The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study.

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Telephone Problem-Solving Treatment Improves Sleep Quality in Service Members With Combat-Related Mild Traumatic Brain Injury: Results From a Randomized Clinical Trial.

OBJECTIVE: Evaluate sleep quality, its correlates, and the effect of telephone-based problem-solving treatment (PST) in active duty postdeployment service members with mild traumatic brain injury (mTBI) SETTING:: Randomized clinical trial. PARTICIPANTS: Active duty service members with combat-related mTBI. STUDY DESIGN: Education-only (EO) and PST groups (N = 178 each) received printed study materials and 12 educational brochures. The PST group additionally received up to 12 PST telephone calls addressing participant-selected issues. Outcomes were evaluated postintervention (6 months) and at 12 months. MAIN MEASURE: Pittsburgh Sleep Quality Index. RESULTS: Sleep quality was manifestly poor in both groups at baseline (Pittsburgh Sleep Quality Index = 12.5 ± 4). Overall sleep quality was significantly different between the PST and EO groups at 6 months (P = .003) but not at 12 months. Longitudinally, PST significantly improved sleep quality at 6 months (P = .001) but not over the follow-up. Low sleep quality was associated with concussion symptoms, pain, depression, and posttraumatic stress disorder at all time points (P < .0001). CONCLUSIONS: Sleep disorders, common in postdeployment service members with mTBI, are strongly associated with the presence of pain, posttraumatic stress disorder, and depression. Telephone-based PST may be an effective therapeutic approach for reducing sleep disorders in this population. Research should focus on maintenance of treatment gains.

The effect of telephone counselling on reducing post-traumatic symptoms after mild traumatic brain injury: a randomised trial.

BACKGROUND: Mild traumatic brain injury (MTBI) is a significant public health problem affecting approximately 1 million people annually in the USA. A total of 10-15% of individuals are estimated to have persistent post-traumatic symptoms. This study aimed to determine whether focused, scheduled telephone counselling during the first 3 months after MTBI decreases symptoms and improves functioning at 6 months. METHODS: This was a two-group, parallel, randomised clinical trial with the outcome assessed by blinded examiner at 6 months after injury. 366 of 389 eligible subjects aged 16 years or older with MTBI were enrolled in the emergency department, with an 85% follow-up completion rate. Five telephone calls were completed, individualised for patient concerns and scripted to address education, reassurance and reactivation. Two composites were analysed, one relating to post-traumatic symptoms that developed or worsened after injury and their impact on functioning, the other related to general health status. RESULTS: The telephone counselling group had a significantly better outcome for symptoms (6.6 difference in adjusted mean symptom score, 95% confidence interval (CI) 1.2 to 12.0), but no difference in general health outcome (1.5 difference in adjusted mean functional score, 95% CI 2.2 to 5.2). A smaller proportion of the treatment group had each individual symptom (except anxiety) at assessment. Similarly, fewer of the treatment group had daily functioning negatively impacted by symptoms with the largest differences in work, leisure activities, memory and concentration and financial independence. CONCLUSIONS: Telephone counselling, focusing on symptom management, was successful in reducing chronic symptoms after MTBI. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, #NCT00483444.

Outcomes of ruptured intracranial aneurysms treated by microsurgical clipping and endovascular coiling in a high-volume center.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze the 3-month outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH) treated from January 2005 to June 2006. This paper describes the outcomes after treatment of aneurysmal SAH and comparison between patients treated by clipping or coiling in a high volume center. MATERIALS AND METHODS: A retrospective chart review was performed of records of 195 consecutive patients with SAH. The overall outcome and the pretreatment variables predicting outcomes and the difference between the clipping and coiling groups were analyzed by logistic regression analysis. RESULTS: A total of 105 (55%) patients had microsurgical clipping and 87 (45%) had endovascular coiling. At 3 months, 69% of patients recovered with no or mild disability. The predictors of a 3-month modified Rankin Scale (mRS) were Hunt and Hess (HH) grade on admission and the presence of intracerebral hemorrhage (ICH). Patients in the coiling group had worse admission grades; they had worse 3-month mRS (2.28 vs 1.73), but this was not significant when the groups were matched (P = .38). Vasospasm rate was significantly higher in the clipping group (66% vs 52%). The immediate incomplete occlusion rate of aneurysms was higher (21.7% vs 7.6%) in the coiling group. CONCLUSION: The overall results of treatment of aneurysmal SAH have improved. There is no significant difference in the outcomes between the patients in the clipping and coiling groups.

Workers' risk of unemployment after traumatic brain injury: a normed comparison.

We examined, among those persons working preinjury, the risk of unemployment 1 year after traumatic brain injury (TBI) relative to expected risk of unemployment for the sample under a validated risk-adjusted econometric model of employment in the U.S. population. Results indicate that 42% of TBI cases were unemployed versus 9% expected, relative risk (RR) = 4.5, 95% confidence interval (CI) (4.12, 4.95). The relative risk for unemployment was higher among males, those with higher education, persons with more severe injuries, and more impaired early neuropsychological or functional status. Difference in unemployment rates gave similar results for gender, severity of injury, and early neuropsychological and functional status. However, for education, the excess was smaller among those more highly educated, but the unemployment rate in the more highly educated in the general population was sufficiently small to yield a larger relative risk. In conclusion, after accounting for underlying risk of unemployment in the general population, unemployment is substantially higher after TBI for people who were employed when they were injured. The differential employment status varies depending on demographics, severity of brain injury, early functional outcome, and neurobehavioral indicators. For characteristics such as education, associated with rates of unemployment in the general population, different methods used to compare the rates may yield different results.

Prediction of functional outcomes after traumatic brain injury: a comparison of 2 measures of duration of unconsciousness.

OBJECTIVE: To compare the usefulness of time until motor localization occurs versus time until commands are followed in predicting outcome after traumatic brain injury (TBI). DESIGN: A retrospective analysis of data from a prospective cohort study of subjects with severe TBI. SETTING: Seventeen Traumatic Brain Injury Model System programs. PARTICIPANTS: A total of 496 subjects, recruited through the TBI Model System programs, with loss of consciousness greater than 1 day, with no late neurosurgical complications, and complete data for all measures. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time until Glasgow Coma Scale (GCS) motor score of 5 (time to motor localization) and time until GCS motor score of 6 (time until commands were followed) were abstracted from medical records. Functional outcomes were assessed at inpatient rehabilitation admission and discharge, along with acute and rehabilitation lengths of stay and charges. RESULTS: Time until commands were followed was a better predictor of all of the outcomes assessed than time until motor localization occurred. In multiple regression models, time until motor localization did not add significantly to the prediction provided by time until commands were followed. The predictive power of time to command following was superior even in the subgroup with poor language comprehension as measured by the Token Test. CONCLUSION: Despite the theoretical appeal of time to motor localization (eg, in persons with language comprehension problems), time to command following appears to be a more powerful predictor of outcome after severe brain injury.

Discharge disposition from acute care after traumatic brain injury: the effect of insurance type.

OBJECTIVE: To determine if persons with traumatic brain injury (TBI) who are insured by Medicaid or health maintenance organizations (HMOs) are more likely to receive postacute care in skilled nursing facilities (SNFs) than in rehabilitation facilities, compared with persons insured by commercial fee-for-service (FFS) plans. DESIGN: Retrospective cohort study. SETTING: County hospital admitting 30% of all Washington State TBI patients. PATIENTS: Patients with moderate to severe TBI discharged to rehabilitation facilities or SNFs between 1992 and 1997 (n = 1271); 56.3% were insured by Medicaid, 26.1% by FFS plans, and 17.6% by HMOs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disposition on discharge from acute care (rehabilitation facilities vs SNF); adjusted relative risk (RR) and confidence interval (CI) for different insurance types. RESULTS: After accounting for confounding factors, Medicaid patients were 68% more likely (RR = 1.68, 95% CI = 1.34-2.11) and HMO patients were 23% more likely (RR = 1.23, 95% CI =.90-1.68) to go to a SNF than FFS patients. However, the latter difference was not statistically significant. CONCLUSIONS: An association exists between insurance type and postacute care site. Efforts should be made to determine the effect this relationship has on the cost and outcomes for TBI patients.

Self-report of extent of recovery and barriers to recovery after traumatic brain injury: a longitudinal study.

OBJECTIVE: To examine the perspective of survivors of traumatic brain injury (TBI) regarding the extent and nature of their recovery over time. DESIGN: Inception cohort, longitudinal study. SETTING: Level I trauma center. PARTICIPANTS: One hundred fifty-seven consecutively hospitalized individuals with TBI (mean age, 36.1 yr; 80% men) with a broad range of injury severity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants reported the extent of their recovery and barriers to full recovery at 1, 6, and 12 months. RESULTS: Participants reported a median return to normal at the 3 follow-up times of 65%, 80%, and 85%. After 1 month, self-reported extent of recovery correlated well with performance on the Glasgow Outcome Scale (p <.001 at 6 and 12 mo) and Wechsler Adult Intelligence Scale Performance IQ (p =.001 at 12 mo). The major reported barrier to recovery was physical difficulties, which constituted over half of the concerns at all time periods. Report of physical-related concerns decreased significantly (p =.002) over time whereas cognition-related concerns increased significantly (p =.02). CONCLUSION: Brain injury survivors consider themselves to have greater recovery than previously reported by clinicians or family members, consider physical problems a significant factor in their recovery, and appear to become more aware of cognitive impairments over time.

Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials.

PURPOSE: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures. METHODS: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel-Haenszel analyses; random effects model used if heterogeneity was significant. RESULTS: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32-0.82) and cerebral malaria (RR, 0.36; CI, 0.23-0.56). Diazepam for contrast media-associated seizures (RR, 0.10; CI, 0.01-0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25-0.71; TBI: RR, 0.33; CI, 0.19-0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17-0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04-0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76-2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75-2.25). CONCLUSIONS: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out.

Antiepileptogenic agents: how close are we?

Epilepsy is a common neurological condition, affecting about 4% of individuals over their lifetime. Epilepsy can be idiopathic, secondary to an underlying genetic abnormality or unknown causes, or acquired. Known potential causes account for about one third of epilepsy. Control of epilepsy has primarily focused on suppressing seizure activity after epilepsy has developed. An intriguing possibility is to control acquired epilepsy by preventing epileptogenesis, the process by which the brain becomes epileptic. Many laboratory models simulate human epilepsy as well as provide a system for studying epileptogenesis. The kindling model involves repeated application of subconvulsive electrical stimulation to the brain, leading to spontaneous seizures. Other models include the cortical or systemic injection of various chemicals. These models suggest that many antiepileptic drugs, from phenobarbital and valproate (valproic acid) to levetiracetam and tiagabine, have antiepileptogenic potential. Some promising other possibilities include N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists as well as the neurotrophins and their receptors. Phenobarbital, phenytoin, valproate, carbamazepine and, to a very limited extent, diazepam have been evaluated in clinical trials to test whether they actually prevent epileptogenesis in humans. Results have been very disappointing. Meta-analyses of 12 different drug-condition combinations show none with significantly lower unprovoked seizure rates among those receiving the active drug. In 4 of the 12, the observed rate was actually slightly higher among treated individuals. None of the newer drugs have been evaluated in antiepileptogenesis trials. Until some drugs demonstrate a clear antiepileptogenic effect in clinical trials, the best course to reduce the incidence of epilepsy is primary prevention of the risk-increasing events--for example, wearing helmets, using seat belts, or decreasing the risk of stroke by reducing smoking.

Utility of a composite measure to detect problematic alcohol use in persons with traumatic brain injury.

OBJECTIVES: To examine factors complicating the study of alcohol-related effects in traumatic brain injury (TBI) patients and to evaluate a composite measure to categorize such patients according to degree of alcohol-related problems. DESIGN: Inception cohort. SETTING: Level I trauma center. PATIENTS: Consecutively hospitalized adult TBI patients (n = 156; 73% men; 87% Caucasian; mean age, 30yr; mean education, 12yr). Selection criteria required objective evidence of brain trauma; minimum survival of 1 month postinjury; age 15 years or older; and English speaking. MAIN OUTCOME MEASURES: An index of problematic drinking based on a measure created by combining blood-alcohol level, quantity-frequency of consumption, and the Short Michigan Alcoholism Screening Test. Preinjury characteristics were obtained through structured interview. RESULTS: Participants with highly problematic drinking showed poorer premorbid psychosocial functioning, including lower educational attainment, greater likelihood of problems with the law, lower perceived social support, and greater prevalence of other substance abuse. CONCLUSION: The composite index is useful in identifying problematic drinkers among TBI patients. Results have implications for interpreting and planning research on the role of alcohol in TBI outcomes.

Functional status examination: a new instrument for assessing outcome in traumatic brain injury.

The Functional Status Examination (FSE) is a new measure designed to evaluate change in activities of everyday life as a function of an event or illness, including traumatic brain injury. The measure covers physical, social, and psychological domains. The FSE is based on a structured interview and includes levels of functioning that accommodate the full spectrum of possible outcomes, from death through recovery to preinjury functioning. Based on 133 prospectively studied patients with moderate to severe traumatic brain injury, the FSE has favorable psychometric properties including good test-retest reliability (r = 0.80) and close correspondence of assessments provided by the patient and their significant other (SO; r = 0.80). The FSE correlated significantly with each of three severity indices with closest relationships occurring between the FSE assessed by the SO and posttraumatic amnesia (r = 0.76). The FSE assessed by the SO was significantly (p < 0.05) more closely related to each severity index than the Glasgow Outcome Scale (GOS) or Sickness Impact Profile and, for two of the three indices, than the SF-36. All measures showed significant change from 1 to 6 months after injury with the FSE showing the largest effect sizes. The FSE is significantly related to important constructs such as family burden, SO depression, and sacrifices the family makes, as well as overall indices of recovery and satisfaction with level of functioning. The latter relationships are significantly stronger than for the GOS. The FSE has demonstrated good reliability, validity, and sensitivity, and appears to be a promising instrument for monitoring recovery and assessing functional status in clinical trials.

Mild head injury: facts and artifacts.

While most would agree that mild traumatic brain injury (TBI) is associated with early neuropsychological problems, disagreement exists regarding their persistence and whether they are the cause of the disabilities experienced by some people. The aim of this study was to examine how the criteria used to define mild TBI and how the pre-injury characteristics of people affect their neuropsychological outcome. A total of 157 unselected hospitalized cases with Glasgow Coma Scale scores of 13-15 and 109 trauma controls were prospectively recruited and administered a number of cognitive measures at 1 month and 12 months after injury. The results indicated early impairments that decreased with time and the stringency of the definition of 'mild' TBI. The contribution of demographics was usually significant and often stronger than the mild TBI effect. Subtle variation of the demographics of the brain injured or the comparison subjects can be sufficient to mimic or mask mild brain injury effects.

Detecting change: A comparison of three neuropsychological methods, using normal and clinical samples.

Detecting change in individual patients is an important goal of neuropsychological testing. However, limited information is available about test-retest changes, and well-validated prediction methods are lacking. Using a large nonclinical subject group (N = 384), we recently investigated test-retest reliabilities and practice effects on the Wechsler Adult Intelligence Scale and Halstead-Reitan Battery. Data from this group also were used to develop models for predicting follow-up test scores and establish confidence intervals around them. In this article we review those findings, examine their generalizability to new nonclinical and clinical groups, and explore the sensitivity of the prediction models to real change. Despite similarities across samples in reliability coefficients and practice effects, limits to the generalizability of prediction methods were found. Also, when multiple test measures were considered together, one or more "significant" changes were common in all (including stable) subject groups. By employing normative cut-offs that correct for this, sensitivity of the models to neurological recovery and deterioration was modest to good. More complex regression models were not more accurate than the simpler Reliable Change Index with correction for practice effects when confidence intervals for all methods were adjusted for variations in level of baseline test performance.

Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin.

OBJECTIVE: To determine the incidence of intravenous site reactions to phenytoin and valproate in a large population of patients with neurotrauma. DESIGN: Retrospective chart review of two double-blind, randomized clinical trials evaluating the use of antiepileptic drugs to prevent posttraumatic seizures in patients with neurotrauma: phenytoin versus placebo (n = 390), and valproate versus phenytoin with placebo (n = 385). Information collected from the charts included the number, type, and location of intravenous lines and intravenous site events. SETTING: Tertiary care trauma and university teaching hospital. MAIN RESULTS: Intravenous site reactions occurred in 18% and 25% of patients receiving valproate or phenytoin, respectively, with the majority of events (70%) occurring in the first intravenous site. Patients received the neurosurgery study drug (NSSD) by either central or peripheral lines; all intravenous site reactions occurred in peripheral administration sites. When patients who received the drug by central line during the course of therapy were excluded, the estimated incidence of site reactions was 21% and 30% for valproate and phenytoin, respectively (p = 0.056). The time to the first event was shorter with phenytoin compared with valproate (2.0 +/- 1.3 vs. 3.0 +/- 1.9 d; p = 0.009). Fewer adverse events were noted with phenytoin in the phenytoin-without-valproate study than in the phenytoin-with-valproate study, with 4.3% and 8.2% of intravenous site events recorded in patients receiving placebo or phenytoin, respectively. There was no significant difference in the number of intravenous lines per patient used during NSSD drug infusion for phenytoin versus placebo or phenytoin versus valproate. CONCLUSIONS: Both intravenous phenytoin and valproate resulted in intravenous site reactions, with the loading doses responsible for the majority of the events.

Neuropsychological effects of valproate in traumatic brain injury: a randomized trial.

OBJECTIVES: To examine the neuropsychological side effects of valproate (VPA) given to prevent posttraumatic seizures. METHODS: In a randomized, double-masked, parallel group clinical trial, we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenytoin. We studied 279 adult subjects who were randomized within 24 hours of injury and examined with a battery of neuropsychological measures at 1, 6, and 12 months after injury. We examined drug effects cross-sectionally at 1, 6, and 12 months and longitudinally by examining differential change from 1 to 6 months and from 6 to 12 months as a function of protocol-dictated changes in treatment. RESULTS: No significant adverse or beneficial neuropsychological effects of VPA were detected. CONCLUSIONS: Valproate (VPA) appears to have a benign neuropsychological side effects profile, making it a cognitively safe antiepileptic drug to use for controlling established seizures or stabilizing mood. However, based on this study, VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent posttraumatic seizures, there was a trend toward more deaths in the VPA groups, and it did not have positive effects on cognition.

Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis.

OBJECT: The goals of this study were to determine if the use of phenytoin to prevent early posttraumatic seizures following head injury was associated with significant adverse side effects and also to determine if the reduction in early posttraumatic seizures after phenytoin administration was associated with a change in mortality rates in head-injured patients. METHODS: The authors performed a secondary analysis of the data obtained in a prospective double-blind placebo-controlled study of 404 patients who were randomly assigned to receive phenytoin or placebo for the prevention of early and late posttraumatic seizures. The incidence of adverse drug effects during the first 2 weeks of treatment, however, was low and not significantly different between the treated and placebo groups. Hypersensitivity reactions occurred in 0.6% of the patients in the phenytoin-treated group compared with 0% in the placebo group (p = 1.0) during week 1, and in 2.5% of phenytoin-treated compared with 0% of placebo-treated patients (p = 0.12) for the first 2 weeks of treatment. Mortality rates were also similar in both groups. Although the mortality rate was higher in patients who developed seizures, this increase was related to the greater severity of the injuries sustained by these patients at the time of the original trauma. CONCLUSIONS: The results of this study indicate that the incidence of early posttraumatic seizure can be effectively reduced by prophylactic administration of phenytoin for 1 or 2 weeks without a significant increase in drug-related side effects. Reduction in posttraumatic seizure during the 1st week, however, was not associated with a reduction in the mortality rate.

Valproate therapy for prevention of posttraumatic seizures: a randomized trial.

OBJECT: Seizures frequently accompany moderate to severe traumatic brain injury. Phenytoin and carbamazepine are effective in preventing early, but not late, posttraumatic seizures. In this study the authors compare the safety and effectiveness of valproate with those of short-term phenytoin for prevention of seizures following traumatic brain injury. METHODS: The study was a randomized, double-blind, single-center, parallel-group clinical trial. Treatment began within 24 hours of injury. One hundred thirty-two patients at high risk for seizures were assigned to receive a 1-week course of phenytoin, 120 were assigned to receive a 1-month course of valproate, and 127 were assigned to receive a 6-month course of valproate. The cases were followed for up to 2 years. The rates of early seizures were low and similar when using either valproate or phenytoin (1.5% in the phenytoin treatment group and 4.5% in the valproate arms of the study; p = 0.14, relative risk [RR] = 2.9, 95% confidence interval [CI] 0.7-13.3). The rates of late seizures did not differ among treatment groups (15% in patients receiving the 1-week course of phenytoin, 16% in patients receiving the 1-month course of valproate, and 24% in those receiving the 6-month course of valproate; p = 0.19, RR = 1.4, 95% CI 0.8-2.4). The rates of mortality were not significantly different between treatment groups, but there was a trend toward a higher mortality rate in patients treated with valproate (7.2% in patients receiving phenytoin and 13.4% in those receiving valproate; p = 0.07, RR = 2.0, 95% CI 0.9-4.1). The incidence of serious adverse events, including coagulation problems and liver abnormalities, was similar in phenytoin- and valproate-treated patients. CONCLUSIONS: Valproate therapy shows no benefit over short-term phenytoin therapy for prevention of early seizures and neither treatment prevents late seizures. There was a trend toward a higher mortality rate among valproate-treated patients. The lack of additional benefit and the potentially higher mortality rate suggest that valproate should not be routinely used for the prevention of posttraumatic seizures.

Emotional and behavioral adjustment after traumatic brain injury.

OBJECTIVES: To examine emotional and behavioral adjustment and recovery over 1 year after traumatic brain injury (TBI), and to determine whether the difficulties, if present, are due to neurologic insult. DESIGN: Longitudinal evaluation of adjustment from 1 month to 1 year after injury. SETTING: Level I trauma center at a university hospital. PATIENTS: One hundred fifty-seven consecutively hospitalized adults with TBI and 125 trauma controls with other system injuries evaluated at 1 and 12 months after injury. MAIN OUTCOME MEASURES: Katz Adjustment Scale (KAS). RESULTS: The TBI group at 1 year follow-up demonstrated significant emotional and behavioral maladjustment, but such difficulties did not appear to be mediated by the brain injury, since the KAS scores for the TBI and trauma control groups were not significantly different. Those with moderate TBI reported greater difficulties than those with mild or severe injuries. Changes in adjustment over 1 year were common for both groups. Within the TBI group there was differential recovery: improvement in cognitive clarity, dysphoric mood, and emotional stability, but increased difficulties with anger management, antisocial behaviors, and self-monitoring. CONCLUSIONS: These results raise questions about commonly held beliefs that those with mild TBI report greater distress, and clarify some misconceptions regarding change in emotional and behavioral functioning over time.

Late cognitive effects of early treatment with phenobarbital.

We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures.