William Theodore, MD
Entry Id: TP-41

Overview
The Clinical Epilepsy Section seeks to improve treatment of epilepsy by studying the relation between brain structure and function, understanding the mechanisms of action of antiepileptic drugs, as well as developing new methods for evaluation and treatment. Our main focus is on neuroimaging evaluation of intractable epilepsy.

Clinical Epilepsy Section
The NINDS Clinical Epilepsy Section (CES) conducts research on the evaluation and treatment of uncontrolled epilepsy, emphasizing neuroimaging approaches to localization of epileptic foci and cognitive mapping. The techniques employed include video-EEG monitoring, transcranial magnetic stimulation (TMS), positron emission tomography (PET), and magnetic resonance imaging (MRI), including functional MRI and MR spectroscopy. We use multimodality image co-registration, and statistical parametric mapping, as well as other image analysis techniques.

Recent imaging work has focused on the use of fMRI for pre-operative language mapping in both children and adults. The results have suggested that imaging is as accurate as subdural electrode stimulation and the intracarotid sodium amytal test, as well as direct cortical stimulation mapping. Imaging should gradually replace more invasive methods for pre-operative cognitive mapping. At present we are investigating the effects of seizure disorders on the functional anatomy of language and memory. We are using PET with 18FCWAY to investigate 5HT1A binding in patients with epilepsy and depression, and 11C-flumazenil to study GABA receptors in patients with succinic semialdehyde dehydrogenase deficiency.

Clinical Associate Program
In the first year, clinical associates have primary responsibility for care of patients on our vide-EEG monitoring unit. They evaluate new patients in outpatient clinic and follow selected patients. They become involved in a research project, usually involving neuroimaging or a treatment trial. They may provide epilepsy consult service to other NINDS units or other institutes after appropriate screening by NINDS consult service. The Preceptor for the first year is Dr. William Theodore. The second year of the fellowship is spent in the EEG lab, under the direction of Dr. Susumu Sato. The fellows learn to interpret EEG and evoked potential recordings, as well as sleep, and have some exposure to EMG. The program is certified by the American Board of Psychiatry and Neurology for training for the Added Qualification in Clinical Neurophysiology. A third year is possible. Close relationships are maintained with Children's National Medical Center, the National Naval Medical Center, and the Walter Reed Army Medical Center.

Recent Clinical Associates

Associate	Years at NIH	Current Position
Dr Anto Bagic	2002-2005	University of Pittsburgh
Dr Giamperio Giavacchini	2005-2007	University of Pisa
Dr Gregor Hasler	2005-2007	University of Zurich

Recent papers

• Fotheringham J, Donati D, Akhyani N, Vortmeyer A, Heiss JD, Williams E, Weinstein S, Bruce DA, Gaillard WD, Sato S, Theodore WH, Jacobson S. Detection of Human Herpesvirus-6B DNA and Antigen in Primary Astrocyte Cultures from Mesial Temporal Lobe Epilepsy Brain Resections. PLoS Med. 2007 May;4(5):e180
• Theodore WH, Hasler G, Giovacchini G, Kelley K, Reeves-Tyer P, Herscovitch P, Drevets W.  Reduced Hippocampal 5HT1A PET Receptor Binding and Depression in Temporal Lobe Epilepsy.  Epilepsia 2007; 48: 1526-30Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA,  Drevets WC, Theodore WH. 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression.  Biological Psychiatry 2007 Dec 1;62(11):1258-64
• Gaillard WD, Berl MM, Moore EA, Ritzl EK, Rosenberger LR, Weinstein SL, Conry JA, Pearl PL, Ritter FF, Sato S, Vezina LG, Vaidya CJ, Wiggs E, Fratalli C, Risse G, Ratner NB, Giooa G, Theodore WH.   Atypical Language in Lesional and Non-lesional Complex Partial Epilepsy.  Neurology 2007 Oct 30;69(18):1761-71

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