William Theodore, MD, Sara Inati, 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. We have an active surgery and clinical trial program.

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 to investigate 5HT1A binding and GABA receptors in patients with epilepsy and depression.

Clinical Associate Program
In the first year, clinical associates (fellows) have primary responsibility for care of patients on our video-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 the NINDS consult service. The Preceptor for the first year is Dr. William Theodore. The second year of the Program is spent in the EEG lab, under the direction of Dr. Sara Inati. 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 in Washington, DC, and the Walter Reed National Military Medical Center in Bethesda, Maryland.

Recent Clinical Associates

Associate	Years at NIH	Current Position
Dr Gregor Hasler	2005-2007	University of Zurich
Dr Sabina Miranda	2007-2009	Medical College of Georgia
Dr Omar Khan	2009-2011	St Luke's Hospital/Temple medical college

Recent papers

• Pearl PL, Gibson KM, Quezado Z,Dustin I, Taylor J, Trzcinski S, Schreiber J, Forester K, Reeves-Tyer P, Liew C, Shamim S, Herscovitch P, Carson R, Butman J, Theodore WH. Decreased GABA-A Binding on FMZ-PET in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency. Neurology 2009; 73: 423-9 PMID: 19667317
• Mbwana J, Berl M, Ritzl ER, Rosenberger L, Mayo J, Weinstein S, Conry J, Pearl PL, Shamim S, Moore EN, Sato S, Vezina LG, Theodore WH Gaillard WD. Limitations to Plasticity of Language Network Reorganization in Localization Related Epilepsy. Brain. 2009;132:347-56.
• Gaillard WD, MM Berl MM, Duke ES, Ritzl E, Miranda S, Liew C, Finegersh A, A Martinez A, Dustin I, Sato S, Theodore WH. fMRI Language Dominance and FDG-PET Hypometabolism. Neurology 2011; 76(15):1322-9.
  
• Theodore WH, Wiggs EA, Martinez AR et al. Serotonin 1A Receptors, Depression, and Memory in Temporal Lobe Epilepsy. Epilepsia, 2012; 53: 129-33
• Acosta MT, Munashinge J, Zhang L, Guerron A, Vortmeyer A, Theodore WH. Isolated Seizures in Rats do not Cause Neuronal Injury. Acta Neurologica Scandinavica 2012;125:30-7
• Hirvonen J, Kreisl W, Fujita M, Dustin I, Khan O, Appel S, Zhang Y, Morse C, Pike VW, Innis RB, Theodore WH. Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy. J Nucl Med 2012;53:234-40 PMID: 22238156

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