Diagnostische Biomarker des Schädel-Hirn-Traumas

Background

Despite advances in medicine in head trauma management, traumatic brain injury (TBI) still remains a serious health concern, affecting people regardless of age. It is a leading cause of morbidity and mortality particularly in children and young adults. Therefore, studies are being carried out to try to establish reliable biomarkers to improve the accuracy of TBI diagnosis and associated secondary pathologies.

Methods

Implementation of valid TBI biomarkers could possibly reduce the necessity to use computed cranial tomography (CCT), especially in patients suffering from mild TBI to rule out intracranial bleeding.

Aim

This review provides a critical assessment of biomarkers currently under investigation and their clinical value for the diagnosis, treatment and outcome prediction of TBI.     

Increased risk of pneumonia among ventilated patients with traumatic brain injury: every day counts!

Background

Patients with traumatic brain injury (TBI) frequently require mechanical ventilation (MV). The objective of this study was to examine the association between time spent on MV and the development of pneumonia among patients with TBI.

Materials and methods

Patients older than 18 y with head abbreviated injury scale (AIS) scores coded 1–6 requiring MV in the National Trauma Data Bank 2007–2010 data set were included. The study was limited to hospitals reporting pneumonia cases. AIS scores were calculated using ICDMAP-90 software. Patients with injuries in any other region with AIS score >3, significant burns, or a hospital length of stay >30 d were excluded. A generalized linear model was used to determine the approximate relative risk of developing all-cause pneumonia (aspiration pneumonia, ventilator-associated pneumonia [VAP], and infectious pneumonia identified by the International Classification of Disease, Ninth Revision, diagnosis code) for each day of MV, controlling for age, gender, Glasgow coma scale motor score, comorbidity (Charlson comorbidity index) score, insurance status, and injury type and severity.

Results

Among the 24,525 patients with TBI who required MV included in this study, 1593 (6.5%) developed all-cause pneumonia. After controlling for demographic and injury factors, each additional day on the ventilator was associated with a 7% increase in the risk of pneumonia (risk ratio 1.07, 95% confidence interval 1.07–1.08).

Conclusions

Patients who have sustained TBIs and require MV are at higher risk for VAP than individuals extubated earlier; therefore, shortening MV exposure will likely reduce the risk of VAP. As patients with TBI frequently require MV because of neurologic impairment, it is key to develop aggressive strategies to expedite ventilator independence.     

Traumatic coagulopathy: the effect of brain injury

Traumatic coagulopathy has several possible mechanisms. In traumatic brain injury (TBI), the principal process involves the release of tissue factor (TF). There is no agreement how common this mechanism is following general trauma. Furthermore, when TF-induced coagulopathy occurs, it is unknown whether the source of TF (TBI or extracranial trauma) influences the course of coagulopathy. We undertook this investigation to address both questions. The temporal course of prothrombin times (PTs) were recorded in a group (n = 441) with isolated TBI (head Abbreviated Injury Scale [AIS] >or= 3, non-head AIS < 3) and a group (n = 101) with extracranial trauma (non-TBI; non-head AIS >or= 3; head AIS < 3). Data were arranged according to preset time intervals after injury. The PT values in both groups were elevated and not significantly different for the first 12 h after trauma. Values then fell to normal in TBI patients, but remained elevated in non-TBI injury. Traumatic coagulopathy can be explained at least in part by TF release into the general circulation with activation of the coagulation cascade in both TBI and non-TBI. We hypothesize that the different time courses of coagulopathy represented by PT values in these populations were due to reconstitution of the blood-brain barrier, although further investigation is warranted. Peripheral hematologic studies may not reflect persistent coagulopathy in cerebral circulation.     

Optic nerve sheath measurement and raised intracranial pressure in paediatric traumatic brain injury

Introduction  

The optimal management of children ventilated for more than 4 h with traumatic brain injury (TBI) necessitates invasive intracranial pressure (ICP) monitoring, though some patients never have raised ICP. If non-invasive screening can reliably rule out elevated ICP, invasive devices can be limited to those in whom neuro-intensive care measures are indicated.     

Severe traumatic brain injuries in children: Does the type of trauma center matter?

Background

Traumatic brain injury (TBI) is the leading cause of death among injured children. Depending on geographic location, and trauma resources, pediatric patients may be treated at pediatric (PTC), adult (ATC), or mixed trauma centers (MTC). The effect of the type of trauma center on outcomes in severe TBI is not known.

‘Long’ pressure reactivity index (L-PRx) as a measure of autoregulation correlates with outcome in traumatic brain injury patients

Background  

Cerebral autoregulation and, consequently, cerebrovascular pressure reactivity, can be disturbed after traumatic brain injury (TBI). Continuous monitoring of autoregulation has shown its clinical importance as an independent predictor of neurological outcome. The cerebral pressure reactivity index (PRx) reflects that changes in seconds of cerebrovascular reactivity have prognostic significance. Using an alternative algorithm similar to PRx, we investigate whether the utilization of lower-frequency changes of the order of minutes of mean arterial blood pressure (MAP) and intracranial pressure (ICP) could have a prognostic value in TBI patients.     

Factor XIII deficiency as a potential cause of supratentorial haemorrhage after posterior fossa surgery

Background  

Postoperative intracranial haemorrhage can be a dramatic event, carrying significant morbidity and mortality. Bleeding at sites remote from the operation area represents a small percentage of haemorrhages whose aetiology remains unclear (Harders et al. Acta Neurochir (Wien) 74(1-2):57–60, 1985).     

Paediatric and adult vascular intracranial complications of sickle-cell disease

Background

To enumerate possible intracranial vascular sequelae of sickle-cell disease, to identify risk factors and outline management strategies.

Method

Retrospective review of a single unit experience managing vascular intracranial complications of sickle-cell disease from 1995 until 2005. Information such as homozygosity/heterozygosity, duration of disease, disease control as indicated by haematology follow-up, concurrent sickle-cell disease (SCD)-related health problems and neurosurgical management was recorded. The pattern of vascular disease was analysed to reveal possible contributory/risk factors towards development of vascular intracranial complications.

Subjects

All patients presenting with vascular intracranial complications of sickle-cell disease from 1995 to 2005 were evaluated.

Outcome measures

Classification of vascular intracranial complications into one or more of the following categories: aneurysmal subarachnoid haemorrhage, non-aneurysmal subarachnoid/intraventricular haemorrhage and vasculitis.

Findings

There were ten patients in the study. All symptomatic vascular intracranial complications of SCD requiring neurosurgical intervention were homozygous for SCD. Aneurysms were likely to be multiple. Ruptured aneursyms in SCD were small (average 4 mm). There was a propensity for aneurysms to occur in the posterior circulation, in particular the posterior cerebral artery was frequently involved. Patients with aneurysms and Moyamoya-type vasculitis were likely to have occlusive disease of the internal carotid arteries.

Conclusions

The vascular intracranial complications of sickle-cell disease have an aggressive natural history. Tight control of SCD may reduce the possibility of complications. Complications that arise should be managed in the context of the disease entity rather than in isolation. Consideration should be given to bypass procedures, parent vessel ligations and revascularization techniques. Transcranial Doppler may be used to identify SCD patients with cerebrovascular occlusive disease, who may have increased risk of aneurysmal rupture.     

Transcranial color-coded duplex sonography allows to assess cerebral perfusion pressure noninvasively following severe traumatic brain injury

Objective  

Assess optimal equation to noninvasively estimate intracranial pressure (eICP) and cerebral perfusion pressure (eCPP) following severe traumatic brain injury (TBI) using transcranial color-coded duplex sonography (TCCDS).     

Description of sensory preservation in children and adolescents with incomplete spinal cord injury

Background/objective

This cross-sectional, multicenter cohort study describes patterns of preserved sensation in persons with American Spinal Injury Association (ASIA) Impairment Scale (AIS) B (sensory incomplete, or SI) and AIS C/D (motor incomplete, or MI).

Methods

A total of 93 subjects with incomplete spinal injuries (58 with tetraplegia and 35 with paraplegia) were included for analysis. Sensation was based on the International Standards for Neurological Classification of SCI (ISNCSCI).

Results

In the 44 subjects with AIS B (SI), some light touch (LT) was present in 35% of dermatomes below the neurological level and pin prick (PP) in 8%. In contrast, in the 49 subjects with AIS C/D (MI), LT was present in 77% of dermatomes and PP in 27%. AIS C/D (MI) subjects with tetraplegia had more dermatomes with preserved sensation than those with paraplegia. When reviewing areas at highest risk for pressure sores, only 4 of 22 (19%) of subjects with AIS B (SI)/tetraplegia had any preserved LT or PP sensation in the periscapular region (dermatomes T1–T6). In the buttocks region (S3 and S4–S5), sensation was preserved in fewer than 50% of patients with either tetraplegia or paraplegia.

Conclusions

(1) Sensory sparing below the neurologic injury was found to be surprisingly sparse in patients classified as AIS B (SI) (35% LT and 8% PP). Sparing was considerably better in patients who were AIS C/D (MI) (77% LT and 27% PP). (2) Preserved sensation in the periscapular region was very low in subjects with tetraplegia (19%) and was also low in the buttocks, with fewer than half of those classified as AIS B (SI) with either tetraplegia or paraplegia reporting sensation.     

Influence of gravity for optimal head positions in the treatment of head injury patients

Background  

Brain edema is a major neurological complication of traumatic brain injury (TBI), commonly including a pathologically increased intracranial pressure (ICP) associated with poor outcome. In this study, gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue and the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a finite element (FE) model.     

Overcoming barriers to population-based injury research: development and validation of an ICD-10�Cto�CAIS algorithm

Background

Hospital administrative databases are a useful source of population-level data on injured patients; however, these databases use the International Classification of Diseases (ICD) system, which does not provide a direct means of estimating injury severity. We created and validated a crosswalk to derive Abbreviated Injury Scale (AIS) scores from injury-related diagnostic codes in the tenth revision of the ICD (ICD-10).

Methods

We assessed the validity of the crosswalk using data from the Ontario Trauma Registry Comprehensive Data Set (OTR-CDS). The AIS and Injury Severity Scores (ISS) derived using the algorithm were compared with those assigned by expert abstractors. We evaluated the ability of the algorithm to identify patients with AIS scores of 3 or greater. We used κ and intraclass correlation coefficients (ICC) as measures of concordance.

Results

In total, 10 431 patients were identified in the OTR-CDS. The algorithm accurately identified patients with at least 1 AIS score of 3 or greater (κ 0.65), as well as patients with a head AIS score of 3 or greater (κ 0.78). Mapped and abstracted ISS were similar; ICC across the entire cohort was 0.83 (95% confidence interval 0.81–0.84), indicating good agreement. When comparing mapped and abstracted ISS, the difference between scores was 10 or less in 87% of patients. Concordance between mapped and abstracted ISS was similar across strata of age, mechanism of injury and mortality.

Conclusion

Our ICD-10–to–AIS algorithm produces reliable estimates of injury severity from data available in administrative databases. This algorithm can facilitate the use of administrative data for population-based injury research in jurisdictions using ICD-10.     

Assessment of medical resource utilization for Taiwanese children hospitalized for intracranial injuries

Background

Compared to adults, children and adolescents are at greater risk for traumatic brain injury (TBI), with increased severity and prolonged recovery when compared to adults. It is a challenge to provide care for those children who are at risk for complications of TBI under health care resource constraints.

Aim

To investigate hospitalization among children with intracranial injuries in terms of incidence and factors related to length of stay (LOS) and medical cost.

Methods

Data from the National Health Insurance Research Database from 2007–2009 were used. In total 8632 children aged <=18 years with acute traumatic intracranial injuries caused by accidents were discharged from hospitals in Taiwan. The associations between patient and hospital covariates (e.g., age, gender, accreditation level of hospital, surgical intervention, and number of comorbid conditions) and log-transferred hospitalization cost and length of stay (LOS) were examined with multivariable regression analysis and mediation analyses.

Results

The incidence rate of hospitalization for acute intracranial injury was 63.3/100,000 per year. Motor vehicle crashes and falls accounted for 63.5% and 23.8% of intracranial injuries, respectively. The mean LOS for children was 5.0 days (median, 3 days), incurring a mean direct medical cost of $US 916.70 (median, $356.2). Boy sustained more injury (64.1%) and greater medicals cost ($965) occurred in boys. Patients with subarachnoid subdural and extradural haemorrhage tended to have a longer LOS and incur greater medical costs. Surgical intervention and type of healthcare institution were also significant predictors for medical costs. Additionally, LOS was the dominant mediator for the relationship between predictor and medical cost.

Conclusions

Acute intracranial injuries among children incur a substantial health care burden. Therefore, health authorities need to optimally allocate medical resources in care.     

Mortality in polytrauma patients with moderate to severe TBI on par with isolated TBI patients: TBI as last frontier in polytrauma patients

BackgroundMortality caused by Traumatic Brain Injury (TBI) remains high, despite improvements in trauma and critical care. Polytrauma is naturally associated with high mortality. This study compared mortality rates between isolated TBI (_ITBI) patients and polytrauma patients with TBI (_PTBI) admitted to ICU to investigate if concomitant injuries lead to higher mortality amongst TBI patients.MethodsA 3-year cohort study compared polytrauma patients with TBI (_PTBI) with AIS head ≥3 (and AIS of other body regions ≥3) from a prospective collected database to isolated TBI (_ITBI) patients from a retrospective collected database with AIS head ≥3 (AIS of other body regions ≤2), both admitted to a single level-I trauma center ICU. Patients <16 years of age, injury caused by asphyxiation, drowning, burns and ICU transfers from and to other hospitals were excluded. Patient demographics, shock and resuscitation parameters, multiple organ dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), and mortality data were collected and analyzed for group differences.Results259 patients were included; 111 _PTBI and 148 _ITBI patients. The median age was 54 [33-67] years, 177 (68%) patients were male, median ISS was 26 [20-33]. Seventy-nine (31%) patients died. Patients with _PTBI developed more ARDS (7% vs. 1%, p = 0.041) but had similar MODS rates (18% vs. 10%, p = 0.066). They also stayed longer on the ventilator (7 vs. 3 days, p=<0.001), longer in ICU (9 vs. 4 days, p=<0.001) and longer in hospital (24 vs. 11 days, p=<0.001). TBI was the most prevalent cause of death in polytrauma patients. Patients with _PTBI showed no higher in-hospital mortality rate. Moreover, mortality rates were skewed towards _ITBI patients (24% vs. 35%, p = 0.06).DiscussionThere was no difference in mortality rates between _PTBI and _ITBI patients, suggesting TBI-severity as the predominant factor for ICU mortality in an era of ever improving acute trauma care.     

The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury

OBJECTIVE: The purpose of this study was to determine the incidence of acute lung injury (ALI) in trauma patients with severe traumatic brain injury (TBI), to evaluate the impact of ALI on mortality and neurologic outcome after severe traumatic brain injury (TBI), and to identify whether the development of ALI correlates with the severity of TBI. METHODS: Clinical data were collected prospectively over a 4-year period in a Level I trauma center. Patients included in the study met the following criteria: mechanical ventilation > 24 hours, head Abbreviated Injury Scale score >or= 3, no other body region Abbreviated Injury Scale score >or= 3, and age between 18 and 54 years. ALI was defined using international consensus criteria. Glasgow Outcome Scale scores were assessed at 3 and 12 months. Bivariate comparisons were made between ALI and non-ALI groups. Multivariate analysis with stepwise logistical regression was used to assess independent factors on mortality. The patient's admission head computed tomographic (CT) scan was graded using the Marshall system, and the presence and size of specific intracranial abnormality was noted. Glasgow Coma Scale (GCS) score, Marshall CT scan score, and intracranial abnormality were correlated with the development of ALI. RESULTS: One hundred thirty-seven patients with isolated head trauma were enrolled in the study over a 4-year period. Thirty-one percent of patients with severe TBI developed ALI. Head trauma patients with ALI had a significantly higher ISS, a greater number of days on the ventilator, and a worse neurologic outcome for those who survived their hospitalization. Mortality was 38% in the ALI group and 15% in the non-ALI group (p = 0.004). Only 3 of 16 (19%) of the deaths within the ALI group were directly related to ALI. By multivariate analysis, only the presence of ALI, older age, and lower initial GCS score were associated with higher mortality. There was no association between ISS, the presence of arterial hypotension (arterial systolic pressure < 90 mm Hg) at admission to the hospital, or the amount of blood transfused and mortality. No correlation was found between the severity of head injury (GCS score, Marshall score, or intracranial abnormality) and development of ALI. CONCLUSION: The development of ALI is a critical independent factor affecting mortality in patients suffering traumatic brain injury and is associated with a worse long-term neurologic outcome in survivors. The risk of developing ALI is not associated with specific anatomic lesions diagnosed by cranial CT scanning.     

Neuromonitoring und operative Therapie beim schweren Schädel-Hirn-Trauma

Background

Traumatic brain injury (TBI) is a leading cause of morbidity, disability and mortality worldwide. From a pathophysiological point of view, a differentiation must be made between primary injury due to mechanical injury to the brain and secondary injury due to the occurrence of secondary noxious events e.g. brain edema and swelling. The major goals of TBI management are prevention and treatment of secondary injuries.

Management and therapy

Many experimental studies have been carried out to find effective neuroregenerative strategies but none of them could successfully be translated from benchmarking to the patient bedside. Thus, the role of neuromonitoring is of decisive importance to avoid secondary injuries in TBI patients. Management of TBI includes monitoring of intracranial pressure (ICP), cerebral tissue oxygenation by oxygen partial pressure (ptiO₂), cerebral perfusion pressure (CPP) as well as neuroradiological and electrophysiological assessments. The surgical removal of TBI-associated lesions with mass effects, such as epidural and subdural hematomas and contusion bleeding, and decompressive craniectomy are well-established neurosurgical procedures which are performed initially or during the critical phase of severe TBI.

     

Relationship of "dose" of intracranial hypertension to outcome in severe traumatic brain injury

OBJECT: It has recently been suggested that the degree of intracranial pressure (ICP) above the treatment goal can be estimated by the area under the curve (AUC) of ICP versus time in patients with severe traumatic brain injury (TBI). The objective of this study was to determine whether the calculated "ICP dose"-the ICP AUC-is related to mortality rate, outcome, and Marshall CT classification. METHODS: Of 135 patients (age range 1-82 years) with severe TBI treated during a 5-year period at the authors' institution, 113 patients underwent ICP monitoring (84%). Ninety-three patients with a monitoring time>24 hours were included for analysis of ICP AUC calculated using the trapezoidal method. Computed tomography scans were assessed according to the Marshall TBI classification. Patients with Glasgow Outcome Scale scores at 6 months and >3 years were separated into 2 groups based on outcome. RESULTS: Sixty patients (65%) had ICP values>20 mm Hg, and 12 (13%) developed severe intracranial hypertension and died secondary to herniation. A multiple regression analysis adjusting for Glasgow Coma Scale score, age, pupillary abnormalities and Injury Severity Scale score demonstrated that the ICP AUC was a significant predictor of poor outcome at 6 months (p=0.034) and of death (p=0.035). However, it did not predict long-term outcome (p=0.157). The ICP AUC was significantly higher in patients with Marshall head injury Categories 3 and 4 (24 patients) than in those with Category 2 (23 patients, p=0.025) and Category 5 (46 patients, p=0.021) TBIs using the worst CT scan obtained. CONCLUSIONS: The authors found a significant relationship between the dose of ICP, the worst Marshall CT score, and patient outcome, suggesting that the AUC method may be useful in refining and improving the treatment of ICP in patients with TBI.     

Clinical applications of intracranial pressure monitoring in traumatic brain injury

Background

Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI.

Methods

A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants.

Summary and conclusions

The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.     

Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis

Purpose  

To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment.