Glasgow Outcome Scale-Extended Score Research Articles

Revisiting the Surgical Outcomes of Non-Acute Subdural Hematomas among Retired Military Personnel : A Single Tertiary Hospital Retrospective Analysis in the Philippines.

Subdural hematomas (SDH) are classified clinically and/or radiologically as acute (ASDH), subacute (SSDH) and chronic (CSDH). The management differ depending on their classification, with only the ASDH having a definite accepted surgical guideline. Non-acute SDH, specifically SSDH and CSDH have no clear surgical guidelines but are managed similarly in some literature. This study was conducted to determine if there is a difference in outcomes among surgically managed non-acute SDH in a specific elderly population of retired military personnel. This is a pre-pandemic retrospective study that utilized data obtained from January 2016 to April 2019, in a subspecialty tertiary hospital that caters to retired military personnel or veterans, in the Philippines. After chart review and application of inclusion and exclusion criteria, twenty-one patients were included, all military retirees, with age 56 years old and above. Chart review and electronic database were retrieved to extract relevant information. In this study, a term 'mixed-type subdural hematoma' (MSDH) was proposed to encompass SDH that have mixed hypo-and-hyperdensity on preoperative CT scan and were subsequently found to have bright red liquefied hematoma instead of the classic engine machinery oil fluid found in a CSDH. Based on the observed cohort, 9 out of 11 CSDH patients attained the Glasgow Outcome Scale Extended (GOS-E) score of 8 while all the respondents in the MSDH group attained the same GOS-E score underscoring the need for early intervention in patients with non-acute subdural hematoma. Moreover, the outcomes of both MSDH and CSDH are comparable with low mortality rate (~9.5%) and immediate postoperative improvement (~90%). MSDH and CSDH, although classified separately using clinical and/or radiologic means, can collectively be categorized as a non-acute SDH and can be managed safely and effectively with burr hole surgery.

Investigating the Effect of High-Dose Vitamin D3 Administration on Inflammatory Biomarkers in Patients with Moderate to Severe Traumatic Brain Injury: A Randomized Clinical Trial.

Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide. We aimed to investigate the efficacy of high-dose vitamin D3 on inflammatory biomarkers in patients with moderate to severe TBI. Thirty-five moderate to severe TBI patients were randomly assigned to intervention and control groups. Patients in the intervention group received a single intramuscular (IM) dose of 300,000 IU vitamin D. The primary endpoints were interleukin levels (IL-1β and IL-6), and the secondary endpoints were changes in neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Glasgow Coma scale (GCS), and Glasgow Outcome Scale-Extended (GOS-E) scores compared between intervention and control arms of the study. The linear Generalized Estimating Equations were used for trend analysis and evaluating the association of independent factors to each outcome. The results revealed a significant decrease in IL-1β levels (-2.71±3.02, in the intervention group: P=0.001 vs. -0.14±3.70, in the control group: P=0.876) and IL-6 (-88.05±148.45, in the intervention group: P=0.0001 vs. -35.54±175.79, in the control groupL P=0.325) 3 days after the intervention. The improvement in the GCS score (P=0.001), reduction in NLR (P=0.001) and PLR (P=0.002), and improvement in the GOS-E score (P=0.039) was found to be greater in the vitamin D3 arm of the study than the control group. Administration of high-dose vitamin D3 in the acute phase of TBI could be effective in lowering the inflammatory markers and improving the level of consciousness and long-term performance outcomes.Trial Registration Number: IRCT20180522039777N2.

Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage: an analysis of clinical samples.

We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. We designed two clinical cohort studies to explore the gut dysbiosis after ICH and their relationship with neurological function prognosis. First, fecal samples from patients with ICH at three time points: T1 (within 24 h of admission), T2 (3 days after surgery), and T3 (7 days after surgery), and healthy volunteers were subjected to 16S rRNA sequencing using Illumina high-throughput sequencing technology. When differential gut microbiota was identified, the correlation between clinical indicators and microbiotas was analyzed. Subsequently, the patients with ICH were categorized into GOOD and POOR groups based on their Glasgow Outcome Scale Extended (GOS-E) score, and the disparities in gut microbiota between the two groups were assessed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The composition and diversity of the gut microbiota in patients with ICH were different from those in the control group and changed dynamically with the extension of the course of cerebral hemorrhage. The abundances of Enterococcaceae, Clostridiales incertae sedis XI, and Peptoniphilaceae were significantly increased in patients with ICH, whereas Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, and Veillonellaceae were significantly reduced. The relative abundance of Enterococcus gradually increased with the extension of the duration of ICH after surgery, and the abundance of Bacteroides gradually decreased. The abundance of Enterococcus before surgery was found to be negatively associated with patient neurological function prognosis. The original ICH score and Lachnospiraceae status were independent risk factors for predicting the prognosis of neurological function in patients with ICH (P < 0.05). Changes in the gut microbiota diversity in patients with ICH were related to prognosis. Lachnospiraceae may have a protective effect on prognosis.IMPORTANCEAcute central nervous system injuries like hemorrhagic stroke are major global health issues. While surgical hematoma removal can alleviate brain damage, severe cases still have a high 1-month mortality rate of up to 40%. Gut microbiota significantly impacts health, and treatments like fecal microbiota transplantation (FMT) and probiotics can improve brain damage by correcting gut microbiota imbalances caused by ischemic stroke. However, few clinical studies have explored this relationship in hemorrhagic stroke. This study investigated the impact of cerebral hemorrhage on the composition of gut microbiota, and we found that Lachnospiraceae were the independent risk factors for poor prognosis in intracerebral hemorrhage (ICH). The findings offer potential insights for the application of FMT in patients with ICH, and it may improve the prognosis of patients.

External lumbar drainage for the management of refractory intracranial hypertension in pediatric severe traumatic brain injury: a retrospective single-center case series

OBJECTIVE Guidelines for the management of pediatric severe traumatic brain injury (TBI) recommend external ventricular drainage for CSF drainage as a first-tier treatment in the intracranial pressure (ICP) pathway. However, ventriculostomy in children can sometimes be challenging because of the small size of the lateral ventricles. External lumbar drainage (ELD) may be a useful alternative; therefore, the authors analyzed the outcome of a cohort of pediatric patients who underwent ELD to manage intracranial hypertension (ICH). METHODS This study retrospectively enrolled pediatric patients with ICH following severe TBI who underwent ELD. Radiological and clinical severity scores (Marshall classification, Rotterdam score, Injury Severity Score, and Pediatric Trauma Score) were noted. ICP and cerebral perfusion pressure (CPP) curves were analyzed 12 hours before and after the procedure. Any change in medical therapy was recorded, as well as the total volume and duration of drainage. Cerebellar tonsillar position according to the McRae line was noted before and after ELD. Glasgow Outcome Scale-Extended score at follow-up was also noted. RESULTS Thirty patients were included, with a mean age of 8 ± 4.4 years, and a median admission Glasgow Coma Scale score of 7 ± 4 (range 3–13). ELD was performed after a median delay of 1 day (range 0–7 days), mean drainage volume/day was 296 ± 129 ml, and median duration of drainage was 7 ± 5 (range 2–12) days. Forty-three percent of the patients underwent ELD as a part of the first-tier therapy. ICP decreased after ELD (mean difference 13.4 ± 6.2 mm Hg, p &lt; 0.001), whereas CPP increased (mean difference 10.6 ± 6.4 mm Hg, p &lt; 0.001). Fifty-three percent of the cohort did not need any further second-tier therapy after ELD. The study found 1 case of drain revision and 3 cases of cerebellar tonsil herniation. CONCLUSIONS These preliminary data suggest ELD is a valuable option to treat ICH in severely head-injured children, limiting the use of second-tier treatments. This pilot study should lay the foundation for a multicenter prospective trial.

A two-center prospective cohort study of serum RIP-3 as a potential biomarker in relation to severity and prognosis after severe traumatic brain injury.

Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1-4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI.

Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.

Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing. We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4). Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01). Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).

Automated Measurement of Cerebral Hemorrhagic Contusions and Outcomes After Traumatic Brain Injury in the TRACK-TBI Study

Because withdrawal of life-sustaining therapy based on perceived poor prognosis is the most common cause of death after moderate or severe traumatic brain injury (TBI), the accuracy of clinical prognoses is directly associated with mortality. Although the location of brain injury is known to be important for determining recovery potential after TBI, the best available prognostic models, such as the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) score, do not currently incorporate brain injury location. To test whether automated measurement of cerebral hemorrhagic contusion size and location is associated with improved prognostic performance of the IMPACT score. This prognostic cohort study was performed in 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018. Adult participants aged 17 years or older from the US-based Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study with moderate or severe TBI (Glasgow Coma Scale score 3-12) and contusions detected on brain computed tomography (CT) scans were included. The data analysis was performed between January 2023 and February 2024. Labeled contusions detected on CT scans using Brain Lesion Analysis and Segmentation Tool for Computed Tomography (BLAST-CT), a validated artificial intelligence algorithm. The primary outcome was a Glasgow Outcome Scale-Extended (GOSE) score of 4 or less at 6 months after injury. Whether frontal or temporal lobe contusion volumes improved the performance of the IMPACT score was tested using logistic regression and area under the receiver operating characteristic curve comparisons. Sparse canonical correlation analysis was used to generate a disability heat map to visualize the strongest brainwide associations with outcomes. The cohort included 291 patients with moderate or severe TBI and contusions (mean [SD] age, 42 [18] years; 221 [76%] male; median [IQR] emergency department arrival Glasgow Coma Scale score, 5 [3-10]). Only temporal contusion volumes improved the discrimination of the IMPACT score (area under the receiver operating characteristic curve, 0.86 vs 0.84; P = .03). The data-derived disability heat map of contusion locations showed that the strongest association with unfavorable outcomes was within the bilateral temporal and medial frontal lobes. These findings suggest that CT-based automated contusion measurement may be an immediately translatable strategy for improving TBI prognostic models.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study

ObjectivesAn estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is...

Early Intravenous Beta-Blockade with Esmolol in Adults with Severe Traumatic Brain Injury: A Phase 2a Intervention Design Study.

Targeted beta-blockade after severe traumatic brain injury may reduce secondary brain injury by attenuating the sympathoadrenal response. The potential role and optimal dosage for esmolol, a selective, short-acting, titratable beta-1 beta-blocker, as a safe, putative early therapy after major traumatic brain injury has not been assessed. We conducted a single-center, open-label dose-finding study using an adaptive model-based design. Adults (18 years or older) with severe traumatic brain injury and intracranial pressure monitoring received esmolol within 24 h of injury to reduce their heart rate by 15% from baseline of the preceding 4 h while ensuring cerebral perfusion pressure was maintained above 60 mm Hg. In cohorts of three, the starting dosage and dosage increments were escalated according to a prespecified plan in the absence of dose-limiting toxicity. Dose-limiting toxicity was defined as failure to maintain cerebral perfusion pressure, triggering cessation of esmolol infusion. The primary outcome was the maximum tolerated dosage schedule of esmolol, defined as that associated with less than 10% probability of dose-limiting toxicity. Secondary outcomes include 6-month mortality and 6-month extended Glasgow Outcome Scale score. Sixteen patients (6 [37.5%] female patients; mean age 36 years [standard deviation 13 years]) with a median Glasgow Coma Scale score of 6.5 (interquartile range 5-7) received esmolol. The optimal starting dosage of esmolol was 10 μg/kg/min, with increments every 30 min of 5 μg/kg/min, as it was the highest dosage with less than 10% estimated probability of dose-limiting toxicity (7%). All-cause mortality was 12.5% at 6 months (corresponding to a standardized mortality ratio of 0.63). One dose-limiting toxicity event and no serious adverse hemodynamic effects were seen. Esmolol administration, titrated to a heart rate reduction of 15%, is feasible within 24 h of severe traumatic brain injury. The probability of dose-limiting toxicity requiring withdrawal of esmolol when using the optimized schedule is low. Trial registrationI SRCTN, ISRCTN11038397, registered retrospectively January 7, 2021 ( https://www.isrctn.com/ISRCTN11038397 ).

Radiologic and Blood Markers Predicting Long-Term Neurologic Outcome Following Decompressive Craniectomy for Malignant Ischemic Stroke: A Preliminary Single-Center Study.

Malignant ischemic stroke (MIS) is defined by progressive cerebral edema leading to increased intracranial pressure (ICP), compression of neural structures, and, eventually, death. Decompressive craniectomy (DC) has been advocated as a lifesaving procedure in the management of patients with MIS. This study aims to identify pre- and postoperative predictive variables of neurologic outcomes in patients undergoing DC for MIS. We conducted a retrospective study of patients undergoing DC in a single center from April 2016 to April 2020. Preoperative workup included baseline clinical status, laboratory data, and brain computed tomography (CT). The primary outcome was the 6-month modified Rankin score (mRS). The secondary outcome was the 30-day mortality. During data capture, a total of 58 patients fulfilled the criteria for MIS, of which 22 underwent DC for medically refractory increased ICP and were included in the present analysis. The overall median age was 58.5 years. An immediate (24 hour) postoperative extended Glasgow Outcome Scale (GOSE) score ≥5 was associated with a good 6-month mRS (1-3; p = 0.004). Similarly, low postoperative neutrophils (p = 0.002), low lymphocytes (p = 0.004), decreased neutrophil-to-lymphocyte ratio (NLR; p = 0.02), and decreased platelet-to-lymphocytes ratio (PLR; p = 0.03) were associated with good neurologic outcomes. Preoperative variables independently associated with worsened 6-month mRS were the following: increased age (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.01-1.20; p = 0.02), increased National Institutes of Health Stroke Scale (NIHSS) score (OR: 7.8; 95% CI: 2.5-12.5; p = 0.035), Glasgow Coma Scale (GCS) score less than 8 at the time of neurosurgical referral (OR: 21.63; 95% CI: 1.42-328; p = 0.02), and increased partial thromboplastin time (PTT) before surgery (OR: 2.11; 95% CI: 1.11-4; p = 0.02). Decreased postoperative lymphocytes confirmed a protective role against worsened functional outcomes (OR: 0.01; 95% CI: 0.01-0.4; p = 0.02). Decreased postoperative lymphocyte count was associated with a protective role against increased mRS (OR: 0.01; 95% CI: 0.01-0.4; p = 0.02). The occurrence of hydrocephalus at the postoperative CT scan was associated with 30-day mortality (p = 0.005), while the persistence of postoperative compression of the ambient and crural cistern showed a trend towards higher mortality (p = 0.07). This study reports that patients undergoing DC for MIS showing decreased postoperative blood inflammatory markers achieved better 6-month neurologic outcomes than patients with increased inflammatory markers. Similarly, poor NIHSS score, poor GCS score, increased age, and larger PTT values at the time of surgery were independent predictors of poor outcomes. Moreover, the persistence of postoperative compression of basal cisterns and the occurrence of hydrocephalus are associated with 30-day mortality.

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.

P.033 Electrophysiological signatures of sedation in pediatric patients

Background: Sedation in PICU masks physical exam findings, leading to diagnostic challenges. In adult models, electroencephalography can evaluate the brain’s response to sedation using feedforward connectivity and anteriorization of alpha hubs, proving useful for prognostication. Feasibility of model translation into pediatric population was assessed, with the hypothesis that the same markers of adaptive reconfiguration would correlate with a higher potential for recovering consciousness. Methods: Electroencephalograms from children undergoing sedation were analyzed for strength and direction of functional connectivity using the weighted and directed phase lag index. Target population was refined with an iterative inclusion criteria. We examined relationships between hub location reconfiguration, directed phase lag index, baseline Glasgow Coma Scale, and 3-month post-treatment Glasgow Outcome Scale-Extended. Results: Evaluation of 14 subjects showed promise in children aged 5-18 undergoing sedation with midazolam, dexmedetomidine, and propofol. Further analysis of five subjects revealed a correlation between adaptive reconfiguration during anesthesia and both higher baseline Glasgow Coma Scale and Glasgow Outcome Scale-Extended scores post-treatment. Conclusions: The findings indicate that the functional brain network connectivity model may have diagnostic and prognostic potential regarding children’s consciousness levels. While the initial data is promising, further analysis of six additional cases is pending and deemed essential to thoroughly evaluate the model’s efficacy.

Clinical and Imaging Characteristics, Care Pathways, and Outcomes of Traumatic Epidural Hematomas: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

GET-UP Trial 1-year results: long-term impact of an early mobilization protocol on functional performance after surgery for chronic subdural hematoma.

Evidence on timing for mobilization after chronic subdural hematoma (cSDH) surgery is heterogeneous, and practices differ considerably among neurosurgical centers. The Impact of an Early Out-of-Bed Paradigm in Postoperative Outcomes of Chronic Subdural Hematomas: GET-UP Randomized Prospective Trial (GET-UP Trial) is a randomized clinical trial comparing a postoperative early mobilization protocol to bed rest. Previously reported results at clinical discharge and 1 month after surgery indicated a decreased risk of medical complications in the early mobilization group. Herein, the authors report outcomes at the 1-year follow-up. The GET-UP Trial is a prospective, randomized, unicentric, open-label study with an intention-to-treat primary analysis designed to evaluate the impact of an early mobilization protocol after burr hole craniostomy for cSDH on the occurrence of medical complications and functional outcomes. Between January 2019 and August 2021, a total of 208 patients were recruited and randomized to either an early mobilization group, in which patients began elevation of the head of the bed within the first 12 hours after surgery, or to a bed rest group, in which patients remained recumbent for 48 hours. Outcomes assessed at the 1-year follow-up included functional status as measured by the Glasgow Outcome Scale-Extended (GOSE) and repeat surgery for hematoma recurrence (surgical recurrence). A total of 203 patients completed 1 year of follow-up: 101 in the bed rest group and 102 in the early mobilization group. No significant baseline pre-randomization clinical differences were observed between the two management groups. At 1 year after surgery, a favorable functional outcome, defined as a GOSE score ≥ 5, was observed in 59 patients (58.4%) in the bed rest group and 78 (76.5%) in the early mobilization group (p = 0.006). Death occurred in 25 patients (24.8%) in the bed rest group and 16 (15.7%) in the early mobilization group (p = 0.108). Surgical recurrence was noted in 6 patients (5.9%) in the bed rest group and 7 (6.9%) in the early mobilization group (p = 0.788). Multivariate analysis showed an independent association between early mobilization and an increase in favorable functional outcomes (OR 2.006, 95% CI 1.076-3.739, p = 0.028). The GET-UP Trial is the first randomized clinical trial assessing the impact of mobilization strategies on medical complications after burr hole craniostomy for cSDH. Regarding functional results 1 year after surgery, early mobilization was associated with an improvement in functional outcomes without an increase in surgical recurrence. These findings support the preference for an early mobilization protocol in cSDH patients over mandatory bed rest strategies.

Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock.

Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores. Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

Importance of AIM2 as a serum marker for reflecting severity and predicting a poor outcome of human severe traumatic brain injury: A prospective longitudinal cohort study

BackgroundAbsent in melanoma 2 (AIM2) participates in neuroinflammation. Here, the prognostic significance of serum AIM2 was explored in severe traumatic brain injury (sTBI). MethodsA total of 135 sTBI patients and 80 healthy controls were recruited in this prospective cohort study. Serum C-reactive protein (CRP) and AIM2 levels were measured. Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) classification were recorded as the severity indicators. Prognostic parameters were posttraumatic six-month extended Glasgow outcome scale (GOSE) scores and poor outcome (GOSE scores of 1–4). ResultsAs opposed to controls, there were significantly elevated serum AIM2 levels after sTBI. Serum AIM2 levels were independently correlated with serum CRP levels, GCS scores, Rotterdam CT scores, GOSE scores and poor outcome. Also, serum AIM2 levels were efficiently predictive of poor outcome under the receiver operating characteristic (ROC) curve. Under the restricted cubic spline, serum AIM2 levels were linearly correlated with risk of poor outcome. Using subgroup analysis, serum AIM2 levels did not significantly interact with other indices, such as age, gender, alcohol drinking, cigarette smoking, etc. Also, combination model, in which serum AIM2, GCS scores and Rotterdam CT scores were merged, was outlined using nomogram and performed well under calibration curve, ROC curve and decision curve. ConclusionsRaised serum AIM2 levels after sTBI, in intimate correlation with systemic inflammation and trauma severity, are independently discriminative of posttraumatic six-month neurological outcome, substantializing serum AIM2 as an inflammatory prognostic biomarker of sTBI.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging After Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on magnetic resonance imaging (MRI) in patients with moderate-severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of TAI lesions on different MRI sequences and its associations to outcome with use of lesion mapping. Included prospectively were 269 patients (8-70 years) with moderate or severe TBI and MRI within six weeks after injury. The TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI), and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by visual reading. Univariable associations to outcome were assessed qualitatively by visual reading and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal and temporal lobes than in the parietal and occipital lobes, and in the upper parts of the brainstem than in the lower. At the group level, all voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions bilaterally in the splenium, the right side of tectum, tegmental mesencephalon, and pons. In conclusion, we found higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon, and pons were associated with poor outcome. If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared with the imaging findings from individual patients, it would offer a new tool in the clinical workup and outcome prediction of the patient with TBI.

Outcome of patients with traumatic cranial nerve palsy admitted to a university hospital in Nepal

BackgroundCranial nerve palsy (CNP) is a common complication of traumatic brain injury (TBI). Despite a high incidence of TBI in Nepal (382 per 100,000), literature on the specific management and outcome of CNP is lacking. This study aimed to examine the outcomes of TBI patients involving single versus multiple CNP.MethodsA retrospective chart review of 170 consecutive TBI patients admitted to the tertiary neurosurgical center in Nepal between April 2020 and April 2022 was conducted. Demographic, clinical, and etiological characteristics; imaging findings; and management strategies were recorded, compared, and analyzed using descriptive statistics. The Glasgow Outcome Scale Extended (GOSE) was used to measure the outcomes in two groups of patients (single and multiple CNP) at 3 months.ResultsOut of 250 eligible patients, 80 were excluded and CNP was noted in 29 (17.1%) of the remaining 170. The median age was 34.9 years, and falls (60.6%) were the most common cause of trauma. TBI severity was categorized based on GCS: mild (82.4%), moderate (15.9%), and severe (1.8%). Cranial nerve involvement was seen in 29 (17.05%) patients: single cranial nerve involvement in 26 (89.65%) and multiple nerve involvement in 3 (10.34%). The most common isolated cranial nerve involved was the oculomotor nerve (37.9%). CT findings revealed a maximum of skull fractures with no significant association between CNP and CT findings.ConclusionsCNP is a common consequence of TBI with the most common etiology being falls followed by RTA. Single CNP was more common than multiple CNP with no significant difference in the outcome in the 3-month GOSE score. Further research is needed to determine the burden of traumatic CNP and establish specific management guidelines for different types of CNP.