The specific aims of this proposal are: 1) to test the hypothesis that prophylactic phenytoin (Dilantin) will lower the incidence of posttraumatic epilepsy in head-injured patients, and 2) to evaluate if that prophylactic phenytoin has any negative side effects on the neuropsychological-psychosocial recovery of head-injured patients. The study will be a longitudinal double blind design with patients randomly assigned to a treatment (phenytoin) or placebo group. Patients with pre-existing head injuries or CNS damage (including chronic alcoholism) will be excluded from this study. Patients will receive either a loading dose of phenytoin or placebo within the first 12 hours of head injury, and then subsequent daily dosages to maintain serum levels within therapeutic range. Study patients will receive treatment for a period of one year and then will be withdrawn from therapy (unless patients have had seizures occur). Both treated and control groups will be followed for a period of two years after injury to determine the incidence of posttraumatic epilepsy. Both groups will undergo extensive neuropsychological and psychosocial testing at one and 12 months (before drug discontinuance) to assess possible drug effects on these aspects of recovery. At the end of follow-up for all patients, the incidence of posttraumatic seizures will be evaluated for the treated and control groups and compared for statistically significant differences. Therefore, the objects of this proposal are to study prospectively the efficacy of prophylactic phenytoin in preventing post-traumatic seizures in head-injured patients and determine any effects this treatment might have on posttraumatic neuropsychologic recovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS019643-04
Application #
3399750
Study Section
Neurology A Study Section (NEUA)
Project Start
1983-07-01
Project End
1989-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Dikmen, Sureyya; Machamer, Joan; Temkin, Nancy (2017) Mild Traumatic Brain Injury: Longitudinal Study of Cognition, Functional Status, and Post-Traumatic Symptoms. J Neurotrauma 34:1524-1530
Alali, Aziz S; Vavrek, Darcy; Barber, Jason et al. (2015) Comparative study of outcome measures and analysis methods for traumatic brain injury trials. J Neurotrauma 32:581-9
Machamer, Joan; Temkin, Nancy; Dikmen, Sureyya (2013) Health-related quality of life in traumatic brain injury: is a proxy report necessary? J Neurotrauma 30:1845-51
Badri, Shide; Chen, Jasper; Barber, Jason et al. (2012) Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med 38:1800-9
Dikmen, Sureyya; Machamer, Joan; Fann, Jesse R et al. (2010) Rates of symptom reporting following traumatic brain injury. J Int Neuropsychol Soc 16:401-11
Anderson, Gail D; Temkin, Nancy R; Dikmen, Sureyya S et al. (2009) Haptoglobin phenotype and apolipoprotein E polymorphism: relationship to posttraumatic seizures and neuropsychological functioning after traumatic brain injury. Epilepsy Behav 16:501-6
Pagulayan, Kathleen Farrell; Hoffman, Jeanne M; Temkin, Nancy R et al. (2008) Functional limitations and depression after traumatic brain injury: examination of the temporal relationship. Arch Phys Med Rehabil 89:1887-92
Pagulayan, Kathleen Farrell; Temkin, Nancy R; Machamer, Joan E et al. (2007) The measurement and magnitude of awareness difficulties after traumatic brain injury: a longitudinal study. J Int Neuropsychol Soc 13:561-70
Chaytor, Naomi; Temkin, Nancy; Machamer, Joan et al. (2007) The ecological validity of neuropsychological assessment and the role of depressive symptoms in moderate to severe traumatic brain injury. J Int Neuropsychol Soc 13:377-85
Anderson, Gail D; Temkin, Nancy R; Awan, Asaad B et al. (2007) Effect of time, injury, age and ethanol on interpatient variability in valproic acid pharmacokinetics after traumatic brain injury. Clin Pharmacokinet 46:307-18

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