Valproate Prophylaxis of Post-Traumatic Seizures. More information on the individual studies can be found in the literature (Temkin et al., 1990, 1999a, 1999b; Dacey et al., 1991; Dikmen et al., 1991, 2000; McLean et al., 1993). Participants in all the studies used in the present report were English-speaking adults who were admitted to the level I trauma center at Harborview Medical Center in Seattle, Washington, with head injuries and were followed for at least a year. Study subjects were consecutively admitted and met at least the following criteria: any period of LOC, PTA for at least an hour, or other objective evidence of head trauma; an injury that was serious enough to require hospitalization; and survival of at least a month after the injury, at which time the first assessment was done. The Behavioral Outcome of Head Injury and Dilantin Prophylaxis of Post-Traumatic Seizures studies both excluded people who had prior hospitalization for head injury, alcoholism, cerebral disease, a psychiatric disorder, or mental retardation. The Patient Characteristics and Head Injury Outcome study did not exclude subjects on the basis of those conditions. The Dilantin Prophylaxis of Post-Traumatic Seizures and the Valproate Prophylaxis of Post-Traumatic Seizures studies enrolled patients who had more severe head injuries that posed an increased risk of seizures, such as intracranial hematoma, cortical contusion, and depressed skull fracture. Studies to assess a variety of neurocognitive and social function outcomes have been conducted with these study populations.

Dikmen et al. (1995b) conducted a prospective study of 436 adults with TBI recruited at the time of injury from a level 1 trauma center for the Behavioral Outcome of Head Injury, Patient Characteristics and Head Injury Outcome, or Dilantin Prophylaxis of Post-Traumatic Seizures study. The subjects made up 85% of the 514 subjects recruited into these studies. The controls were 132 patients enrolled as part of the Patient Characteristics and Head Injury Outcome study who were admitted to the emergency room at Harborview Medical Center of University Hospital after trauma to any part of the body except the head; they were group-matched on age, sex, and education. Analyses weighted the cases to adjust the mix of severity and pre-existing conditions to approximate that of the unselected Patient Characteristics and Head Injury Outcome Study. A variety of neuropsychologic tests were conducted a year after injury. A year after injury, the TBI group performed significantly worse than controls on all the neurocognitive tests except the category test, on which the groups did not differ. A dose–response relationship between length of coma and level of performance on neurocognitive tests was observed at 1 year after injury; increasing degree of impairment was associated with increasing severity of brain injury. Subjects with the most severe TBI were significantly impaired on all neurocognitive measures.

Several other studies by Dikmen and colleagues used subsets of the same cohort of head-injured patients, but controls were friends of the head-injured patients (Dikmen et al., 1986, 1990) so they might not have controlled as well for general health effects of trauma. A study based on mild TBI found mild subtle neuropsychologic effects at 1 month that could no longer be detected at 1 year (Dikmen et al., 1986), whereas those with moderate to severe injuries demonstrated significant impairments at 1, 12, and 24 months after injury compared with healthy controls (Dikmen et al., 1990). Motor dexterity and speed were found to be sensitive to the effects of TBI even at 1 year after injury (Haaland et al., 1994). Memory functions were examined at 1 and 12 months after injury. At 1 year, only those with deep or prolonged impaired consciousness (represented by more than 1 day of coma, GCS score of 8 or lower, and PTA of 2 weeks or longer) were performing significantly worse than controls (Dikmen et al., 1987).

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