during epilepsy surgery evaluation, with a goal towards better surgical outcome in children whose surgical success remains suboptimal at present.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Clinical Neuroscience and Disease Study Section (CND)
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Jacobs, Margaret
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Wayne State University
Schools of Medicine
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Chugani, Harry T; Ilyas, Mohammed; Kumar, Ajay et al. (2015) Surgical treatment for refractory epileptic spasms: The Detroit series. Epilepsia 56:1941-9
Tiwari, Vijay Narayan; Kumar, Ajay; Chakraborty, Pulak K et al. (2012) Can diffusion tensor imaging (DTI) identify epileptogenic tubers in tuberous sclerosis complex? Correlation with ?-[11C]methyl-L-tryptophan ([11C] AMT) positron emission tomography (PET). J Child Neurol 27:598-603
Chugani, Harry T; Kumar, Ajay; Kupsky, William et al. (2011) Clinical and histopathologic correlates of 11C-alpha-methyl-L-tryptophan (AMT) PET abnormalities in children with intractable epilepsy. Epilepsia 52:1692-8
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Tiwari, Vijay Narayan; Jeong, Jeong-Won; Asano, Eishi et al. (2011) A sensitive diffusion tensor imaging quantification method to detect language laterality in children: correlation with the Wada test. J Child Neurol 26:1516-21
Kumar, Ajay; Asano, Eishi; Chugani, Harry T (2011) ?-[¹¹C]-methyl-L-tryptophan PET for tracer localization of epileptogenic brain regions: clinical studies. Biomark Med 5:577-84
Goradia, Dhruman; Chugani, Harry T; Govindan, Rajkumar Munian et al. (2011) Reorganization of the right arcuate fasciculus following left arcuate fasciculus resection in children with intractable epilepsy. J Child Neurol 26:1246-51
Juhász, Csaba; Asano, Eishi; Shah, Aashit et al. (2009) Focal decreases of cortical GABAA receptor binding remote from the primary seizure focus: what do they indicate? Epilepsia 50:240-50
Kumar, A; Juhasz, C; Asano, E et al. (2009) Diffusion tensor imaging study of the cortical origin and course of the corticospinal tract in healthy children. AJNR Am J Neuroradiol 30:1963-70

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