CNCS Center for Nonlinear and Complex Systems
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Darrell V. Lewis, Professor of Pediatrics and CNCS: Center for nonlinear and complex systems

Current Research Efforts:
Explore the relationship between prolonged febrile convulsions, temporal lobe epilepsy and hippocampal sclerosis; The hypothesis that prolonged febrile convulsions cause hippocampal injury that evolves to sclerosis and then to temporal lobe epilepsy has been promulgated for decades since the advent of surgical treatment of temporal lobe epilepsy. However, this concept has never been addressed with a prospective clinical study. With the availability of magnetic resonance imaging techniques capable of discerning hippocampal edema and measuring hippocampal volume, patients suffering from these seizures can now be studied acutely and chronically to determine if hippocampal injury does occur during them and under what clinical circumstances. We are conducting a longterm study of this phenomenon in cooperation with 5 other medical centers which will prospectively enroll 200 infants presenting with febrile status epilepticus and follow these infants for 10 - 15 years with sequential neuroimaging, electroencephalographic and developmental testing to determine the long term consequences of these infantile seizures.

Contact Info:
Office Location:  125 Bell Bldg, Durham, NC 27710
Email Address: send me a message
Web Page:  http://faculty.duhs.duke.edu/faculty/info?pid=1132

Education:

M.D.University of Minnesota, Twin Cities1969
Research Interests:

Current Research Efforts:
A) Basic Science:
1) Mechanism of NMDA receptor antagomist neuroneurotoxicity: Although NMDA receptor antagonists are useful in protecting against excitotoxicity and ischemic injury, they also can cause neuronal apoptosis in the cingulate gyrus and clinically abused NMDA receptor antagomists such as angels dust can produce a schizoprenic like syndrome. We are studying the disinhibitory effects of NMDA receptor antagonists on the cortical puramidal cells of the posterior cingulate region to determine how these agents produce neuronal injury (Li, Q, Clark, S, Lewis, DV, and Wilson, WA. NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: A potential mechanism of neurotoxicity. J Neurosci, In Press, 2001).
2) Mechanism of development of tolerance and dependence to GHB (gammahydroxybutyric acid), a commonly abused sedative agent. We are studying the effect of GHB on the inhibitory circuitry of the neocortex in rats to determine the changes in GABA receptor expression and sensitivity that may underlie the development of tolerance, dependence and withdrawal phenomena associated with GHB abuse.
B) Clinical Research
1) Relationship between complex febrile convulsions and hippocampal sclerosis; The hypothesis that complex febrile convulsions (CFCs) cause hippocampal injury that evolves to sclerosis and then to temporal love epilepsy has been promulgated for decades since the advent of surgical treatment of temporal love epilepsy. However, this concept has never been addressed with a prospective clinical study. With the availability of magnetic resonance imaging techniques capable of discerning hippocampal edema and measuring hippocampal volume, patients suffering CFCs can now be studied acutely and chronically to determine if hippocampal injury does occur using CFCs and under what clinical circumstances. We are planning a multicenter study of this phenomenon based on the publication describing our initial findings ina small group of infants with CFCs (VanLandingham et al., Annals of Neurology, 43:413-426, 1998; Lewis DV. Febrile convulsions and mesial temporal sclerosis. Current Opinion in Neurology, 12:197-201, 1999; Lewis, DV et al. Do Prolonged Febrile Seizures Produce Mesial Temporal Sclerosis? Hypotheses, MRI Evidence and Unanswered Questions, Prog. Brain Res. In Press, 2001; Mitchell, TV and Lewis, DV. Do prolonged febrile seizures injure the hippocampus: Human MRI studies. In, Febrile Seizures, Eds. TZ Baram and S Shinnar, In Press, 2001.

Keywords:

2-Amino-5-phosphonovalerate • Abdomen • Action Potentials • Adaptation, Physiological • Adolescent • Adult • Afferent Pathways • Age Factors • Aluminum • Aluminum Oxide • Amygdala • Analgesia • Analysis of Variance • Anesthetics, Intravenous • Animals • Animals, Newborn • Arsenazo III • Atrophy • Autoimmune Diseases • Automation • Axons • Baclofen • Behavior, Animal • Benzoates • Bicuculline • Blood Circulation • Blood Volume • Body Mass Index • Body Temperature • Body Weight • Brain • Brain Diseases • Calcium • Carboxylic Acids • Cats • Cell Count • Cell Membrane • Cell Membrane Permeability • Cell Movement • Cell Size • Central Nervous System • Cerebral Hemorrhage • Cerebral Ventricles • Cerebrovascular Circulation • Chelating Agents • Chemical Phenomena • Chemistry • Chemistry, Physical • Child • Child, Preschool • Cholinesterase Inhibitors • Chromium Isotopes • Coloring Agents • Continental Population Groups • Culture Media • Culture Techniques • Data Interpretation, Statistical • Delirium • Demyelinating Diseases • Dendrites • Dentate Gyrus • Deoxyglucose • Diagnosis, Differential • Dietary Supplements • Disease Models, Animal • Dose-Response Relationship, Drug • Drug Interactions • Drug Therapy, Combination • Electric Stimulation • Electrodes, Implanted • Electroencephalography • Electron Transport Complex IV • Electrophysiology • Encephalitis • Encephalitis, Viral • Epilepsy • Epilepsy, Complex Partial • Epilepsy, Temporal Lobe • Erythrocytes • Esters • Ethanol • Evaluation Studies as Topic • Evoked Potentials • Excitatory Amino Acid Agents • Excitatory Postsynaptic Potentials • Extracellular Space • Facial Hemiatrophy • Female • Fetal Blood • Fever • Fluorescence • Functional Laterality • GABA Agents • GABA-A Receptor Antagonists • GABA-B Receptor Agonists • GABA-B Receptor Antagonists • Ganglia • Genetic Predisposition to Disease • Gliosis • Heart Conduction System • Hemodynamics • Hemoglobins • Hemolysis • Hippocampus • Homeostasis • Humans • Hypertension • Image Processing, Computer-Assisted • Immunocompromised Host • Immunohistochemistry • Infant • Infant, Newborn • Infant, Premature • Infant, Premature, Diseases • Infrared Rays • Inhibitory Postsynaptic Potentials • Intensive Care Units, Neonatal • Interneurons • Invertebrates • Iodine Isotopes • Kinetics • Lasers • Learning • Leukemia • Linear Models • Long-Term Potentiation • Magnesium • Magnetic Resonance Imaging • Male • Manganese Compounds • Mathematics • Membrane Potentials • Memory Disorders • Middle Aged • Monitoring, Intraoperative • Monitoring, Physiologic • Movement • Muscles • NAD • Naloxone • Naltrexone • Narcotic Antagonists • Neocortex • Neoplasm Transplantation • Neoplasms, Experimental • Nerve Fibers • Nerve Tissue Proteins • Neural Inhibition • Neural Pathways • Neuronal Plasticity • Neurons • Neurotoxicity Syndromes • Observer Variation • Opioid Peptides • Optics and Photonics • Organ Culture Techniques • Organophosphorus Compounds • Oxidation-Reduction • Oxygen • Oxygen Consumption • Patch-Clamp Techniques • Penicillin G • Pertussis Toxin • Phosphinic Acids • Phosphorylation • Physicochemical Phenomena • Picrotoxin • Piperidines • Plasmapheresis • Polyradiculoneuropathy • Porphyrias • Postoperative Complications • Postoperative Period • Potassium • Prognosis • Prospective Studies • Psychosurgery • Psychotic Disorders • Pyramidal Cells • Quinoxalines • Radioisotopes • Rats • Rats, Inbred Strains • Rats, Sprague-Dawley • Reaction Time • Receptors, Drug • Receptors, GABA-A • Receptors, GABA-B • Receptors, N-Methyl-D-Aspartate • Reproducibility of Results • Retrospective Studies • Sarcoma, Experimental • Scalp • Scleroderma, Localized • Sclerosis • Seizures • Seizures, Febrile • Sensitivity and Specificity • Skin • Sleep Disorders • Sodium Oxybate • Software • Status Epilepticus • Stereotyped Behavior • Structure-Activity Relationship • Subacute Sclerosing Panencephalitis • Survival Analysis • Synapses • Synaptic Membranes • Synaptic Transmission • Television • Temperature • Temporal Lobe • Thermodynamics • Theta Rhythm • Time Factors • Tomography, Emission-Computed • Treatment Outcome • Vagus Nerve Stimulation • Virus Diseases • Young Adult

Representative Publications   (More Publications)

  1. Provenzale, JM; Barboriak, DP; VanLandingham, K; MacFall, J; Delong, D; Lewis, DV, Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis., AJR. American journal of roentgenology, vol. 190 no. 4 (April, 2008), pp. 976-983, ISSN 1546-3141 [18356445], [doi]  [abs]
  2. Li, Q; Kuhn, CM; Wilson, WA; Lewis, DV, Effects of gamma hydroxybutyric acid on inhibition and excitation in rat neocortex., Neuroscience, vol. 150 no. 1 (November, 2007), pp. 82-92, ISSN 0306-4522 [17904295], [doi]  [abs]
  3. Lewis, DV, Losing neurons: selective vulnerability and mesial temporal sclerosis., Epilepsia, vol. 46 Suppl 7 (2005), pp. 39-44, ISSN 0013-9580 [16201994], [doi]  [abs]
  4. Li, Q, Guo-Ross, S, Lewis, DV, Turner, D, White, AM, Wilson, WA, and Swartzwelder, HS.  Dietary prenatal choline supplementation enhances excitatory function and morphology of hippocampal CA1 pyramidal cells. Journal of Neurophysiology. 91(4):1545-55, 2004 Apr.
  5. Li, Q; Clark, S; Lewis, DV; Wilson, WA, NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: a potential mechanism of neurotoxicity., The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 22 no. 8 (April, 2002), pp. 3070-3080, ISSN 1529-2401 [11943810], [doi]  [abs]
  6. Lewis, DV; Barboriak, DP; MacFall, JR; Provenzale, JM; Mitchell, TV; VanLandingham, KE, Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions., Progress in Brain Research, vol. 135 (2002), pp. 263-278, ISSN 0079-6123 [12143347]  [abs]
  7. Wainwright, MS; Martin, PL; Morse, RP; Lacaze, M; Provenzale, JM; Coleman, RE; Morgan, MA; Hulette, C; Kurtzberg, J; Bushnell, C; Epstein, L; Lewis, DV, Human herpesvirus 6 limbic encephalitis after stem cell transplantation., Annals of Neurology, vol. 50 no. 5 (November, 2001), pp. 612-619, ISSN 0364-5134 [11706967]  [abs]
  8. Verma, A, Lewis, D, Vanlandingham, KE, Husain, AM, Friedman, AH, Thompson, E, and Radtke, RA.  Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy.  Epil Res  47:9-15, 2001.
  9. Kassem-Moussa, H; Provenzale, JM; Petrella, JR; Lewis, DV, Early diffusion-weighted MR imaging abnormalities in sustained seizure activity., AJR. American journal of roentgenology, vol. 174 no. 5 (May, 2000), pp. 1304-1306, ISSN 0361-803X [10789783], [doi]
  10. Foldvary, N; Nashold, B; Mascha, E; Thompson, EA; Lee, N; McNamara, JO; Lewis, DV; Luther, JS; Friedman, AH; Radtke, RA, Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis., Neurology, vol. 54 no. 3 (February, 2000), pp. 630-634, ISSN 0028-3878 [10680795]  [abs]
  11. Mott, DD; Li, Q; Okazaki, MM; Turner, DA; Lewis, DV, GABAB-Receptor-mediated currents in interneurons of the dentate-hilus border., Journal of neurophysiology, vol. 82 no. 3 (September, 1999), pp. 1438-1450, ISSN 0022-3077 [10482760]  [abs]
  12. Xie, C.W. and Lewis, D.V. Blocking opioid receptors unmasks LTP of synaptic inhibition in the dentate gyrus. Regulatory Peptides 54:73-74,1994.