In collaboration with Dr. Giovanni di Chiro and others in the NIH nuclear medicine and PET departments, Dr. Theodore performed early studies of the use of Fluorine-18 2-deoxy-d-glucose (FDG-PET) in epilepsy, including evaluation of the effects of anti-seizure drugs on cerebral glucose metabolism, and the first blinded study to show that hypometabolism predicted surgical outcome. Subsequent FDG studies showed progression of hypometabolism in patients with drug-resistant epilepsy, in concert with progressive atrophy on magnetic resonance imaging. Additional FDG-PET and structural MRI studies showed the role of imaging in presurgical epilepsy evaluation.
Dr. Theodore performed a series of studies of neurotransmitter receptor ligands using PET. He showed that serotonin (5HT) 1A receptor binding was reduced in mesial temporal lobe foci, with further reductions in patients who had a diagnosis of major depressive disorder as well las epilepsy. These findings provided strong support for the use of selective serotonin reuptake inhibitors in patients with epilepsy and depression as an epilepsy co-morbidity. Other PET studies showed the role of inflammation in focal epilepsy through detection of increased binding to the translocator protein 18kd. Benzodiazepine receptor imaging in succinic semialdehyde dehydrogenase deficiency (with Dr. Phil Pearl) showed decreased receptor availability, consistent with increased endogenous GABA levels, and helping to explain increased cortical excitability and seizures.
Dr. Theodore performed a long series of studies of language and memory in epilepsy using fMRI, in association with many collaborators, particularly Dr. William Gaillard, showing that non-invasive functional anatomy mapping could provide data for preoperative evaluation. These studies also showed how epilepsy leads to cortical functional reorganization, depending on age at onset, and presence or absence of structural lesions and etiologies.
Dr. Theodore has been very active in the international epilepsy community, serving as a consultant to the World Health and Pan American Health Organizations. He has made frequent trips to Zambia as a Visiting Professor at the University Teaching Hospital in Lusaka where in addition to teaching and patient care he studied the relationship of HIV infection to seizures in collaboration with Dr. Gretchen Birbeck and others.
He has trained many fellows who have gone on to direct outstanding epilepsy programs. Active in AAN, ANA and other societies, he co-initiated (with Dr. Greg Cascino) development of the American Board of Neurology and Psychiatry Epilepsy Added Qualification. Past President of the American Epilepsy Society, his awards include the International League Against Epilepsy Ambassador for Epilepsy Award, the American Epilepsy Society Clinical Science Research Award, and the Columbia University College of Physicians and Surgeons Gold Medal for Clinical Medicine.