Neutrophil to lymphocyte ratio predicts early growth of traumatic intracerebral haemorrhage.

OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been proposed to capture the inflammatory status of patients with various conditions involving the brain. This retrospective study aimed to explore the association between the NLR and the early growth of traumatic intracerebral haemorrhage (tICH) in patients with traumatic brain injury (TBI). METHODS: A multicentre, observational cohort study was conducted. Patients with cerebral contusion undergoing baseline computed tomography for haematoma volume analysis within 6 h after primary injury and follow-up visits within 48 h were included. Routine blood tests were performed upon admission, and early growth of tICH was assessed. Prediction accuracies of the NLR for the early growth of tICH and subsequent surgical intervention in patients were analysed. RESULTS: There were a total of 1077 patients who met the criteria included in the study cohort. Univariate analysis results showed that multiple risk factors were associated with the early growth of tICH and included in the following multivariate analysis models. The multivariate logistic regression analysis results revealed that the NLR was highly associated with the early growth of tICH (p < 0.001) while considering other risk factors in the same model. The prediction accuracy of the NLR for the early growth of tICH in patients is 82%. INTERPRETATION: The NLR is easily calculated and might predict the early growth of tICH for patients suffering from TBI.

Very High Blood Alcohol Concentration and Fatal Hemorrhage in Acute Subdural Hematoma.

INTRODUCTION: Alcohol intoxication is often present concurrently with traumatic brain injury (TBI). Recent studies have looked at the effect alcohol has on TBI and on coagulopathy. Typically, cases reviewed in the current literature report only on the effects of modest alcohol intoxication. CASE DESCRIPTION: A 43-year-old male presented to the trauma center after a fall, with rapidly deteriorating mental status. Computed tomography of the head demonstrated a 1.9-cm acute subdural hematoma. Of note, classical coagulation studies were normal, but blood ethanol level was high, 436 mg/dL. Postoperatively, the patient suffered an intracerebral hemorrhage requiring emergent return to the operating room, where a large volume of unclotted blood and clinical coagulopathy was encountered. DISCUSSION: We review the literature pertaining to coagulopathy in the context of TBI and ethanol intoxication. This case is a cautionary tale of a phenomenon of unmeasured coagulopathy in the face of severe alcohol intoxication manifested by intraoperative coagulopathy with new postoperative hemorrhage. Although routine preoperative testing indicated normal clotting function, a thromboelastogram demonstrated delayed clot formation. The protective effects of alcohol are well described; however, we believe that there is a population of patients with severe acute intoxication who have coagulopathy that may go undetected by routine preoperative screening. CONCLUSIONS: Caution should be exercised when taking care of patients with very high levels of alcohol because physiologic derangements may be unpredictable. Additional research is needed for patients with very high levels of alcohol intoxication and the effect it may have on coagulation.

Progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage: characteristics, risk factors and impact on management.

BACKGROUND: Progressive hemorrhagic injury (PHI) is a common occurrence in clinical practice; however, how PHI affects clinical management remains unclear. We attempt to evaluate the characteristics and risk factors of PHI and also investigate how PHI influences clinical management in traumatic intracerebral hemorrhage (TICH) patients. METHODS: This retrospective study included a cohort of 181 patients with TICH who initially underwent conservative treatment and they were dichotomized into a PHI group and a non-PHI group. Clinical data were reviewed for comparison. Multivariate logistic regression analysis was applied to identify predictors of PHI and delayed operation. RESULTS: Overall, 68 patients (37.6%) experienced PHI and 27 (14.9%) patients required delayed surgery. In the PHI group, 17 patients needed late operation; in the non-PHI group, 10 patients received decompressive craniectomy. Compared to patients with non-PHI, the PHI group was more likely to require late operation (P = 0.005, 25.0 vs 8.8%), which took place within 48 h (P = 0.01, 70.6 vs 30%). Multivariate logistic regression identified past medical history of hypertension (odds ratio [OR] = 4.56; 95% confidence interval [CI] = 2.04-10.45), elevated international normalized ratio (INR) (OR = 20.93; 95% CI 7.72-71.73) and linear bone fracture (OR = 2.11; 95% CI = 1.15-3.91) as independent risk factors for PHI. Hematoma volume of initial CT scan >5 mL (OR = 3.80; 95% CI = 1.79-8.44), linear bone fracture (OR = 3.21; 95% CI = 1.47-7.53) and PHI (OR = 3.49; 95% CI = 1.63-7.77) were found to be independently associated with delayed operation. CONCLUSIONS: Past medical history of hypertension, elevated INR and linear bone fracture were predictors for PHI. Additionally, the latter was strongly predictive of delayed operation in the studied cohort.

Neuropeptide proenkephalin A is associated with in-hospital mortality in patients with acute intracerebral hemorrhage.

High plasma proenkephalin A (PENK-A) levels are associated with poor clinical outcome after ischemic stroke. However, not much is known regarding the change of its level in acute intracerebral hemorrhage. Thus, we sought to determine PENK-A in plasma of patients with acute spontaneous basal ganglia hemorrhage and evaluate its relation with disease severity and in-hospital mortality. One hundred and two patients and 100 healthy controls were recruited. Plasma samples were obtained on admission for patients and at study entry for controls. Its concentration was measured by chemoluminescence sandwich immunoassay. Plasma PENK-A levels were substantially higher in patients than in healthy controls (235.5±85.4 pmol/L vs. 90.1±31.3 pmol/L; P<0.0001). A forward stepwise logistic regression selected plasma PENK-A as an independent predictor for in-hospital mortality of patients (odds ratio 1.080, 95% confidence interval 1.018-1.147, P<0.001). A multivariate linear regression demonstrated that plasma PENK-A level was positively associated with National Institutes of Health Stroke Scale (NIHSS) score (t=6.189, P<0.001) and hematoma volume (t=5.388, P<0.001). A receiver operating characteristic curve identified a plasma PENK-A level>267.1 pmol/L predicted in-hospital mortality of patients with 80.0% sensitivity and 74.7% specificity (area under curve, 0.836; 95% confidence interval, 0.750-0.902). Its predictive value was similar to NIHSS score's and hematoma volume's (both P>0.05). However, it did not statistically significantly improve the predictive values of NIHSS score and hematoma volume (both P>0.05). Thus, increased plasma PENK-A levels are associated with disease severity and in-hospital mortality after acute intracerebral hemorrhage.

Effect of erythrocytes on brain water content and haem oxygenase-1 expression in rats with traumatic intracerebral haemorrhage.

BACKGROUND: Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS: In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.

Cerebral arterial oxygen saturation measurements using a fiber-optic pulse oximeter.

BACKGROUND: A pilot investigation was undertaken to assess the performance of a novel fiber-optic cerebral pulse oximetry system. A fiber-optic probe designed to pass through the lumen of a cranial bolt of the type used to make intracranial pressure measurements was used to obtain optical reflectance signals directly from brain tissue. METHODS: Short-duration measurements were made in six patients undergoing neurosurgery. These were followed by a longer duration measurement in a patient recovering from an intracerebral hematoma. Estimations of cerebral arterial oxygen saturation derived from a frequency domain-based algorithm are compared with simultaneous pulse oximetry (SpO2) and hemoximeter (SaO2) blood samples. RESULTS: The short-duration measurements showed that reliable photoplethysmographic signals could be obtained from the brain tissue. In the long-duration study, the mean (±SD) difference between cerebral oxygen saturation (ScaO2) and finger SpO2 (in saturation units) was -7.47(±3.4)%. The mean (±SD) difference between ScaO2 and blood SaO2 was -7.37(±2.8)%. CONCLUSIONS: This pilot study demonstrated that arterial oxygen saturation may be estimated from brain tissue via a fiber-optic pulse oximeter used in conjunction with a cranial bolt. Further studies are needed to confirm the clinical utility of the technique.

D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases.

This study sought to describe and evaluate any relationship between D-dimer values and progressive hemorrhagic injury (PHI) after traumatic brain injury (TBI). In patients with TBI, plasma D-dimer was measured while a computed tomography (CT) scan was conducted as soon as the patient was admitted to the emergency department. A series of other clinical and laboratory parameters were also measured and recorded. A logistic multiple regression analysis was used to identify risk factors for PHI. A cohort of 194 patients with TBI was evaluated in this clinical study. Eighty-one (41.8%) patients suffered PHI as determined by a second CT scan. The plasma D-dimer level was higher in patients who demonstrated PHI compared with those who did not (P < 0.001. Using a receiver-operator characteristic curve to predict the possibility by measuring the D-dimer level, a value of 5.00 mg/L was considered the cutoff point, with a sensitivity of 72.8% and a specificity of 78.8%. Eight-four patients had D-dimer levels higher than the cut point value (5.0 mg/L); PHI was seen in 71.4% of these patients and in 19.1% of the other patients (P < 0.01). Factors with P < 0.2 on bivariate analysis were included in a stepwise logistic regression analysis to identify independent risk factors for TBI coagulopathy. Logistic regression analysis showed that the D-dimer value was a predictor of PHI, and the odds ratio (OR) was 1.341 with per milligram per liter (P = 0.020). The stepwise logistic regression also identified that time from injury to the first CT shorter than 2 h (OR = 2.118, P = 0.047), PLT counts lesser than 100 x 109/L (OR = 7.853, P = 0.018), and Fg lower than 2.0 g/L (OR = 3.001, P = 0.012) were risk factors for the development of PHI. When D-dimer values were dichotomized at 5 mg/L, time from injury to the first CT scan was no longer a risk factor statistically while the OR value of D-dimer to the occurrence of PHI elevated to 11.850(P < 0.001). The level of plasma D-dimer after TBI can be a useful prognostic factor for PHI and should be considered in the clinical management of patients in combination with neuroimaging and other data.

Cerebral endothelial injury in severe head injury: the significance of measurements of serum thrombomodulin and the von Willebrand factor.

Thrombomodulin (TM), which is located in the surface of the endothelium in the arteries, veins, and capillaries of major organs such as the brain, lungs, liver, kidneys, skeletal muscles, and gastrointestinal tract, is one of several indicators of endothelial injury. Von Willebrand factor (vWf), which is synthesized by endothelial cells, is also an endothelial specific glycoprotein. The serum level of vWf increases in response to various stimuli without endothelial injury. An elevated serum level of vWf may suggest endothelial activation in severe head injury. We hypothesize that the degree of cerebral endothelial activation or injury depends on the type of head injury and that measuring the TM and vWf is useful for predicting delayed traumatic intracerebral hematoma (DTICH), produced by weakness of the vessel wall, occuring either as a direct or indirect effect of head injury. The values of vWf in focal brain injury (ranging from 332.5 +/- 52.8% to 361.7 +/- 86.2%) were significantly higher than those in diffuse axonal injury from 2 h to 7 days after the injury occurred (ranging from 201.6 +/- 59.5% to 242.5 +/- 51.7%). The serum level of TM in focal brain injury (ranging from 3.84 +/- 1.54 to 4.12 +/- 1.46 U/mL) was higher than that in diffuse axonal injury (ranging from 2.96 +/- 0.63 to 3.67 +/- 1.70 U/mL), but these differences were not statistically significant. In patients with DTICH, TM was significantly higher than in patients without DTICH (p < 0.01). The results of our study demonstrate that the degree of endothelial activation in focal brain injury was significantly higher than in diffuse brain injury. In addition, the serum level of TM in patients with DTICH was significantly higher than in patients without DTICH. These findings suggest that cerebral tissue injury is often accompanied by cerebral endothelial activation, and that these two phenomena should be distinguished from each other. The levels of serum TM and vWf appear to be good indicators of the cerebral endothelial injury and of endothelial activation in severe head injury.

Effect of apolipoprotein E genotype on hematoma volume after trauma.

OBJECT: The apolipoprotein E-epsilon4 (APOE-epsilon4) allele is associated with poor outcome after head injury and spontaneous intracerebral hemorrhage (SICH). The aims of this study were to determine if patients in whom one or more APOE-epsilon4 alleles are present are more likely to sustain intracranial mass lesions after head injury and to determine whether there is an isoform-specific effect on the size of the intracranial hematoma. METHODS: The authors performed a computerized volumetric analysis of 142 hematomas visible on computerized tomography (CT) scans obtained in 129 patients. The APOE genotype was determined by subjecting buccal smear samples to polymerase chain reaction and restriction enzyme digestion. Allele frequencies were similar in head-injured patients with and without intracranial hematomas (p = 0.36). Univariate analysis revealed that in those patients with one or more APOE-epsilon4 alleles hematoma volume was greater (cube root-transformed values) than that found in patients without the APOE-epsilon4 allele (3.1 cm compared with 2.5 cm, p = 0.0039). The results of univariate analysis also suggested significant effects of patient age, injury severity (mild, moderate, or severe according to admission Glasgow Coma Scale scores) and hematoma location (extraaxial, intraaxial, or both) on hematoma volume. The mechanism of injury (assault, fall, or other) was marginally associated with hematoma volume (p = 0.052). Time from injury to CT scan, hypoxia, and hypotension had no significant effect on hematoma volume. The results of multiple linear regression analysis showed that the presence of an APOE-epsilon4 allele and an extraaxial hematoma location were independent predictors of hematoma volume, after adjusting for patient age, hours between injury and CT scan, injury severity, and injury mechanism. CONCLUSIONS: Larger hematomas were found in head-injured patients with one or more APOE-epsilon4 alleles than in patients without the allele. This may contribute to the poorer outcomes observed in these patients.