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Senior Investigator

William H. Theodore, M.D.

Clinical Epilepsy Section

Building 10 Room 5N250
10 Center Drive MSC 1408
Bethesda MD 20892-1408
Office: (301) 496-1505
Lab: (301) 496-1505
Fax: (301) 402-2871

Dr. Theodore received his B.A. degree from Harvard College and M.D. degree from Columbia University College of Physicians and Surgeons. After a medical internship and residency, and a neurology residency at Mount Sinai School of Medicine, he came to the National Institutes of Health for a fellowship in Epilepsy and Clinical Neurophysiology. He is board certified in Internal Medicine, Neurology, and Clinical Neurophysiology. In 1988 he became Chief of the Clinical Epilepsy Section, NINDS. He received the American Epilepsy Society Outstanding Clinical Investigator Award in 1991. Dr. Theodore's section is investigating new therapeutic approaches to uncontrolled epilepsy, and using neuroimaging techniques to study cerebral metabolism, neuropharmacology, and functional cognitive anatomy.

The Epilepsy Research Branch seeks to improve treatment of epilepsy by understanding the mechanisms of action of antiepileptic drugs, as well as developing new methods for evaluation and treatment. The two sections, Neuronal Excitability and Clinical Epilepsy, collaborate to study the relationship between drug actions at the cellular and subcellular level and clinical effects, both on seizure control and neuropsychological function.

The NINDS Clinical Epilepsy Section (CES) conducts research on the evaluation and treatment of uncontrolled epilepsy, emphasizing non-invasive 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. In addition to drug trials, In a double-blind trial, we are exploring the use of transcranial magnetic stimulation, a novel approach to treatment of focal epilepsy.

Current studies include a trial of the therapeutic effect of rTMS on neocortical epileptic foci. We are using PET to study 5HT-1A receptors in localization-related epilepsy, and in patients with both epilepsy and depression. We are using diffusion weighted MRI and BOLD to study the extent of neuronal injury associated with seizures in rats exposed to specific glutamate receptor subtype agonists. In a collaboration with Johns Hopkins University we are investigating the role of the anterior temporal cortex in semantic processing, the amygdala in affective processing, and the effect of white matter pathway resection on cognitive outcome after temporal lobectomy. With Columbia University, we are investigating structural and functional correlates of epilepsy in LGI1 positive kindreds.

Clinical Protocols

  • Evaluation and Treatment of Patients with Epilepsy  ( 01-N-0139 )

  • Noninvasive language mapping in patients with localization-related epilepsy ( 08-N-0161 )

  • A Phase II Clinical Trial of PRX-00023 Therapy in localization-related Epilepsy ( 11-N-0039 )

  • Succinic Semialdehyde Dehydrogenase Deficiency: Physiological Markers of Taurine Therapy ( 12-N-0123 )

  • Positron emission tomography measurement of neuroinflammation and P-glycoprotein in localization-related epilepsy ( 12-N-0182 )

Staff Image
  • Maria Chroneos, B.A.

  • William Gaillard, M.D.
    (301) 402-3745

  • Sara Inati
    Chief EEG Laboratory

  • Leigh Sepeta, Ph.D.

  • 1) Rolinski R, Austermuehle A, Wiggs E, Agrawal S, Sepeta L, Gaillard WD, Zaghloul K, Inati SK, Theodore WH (2020)
  • Functional MRI and Direct Cortical Stimulation: Prediction of Postoperative Language Decline
  • Epilepsia, 2019;60:560-570, doi: 10.1111/epi.14666
  • 2) Rolinski R, You X, Gonzalez-Castillo J, Norato G, Reynolds RC, Inati SK, Theodore WH (2020)
  • Language lateralization from task-based and resting state functional MRI in patients with epilepsy
  • Human Brain Mapping, In press
  • 3) You Z, Zachery AN, Fanto E, Norato G, Germeyan S, Emery EJ, Sepeta LN, Berl MB, Black CL, Wiggs E, Zaghloul K, Inati SK, Gaillard WD, Theodore WH (2019)
  • fMRIPrediction of Naming Change after Adult Temporal Lobe Epilepsy Surgery: Activation Matters
  • Epilepsia, 2019;60:527-538, doi: 10.1111/epi.14656
  • 4) Dickstein LP, Liow J-S, Austermuehle A, Zoghbi S, Inati SK, Zaghloul K, Zanotti-Fregonara P, Theodore WH (2019)
  • Neuroinflammation in Neocortical Epilepsy Measured by PET imaging of Translocator Protein
  • Epilepsia, 2019 60(6):1248-1254. PMID: 31144767, DOI: 10.1111/epi.15967
  • 5) Holtkamp M, Theodore WH (2018)
  • Generic antiepileptic drugs – safe or harmful in patients with epilepsy?
  • Epilepsia, 2018 Jul;59(7):1273-1281, doi: 10.1111/epi.14439. Epub 2018 Jun 12
  • 6) Szaflarski JP, Gloss D, Binder JR, Gaillard WD, Golby A, Holland S, Ojemann JG, Spencer DC, Swanson S, French J, Theodore WH (2017)
  • Use of fMRI in the presurgical evaluation of patients with epilepsy
  • Neurology, 2017 Jan 24;88(4), 395-402. PMID: 28077494 PMCID: PMC5272968
  • 7) Austermuehle A, Cocjin J, Reynolds R, Agrawal S, Sepeta L, Gaillard WD, Zaghloul K, Inati S, Theodore WH (2017)
  • Language fMRI and Direct Cortical Stimulation in Epilepsy Preoperative Planning
  • Annals of Neurology, 2017 Apr;81(4), 526-537 PMID: 28220524
  • 8) Goldenholz DM, Tharayll J, Moss R, Myers E, Theodore WH (2017)
  • Monte Carlo Simulations of Randomized Clinical Trials in Epilepsy
  • Annals of Clinical and Translational Neurology, 2017 May 24;4(8), 544-552
  • 9) Goldenholz D, Kuhn A, Austermuehle A, Bachler M, Mayer C, Wassertheurer S, Inati S, Theodore WH (2017)
  • Long Term Monitoring of Cardiorespiratory Patterns in Drug Resistant Epilepsy
  • Epilepsia, 2017 Jan;58(1):77-84, PMID: 27864903
  • 10) Goldenholz DM, Jow A, Khan OI, Bagic A, Sato S, Auh S, Kufta C, Inati S, Theodore WH (2016)
  • Preoperative Prediction of Temporal Lobe Epilepsy Surgery Outcome
  • Epilepsy Res, 2016 Sep 22;127:331-338, doi: 10.1016/j
  • 11) Goldenholz DM, Moss R, Scott J, Auh S, Theodore WH (2015)
  • Confusing Placebo Effect with Natural History in Epilepsy: A Big Data Approach|Ann Neurol
  • 2015;78(3):329-36, PMID: 26150090 PMCID: PMC4546516
  • 12) Gershen LP, Zanotti-Fregonara P, Dustin IM, Liow J-S, Jussi Hirvonen J, Kreisl WC, Jenko KJ, Inati SK, Fujita M, Morse CL, Brouwer C, Hong JS, Pike VW, Zoghbi SS, Innis RB, Theodore WH (2015)
  • Neuroinflammation in Temporal Lobe Epilepsy Measured Using PET Imaging of Translocator Protein
  • JAMA Neurology, 2015;72(8):882-8, PMID: 26052981
  • 13) Siddiqi OK, Elafros MA, Birbeck GL, Sikazwe. I, Kalungwana L, Michael J. Potchen MJ, Bositis CM, Koralnik IJ, Theodore WH (2015)
  • EEG Evaluation of HIV+ Zambian Adults with New-Onset Seizure
  • Neurology, 2015 Mar 31;84(13):1317-22, PMID: 25740861
  • 14) Reis J, Cohen LG, Pearl PL, Fritsch B, Jung N, Dustin I, Theodore WH (2012)
  • GABA-(B)-ergic Motor Cortex Dysfunction in SSADH Deficiency
  • Neurology, 79, 47-54
  • 15) Reis J, Cohen LG, Pearl PL, Fritsch B, Jung N, Dustin I, Theodore WH (2012)
  • GABA-(B)-ergic Motor Cortex Dysfunction in SSADH Deficiency
  • Neurology, 79, 47-54
  • 16) Theodore WH, Wiggs EA, Martinez AR et al (2012)
  • Serotonin 1A Receptors, Depression, and Memory in Temporal Lobe Epilepsy
  • Epilepsia, 53, 129-33
  • 17) Hirvonen J, Kreisl W, Fujita M, Dustin I, Khan O, Appel S, Zhang Y, Morse C, Pike VW, Innis RB, Theodore WH (2012)
  • Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy
  • J Nucl Med, 53, 234-40 PMID: 22238156
  • 18) Appel S, Duke ES, Martinez AR, Khan OI, Dustin IM, Reeves-Tyer P, Berl MB, Sato S, Gaillard WD, Theodore WH (2012)
  • Cerebral Blood Flow and fMRI BOLD Auditory Language Activation in Temporal Lobe Epilepsy
  • Epilepsia, 53(4), 631-8
  • 19) Duke ES, Tesfaye M, Berl MM, Walker JE, Ritzl EK, Fasano RE, Conry JA, Pearl PL, Sato S, Theodore WH, Gaillard WD (2012)
  • The effect of seizure focus on regional language processing areas
  • Epilepsia, 53(6), 1044-50
  • 20) Theodore WH, Martinez AR, Khan OI, LIew CJ, Auh S, Dustin IM, Heiss J, Sato S (2012)
  • PET Imaging of Serotonin 1A Receptors and Cerebral Glucose Metabolism for Temporal Lobectomy
  • J Nucl Med, Sep;53(9), 1375-82
  • 21) Acosta MT, Munashinge J, Zhang L, Guerron A, Vortmeyer A, Theodore WH (2012)
  • Isolated Seizures in Rats do not Cause Neuronal Injury
  • Acta Neurologica Scandinavica, 125, 30-7
  • 22) Granata T, Cross H, Theodore W, Avanzini G (2011)
  • Immune-mediated epilepsies
  • Epilepsia, 52 Suppl 3:5-11
  • 23) Finegersh A, Avedissian C, Shamim S, Dustin I, Thompson PM, Theodore WH (2011)
  • Bilateral Hippocampal Atrophy in Temporal Lobe Epilepsy: Effect of Depressive Symptoms and Febrile Seizures
  • Epilepsia, 52(4), 689-97
  • 24) Gaillard WD, MM Berl MM, Duke ES, Ritzl E, Miranda S, Liew C, Finegersh A, A Martinez A, Dustin I, Sato S, Theodore WH (2011)
  • fMRI Language Dominance and FDG-PET Hypometabolism
  • Neurology, 76(15), 1322-9
  • 25) Gaillard WD, Cross HJ, Duncan JS, Stefan H, Theodore WH (2011)
  • Epilepsy Imaging Study Guideline Criteria: Commentary on Diagnostic Testing Study Guidelines & Practice Parameters
  • Epilepsia, 52, 1750-6
  • 26) Bae EH, Theodore WH, Fregni F, Cantello R, Pascual-Leone A (2011)
  • An estimated placebo effect of repetitive transcranial magnetic stimulation in epilepsy
  • Epilepsy Behav, 20(2), 355-9
  • 27) Acosta MT, Munasinghe J, Pearl PL, Gupta M, Finegersh A, Gibson KM, Theodore WH (2010)
  • Cerebellar Atrophy in Human and Murine SSADH Deficiency
  • J Child Neurol, 25, 1457-61
  • 28) Munasinghe JO, Acosta MT, Banks M, Heffer A, Silva AC, Koretsky A, Theodore WH (2010)
  • Arterial Spin Labeling Demonstrates that Focal Amygdalar Glutamatergic Agonist Infusion Leads to Rapid Diffuse Cerebral Activation Acta Neurol Scand
  • 121:209-16
  • 29) Suarez RO, Golby A, Whalen S, Sato S, Theodore WH, Kufta CV, Devinsky O, Balish M, Bromfield EB (2010)
  • Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: First evidence from subdural cortical stimulation, Wada testing, and fMRI
  • Cortex, 46, 343-53
  • 30) 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 (2009)
  • Limitations to Plasticity of Language Network Reorganization in Localization Related Epilepsy
  • Brain, 132, 347-56
  • 31) 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 (2009)
  • Decreased GABA-A Binding on FMZ-PET in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency
  • Neurology, 73, 423-9
  • 32) Shamim S, Hasler G, Liew C, Sato S, Theodore WH (2009)
  • Temporal Lobe Epilepsy, Depression, and Hippocampal Volume
  • Epilepsia, 50, 1067-71
  • 33) Shamim S, Edythe Wiggs E, Heiss J, Sato S, Liew C, Solomon J, Theodore WH (2009)
  • Temporal Lobectomy: Resection Volume, Neuropsychological Effects and Seizure Outcome
  • Epilepsy and Behav, 16, 311-4
  • 34) Theodore WH, Epstein L, Gaillard WD, Shinnar S, Wainwright MS, Jacoboson S (2008)
  • Human Herpes Virus 6B: A possible Role in Epilepsy?
  • Epilepsia, 49, 1828-37
  • 35) 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. (2007)
  • Atypical Language in Lesional and Non-lesional Complex Partial Epilepsy.
  • Neurology, 69(18), 1761-71
  • 36) Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA, Drevets WC, Theodore WH. (2007)
  • 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression.
  • Biological Psychiatry, 62(11), 1258-64
  • 37) Theodore WH, Hasler G, Giovacchini G, Kelley K, Reeves-Tyer P, Herscovitch P, Drevets W. (2007)
  • Reduced Hippocampal 5HT1A PET Receptor Binding and Depression in Temporal Lobe Epilepsy.
  • Epilepsia, 48, 1526-30
  • 38) Fotheringham J, Donati D, Akhyani N, Vortmeyer A, Heiss JD, Williams E, Weinstein S, Bruce DA, Gaillard WD, Sato S, Theodore WH, Jacobson S. (2007)
  • Detection of Human Herpesvirus-6B DNA and Antigen in Primary Astrocyte Cultures from Mesial Temporal Lobe Epilepsy Brain Resections.
  • PLoS Med, 4(5), e180
  • 39) Harden CL, Huff JS, Schwartz T, Zimmerman RD, Weinstein S, Foltin JC, Theodore WH. (2007)
  • Neuroimaging in the emergency patient presenting with seizure
  • Neurology, 69(18), 1772-80
  • 40) Fotheringham J, Donati D, Akhyani N, Vortmeyer A, Heiss JD, Williams E, Weinstein S, Bruce DA, Gaillard WD, Sato S, Theodore WH, Jacobson S (2007)
  • Detection of Human Herpesvirus-6B DNA and Antigen in Primary Astrocyte Cultures from Mesial Temporal Lobe Epilepsy Brain Resections
  • PLoS Med, 4:e180
  • 41) Hasler G, Bonwetsch R, Giovacchini G, Toczek MT, Bagic A, Luckenbaugh DA, Drevets WC, Theodore WH (2007)
  • 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression
  • Biological Psychiatry, 62, 1258-64
  • 42) Giovacchini G, Toczek MT, MD Bonwetsch R, Bagic A, Lang L, Fraser C, Reeves-Tyer P, Herscovitch P, Eckelman WC, Carson RE, Theodore WH (2005)
  • 5-HT1a receptors are reduced in temporal lobe epilepsy after partial volume correction
  • J Nucl Med, 46, 1128-35
  • 43) Toczek MT, Carson RE, Lang L , Ma Y, Spanaki MV, Der MG, Fazilat S, Fazilat S, Kopylev L, Herscovitch P, Eckelman WC, Theodore WH. (2003)
  • PET Imaging of 5-HT1A Receptor Binding in Patients with Temporal Lobe Epilepsy
  • Neurology, 2003, 749-756
  • 44) Theodore WH, De Carli C, Gaillard WD. (2003)
  • Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures
  • Arch Neurol , 60, 250-252
  • 45) Donati D, Akhyani N, Fogdell-Hahn A, Cermelli C, Cassiani Ingoni R, Vortmeyer A, Heiss JD, Cogen P, Gaillard WD, S. Sato S, Theodore WH, Jacobson S. (2003)
  • Detection of Human Herpesvirus 6 (HHV-6) in Mesial Temporal Lobe Epilepsy Surgical Brain Resections
  • Neurology, 61, 1405-1411
  • 46) Theodore WH, Hunter K, Chen R, Vega-Bermudez F, Boroojerdi B, Reeves P, Werhahn K, Kelley K and LG Cohen. (2002)
  • Transcranial magnetic stimulation for the treatment of seizures: a controlled study
  • Neurology , 59, 560-562
  • 47) Gaillard WD, Kopylev L, Weinstein S, Conry J, Pearl PL, Spanaki MV, Fazilat S, Vezina LG, Dubovsky E, Theodore WH (2002)
  • 18FDG-PET In Children With New Onset Partial Epilepsy.
  • Neurology
  • 48) Xu B, Grafman J, Gaillard WD, Spanaki S, Ishii K, Balsamo L, Makale M, Theodore WH. (2002)
  • Neuroimaging reveals automatic speech coding during perception of written word meaning
  • Neuroimage, 2, 859-870
  • 49) Xu B, Grafman J , Gaillard WD, Ishii K, Vega-Bermudez F, Pietrini P, Reeves-Tyer P, DiCamillo P, Theodore WH. (2001)
  • Conjoint and Extended Neural Networks for the Computation of Speech Codes: The Neural Basis of Selective Impairment in Reading Words and Pseudowords
  • Cerebral Cortex, 11, 267-77
  • 50) Frattali CM, Liow K, Craig GH, Korenman LM, Makhlouf F, Sato S, Biesecker L, Theodore WH (2001)
  • Cognitive Deficits in Children with Gelastic Seizures and Hypothalamic Hamartoma
  • Neurology , 57, 43-6
  • 51) Theodore WH, Gaillard WD, DeCarli C, Bhatia S, Hatta J. (2001)
  • Hippocampal volume and glucose metabolism in temporal lobe epileptic foci
  • Epilepsia, 42, 130-3
  • 52) Gaillard WD, Hertz-Pannier L, Mott SH, Barnett AS, LeBihan D, Theodore WH (2000)
  • Functional Anatomy of Cognitive Development: fMRI of Verbal Fluency in Children and Adults
  • Neurology, 54, 180-185
  • 53) Theodore WH, Bhatia S, Hatta J, Fazilat S, DeCarli C, Bookheimer S, Gaillard WD (1999)
  • Hippocampal Atrophy, Epilepsy Duration, and Febrile Seizures in Patients with Partial Seizures
  • Neurology, 52, 132-6
  • 54) Hunter KE, Blaxton TA, Bookheimer SY, Figlozzi C, Gaillard WD, Grandin C, Anyanwu A, Theodore WH (1999)
  • 15O Water Positron Emission Tomography in Language Localization: A Study Comparing PET Visual and Computerized Region of Interest Analysis with the Wada test.
  • Annals of Neurology , 45, 662-5
  • 55) Spanaki MV, Siegel H, Kopylev L, Fazilat S, Dean A, Liow K, Ben Menachem E, Gaillard W, Theodore WH. (1999)
  • The Effect of Vigabatrin (g- vinyl gaba) on Cerebral Blood Flow and Metabolism.
  • Neurology, 53, 1518-22
  • 56) DeCarli C, Hatta J, Fazilat S, Fazilat S, Gaillard WD and Theodore WH (1998)
  • Extratemporal Atrophy in patients with Complex Partial Seizures of Left Temporal Origin
  • Annals of Neurology , 43, 41-45
  • 57) Theodore WH, Porter RJ, Albert P, et al (1994)
  • The Secondary Generalized Tonic-Clonic Seizure: a Videotape Analysis
  • Neurology, 44, 1403-1408
  • 58) Theodore WH, Sato S, Kufta C, et al (1992)
  • Temporal lobectomy for uncontrolled seizures: the role of positron emission tomography
  • Ann Neurol , 32, 789-794
  • 59) Theodore WH, Porter RJ, Raubertas RF (1987)
  • Seizures during barbiturate withdrawal: relation to blood level
  • Ann Neurol, 22, 644-647
  • 60) Theodore WH, Porter RJ (1983)
  • Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy
  • Ann Neurol, 13, 320-324
  • 61) Theodore WH, Porter RJ (1983)
  • Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy
  • Ann Neurol, 13, 320-324
  • 62) Ketter TA, Malow BA, Flamini R, White SR, Post RM, Theodore WH (1194)
  • Anticonvulsant withdrawal-emergent psychopathology
  • Neurology, 44, 55-61
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