Medical Student Research Fellowship for Summer 2009

Mentor: Ramon Diaz-Arrastia, MD, PhD
Department: Neurology
Room number: F2.318
Mail Code: 9036
Phone number: 214-648-6409
E-mail: Ramon.Diaz-Arrastia@UTSouthwestern.edu
Project titles: Evaluation of Diffuse Axonal Injury in patients with Traumatic Brain Injury Using Diffusion Tensor Imaging; Continuous video-EEG monitoring in Traumatic Brain Injury; and Genetic Factors in Outcome after Traumatic Brain Injury

Human subjects IRB approved project numbers (where applicable): IRB # 012005-073; 012004-003; and 0399-123
Animal subjects IRB approved project number (where applicable): Not applicable

Project Type: Patient-oriented research

Brief Description of Projects:

Traumatic brain injury (TBI) is a major cause of mortality and morbidity, particularly among persons below the age of 45. In the US, approximately 55,000 deaths each year are attributed to TBI, and an additional 50,000 individuals each year suffer long-term physical and psychological problems that limit their independence and ability to work. TBI is a heterogeneous disease, and multiple pathophysiologic mechanisms may be operating to produce neural injury. The TBI Research Center at UT Southwestern has several projects suitable for participation during the summer by medical students.

Diffuse Axonal Injury (DAI) results from high velocity deceleration and shear strain, and is believed to be the predominant mechanism of injury in 40 - 50% of TBIs requiring hospital admission in the US. CT scanning is usually unrevealing in DAI, and while structural MRI scanning may add some sensitivity, currently used neuroimaging methods are not associated with injury severity of predictive of outcome. The anatomy and integrity of white matter fiber tracts can be determined noninvasively with DTI, providing new information about brain networks and connectivity.
The fellow will be primarily involved in identifying eligible patients, prospectively collecting clinical information relating to the severity of the initial traumatic injury, following the patients daily during their acute hospitalization, as well as obtaining outcome data at 6 months post-injury. These tasks will be accomplished by having the fellow attend daily morning rounds with the neurosurgical service at Parkland Memorial Hospital, identifying patients who meet eligibility criteria for the study, obtaining informed consent from patients or family members, and collecting intake information. Afternoons will be spent obtaining outcome information via telephone interviews and analyzing MRI data using MRICro and DTI Studio.

Continuous video-EEG monitoring - Convulsive seizures occur during the acute period in 4-10% of patients with severe TBI, and it is likely that these behaviorally evident seizures represent only a small fraction of all epileptic phenomena. Nonconvulsive seizures, which have either no or very subtle behavioral manifestations and can be reliably diagnosed only by EEG monitoring, are substantially more common and occur in 20-35% of patients with severe TBI. The occurrence of nonconvulsive seizures is a poor prognostic sign, but it is unclear whether they a simply a reflection of an extensive insult or whether they contribute to ongoing secondary injury. Further, it is unknown whether treatment with high dose antiepileptic drugs is effective in controlling nonconvulsive seizures or in improving the neurologic outcome. Finally, such treatments, which usually include high dose benzodiazepines, phenobarbital, and occasionally even anesthetic doses of pentobarbital, carry a small but appreciable risk. The goal of this project is to determine the feasibility efficacy of continuous video-EEG (CVEEG) monitoring and aggressive treatment of nonconvulsive seizures in patients with severe TBI. Eligible patients will be those with TBI, GCS < 12, or any unexplained deterioration in sensorium within 72 hours of admission.
The fellow will be primarily involved in identifying eligible patients, coordinating with the clinical neurophysiology department the performance of video-EEG monitoring and, with the assistance of a clinical neurophysiologist (Drs. Van Ness, Agostini and Diaz-Arrastia), monitoring the EEG for nonconvulsive seizures. Duties will also include prospectively collecting clinical information relating to the severity of the initial injury, following the patients daily during their acute hospitalization, and obtaining outcome data at 6 months post-injury. Opportunities to learn about EEG interpretation of patients in coma will also be available.

Genetic Factors in Outcome after Traumatic Brain Injury - Factors such as severity of injury, age, and complications during the acute hospitalization only partly account for outcome, and it is likely that inherited genetic factors predispose certain individuals to have a poor functional outcome after brain trauma. Recent progress in the Human Genome Project has identified common polymorphisms in a number of genes that have been proposed, on the basis of human and animal studies, to regulate the response of neural tissue to injury. Our hypothesis is that inheritance of certain alleles of these polymorphic candidate genes is predictive of poor neurologic recovery after TBI. Understanding which genes may predispose to poor outcome after TBI will be useful in developing tailored therapy to limit damage or improve functional recovery after TBI.
The fellow will be primarily involved in identifying eligible patients, prospectively collecting clinical information relating to the severity of the initial traumatic injury, following the patients daily during their acute hospitalization, as well as obtaining outcome data at 6 months post-injury. These tasks will be accomplished by having the fellow attend daily morning rounds with the neurosurgical service at Parkland Memorial Hospital, identify patients who are meet eligibility criteria for the studies, obtaining informed consent from patients or family members, and collecting intake information. Afternoons will be spent obtaining outcome information via telephone interviews. The opportunity for performing genotype analysis using the polymerase chain reaction also exists.

Previous Research Activities or Publications with Medical Students:

Eleven medical students have done summer research in Dr. Diaz-Arrastia's laboratory over the past 10 years. This has led to 14 abstracts presented at national meetings and 8 publications.