Jason Barber

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.).

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.

Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial

BACKGROUND Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients. METHODS In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number . FINDINGS Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect. INTERPRETATION Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury.

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

Does glucocorticoid administration prevent late seizures after head injury

Summary:  Purpose: Preventing posttraumatic epilepsy has been a difficult challenge. In this study we evaluated the association between glucocorticoid administration after traumatic brain injury (TBI) and posttraumatic seizures.

Treatment outcomes of unruptured arteriovenous malformations with a subgroup analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-eligible patients.

BACKGROUND The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment. OBJECTIVE To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBA-eligible patients. METHODS One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome. RESULTS Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up. CONCLUSION The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

Managing epilepsy well: Self-management needs assessment

Epilepsy self-management interventions have been investigated with respect to health care needs, medical adherence, depression, anxiety, employment, and sleep problems. Studies have been limited in terms of representative samples and inconsistent or restricted findings. The direct needs assessment of patients with epilepsy as a basis for program design has not been well used as an approach to improving program participation and outcomes. This study investigated the perceived medical and psychosocial problems of adults with epilepsy, as well as their preferences for self-management program design and delivery format. Results indicated a more psychosocially challenged subgroup of individuals with significant depressive and cognitive complaints. A self-management program that involves face-to-face individual or group meetings led by an epilepsy professional and trained peer leader for 60 minutes weekly was preferred. Six to eight sessions focused on diverse education sessions (e.g., managing disability and medical care, socializing on a budget, and leading a healthy lifestyle) and emotional coping strategies delivered on weeknights or Saturday afternoons were most highly endorsed. Emotional self-management and cognitive compensatory strategies require special emphasis given the challenges of a large subgroup.

Imaging features of invasion and preoperative and postoperative tumor burden in previously untreated glioblastoma: Correlation with survival.

Background: A paucity of data exists concerning the prognostic usefulness of preoperative and postoperative imaging after resection of glioblastoma multiforme (GBM). This study aimed to connect outcome with imaging features of GBM. Methods: Retrospective computer-assisted volumetric calculations quantified central necrotic (T0), gadolinium-enhanced (T1) and increased T2-weighted signal volumes (T2) in 70 patients with untreated GBM. Clinical and treatment data, including extent of resection (EOR), were obtained through chart review. T1 volume was used as a measure of solid tumor burden; and T2 volume, as an indicator of invasive isolated tumor cell (ITC) burden. Indicators of invasiveness included T2:T1 ratios as a propensity for ITC infiltration compared to solid tumor volumes and qualitative analysis of subependymal growth and infiltration of the basal ganglia, corpus callosum or brainstem. Cox multivariate analysis (CMVA) was used to identify significant associations between imaging features and survival. Results: In the 70 patients studied, significant associations with reduced survival existed for gadolinium-enhancing tumor crossing the corpus callosum (odds ratio, 3.14) and with increased survival with gross total resection (GTR) (GTR median survival, 62 weeks versus 37 and 34 weeks for sub-total resection and biopsy, respectively). For a selected “GTR-eligible” subgroup of 52 patients, prolonged survival was associated with smaller preoperative gadolinium-enhancing volume (T1) and actual GTR. Conclusion: Some magnetic resonance (MR) imaging indicators of tumor invasiveness (gadolinium-enhancing tumor crossing the corpus callosum) and tumor burden (GTR and preoperative T1 volume in GTR-eligible subgroup) correlate with survival. However, ITC-infiltrative tumor burden (T2 volume) and “propensity” for ITC invasiveness (T2:T1 ratio) did not impact survival. These results indicate that while the ITC component is the ultimate barrier to cure for GBM, the pattern of spread and volumes of gadolinium-enhancing solid tumor are more robust indicators of prognosis.

Basilar tip aneurysms: a microsurgical and endovascular contemporary series of 100 patients.

BACKGROUND Endovascular therapy has largely replaced microsurgical clipping for the treatment of basilar tip aneurysms. OBJECTIVE We describe the variables our center evaluates when choosing to clip or coil basilar tip aneurysms and our outcomes. Four case illustrations are presented. METHODS All patients with ruptured or unruptured basilar tip aneurysms from 2005 to April 2012 were examined. The patients were treated by 2 interventional neuroradiologists and 2 dually trained neurosurgeons. RESULTS There were 63 ruptured (clipped 38%, coiled 62%) and 37 unruptured (clipped 35%, coiled 65%) aneurysms in this 100-patient study. Seventy percent of the patients with ruptured aneurysms and 92% of the patients with unruptured aneurysms had a good outcome (modified Rankin scale 0-2) at 3 months. For ruptured aneurysms, there was a statistically significant difference in clipping and coiling with respect to age and treatment modality (clip 48.8 years, coil 57.6 years). Patients in the coiled group had higher dome-to-neck (1.3 vs 1.1) (P = .01) and aspect ratios (1.6 vs 1.2) (P = .007). In the ruptured coiling group, 69.5% achieved a Raymond 1 radiographic outcome, 28% Raymond 2, and 2.5% Raymond 3. Eleven (17.4%) patients required re-treatment, and 3 (4.4%) patients were re-treated more than twice. Coiling of unruptured aneurysms resulted in 75% Raymond 1. There were no residual lesions for unruptured clipped aneurysms. There were no differences in outcome between clipping and coiling in the ruptured and unruptured group. CONCLUSION In our current management of basilar tip aneurysms, the majority can be treated via endovascular means, albeit with the expectation of a higher percentage of residual lesions and recurrences. Microsurgery is still appropriate for aneurysms with complex neck morphologies and in young patients desiring a more durable treatment.

Telephone and in-person cognitive behavioral therapy for major depression after traumatic brain injury: a randomized controlled trial.

Major depressive disorder (MDD) is prevalent after traumatic brain injury (TBI); however, there is a lack of evidence regarding effective treatment approaches. We conducted a choice-stratified randomized controlled trial in 100 adults with MDD within 10 years of complicated mild to severe TBI to test the effectiveness of brief cognitive behavioral therapy administered over the telephone (CBT-T) (n = 40) or in-person (CBT-IP) (n = 18), compared with usual care (UC) (n = 42). Participants were recruited from clinical and community settings throughout the United States. The main outcomes were change in depression severity on the clinician-rated 17 item Hamilton Depression Rating Scale (HAMD-17) and the patient-reported Symptom Checklist-20 (SCL-20) over 16 weeks. There was no significant difference between the combined CBT and UC groups over 16 weeks on the HAMD-17 (treatment effect = 1.2, 95% CI: -1.5-4.0; p = 0.37) and a nonsignificant trend favoring CBT on the SCL-20 (treatment effect = 0.28, 95% CI: -0.03-0.59; p = 0.074). In follow-up comparisons, the CBT-T group had significantly more improvement on the SCL-20 than the UC group (treatment effect = 0.36, 95% CI: 0.01-0.70; p = 0.043) and completers of eight or more CBT sessions had significantly improved SCL-20 scores compared with the UC group (treatment effect = 0.43, 95% CI: 0.10-0.76; p = 0.011). CBT participants reported significantly more symptom improvement (p = 0.010) and greater satisfaction with depression care (p < 0.001), than did the UC group. In-person and telephone-administered CBT are acceptable and feasible in persons with TBI. Although further research is warranted, telephone CBT holds particular promise for enhancing access and adherence to effective depression treatment.