Division of Neurology

Research

Overview

The research program in child neurology uses state-of-the-art scientific methods to improve the understanding of neurological disorders affecting children of all ages, focusing on both common conditions and unusual diseases that can lead to serious complications. Examples include autism, epilepsy, neuromuscular disorders, neurofibromatosis, and neurogenetic diseases. Our faculty and staff utilize cutting edge techniques such as advanced neuroimaging, molecular biology and cell signaling in a partnership with basic scientists and multidisciplinary clinical teams.

Research Faculty

Name	Areas of Special Interest
Mohamad Mikati, MD, Chief	Clinical epilepsy (pharmacology, genetics, pharmacogenetics), genetics of febrile seizures, basic mechanisms of seizure related neuronal injury
Martha McLean Bolton, PhD	Neurodegenerative disorders, Huntington disease, epileptic channelopathies
George Robert DeLong, MD	Neuropsychiatric disorders, autism
William Brian Gallentine, DO	Clinical epilepsy (pharmacology and genetics), continuous electroencephalographic monitoring
Darrell V. Lewis, MD	Febrile seizures, clinical epilepsy
Edward C. Smith, MD	Neuromuscular disorders, muscular dystrophy

Senior Research Associate

Soren Leonard, PhD Neurobiology

Clinical Research

In Clinical Research, we are addressing several important questions:

The relationship between febrile seizures and medial temporal sclerosis. The use of new structural MRI diagnostic techniques allows the testing of the intriguing hypothesis that prolonged febrile seizures lead to medial temporal sclerosis.
The development and testing of new anti-epileptic drugs and the investigation of the role of continuous EEG monitoring in the management of patients with acute brain insults and traumatic brain injury.
The long-term outcome after acute neurological insults in neonates and older children. A team of specialists including neurologists, neonatologists, and psychologists, and others are joining forces to assess these outcomes and determine the predictors that influence them.

Basic Research

In Basic Research, we seek to:

Determine the genetic basis of a number of neurogenetic diseases, including familial epilepsy syndromes and autism. The ultimate aim of this research is to achieve a better understanding of the causes of these disorders and the factors that influence resistance to therapy.
Define the basic mechanisms of neuronal injury in the developing brain, with the hope that this information will ultimately lead to new therapeutic approaches to protect children from the effects of insults that damage the brain and from the effects of seizure related injuries.

Translational Research

In Translational Research, we are collaborating with basic science and clinical research programs in several departments. These collaborative efforts focus on the identification of genetic markers for prediction of clinical outcome and on the response to novel interventions and therapies in a number of serious diseases. Specifically these efforts include defining the following:

The nature of the mechanisms underlying autism and the chromosomal abnormalities that could contribute to this and related conditions. Among these is the GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder.
The identification of biochemical markers and therapeutic targets in cell signaling pathways in NF-1. This work is performed via the Duke Neurofibromatosis Clinic, which is an Affiliate Clinic of the Children’s Tumor Foundation Neurofibromatosis Clinical Network
The response of a variety of neuromuscular and neurogenetic disorders to enzyme therapy and vector-mediated gene therapy. 4. The identification of mutations that result in febrile seizures and intractable epilepsy.
The pharmacogenetics of epilepsy.
Utilization of novel in vitro models of neurodegenerative diseases with transgene expression by nucleofection, aiming to facilitate drug discovery.

Clinical and Basic Science Research Studies

Genetics of Epilepsy. PI: David Goldstein, PhD. Co-Investigator: Mohamad Mikati, MD; William Gallentine, DO.

Ultrasonographic Characteristics of the Peripheral Nervous System in Diabetic Polyneuropathy. PI: Lisa D. Hobson-Webb, MD. Co-Investigator: Edward Smith, MD.

EEG Monitoring Consortium. PI: Aatif Husain, MD. Co-Investigators: William Gallentine, DO; Mohamad Mikati, MD.

Down Syndrome Disintegrative Disorder: Possible Hashimoto’s Encephalopathy? PI: Priya Kishnani, MD. Co-Investigators: Edward Smith, MD; Gordon Worley, MD.

Consequences of Prolonged Febrile Seizures. PI: Darrell Lewis, MD. Co-Investigator: William Gallentine, DO.

Life Events and Childhood Brain. Development. PI: Michael De Bellis, MD, MPH. Co-Investigators: James Provenzale, MD; Mohamad Mikati, MD.

Duke Neurofibromatosis Registry. PI: Mohamad Mikati, MD. Co-Investigators: William Gallentine, DO; Edward Smith, MD.

Prediction of EEG Seizures. PI: Mohamad Mikati, MD. Co-Investigators: Leslie Collins, PhD; Chandra Throckmorton, PhD.

Connectivity Networks in Normal Children and those with Partial Epilepsy. PI: Mohamad Mikati, MD. Co-Investigators: Rebecca Kozitza, BS; Allen Song, PhD; Nan-kuei Chen, PhD; Helen Egger, MD.

CURE Consortium Database. Site PI: Mohamad Mikati, MD.

Effects of Vagus Nerve Stimulator Placement on Body Mass Index. PI: Mohamad Mikati, MD. Co-Investigators: Sujay Kansagra, MD.

DTI in Pediatric Partial Epilepsy. PI: Mohamad Mikati, MD. Co-Investigators: James Provenzale, MD; Michael De Bellis, MD, MPH.

A Mouse Model of Neonatal Hypoxia and its Long Term Consequences. PI: Mohamad Mikati, MD. Co-Investigators: James O. McNamara, MD; Bradley Kolls, MD; A. Soren Leonard, PhD.

Screening for Creatine Pathway and Molybdenum Cofactor Disorders in a Bank of Samples from Patients with Seizures, Mental Retardation and Autism. PI: David Millington, MD. Co-Investigator: Edward Smith, MD.

A Pilot Study of Ultrasonography of the Median Nerve and Flexor Retinaculum in Hurler Syndrome. PI: Edward Smith, MD.