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Background: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed., Objective: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion., Methods: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression., Results: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations., Conclusion: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Context: Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury., Objective: To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI., Design, Setting, and Patients: The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe., Intervention: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo., Main Outcome Measures: Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects., Results: Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04])., Conclusion: Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status., Trial Registration: clinicaltrials.gov Identifier: NCT00545662.

Comparative effectiveness research (CER) is emerging as a commonly applied technique to determine the usefulness of medical interventions. Such research aims to compare various treatments for specific disease entities for overall effectiveness and potential for harm. According to the Centers for Disease Control, an estimated 1.7 million patients sustain a traumatic brain injury (TBI) annually in the US. In this review the authors examine the existence of CER reports in the area of neurotrauma to date and consider the context in which clinical research and evidence-based guidelines have and will continue to inform such analyses, with special attention to TBI.

Background: Prediction of outcome after traumatic brain injury (TBI) remains elusive. We tested the use of a single hospital Glasgow Coma Scale (GCS) Score, GCS Motor Score, and the Head component of the Abbreviated Injury Scale (AIS) Score to predict 2-week cumulative mortality in a large cohort of TBI patients admitted to the eight U.S. Level I trauma centers in the TBI Clinical Trials Network., Methods: Data on 2,808 TBI patients were entered into a centralized database. These TBI patients were categorized as severe (GCS score, 3-8), moderate (9-12), or complicated mild (13-15 with positive computed tomography findings). Intubation and chemical paralysis were recorded. The cumulative incidence of mortality in the first 2 weeks after head injury was calculated using Kaplan-Meier survival analysis. Cox proportional hazards regression was used to estimate the magnitude of the risk for 2-week mortality., Results: Two-week cumulative mortality was independently predicted by GCS, GCS Motor Score, and Head AIS. GCS Severity Category and GCS Motor Score were stronger predictors of 2-week mortality than Head AIS. There was also an independent effect of age (<60 vs. ≥60) on mortality after controlling for both GCS and Head AIS Scores., Conclusions: Anatomic and physiologic scales are useful in the prediction of mortality after TBI. We did not demonstrate any added benefit to combining the total GCS or GCS Motor Scores with the Head AIS Score in the short-term prediction of death after TBI.

Severe traumatic brain injury remains a significant cause of mortality and morbidity worldwide. The use of therapeutic interventions such as hypertonic saline administration and decompressive craniectomy have solid foundations and can improve outcomes, although questions remain about patient selection, optimal timing, and comparisons to other treatments. Hypothermia, while having promise, has not definitively been shown to benefit patients with traumatic brain injury, although clinical trials are underway. The use of beta-blockers in traumatic brain injury has been proposed as a neuroprotective measure, but data are lacking to support widespread clinical use. Brain tissue oxygenation monitoring is gaining widespread acceptance as a safe tool to provide additional information both to guide therapeutic interventions and to further elucidate mechanisms of secondary brain injury. Evidence is also mounting that guided therapy using brain tissue oxygenation in addition to intracranial pressure and cerebral perfusion pressure monitoring leads to better outcomes after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.

Background: The beneficial effect of decompressive craniectomy (DC) in the treatment of traumatic brain injury (TBI) remains controversial. In many centers, it is used as a salvage procedure for uncontrollable intracranial pressure (ICP). It is our contention that DC represents a viable early option for head trauma patients. The purpose of this study was to evaluate the efficacy of DC on functional outcome after severe TBI in the largest single institutional series reported in the literature., Methods: Patients with severe TBI (Abbreviated Injury Score 4-5) treated with DC for the management of increased ICP during 6-year period were identified from the trauma registry. Functional outcome was measured 1 year to 6 years postinjury using the Glasgow Outcome Score Extended (GOSE) via telephone interview and classified as good (GOSE 5-8) or poor (GOSE 1-4, including death). Outcomes were compared using Wilcoxon rank-sum and chi2 tests where appropriate., Results: One hundred and seventy-one patients were identified: 137 (80%) men and 34 (20%) women. Overall mortality (all in-hospital) was 32% (head-related = 22%). Of the 117 survivors, follow-up was obtained in all but 6 (95%). Good outcome was achieved in 96 patients (56% overall, 82% of survivors). Those with good outcome were younger (26 years vs. 43 years, p = 0.0028) and experienced a greater change in predecompression to postdecompression ICP (ICP reduced by 23 mm Hg vs. 10 mm Hg, p < 0.0001). Not surprisingly, unchanged ICP (predecompression to postdecompression) was associated with poor outcome (p = 0.0031). There was no difference in immediate predecompression ICP between survivors versus nonsurvivors. However, immediate predecompression Glasgow Coma Score was significantly higher in survivors compared with nonsurvivors (7 vs. 5, p < 0.0001)., Conclusions: DC resulted in good functional outcome in >50% of patients with severe TBI. The greatest benefit was observed in younger patients with a demonstrable reduction in ICP after decompression. The prospect of improved functional outcome offered by this procedure in the treatment of severe TBI warrants prospective investigation.

Background and Purpose: Development of a method to continuously assess cerebrovascular autoregulation of patients with traumatic brain injury would facilitate therapeutic intervention and thus reduce secondary complications., Methods: Changes in arterial blood pressure (ABP), intracranial pressure (ICP), cerebral blood flow velocity (CBFV), and pial arteriolar diameter (PAD) induced by acute pressor challenge (norepinephrine; 1 microg/[kg. min]) were evaluated in both uninjured and fluid percussion injured piglets equipped with cranial windows. The linear correlation coefficient and corresponding slope of the regression line of the relationship between highest modal frequency (HMF) of cerebrovascular pressure transmission of ABP to ICP and cerebral perfusion pressure (CPP) were determined for each challenge., Results: For all uninjured piglets, pressor challenge resulted in an inverse relationship between HMF and CPP characterized by significant negative correlation values and negative corresponding regression line slopes with respective group mean values (+/-SD) of -0.50 (+/-0.14) and -0.6 (+/-0.44) Hz/mm Hg, respectively. Consistent with functional autoregulation of the uninjured preparations, pressor challenge resulted in a decrease of PAD, and CBFV remained relatively constant. For all injured piglets, pressor challenge resulted in direct relationship between HMF and CPP, characterized by positive correlation values and corresponding regression line slopes with group mean values of 0.48 (+/-0.21) and 1.13 (+/-2.08) Hz/mm Hg, respectively. Consistent with impaired autoregulation, PAD and CBFV increased during pressor challenge after brain injury., Conclusions: Evaluation of changes of the HMF of cerebrovascular pressure transmission with respect to CPP changes permits continuous monitoring of cerebral autoregulation.

BackgroundTwo randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach.MethodsThe International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.ResultsThe invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.ConclusionsIn this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

The article focuses on the randomized trial comparing prescribed light exercise to standard management for emergency department patients with acute mild traumatic brain injury. Topics discussed include Persistent post concussion symptoms (PCS) after a mild traumatic brain injury (mTBI) or concussion do not occur in the majority of patients sustaining such injuries; and the authors are to be commended for this attempt to detect a viable intervention.

The author reflects on the Randomised Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) trial. Topics discussed include decompressive craniectomy, and continued medical management for refractory elevation of intracranial pressure after severe traumatic brain injury.

Cross-sectional approaches to outcome assessment may not adequately capture heterogeneity in recovery after traumatic brain injury (TBI). Using latent class mixed models (LCMM), a data-driven analytic that identifies groups of patients with similar trajectories, we identified distinct 6 month functional recovery trajectories in a large cohort (n = 1046) of adults 18–70 years of age with complicated mild to severe TBI who participated in the Citicoline Brain Injury Treatment Trial (COBRIT). We used multinomial logistic fixed effect models and backward elimination, forward selection, and forward stepwise selection with several stopping rules to explore baseline predictors of functional recovery trajectory. Based on statistical and clinical considerations, the seven-class model was deemed superior. Visualization of these seven functional recovery trajectories revealed that each trajectory class started at one of three recovery levels at 1 month, which, for ease of reference we labeled groups A–C: Group A, good recovery (two classes; A1 and A2); Group B, moderate disability (two classes; B1 and B2); and Group C, severe disability (three classes; C1, C2, and C3). By 6 months, these three groups experienced dramatically divergent trajectories. Group A experienced stable good recovery (A1, n = 115) or dramatic decline (A2, n = 4); Group B experienced rapid complete recovery (B1, n = 71) or gradual recovery (B2, n = 742); Group C experienced dramatic rapid recovery (C1, n = 12), no recovery (C2, n = 91), or death (C3, n = 11). Trajectory class membership was not predicted by citicoline treatment (p = 0.57). The models identified demographic, pre-injury, and injury-related predictors of functional recovery trajectory, including: age, race, education, pre-injury employment, pre-injury diabetes, pre-injury psychiatric disorder, site, Glasgow Coma Scale (GCS) score, post-traumatic amnesia, TBI mechanism, major extracranial injury, hemoglobin, and acute computed tomographic (CT) findings. GCS was the most consistently selected predictor across all models. All models also selected at least one demographic or pre-injury medical predictor. LCMM successfully identified dramatically divergent, clinically meaningful 6 month recovery trajectories with utility to inform clinical trial design. [ABSTRACT FROM AUTHOR]