Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage: Location, Distribution Patterns, Infarct Load, and Effect on Outcome.

BACKGROUND AND OBJECTIVES: Delayed cerebral ischemia (DCI) is one of the main contributing factors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Unsuccessful treatment can cause irreversible brain injury in the form of DCI-related infarction. We aimed to assess the association between the location, distribution, and size of DCI-related infarction in relation to clinical outcome. METHODS: Consecutive patients with SAH treated at 2 university hospitals between 2014 and 2019 (Helsinki, Finland) and between 2006 and 2020 (Aachen, Germany) were included. Size of DCI-related infarction was quantitatively measured as absolute volume (in milliliters). In a semiquantitative fashion, infarction in 14 regions of interest (ROIs) according to a modified Alberta Stroke Program Early CT Score (ASPECTS) was noted. The association of infarction in these ROIs along predefined regions of eloquent brain, with clinical outcome, was assessed. For this purpose, 1-year outcome was measured by the Glasgow Outcome Scale (GOS) and dichotomized into favorable (GOS 4-5) and unfavorable (GOS 1-3). RESULTS: Of 1,190 consecutive patients with SAH, 155 (13%) developed DCI-related infarction. One-year outcome data were available for 148 (96%) patients. A median overall infarct volume of 103 mL (interquartile range 31-237) was measured. DCI-related infarction was significantly associated with 1-year unfavorable outcome (odds ratio [OR] 4.89, 95% CI 3.36-7.34, p < 0.001). In patients with 1-year unfavorable outcome, vascular territories more frequently affected were left middle cerebral artery (affected in 49% of patients with unfavorable outcome vs in 30% of patients with favorable outcome; p = 0.029), as well as left (44% vs 18%; p = 0.003) and right (52% vs 14%; p < 0.001) anterior cerebral artery supply areas. According to the ASPECTS model, the right M3 (OR 8.52, 95% CI 1.41-51.34, p = 0.013) and right A2 (OR 7.84, 95% CI 1.97-31.15, p = 0.003) regions were independently associated with unfavorable outcome. DISCUSSION: DCI-related infarction was associated with a 5-fold increase in the odds of unfavorable outcome, after 1 year. Ischemic lesions in specific anatomical regions are more likely to contribute to unfavorable outcome. TRIAL REGISTRATION INFORMATION: Data collection in Aachen was registered in the German Clinical Trial Register (DRKS00030505); on January 3, 2023.

Serum secretoneurin as a promising biomarker for predicting poor prognosis in intracerebral hemorrhage: A prospective cohort study.

OBJECTIVE: Secretoneurin may play a brain-protective role. We aim to discover the relationship between serum secretoneurin levels and severity plus neurological outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, serum secretoneurin levels were measured in 110 ICH patients and 110 healthy controls. Glasgow Coma Scale (GCS) and hematoma volume were used to assess stroke severity. Poor prognosis was defined as Glasgow Outcome Scale (GOS) scores of 1-3 at 90 days after ICH. A multivariate logistic regression model was constructed to determine independent correlation of serum secretoneurin levels with severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic ability of serum secretoneurin levels was assessed. Restricted cubic spline (RCS) model and subgroups analysis were used for discovering association of serum secretoneurin levels with risk of poor prognosis. Calibration curve and decision curve were evaluated to confirm performance of nomogram. RESULTS: Serum secretoneurin levels of patients were significantly higher than those of healthy controls. Serum secretoneurin levels of patients were independently correlated with GCS scores and hematoma volume. There were 42 patients with poor prognosis at 90 days following ICH. Serum secretoneurin levels were significantly higher in patients with poor outcome than in those with good outcome. Under the ROC curve, serum secretoneurin levels significantly differentiated poor outcome. Serum secretoneurin levels ≥ 22.8 ng/mL distinguished patients at risk of poor prognosis at 90 days with a sensitivity of 66.2% and a specificity of 81.0%. Besides, serum secretoneurin levels independently predicted a 90-day poor prognosis. Subgroup analysis showed that serum secretoneurin levels had non-significant interactions with other variables. The nomogram, including independent prognostic predictors, showed reliable prognosis capability using calibration curve and decision curve. Area under the curve of the predictive model was significantly higher than those of GCS scores and hematoma volume. CONCLUSION: Serum secretoneurin levels are strongly related to ICH severity and poor prognosis at 90 days after ICH. Thus, serum secretoneurin may be a promising prognostic biomarker in ICH.

Comfort nursing theory on the postoperative rehabilitation quality and nursing satisfaction of patients with intracranial aneurysm.

To explore the influence of comfort nursing theory on the postoperative rehabilitation quality of patients with intracranial aneurysms. From October 2017 to December 2022, 315 patients with intracranial aneurysms underwent interventional surgery in our hospital were included in this retrospective study and divided into the routine group (n = 105) and comfort nursing group (n = 210) based on different nursing methods. The Glasgow Outcome Scale (GOS) was used to assess patient rehabilitation outcomes. Patients' anxiety, pain, quality of life, and their satisfaction with treatment were compared. Compared with the patients receiving routine nursing, the time for comfortable nursing patients to resume normal diet, get out of bed and exercise, and the total hospital stay were significantly shortened. And the GOS score of patients receiving comfort nursing was significantly higher than that of patients receiving routine nursing. After nursing, self-rating anxiety scale and visual analog scale scores of comfortable nursing patients were significantly lower than those of routine nursing, and Karnofsky performance status scores were significantly higher than those of routine nursing. This showed that receiving comfortable nursing was beneficial to improve perioperative anxiety and depression in patients with intracranial aneurysm, and significantly improve the quality of life of patients. The total satisfaction of comfortable nursing patients was 95.24%, while that of routine nursing patients was 76.19%. Complications occurred in 30 patients receiving routine nursing, while only 15 patients received comfort nursing. The immune indexes such as CD3+, CD4+, and CD23+ of comfortable nursing patients were significantly higher than the routine nursing patients within 1 and 5 days after operation, while the immune indexes of CD8+ were lower than the routine nursing patients 5 days after operation. Comfortable nursing from the perspective of quality nursing can significantly improve the physiological indicators of patients with intracranial aneurysms, accelerate the progress of postoperative rehabilitation, improve the anxiety, pain and quality of life of patients, and improve the satisfaction of patients with nursing. Comfort nursing from the perspective of quality nursing can reduce the occurrence of postoperative complications, which may be achieved by improving the patient's immune function.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.

Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma.

OBJECTIVE: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). DESIGN: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. SETTING: UK secondary care. PARTICIPANTS: 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). INTERVENTIONS: Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). MAIN OUTCOME MEASURES: In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. RESULTS: In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be -£5520 (95% CI -£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be -£4536 (95% CI -£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. CONCLUSIONS: In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). ETHICS: Ethical approval for the trial was obtained from the North West-Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). TRIAL REGISTRATION NUMBER: ISRCTN87370545.

Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury.

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6-12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8-8.8, p < 0.01; T-Tau 7.2-11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2-17.5, p < 0.01; T-Tau 8.7-12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8-9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.

Caregiver reported long-term outcomes in children with major trauma and traumatic brain injuries: A single-centre retrospective study.

Introduction: We aim to investigate the functional outcomes and long-term health-related quality of life (HRQOL) in children with major trauma associated with traumatic brain injury (TBI). Method: We performed a retrospective review of records among patients >2 and ≤16 years old in a tertiary paediatric hospital between January 2014 and October 2019 with major trauma (Injury Severity Score of ≥16) and TBI of all severities. We recorded each child's Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) at 12 months post-injury and Pediatric Quality of Life Inventory (PedsQL) scores at 6 and 12 months post-injury based on the parent proxy-report scales. Results: We included 53 patients with a median age of 9.0 years old (interquartile range 2.3-15.5). Most injuries were due to falls (30, 56.6%) or road traffic collisions (15, 28.3%); 41 patients (77.3%) required intensive care while 30 patients (56.6%) underwent neurosurgical intervention. Most patients (43, 81.1%) had GOS-E Peds scores of ≤2 at 12 months post-injury. We reported a significant mean difference between the 6- and 12-month parent-reported scores for physical functioning (6.6, 95% confidence interval [CI] 0.3-12.8, P=0.041), psychosocial functioning (4.1, 95% CI 1.0-7.2, P=0.012) and overall scores (5.0, 95% CI 1.4-8.7, P=0.008). Compared with the validated PedsQL scores, our mean scores were higher across all domains at 12 months. Conclusion: With current standard of care, parents of children with major trauma and TBI reported gains in quality of life, physical, psychosocial and overall function between 6 and 12 months post-injury.

Utility of serum chemokine-like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study.

BACKGROUND: Chemokine-like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180-day mortality of sTBI. METHODS: Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1-3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180-day poor prognosis (GOSE scores of 1-4) and 180-day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver-operating characteristic (ROC) curve was built to investigate prognostic predictive capability. RESULTS: Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non-survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180-day poor prognosis and 180-day mortality, and had high 180-day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. CONCLUSION: Serum CKLF1 levels are significantly associated with disease severity, poor 180-day prognosis, and 180-day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI.

Surgical Treatment Strategies for Residual or Recurrent Intracranial Aneurysms Following Endovascular Embolization.

OBJECTIVE: To explore how to effectively manage the residual or recurrent intracranial aneurysms after embolization. METHODS: The authors retrospectively reviewed our experience of endovascular interventional therapy, surgical clipping, and cerebrovascular bypass surgery in the treatment of residual or recurrent aneurysms after embolization at the authors' institution from 2018 to 2022. RESULTS: The Glasgow Outcome Scale of 28 patients after the procedure and at discharge showed that 24 recovered well, 3 had severe disability, and 1 died. During the 24-month follow-up, 26 had a good recovery, 1 suffered from disability, and 1 died. Two cases of aneurysm recurrence were detected, and both were treated through endovascular therapy. Among them, 1 case underwent a repeat endovascular embolization, and 1 case was switched to surgical clipping. No residual aneurysms were observed in the remaining patients who underwent bypass surgery, and their bypass grafts were all patent. CONCLUSION: Based on the clinical status of patients, aneurysmal characteristics, surgical risk, and possibility of rerupture of aneurysms, an individualized strategy was proposed for residual or recurrent aneurysms after embolization. The use of endovascular interventional therapy or surgical clipping can be safely and effectively managed, and cerebrovascular bypass surgery can effectively manage complex aneurysms.

A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury.

INTRODUCTION: Severe traumatic brain injury (TBI) presentation and late clinical outcomes are usually evaluated by the Glasgow Outcome Scale-Extended (GOS-E), which lacks strong prognostic predictability. Several blood biomarkers have been linked to TBI, such as Tau, GFAP, UCH-L1, S-100B, and NSE. Clinical values of TBI biomarkers have yet to be evaluated in a focused multi-study meta-analysis. We reviewed relevant articles evaluating potential relationships between TBI biomarkers and both early and 6-month outcomes. METHODS: All PubMed article publications from January 2000 to November 2023 with the search criteria "Protein Biomarker" AND "Traumatic Brain Injury" were included. Amongst all comparative studies, the sensitivity means and range values of biomarkers in predicting CT Rotterdam scores, ICU admission in the early period, or predicting GOS-E < 4 at the 6-month period were calculated from confusion matrices. Sensitivity values were modeled for each biomarker across studies and compared statistically for heterogeneity and differences. RESULTS: From the 65 articles that met the criteria, 13 were included in this study. Six articles involved early-period TBI outcomes and seven involved 6-month outcomes. In the early period TBI outcomes, GFAP had a superior sensitivity to UCH-L1 and S-100B, and similar sensitivity to the CT Rotterdam score. In the 6-month period TBI outcomes, total Tau and NSE both had significant interstudy heterogeneity, making them inferior to GFAP, phosphorylated Tau, UCH-L1, and S-100B, all four of which had similar sensitivities at 75 %. This sensitivity range at 6-month outcomes was still relatively inferior to the CT Rotterdam score. Total Tau did not show any prognostic advantage at six months with GOS-E < 4, and phosphorylated Tau was similar in its sensitivity to other biomarkers such as GFAP and UCH-L1 and still inferior to the CT Rotterdam score. CONCLUSION: This data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes.

Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1ß, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines. CONCLUSION: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022. WHAT IS KNOWN: • Inflammation is an important secondary physiological response to TBI. WHAT IS NEW: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

Predicting outcome after aneurysmal subarachnoid hemorrhage by exploitation of signal complexity: a prospective two-center cohort study.

BACKGROUND: Signal complexity (i.e. entropy) describes the level of order within a system. Low physiological signal complexity predicts unfavorable outcome in a variety of diseases and is assumed to reflect increased rigidity of the cardio/cerebrovascular system leading to (or reflecting) autoregulation failure. Aneurysmal subarachnoid hemorrhage (aSAH) is followed by a cascade of complex systemic and cerebral sequelae. In aSAH, the value of entropy has not been established yet. METHODS: aSAH patients from 2 prospective cohorts (Zurich-derivation cohort, Aachen-validation cohort) were included. Multiscale Entropy (MSE) was estimated for arterial blood pressure, intracranial pressure, heart rate, and their derivatives, and compared to dichotomized (1-4 vs. 5-8) or ordinal outcome (GOSE-extended Glasgow Outcome Scale) at 12 months using uni- and multivariable (adjusted for age, World Federation of Neurological Surgeons grade, modified Fisher (mFisher) grade, delayed cerebral infarction), and ordinal methods (proportional odds logistic regression/sliding dichotomy). The multivariable logistic regression models were validated internally using bootstrapping and externally by assessing the calibration and discrimination. RESULTS: A total of 330 (derivation: 241, validation: 89) aSAH patients were analyzed. Decreasing MSE was associated with a higher likelihood of unfavorable outcome independent of covariates and analysis method. The multivariable adjusted logistic regression models were well calibrated and only showed a slight decrease in discrimination when assessed in the validation cohort. The ordinal analysis revealed its effect to be linear. MSE remained valid when adjusting the outcome definition against the initial severity. CONCLUSIONS: MSE metrics and thereby complexity of physiological signals are independent, internally and externally valid predictors of 12-month outcome. Incorporating high-frequency physiological data as part of clinical outcome prediction may enable precise, individualized outcome prediction. The results of this study warrant further investigation into the cause of the resulting complexity as well as its association to important and potentially preventable complications including vasospasm and delayed cerebral ischemia.

Traumatic Cerebral Venous Sinus Thrombosis: Management and Outcomes.

BACKGROUND: Traumatic brain injury (TBI) with skull fractures parallel to or crossing venous sinuses is a recognized risk factor for traumatic cerebral venous sinus thrombosis (tCVST). Despite the recognition of this traumatic pathology in the literature, no consensus regarding management has been achieved. This study aimed to evaluate the impact of tCVST on TBI outcomes and related complications. METHODS: Patients within a prospective registry at a level I trauma center from 2014 to 2023 were reviewed to identify tCVST cases. The impact of tCVST presence on Glasgow Outcome Scale scores at 6 months, 30-day mortality, and hospital length of stay were evaluated in multivariable-adjusted analyses. RESULTS: Among 607 patients with TBI, 61 patients were identified with skull fractures extending to the vicinity of venous sinuses with dedicated venography. Twenty-eight of these 61 patients (44.3%) had tCVST. The majority (96.4%) of tCVST were located in a unilateral transverse or sigmoid sinus. Complete recanalization was observed in 28% of patients on follow-up imaging (7/25 with follow-up imaging). None of the 28 patients suffered attributable venous infarcts or thrombus propagation. In the adjusted analysis, there was no difference in the 30-day mortality or Glasgow Outcome Scale at 6 months between patients with and without tCVST. CONCLUSIONS: Unilateral tCVST follows a benign clinical course without associated increased mortality or morbidity. The management of tCVST should be distinct as compared to spontaneous CVST, likely without the need for anticoagulation.

Long-term pituitary function and functional and patient-reported outcomes in severe acquired brain injury.

OBJECTIVE: Assessment of posttraumatic hypothalamic-pituitary dysfunctions is expected to be the most relevant assessment to offer patients with severe intracranial affection. In this study, we aim to investigate the prevalence of hypopituitarism in patients with severe acquired traumatic brain injury (TBI) compared with nontraumatic brain injury (NTBI) and to relate pituitary insufficiency to functional and patient-reported outcomes. DESIGN: This is a prospective study. METHODS: We included patients admitted for inpatient neurorehabilitation after severe TBI (N = 42) and NTBI (N = 18). The patients underwent a pituitary function assessment at a mean of 2.4 years after the injury. Functional outcome was assessed by using Functional Independence Measure and Glasgow Outcome Scale-Extended (both 1 year after discharge from neurorehabilitation) and patient-reported outcome was assessed by using Multiple Fatigue Inventory-20 and EQ-5D-3L. RESULTS: Hypopituitarism was reported in 10/42 (24%) patients with TBI and 7/18 (39%) patients with NTBI (P = .23). Insufficiencies affected 1 axis in 14/17 (82%) patients (13 hypogonadotropic hypogonadism and 1 growth hormone [GH] deficiency) and 2 axes in 3/17 (18%) patients (1 hypogonadotropic hypogonadism and GH deficiency, and 2 hypogonadotropic hypogonadism and arginin vasopressin deficiency). None had central hypoadrenalism or central hypothyroidism. In patients with both TBI and NTBI, pituitary status was unrelated to functioning and ability scores at 1 year and to patient-reported outcome scores at a mean of 2.4 years after the injury. CONCLUSION: Patients with severe acquired brain injury may develop long-term hypothalamus-pituitary insufficiency, with an equal occurrence in patients with TBI and NTBI. In both types of patients, mainly isolated deficiencies, most commonly affecting the gonadal axis, were seen. Insufficiencies were unrelated to functional outcomes and patient-reported outcomes, probably reflecting the complexity and heterogeneous manifestations in both patient groups.

A systematic review and meta-analysis on abnormal posturing among brain injury patients.

BACKGROUND: Abnormal motor posturing (AMP), exhibiting as decorticate, decerebrate, or opisthotonos, is regularly noticed among children and adults. OBJECTIVE: This systematic review and meta-analysis examined the risk factors and outcome of posturing among severe head and brain injury subjects. METHODS: Based on the inclusion and exclusion criteria and using MeSH terms: "decerebrate posturing", "opisthotonic posturing", "brain injury", and/or "cerebral injury" articles were searched on Scopus, PubMed, Science Direct, and google scholar databases. Observational studies, case series, and case reports were included. RESULTS: A total of 1953 studies were retrieved initially, and based on the selection criteria, 20 studies were finally selected for review and were analyzed for meta-analysis based on the mortality between the hematomas. The functional outcomes of this study are the risk factors, mortality rate and Glasgow Outcome Scale. Decerebrative patients were higher among the studies related to head injury surgeries. Males were mainly treated for decerebrate postures compared with the female subjects. Extradural hematoma and acute subdural hematoma with cerebral contusion were quite common in the surgical mass lesions. CONCLUSION: The findings reported that the lesion types, the operative procedures, and the age of the decerebrating patients with brain injuries are the significant prognostic factors determining the survival outcomes.

ANTECEDENTES: Postura motora anormal (AMP), exibindo-se como decorticada, descerebrada ou opistótono, é regularmente observada entre crianças e adultos. OBJETIVO: Esta revisão sistemática e metanálise examinou os fatores de risco e os resultados da postura entre indivíduos com lesões graves na cabeça e no cérebro. MéTODOS: Com base nos critérios de inclusão e exclusão e usando termos MeSH: artigos sobre "postura descerebrada", "postura opistótona", "lesão cerebral" e/ou "lesão cerebral" foram pesquisados nas bases de dados Scopus, PubMed, Science Direct e Google Scholar. Foram incluídos estudos observacionais, séries de casos e relatos de casos. RESULTADOS: Um total de 1.953 estudos foram recuperados inicialmente e, com base nos critérios de seleção, 20 estudos foram finalmente selecionados para revisão e analisados para metanálise com base na mortalidade entre os hematomas. Os resultados funcionais deste estudo são os fatores de risco, taxa de mortalidade e Escala de Resultados de Glasgow. Os pacientes descerebrados foram maiores entre os estudos relacionados a cirurgias de traumatismo cranioencefálico. Os homens foram tratados principalmente para posturas descerebradas em comparação com as mulheres. Hematoma extradural e hematoma subdural agudo com contusão cerebral foram bastante comuns nas lesões de massa cirúrgica. CONCLUSãO: Os achados relataram que os tipos de lesões, os procedimentos operatórios e a idade dos pacientes descerebrados com lesões cerebrais são os fatores prognósticos significativos que determinam os resultados de sobrevivência.

Refining outcome prediction after traumatic brain injury with machine learning algorithms.

Outcome after traumatic brain injury (TBI) is typically assessed using the Glasgow outcome scale extended (GOSE) with levels from 1 (death) to 8 (upper good recovery). Outcome prediction has classically been dichotomized into either dead/alive or favorable/unfavorable outcome. Binary outcome prediction models limit the possibility of detecting subtle yet significant improvements. We set out to explore different machine learning methods with the purpose of mapping their predictions to the full 8 grade scale GOSE following TBI. The models were set up using the variables: age, GCS-motor score, pupillary reaction, and Marshall CT score. For model setup and internal validation, a total of 866 patients could be included. For external validation, a cohort of 369 patients were included from Leuven, Belgium, and a cohort of 573 patients from the US multi-center ProTECT III study. Our findings indicate that proportional odds logistic regression (POLR), random forest regression, and a neural network model achieved accuracy values of 0.3-0.35 when applied to internal data, compared to the random baseline which is 0.125 for eight categories. The models demonstrated satisfactory performance during external validation in the data from Leuven, however, their performance were not satisfactory when applied to the ProTECT III dataset.

Psychometric properties and factor structure of the traditional Chinese version of the Community Integration Questionnaire-Revised in traumatic brain injury survivors.

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure - 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors - home integration, social integration, productivity, and electronic social networking - which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P  < 0.001). The TC-CIQ-R exhibited acceptable Cronbach's α values (0.68-0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI.

Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

OBJECTIVES: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. DESIGN: Observational cohort study. SETTING: Neurocritical care unit, Cambridge, United Kingdom. PATIENTS: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. CONCLUSIONS: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.