While the cortex has long been recognized as a site of abnormal function in epilepsy, data from experimental models of epilepsy suggest that subcortical nuclei are important in modulating cortical excitability. This proposal describes a series of studies, using PET-FDG, EEG, and histopathological and brain imaging techniques, to investigate the subcortical-cortical functional relationships and underlying neuronal function in partial and generalized epilepsy in humans, and to extend the value of PET in clinical epilepsy. Studies in partial epilepsy will identify subcortical dysfunction by study of metabolism with PET, and characterize those alterations with regard to anatomical location of the cortical epileptogenic focus, which will be defined using electrophysiologic and histopathologic measures. Relationships between degree and location of subcortical metabolic derangement and seizure frequency, degree of seizure propagation, seizure duration, and degree of pathologic alteration will be determined. Studies to investigate patterns of metabolic derangement in an epileptogenic temporal lobe will determine precise electrophysiologic (using intracranial EEG) and histopathologic correlates of these metabolic patterns, define the effect of structural change on function, and extend the use of PET in localization for epilepsy surgery. Patients will be intensively studied with extra- and intra- cranial EEG, MRI, psychometrics, and pathology in resected specimens. Studies in primary generalized epilepsy will identify subcortical dysfunction by study of metabolism with PET, and characterize those alterations with regard to seizure type and seizure frequency so that subcortical-cortical interactions can be defined. The relationship of subcortical metabolism to successful and unsuccessful treatment will be determined exploring mechanisms of anticonvulsant action. Overall objectives are to better define pathophysiological mechanisms of human epilepsy so that more effective therapeutic measures can be taken.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026178-04
Application #
3411877
Study Section
Neurology A Study Section (NEUA)
Project Start
1989-04-01
Project End
1994-01-31
Budget Start
1992-04-01
Budget End
1994-01-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Dlugos, D J; Jaggi, J; O'Connor, W M et al. (1999) Hippocampal cell density and subcortical metabolism in temporal lobe epilepsy. Epilepsia 40:408-13
Sperling, M R; Skolnick, B E (1995) Cerebral blood flow during spike-wave discharges. Epilepsia 36:156-63
Sperling, M R; Alavi, A; Reivich, M et al. (1995) False lateralization of temporal lobe epilepsy with FDG positron emission tomography. Epilepsia 36:722-7
Sperling, M R; Saykin, A J; Glosser, G et al. (1994) Predictors of outcome after anterior temporal lobectomy: the intracarotid amobarbital test. Neurology 44:2325-30
Manno, E M; Sperling, M R; Ding, X et al. (1994) Predictors of outcome after anterior temporal lobectomy: positron emission tomography. Neurology 44:2331-6
Sperling, M R (1993) Neuroimaging in epilepsy: recent developments in MR imaging, positron-emission tomography, and single-photon emission tomography. Neurol Clin 11:883-903
Sperling, M R; O'Connor, M J; Saykin, A J et al. (1992) A noninvasive protocol for anterior temporal lobectomy. Neurology 42:416-22