Associations between neuropsychiatric and health status outcomes in individuals with probable mTBI

Mild traumatic brain injury (mTBI) is a common occurrence, and may impact distal outcomes in a subgroup of individuals. Improved characterization of health outcomes and identification of factors associated with poor outcomes is needed to better understand the impact of mTBI, particularly in those with co-occurring posttraumatic stress disorder (PTSD). Participants in a data repository of the Injury and Traumatic Stress (INTRuST) Clinical Consortium (n = 625) completed functional disability [FD] and health-related quality of life [HRQOL] questionnaires, and a subset completed a neuropsychological assessment. FD and HRQOL were compared among participants with probable mTBI (mTBI), probable mTBI with PTSD (mTBI/PTSD), and health comparison participants (HC). Associations between symptoms, neuropsychological performance, and health outcomes were examined in those with probable mTBI with and without PTSD (n = 316). Individuals in the mTBI/PTSD group endorsed poorer health outcomes than those in the mTBI group, who endorsed poorer outcomes than those in the HC group. Individuals in either mTBI group performed worse than those in the HC on verbal learning and memory and psychomotor speed. Health outcomes were correlated with mental health and postconcussive symptoms, as well as neuropsychological variables. mTBI may adversely impact self-reported health, with the greatest effect observed in individuals with co-occurring mTBI/PTSD

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma

Age-dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q \u3c 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans

The Curing Coma Campaign: Framing Initial Scientific Challenges—Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting

Abstract: Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the “grand challenge” of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the “curing coma community” to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients

Intracranial Dural Sinus Thrombosis: Novel Use of a Mechanical Thrombectomy Catheter and Review of Management Strategies

Management of intracranial dural sinus thrombosis with involvement of multiple sinuses is complex, often involving not only the primary problem (thrombosis) but acute adverse events consequent to the disease. We highlight the novel use of an endovascular device (typically for suction thrombectomy in the peripheral vascular system) used in our patient with a life-threatening multi-sinus thrombosis. As there is no standard treatment yet for cranial sinus thrombosis, our review of the literature highlights some effective management strategies. A 35-year-old woman developed associated complications of cranial sinus thrombosis that included intracranial hypertension caused by an expanding intracranial hematoma, pulmonary embolism treated by placement of filters in superior and inferior vena cava to eliminate intra- and extracranial sources of emboli, and procedure-related retroperitoneal hematoma that necessitated peripheral vascular intervention. After failure of several common devices during mechanical thrombolysis, a thrombectomy catheter (typically for peripheral vascular intervention to aide in the clot removal) was used. Our case highlights the fine balance of anticoagulation and thrombolysis and the proactive, aggressive approach used by our multispecialty team to manage concurrent factors

What Families Need and Physicians Deliver: Contrasting Communication Preferences Between Surrogate Decision-Makers and Physicians During Outcome Prognostication in Critically Ill TBI Patients

BACKGROUND: Surrogate decision-makers ( surrogates ) and physicians of incapacitated patients have different views of prognosis and how it should be communicated, but this has not been investigated in neurocritically ill patients. We examined surrogates\u27 communication preferences and physicians\u27 practices during the outcome prognostication for critically ill traumatic brain injury (ciTBI) patients in two level-1 trauma centers and seven academic medical centers in the USA. METHODS: We used qualitative content analysis and descriptive statistics of transcribed interviews to identify themes in surrogates (n = 16) and physicians (n = 20). RESULTS: The majority of surrogates (82%) preferred numeric estimates describing the patient\u27s prognosis, as they felt it would increase prognostic certainty, and limit the uncertainty perceived as frustrating. Conversely, 75% of the physicians reported intentionally omitting numeric estimates during prognostication meetings due to low confidence in family members\u27 abilities to appropriately interpret probabilities, worry about creating false hope, and distrust in the accuracy and data quality of existing TBI outcome models. Physicians felt that these models are for research only and should not be applied to individual patients. Surrogates valued compassion during prognostication discussions, and acceptance of their goals-of-care decision by clinicians. Physicians and surrogates agreed on avoiding false hope. CONCLUSION: We identified fundamental differences in the communication preferences of prognostic information between ciTBI patient surrogates and physicians. These findings inform the content of a future decision aid for goals-of-care discussions in ciTBI patients. If validated, these findings may have important implications for improving communication practices in the neurointensive care unit independent of whether a formal decision aid is used

Downstream Polymorphisms Are Associated with Intracranial Hypertension and Statistically Interact with Polymorphisms in a Prospective Cohort of Severe Traumatic Brain Injury

Sulfonylurea-receptor-1(SUR1) and its associated transient-receptor-potential cation channel subfamily-M (TRPM4) channel are key contributors to cerebral edema and intracranial hypertension in traumatic brain injury (TBI) and other neurological disorders. Channel inhibition by glyburide is clinically promising. (encoding SUR1) single-nucleotide polymorphisms (SNPs) are reported as predictors of raised intracranial pressure (ICP). This project evaluated whether SNPs predicted ICP and TBI outcome. DNA was extracted from 435 consecutively enrolled severe TBI patients. Without selection, all 11 SNPs available on the multiplex platform (Illumina:Human-Core-Exome v1.0) were genotyped spanning the 25 exon gene. A total of 385 patients were analyzed after quality control. Outcomes included ICP and 6 month Glasgow Outcome Scale (GOS) score. Proxy SNPs, spatial modeling, and functional predictions were determined using established software programs. rs8104571 (intron-20) and rs150391806 (exon-24) were predictors of ICP. rs8104571 heterozygotes predicted higher average ICP (β = 10.3 mm Hg,  = 0.00000029), peak ICP (β = 19.6 mm Hg,  = 0.0007), and proportion ICP \u3e25 mm Hg (β = 0.16  = 0.004). rs150391806 heterozygotes had higher mean (β = 7.2 mm Hg,  = 0.042) and peak (β = 28.9 mm Hg,  = 0.0015) ICPs. rs8104571, rs150391806, and 34 associated proxy SNPs in linkage-disequilibrium clustered downstream. This region encodes TRPM4\u27s channel pore and a region postulated to juxtapose SUR1 sequences encoded by an DNA segment containing previously identified relevant SNPs. There was an interaction effect on ICP between rs8104571 and a cluster of predictive SNPs (rs2237982, rs2283261, rs11024286). Although not significant in univariable or a basic multivariable model, in an expanded model additionally accounting for injury pattern, computed tomographic (CT) appearance, and intracranial hypertension, heterozygous rs8104571 was associated with favorable 6 month GOS (odds ratio [OR] = 16.7,  = 0.007951). This trend persisted in a survivor-only subcohort (OR = 20.67,  = 0.0168). In this cohort, two SNPs predicted increased ICP with large effect sizes. Both clustered downstream, spanning a region encoding the channel pore and interacting with SUR1. If validated, this may guide risk stratification and eventually inform treatment-responder classification for SUR1-TRPM4 inhibition in TBI. Larger studies are warranted