Summary
Posttraumatic epilepsy presents an ideal target for prevention efforts. Traumatic brain injury (TBI) is common, characteristics that put people at high risk such as penetrating injury or ...subdural hematoma or provoked seizures are easily identified, and the latency between the injury and the onset of epileptic seizures is frequently short. Several drugs have been tested for their ability to prevent provoked seizures and epilepsy after TBI. We describe the design of those studies and their results. Phenytoin and carbamazepine significantly reduce the incidence of provoked seizures. Phenobarbital and the combination of phenobarbital and phenytoin also look promising for reducing provoked seizures, but small sample sizes in the studies evaluating these drugs do not allow definitive conclusions. None of the drugs studied (phenytoin, phenobarbital, their combination, carbamazepine, valproate, or magnesium) have shown reliable evidence that they prevent, or even suppress, epileptic seizures after TBI. For most of the regimens tested (the phenytoin/phenobarbital combination being the exception), the best estimate of effect is under a 25% reduction in posttraumatic seizures, well less than the 50% reduction most studies were designed to detect. The evaluation of the tested drugs has serious limitations, however, and antiepileptic drugs (AEDs) developed since 1980 and other compounds have barely been tested at all. Better understanding the process of epileptogenesis, testing treatments that demonstrate antiepileptogenic effects in the laboratory, and performing thorough preclinical and phase II evaluations before attempting definitive trials should greatly improve the chance of identifying ways to prevent posttraumatic epilepsy, providing the ultimate cure for this condition.
The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts ...continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden.
To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability.
This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n = 50) in the acute to subacute stage and combat-deployed control individuals (n = 44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuries met the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016.
Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability.
Among the 94 participants (87 men 93% and 7 women 7%; mean SD age, 34 8 years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended Glasgow Outcome Scale (GOS-E) at 5 years as a measure of overall disability identified brain injury diagnosis, preinjury intelligence, motor strength, verbal fluency, and neurobehavioral symptom severity at 1 year as risk factors for a poor outcome at 5 years, with an area under the curve of 0.92 indicating excellent prediction strength. Thirty-six of 50 patients with concussive blast TBI (72%) had a decline in the GOS-E from the 1- to 5-year evaluations, in contrast with only 5 of 44 combat-deployed controls (11%). Worsening of symptoms in concussive blast TBI was also observed on measures of posttraumatic stress disorder and depression. Service members with concussive blast TBI experienced evolution, not resolution, of symptoms from the 1- to 5-year outcomes.
Considerable decline was observed in military service members with concussive blast TBI when comparing 1- and 5-year clinical outcomes. These results advocate for new treatment strategies to combat the long-term and extremely costly effect of these wartime injuries.
A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess ...whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study.
Randomized prospective clinical trial.
Ten ICUs in the United States.
One hundred nineteen severe traumatic brain injury patients.
Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended.
A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p < 0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy.
Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.
The Glasgow Outcome Scale-Extended (GOSE) has become one of the most widely used outcome instruments to assess global disability and recovery after traumatic brain injury. Achieving consistency in ...the application of the assessment remains a challenge, particularly in multi-center studies involving many assessors. We present a manual for the GOSE interview that is designed to support both single- and multi-center studies and promote inter-rater agreement. Many patients fall clearly into a particular category; however, patients may have outcomes that are on the borderline between adjacent categories, and cases can present other challenges for assessment. The Manual includes the general principles of assessment, advice on administering each section of the GOSE interview, and guidance on "borderline" and "difficult" cases. Finally, we discuss the properties of the GOSE, including strengths and limitations, and outline recommendations for assessor training, accreditation, and monitoring.
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.
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).
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.
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.).
This study examines rates of reporting of new or worse post-traumatic symptoms for patients with a broad range of injury severity at 1 month and 1 year after traumatic brain injury (TBI), as compared ...with those whose injury spared the head, and assesses variables related to symptom reporting at 1 year post-injury. Seven hundred thirty two TBI subjects and 120 general trauma comparison (TC) subjects provided new or worse symptom information at 1 month and/or 1 year post-injury. Symptom reporting at 1 year post-injury was compared in subgroups based on basic demographics, preexisting conditions, and severity of brain injury. The TBI group reported significantly more symptoms at 1 month and 1 year after injury than TCs (each p < .001). Although symptom endorsement declined from 1 month to 1 year, 53% of people with TBI and 24% of TC continued to report 3 or more symptoms at 1 year post-injury. Symptom reporting in the TBI group was significantly related to age, gender, preinjury alcohol abuse, pre-injury psychiatric history, and severity of TBI. Symptom reporting is common following a traumatic injury and continues to be experienced by a substantial number of TBI subjects of all severity levels at 1 year post-injury.
Uncertainties exist about the rates, predictors, and outcomes of major depressive disorder (MDD) among individuals with traumatic brain injury (TBI).
To describe MDD-related rates, predictors, ...outcomes, and treatment during the first year after TBI.
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).
Harborview Medical Center, a level I trauma center in Seattle, Washington.
Five hundred fifty-nine consecutively hospitalized adults with complicated mild to severe TBI.
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.
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.
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.
Purpose
Elevated intracranial pressure (ICP) has been associated with increased mortality in patients with severe traumatic brain injury (TBI). We have examined whether raised ICP is independently ...associated with mortality, functional status and neuropsychological functioning in adult TBI patients.
Methods
Data from a randomized trial of 499 participants were secondarily analyzed. The primary endpoints were mortality and a composite measure of functional status and neuropsychological function (memory, speed of information processing, executive function) over a 6-month period. The area under the curve of the ICP profile (average ICP) during the first 48 h of monitoring was the main predictor of interest. Multivariable regression was used to adjust for a priori defined confounders: age, Glasgow Coma Score, Abbreviated Injury Scale–head and hypoxia.
Results
Of the participants, 365 patients had complete 48-h ICP data. The overall 6-month mortality was 18 %. The adjusted odds ratio of mortality comparing 10-mmHg increases in average ICP was 3.12 (95 % confidence interval 1.79, 5.44;
p
< 0.01). Overall, higher average ICP was associated with decreased functional status and neuropsychological functioning (
p
< 0.01). Importantly, among survivors, increasing average ICP was not independently associated with worse performance on neuropsychological testing (
p
= 0.46).
Conclusions
Average ICP in the first 48 h of monitoring was an independent predictor of mortality and of a composite endpoint of functional and neuropsychological outcome at the 6-month follow-up in moderate or severe TBI patients. However, there was no association between average ICP and neuropsychological functioning among survivors.
To determine the longitudinal incidence of dizziness and its association with demographic factors, neurocognitive effects, functionality, and quality of life.
Transforming Research and Clinical ...Knowledge in Traumatic Brain Injury (TRACK-TBI) is a prospective, longitudinal cohort study in which TBI patients were assessed at the emergency department and 2-week, 3-month, 6-month, and 12-month follow-up via telephone and/or in-person visits.
Multicenter study in emergency departments of 18 academic medical centers in the United States.
A total of 1,514 patients 17 years or older with a diagnosis of TBI, injury occurrence within 24 hours of admission, fluency in English or Spanish, and completed Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at 12 months were enrolled between February 2014 and August 2018.
RPQ, Short Form-12 Version 2, Wechsler Adult Intelligence Scale IV, Trail Making Test, Patient Health Questionnaire-9, PROMIS-PAIN, and Glasgow Outcome Scale-Extended Revised. The primary outcome measure was a self-report of "feelings of dizziness" on RPQ at 12 months post-TBI.
Of the 1,514 participants, 1,002 (66%) were male and 512 (34%) were female. The mean age was 41.6 (SD, 17.4) years. At 12 months, 26% experienced dizziness, with 9% experiencing moderate or severe dizziness. Dizziness was strongly associated with headache (odds ratio OR, 3.45; 95% confidence interval CI, 2.92-4.07; p < 0.001), nausea (OR, 4.43; 95% CI, 3.45-5.69; p < 0.001), worse hearing (OR, 3.57; 95% CI, 2.64-4.82; p < 0.001), noise sensitivity (OR, 3.02; 95% CI, 2.54-3.59; p < 0.001), and light sensitivity (OR, 3.51; 95% CI, 2.91-4.23; p < 0.001). In multivariable regression models, participants with severe dizziness demonstrated lower performance compared with those without new or worse dizziness on the Wechsler Adult Intelligence Scale IV (-6.64; p < 0.001), Trail Making Test part A (7.90; p = 0.003) and part B (19.77; p = 0.028), and Short Form-12 physical (-13.60; p < 0.001) and mental health (-11.17; p < 0.001), after controlling for age, sex, education, and TBI severity.
Dizziness is common among TBI patients and relates to quality of life and neurocognitive performance.
This study evaluated frontal behavioural symptoms, via the FrSBe self-report, in military personnel with and without a history of blast-related mild traumatic brain injury (mild TBI).
Prospective ...observational cohort study of combat-deployed service members leveraging 1-year and 5-year demographic and follow up clinical outcome data.
The blast mild TBI group (n = 164) showed greater frontal behavioural symptoms, including clinically elevated apathy, disinhibition, and executive dysfunction, during a 5-year follow-up, compared to a group of combat-deployed controls (n = 107) without mild TBI history or history of blast exposure. We also explored changes inbehaviourall symptoms over a 4-year span, which showed clinically significant increases in disinhibition in the blast mild TBI group, whereas the control group did not show significant increases in symptoms over time.
Our findings add to the growing evidence that a proportion of individuals who sustain mild TBI experience persistent behavioural symptoms. We also offer a demonstration of a novel use of the FrSBe as a tool for longitudinal symptom monitoring in a military mild TBI population.
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