Nancy Temkin

Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures.

BACKGROUND Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive. METHODS To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat. RESULTS Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group. CONCLUSIONS Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.

A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury

BACKGROUND Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). RESULTS There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups. CONCLUSIONS For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

Neuropsychological and psychosocial consequences of minor head injury.

Twenty subjects with minor head injury were compared to an uninjured group at 1 and 12 months after injury on a battery of neuropsychological and psychosocial measures. The results indicate that single minor head injury in persons with no prior compromising condition is associated with mild but probably clinically non-significant difficulties at 1 month after injury. Disruptions of everyday activities, however, are extensive with other system injuries significantly contributing to these problems. Recent reports in the literature may represent overestimation of head injury related losses due to lack of control for the effects of pre-injury characteristics and other system injuries.

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

Summary:  Purpose: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures.

Test-retest reliability and practice effects of expanded Halstead-Reitan Neuropsychological Test Battery.

Test-retest reliabilities and practice effects of a broad range of neuropsychological measures were examined in 384 normal or neurologically stable adults. Median test-retest interval was 11 months (range 3-16 months). The reliability estimates for most of the measures are reasonably good, ranging from .70 to low .90s. An exception is the relatively poor reliabilities of most memory measures. For all test measures, the value on initial testing is a strong determinant of the value on the second examination. Practice effects are seen on most measures. The magnitude of the practice effects, however, varies as a function of type of measure, test-retest interval, age, and overall competency level of the participant. This study provides several types of retest information that may be useful for future research and clinical work: comparative reliabilities of the various measures, estimate of error variability associated with each administration, standard deviation of the change, and comparative magnitude of practice effects on various tests.

Rates of major depressive disorder and clinical outcomes following traumatic brain injury.

CONTEXT Uncertainties exist about the rates, predictors, and outcomes of major depressive disorder (MDD) among individuals with traumatic brain injury (TBI). OBJECTIVE To describe MDD-related rates, predictors, outcomes, and treatment during the first year after TBI. DESIGN Cohort from June 2001 through March 2005 followed up by structured telephone interviews at months 1 through 6, 8, 10, and 12 (data collection ending February 2006). SETTING Harborview Medical Center, a level I trauma center in Seattle, Washington. PARTICIPANTS Five hundred fifty-nine consecutively hospitalized adults with complicated mild to severe TBI. MAIN OUTCOME MEASURES The Patient Health Questionnaire (PHQ) depression and anxiety modules were administered at each assessment and the European Quality of Life measure was given at 12 months. RESULTS Two hundred ninety-seven of 559 patients (53.1%) met criteria for MDD at least once in the follow-up period. Point prevalences ranged between 31% at 1 month and 21% at 6 months. In a multivariate model, risk of MDD after TBI was associated with MDD at the time of injury (risk ratio [RR], 1.62; 95% confidence interval [CI], 1.37-1.91), history of MDD prior to injury (but not at the time of injury) (RR, 1.54; 95% CI, 1.31-1.82), age (RR, 0.61; 95% CI, 0.44-0.83 for > or = 60 years vs 18-29 years), and lifetime alcohol dependence (RR, 1.34; 95% CI, 1.14-1.57). Those with MDD were more likely to report comorbid anxiety disorders after TBI than those without MDD (60% vs 7%; RR, 8.77; 95% CI, 5.56-13.83). Only 44% of those with MDD received antidepressants or counseling. After adjusting for predictors of MDD, persons with MDD reported lower quality of life at 1 year compared with the nondepressed group. CONCLUSIONS Among a cohort of patients hospitalized for TBI, 53.1% met criteria for MDD during the first year after TBI. Major depressive disorder was associated with history of MDD and was an independent predictor of poorer health-related quality of life.

Outcome 3 to 5 years after moderate to severe traumatic brain injury

OBJECTIVE To investigate neuropsychologic, emotional, and functional status and quality of life (QOL) 3 to 5 years after moderate to severe traumatic brain injury (TBI). DESIGN Observational cohort. SETTING Level I trauma center. PARTICIPANTS Consecutive adult admissions with TBI involving intracranial abnormalities, prospectively followed up for 3 to 5 years, with 80% follow-up. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Neuropsychologic functioning (Paced Auditory Serial Addition Test, California Verbal Learning Test), emotional status (Center for Epidemiologic Studies Depression Scale, Brief Symptom Inventory), functional status (Functional Status Examination, Glasgow Outcome Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, employment), and perceived QOL. RESULTS Significant functional limitations were observed in all areas. Recovery to preinjury levels ranged from 65% of cases in personal care to approximately 40% in cognitive competency, major activity, and leisure and recreation. Brain injury severity, measured by the modified Abbreviated Injury Scale, related to functional status and neuropsychologic functioning, but not to emotional or QOL measures. Length of impaired consciousness appeared to contribute to outcome more than did anatomic lesions. CONCLUSIONS The results provide representative estimates of long-term morbidity in patients with TBI involving intracranial lesions. The magnitude of morbidity was high. Although direct costs of TBI have received the most attention, the long-term consequences and their cost implications are much larger, unfold over time, and are borne by the survivors, their families, and the public subsidy system.

An Objective Method for the Assessment of Psychological and Social Problems Among Epileptics

Summary: Numerous investigators have identified psychological and social problems among epileptics and in many instances these appear to be more debilitating than the seizures themselves. However, assessment of these problems has most frequently been done by subjective means and when objective tests have been used, they were almost always developed for and standardized on populations other than epileptics. The development of the Washington Psychosocial Seizure Inventory (WPSI) is presented in this paper. After pilot work, 127 adult epileptics were evaluated for psychosocial problems and they completed the 132‐item Inventory. Professional assessment of difficulties was made with respect to family background, emotional adjustment, interpersonal adjustment, vocational adjustment, financial status, adjustment to seizures, and medical management. Finally, an assessment of overall psychosocial functioning was made. Through an item‐by‐item correlation technique, scales were empirically developed for each of these areas and a profile was produced which gives both the absolute and the relative extents of difficulties for each patient with respect to each area. Potential applications for the WPSI are presented.

Detecting significant change in neuropsychological test performance : a comparison of four models

A major use of neuropsychological assessment is to measure changes in functioning over time; that is, to determine whether a difference in test performance indicates a real change in the individual or just chance variation. Using 7 illustrative test measures and retest data from 384 neurologically stable adults, this paper compares different methods of predicting retest scores, and of determining whether observed changes in performance are unusual. The methods include the Reliable Change Index, with and without correction for practice effect, and models based upon simple and multiple regression. For all test variables, the most powerful predictor of follow-up performance was initial performance. Adding demographic variables and overall neuropsychological competence at baseline significantly but slightly improved prediction of all follow-up scores. The simple Reliable Change Index without correction for practice performed least well, with high error rates and large prediction intervals (confidence intervals). Overall prediction accuracy was similar for the other three methods; however, different models produce large differences in predicted scores for some individuals, especially those with extremes of initial test performance, overall competency, or demographics. All 5 measures from the Halstead-Reitan Battery had residual (observed--predicted score) variability that increased with poorer initial performance. Two variables showed significant nonnormality in the distribution of residuals. For accurate prediction with smallest prediction--confidence intervals, we recommend multiple regression models with attention to differential variability and nonnormality of residuals.