Acute Closed Head Injury Research Articles

Changes and significance of serum intestinal fatty acid binding protein in children with traumatic brain injury complicated with gastrointestinal dysfunction

Objective To study the changes and significance of serum intestinal fatty acid binding protein (IFABP) in children with traumatic brain injury(TBI) complicaled with acute gastrointestinal injury(AGI). Methods A total of 95 children suffering from TBI hospitalized in the PICU of the First Affiliated Hospital of Zhengzhou University from January 2017 to March 2018 were enrolled in the study.According to the modified Glasgow coma score combined with clinical classification criteria for acute closed head injury, the cases were devided into mild(43 cases), moderate (23 cases), and severe(29 cases). Children were graded according to AGI (AGI Ⅰ42 cases, AGI Ⅱ 30 cases, AGI Ⅲ 13 cases, and AGI Ⅳ 10 cases). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group.Blood samples were collected at the time of admission and on the 3rd day after admission.Serum IFABP was detected by ELISA, and the differences of serum IFABP concentrations were compared among groups.The correlations between IFABP with TBI classification and AGI grade were analyzed.The receiver operating characteristic (ROC) curve was drawn, and the predictive values of IFABP for the diagnosis of children with TBI complicated with AGI were evaluated. Results On the day of admission, the serum levels of IFABP in mild, moderate and severe brain injury group were significantly higher than that in control group (all P<0.01). And serum IFABP concentration gradually increased with the increase of brain injury (all P<0.01). Serum IFABP levels in children with AGI grade Ⅰto Ⅳ were significantly higher than those in control group (all P<0.01). The levels of serum IFABP also increased with the increase of AGI level (all P<0.01). The concentration of serum IFABP was positively correlated with the grade of TBI and AGI (rs=0.82, P<0.01; rs=0.70, P<0.01). In each group, the levels of serum IFABP on the 3rd day after admission were lower than those on admission (all P<0.01). The ROC curve analysis showed that serum IFABP was of high diagnostic value in children with TBI complicated with AGI, and the area under the ROC curve was 0.88.When the cutoff value of IFABP was 431.36 ng/L, the sensitivity and specificity were 71.61% and 90.00%, respectively. Conclusion Serum IFABP can be used as a sensitive indicator for the early diagnosis and disease assessment in children with TBI complicated with gastrointestinal dysfunction. Key words: Intestinal fatty acid binding protein; Traumatic brain injury; Gastrointestinal dysfunction; Children

Neuroimaging of brain trauma

The purpose of this review is to provide an update on advanced neuroimaging techniques in traumatic brain injury (TBI). We will focus this review on recent literature published within the last 18 months and the advanced neuroimaging techniques of perfusion imaging and diffusion tensor imaging (DTI). In the setting of a moderate or severe acute closed head injury (Glasgow Coma Scale <13), the most appropriate neuroimaging study is a noncontrast computed tomography (CT) scan. In the setting of mild TBI, the indication for neuroimaging can be determined using the New Orleans Criteria or Canadian CT Head Rules or National Emergency X-Ray Utilization Study-II clinical criteria. Two advanced neuroimaging techniques that are currently being researched in TBI include perfusion imaging and DTI. Perfusion CT has a higher sensitivity for detecting cerebral contusions than noncontrast CT examinations. DTI is a sensitive at detecting TBI at the group level (TBI-group versus control group), but there is insufficient evidence to suggest that DTI plays a clinical role for diagnosing mild TBI at the individual patient level. Future research in advanced neuroimaging techniques including perfusion imaging and DTI may improve the accuracy of the diagnosis and prognosis as well as improve the management of TBI.

Utility of Emergency Department Observation Units for Neurologically Intact Children With Head CT Abnormalities Secondary to Acute Closed Head Injury.

The aim of the study was to evaluate the utility of the emergency department observation unit (EDOU) for neurologically intact children with closed head injuries (CHIs) and computed tomography (CT) abnormalities. A retrospective cohort study of children aged 0 to 18 years with acute CHI, abnormal head CT, and a Glasgow Coma Scales score of 14 or higher admitted to the EDOU of a tertiary care children's hospital from 2007 to 2010. Children with multisystem trauma, nonaccidental trauma, and previous neurosurgical or coagulopathic conditions were excluded. Medical records were abstracted for demographic, clinical, and radiographic findings. Poor outcome was defined as death, intensive care unit admission, or medically/surgically treated increased intracranial pressure. Two hundred two children were included. Median (range) age was 14 (4 days-16 years) months; 51% were male. The most common CT findings were nondisplaced (136, 67%) or displaced (46, 23%) as well as skull fractures and subdural hematomas (38, 19%); 54 (27%) had less than 1 CT finding. The most common interventions included repeat CT (42, 21%), antiemetics (26, 13%), and pain medication (29, 14%). Eighty-nine percent were discharged in less than 24 hours. Inpatient admission from the EDOU occurred in 6 (3%); all were discharged in less than 3 days. One patient required additional intervention (corticosteroid therapy). She had a subdural hematoma, persistent vomiting, intractable headache, and a nonevolving CT. Neurologically intact patients on initial ED evaluation had a very low likelihood of requiring further interventions, irrespective of CT findings. Although prospective evidence is necessary, this supports reliance on clinical findings when evaluating a well-appearing child with an acute CHI.

Differentiating Concussion From Intracranial Pathology in Athletes.

Clinical Scenario: A cerebral concussion is a traumatically induced transient disturbance of brain function characterized by a complex pathophysiologic process and is classified as a subset of mild traumatic brain injury. The occurrence of intracranial lesions after sport-related head injury is relatively uncommon, but the possibility of serious intracranial injury (ICI) should be included in the differential diagnosis. ICIs are potentially life threatening and necessitate urgent medical management; therefore, prompt recognition and evaluation are critical to proper medical management. One of the primary objectives of the initial evaluation is to determine if the concussed athlete has an acute traumatic ICI. Athletic trainers must be able promptly recognize clinical signs and symptoms that will enable them to accurately differentiate between a concussion (ie, a closed head injury not associated with significant ICI) and an ICI. The identification of predictors of intracranial lesions is, however, relatively broad. Focused Clinical Question: Which clinical examination findings (ie, clinical signs and symptoms) indicate possible intracranial pathology in individuals with acute closed head injuries?

ACR Appropriateness Criteria Head Trauma

Neuroimaging plays an important role in the management of head trauma. Several guidelines have been published for identifying which patients can avoid neuroimaging. Noncontrast head CT is the most appropriate initial examination in patients with minor or mild acute closed head injury who require neuroimaging as well as patients with moderate to severe acute closed head injury. In short-term follow-up neuroimaging of acute traumatic brain injury, CT and MRI may have complementary roles. In subacute to chronic traumatic brain injury, MRI is the most appropriate initial examination, though CT may have a complementary role in select circumstances. Advanced neuroimaging techniques are areas of active research but are not considered routine clinical practice at this time. In suspected intracranial vascular injury, CT angiography or venography or MR angiography or venography is the most appropriate imaging study. In suspected posttraumatic cerebrospinal fluid leak, high-resolution noncontrast skull base CT is the most appropriate initial imaging study to identify the source, with cisternography reserved for problem solving.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Expression and Activation of EphA4 in the Human Brain After Traumatic Injury

Glial scars that consist predominantly of reactive astrocytes create a major barrier to neuronal regeneration after traumatic brain injury (TBI). In experimental TBI, Eph receptors and their ephrin ligands are upregulated on reactive astrocytes at injury sites and inhibit axonal regeneration, but very little is known about Eph receptors in the human brain after TBI. A better understanding of the functions of glial cells and their interactions with inflammatory cells and injured axons will allow the development of treatment strategies that may promote regeneration. We analyzed EphA4 expression and activation in postmortem brain tissue from 19 patients who died after acute closed head injury and had evidence of diffuse axonal injury and 8 controls. We also examined downstream pathways that are mediated by EphA4 in human astrocyte cell cultures. Our results indicate that, after TBI in humans, EphA4 expression is upregulated and is associated with reactive astrocytes. The expression was increased shortly after the injury and remained activated for several days. EphA4 activation induced under inflammatory conditions in vitro was inhibited using unclustered EphA4 ligand. These results suggest that blocking EphA4 activation may represent a therapeutic approach for TBI and other types of brain injuries in humans.

Plasma 24S-hydroxycholesterol and other oxysterols in acute closed head injury

Primary objective: To determine if plasma levels of 24S-hydroxycholesterol, the primary catabolite of brain cholesterol, provide a measure of axonal damage in acute brain trauma.Research design: Determination of plasma 24S-hydroxycholesterol in a series of persons admitted to an intensive care unit for treatment of closed head injury.Methods and procedures: Levels of 24-S-hydroxycholesterol, 27-hydroxycholesterol, lathosterol and total cholesterol were measured in peripheral blood from 38 persons from 14–55 years of age treated by craniotomy and ventriculostomy for intractable intracerebral hypertension. Severity of brain injury was estimated by the Glasgow Coma Scale (range = 3–13, median = 6 points) and overall injury by the Injury Severity Scale (range = 10–48, median = 29). All subjects were intubated and anaesthetized with intravenous propofol. Plasma sterol levels were compared with those of age-matched control subjects.Outcomes and results: There was no significant increase in plasma 24-S-hydroxycholesterol in subjects with head injury, but measures of peripheral cholesterol synthesis were markedly reduced as compared with values for age-matched normal control subjects.Conclusion: Plasma 24S-hydroxycholesterol levels do not change with severe closed head injury.

Over-Complete Discrete Wavelet Transformation of the Normal Auditory Brainstem Response Improves Prediction of Outcome following Severe Acute Closed Head Injury

Previous research has shown that complex statistical analysis (discriminant function analysis) of a ‘normal’ auditory brainstem response (ABR) result can improve this measure’s ability to predict subject outcome following severe acute closed head injury (ACHI). We hypothesized that adding the ABR’s time-frequency information to such an analysis would improve this predictive value even further. ‘Normal’ ABR results were sampled from 69 severe ACHI subjects (22 of whom died and 47 of whom lived) and their time-frequency information extracted using an over-complete discrete wavelet transformation (OCDWT). A series of logistic regression analyses then showed correct predictions of death and survival as follows: ABR measures only 72 and 89% (respectively), ABR OCDWT measures only 82 and 89% (respectively), and ABR and ABR OCDWT measures combined 86 and 93% (respectively). These results showed that the addition of time-frequency information can improve the ability of the ‘normal’ ABR result to predict outcome following severe ACHI.

Differences between CT and MR imaging in acute closed head injuries

The authors sought to compare the early MRI and CT findings in patients suffering closed head injury and to investigate the impact of imaging discrepancies on treatment management. A group of 62 patients with closed head injury and discrepancy between the apparently normal or with minor findings CT scan, and their neurological statuses were prospectively studied with MRI. Both CT and MRI were performed within the first 6 days after injury. According to the Glasgow Coma Scale (GCS), 46 patients suffered severe head injury (GCS≤8) and 16 patients moderate head injury (GCS 9–12). Four MRI sequences in various planes were applied using a 1T MR scanner. CT findings were present in 19 out of 62 patients and MRI findings in 61. Extra-axial lesions were found in 52 patients with MRI and in 16 with CT. Subarachnoid hemorrhage (SAH) was observed in 40 patients with MRI and in 12 with CT. Intraventricular hemorrhage was observed in 15 patients with MRI and in 6 with CT. Intraaxial lesions were demonstrated in 54 patients with MRI and in 17 patients with CT. MRI demonstrated diffuse axonal injuries (DAI) type I in 27 patients, type II in 32 and type III in 9 as opposed to 2, 1 and 0 patients with CT respectively. Subcortical gray matter injuries were shown in 12 patients with MRI and 4 with CT. Primary brainstem injuries were shown in 6 patients with MRI and 1 with CT. The FLAIR sequence alone, revealed 89% of the findings demonstrated by all 4 MRI sequences. No statistically significant difference on GCS versus the hemorrhagic and non-hemorrhagic nature of the lesions was found ( p>0.05). In conclusion, in closed head injury patients with minor or absent CT findings and severe or moderate injury, MRI findings are almost always present and include particularly DAI lesions and SAH. These differences in favor of MRI do not alter the treatment management.

Improving the prediction of outcome in severe acute closed head injury by using discriminant function analysis of normal auditory brainstem response latencies and amplitudes.

The auditory brainstem response (ABR) is a useful addition to standard medical measures for predicting outcome in patients with severe acute closed head injury (ACHI). Limiting this success, however, is the poor predictive value of a so-called "normal" ABR. In this study the authors used discriminant function analysis (DFA) of ABR Wave I, III, and V latencies and amplitudes to improve the predictive accuracy of the normal ABR, both as a single measure and in combination with other standard medical measures. The DFAs were conducted using the ABR and medical results in 68 patients with severe ACHI (30 who died [ACHI-died], and 38 who survived [ACHI-lived]) who presented with normal ABR responses in the neurosurgical intensive care unit of the authors' hospital in Johannesburg. All patients had undergone surgery to remove an intracranial hematoma. Correct predictions of outcome by ABR DFA measures were 83% for the ACHI-died group (48% at > or = 90% confidence level) and 87% for the ACHI-lived group (71% at > or = 90% confidence level); by medical DFA measures the correct predictions were 83% for the ACHI-died group (96% at >; or = 90% confidence level) and 95% for the ACHI-lived group (94% at > or = 90% confidence level); and by combined ABR and medical DFA measures correct predictions were 100% for the ACHI-died group (100% at > or = 90% confidence level) and 97% for the ACHI-lived group (100% at > or = 90% confidence level). The DFA of ABR Wave I, III, and V latencies and amplitudes improved the predictive ability of normal ABR results to rates similar to those obtained using DFA for the medical measures, although at lower confidence levels. The DFA of the combined ABR and medical measures improved correct predictions to rates significantly higher than for either of the measures on its own.

Coagulopathy in acute head injury-a study of its role as a prognostic indicator

The aim of this investigation was to determine the prognostic value of coagulation abnormalities in a defined subset of patients with acute head injury. Prothrombin time, accelerated partial thromboplastin time (APTT), thrombin clotting time, fibrinogen assay, platelet count, fibrin degradation products (FDP) were assayed in 204 patients with acute closed head injury. Their values were graded on a score 0-3 and the sum score for each patient regarded as the disseminated intravascular coagulation (DIC) score. Moderate to severe DIC scores were evident in 38% of the cohort. At least one parameter was abnormal in 71% of patients. The DIC score correlated inversely with the Glasgow coma score (GCS) ( p 0.0001). In the GCS 13-15 subset, FDP scores were significant predictors of poor outcome ( p 0.001). In the GCS 6-12 subset, the APTT score ( p 0.001), and DIC score ( p 0.0001) predicted an adverse outcome. The DIC scores were significantly abnormal in most patients who had a poor outcome, without evidence of adverse predictors on CT. Logistic regression analysis confirmed the independent predictive capacity of APTT, FDP and DIC scores when values for GCS were fixed. Abnormal haemostatic parameters may enhance the predictive ability in subsets of patients with acute head injury defined by clinical or CT predictors.

Dual task performance after focal cerebral lesions and closed head injuries

The aim of this study was to demonstrate that focal frontal lobe lesions and closed head injuries cause a deficit in the deliberate minimizing of dual task decrements that follow when two separate tasks should be done concurrently. In single tasks, subjects counted backwards and cancelled visual targets as quickly and accurately as possible on separate 1 min trials. In the dual task, they were required to do both tasks simultaneously, taking care that performance on neither task would be notably more impaired than on the other, as only the performance showing a larger percentage decrement from the corresponding single task performance was taken into account as the result of the test. Patients with acute closed head injury displayed more pronounced dual task decrement than the controls. This deficit was not secondary to inefficiency on the single tasks but was related to the depth of coma at admission, the acuteness of injury and age. Contrary to expectation, patients with focal frontal lobe lesions or patients with subacute closed head injury did not demonstrate abnormal dual task decrement.

SEVERE, ACUTE NEUROTRAUMA ALTERS PHENYTOIN (DPH) PHARMACOKINETICS (PK) IN CHILDREN. † 463

In adults following acute, severe neurotrauma the metabolism of DPH is increased and albumin concentrations decrease. We evaluated 10 prepubescent children (3-11 yrs) who had severe, acute closed head injury (GCS 3-6) to determine the PK of IV DPH. Patients received a loading dose (17.7 ± 3.3 mg/kg) followed by a maintenance dose of 6.8 ± 1.6 mg/kg/day. DPH serum concentration-time data were collected up to 10 days following injury. DPH and albumin concentrations were determined by FPIA and RID, respectively. The Michaelis-Menten (MM) PK model and a time-variant MM model were fit to the total and unbound DPH concentration-time data (ADAPT II™). Unbound concentration-time data were the most reliable since albumin decreased over time (p<0.001). Also, the unbound fraction of DPH was inversely correlated with albumin concentration (r=0.578, p<0.001). The DPH PK parameters (mean ± sd) are summarized as follows:Table V, volume; Km, MM constant; Kind, rate constant of induction; Vmax, maximal velocity †Time variant MM model[Vmax=Vmaxinitial + Vmaxinduced (l-e-kind•T) for time-variant MM model] The time-variant MM model provided a superior fit of the data in 8 patients with no difference between models in 2 patients. In view of the Vmax for DPH reported for normal, non-stressed children (ie. 9.5-11 mg/kg/day), our PK data demonstrate that severe, acute neurotrauma markedly alters the metabolism of this drug. Specifically, a previously unrecognized rapid inhibition of metabolism (ie. mean Vmax = 0.11 mg/kg/day) occurs during the first hours post injury. This is followed by an induction of clearance as reflected by a Vmax (20.8 mg/kg/day) which is approximately 2 fold higher than “normal” values by 10 days post injury. These changes in DPH metabolism are associated with neurotrauma, and explain to a great degree, the variable dose requirements for DPH in these patients.

Detection of cerebral venous desaturation by continuous jugular bulb oximetry following acute neurotrauma.

A prospective observational study was performed to assess the reliability of fibreoptic oximetric catheters and to identify the incidence and causes of jugular bulb oxygen desaturation in patients with acute closed head injury. There were twenty-five patients (30 +/- 16 years) with GCS < or = 8 in this study. Jugular bulb oximetry, mean arterial pressure, intracranial pressure, end-tidal CO2 and pulse oximetry were monitored continuously. Catheter calibration against a laboratory oximeter was performed post insertion and thereafter eight-hourly. Cerebral venous desaturation was defined as a jugular bulb oxygen saturation < 55% of > 10 minutes duration. There was a poor correlation for the first in vivo calibration (r2 = 0.602, P < 0.001, n = 25). Thereafter a close correlation between jugular bulb catheter and oximetry values was demonstrated (r2 = 0.868, P < 0.001, n = 205). Forty-two episodes of jugular bulb oxygen desaturation of 88 minutes mean duration (range 10 to 555) were observed. 83% occurred within 48 hours following injury. Hypocapnia was associated in 45% of episodes; hypoperfusion in 22%; raised ICP in 9% and a combination of the above in 24%. Validation with a laboratory oximeter is essential prior to continuous jugular bulb oximetry. Sustained episodes of cerebral venous desaturation are frequent within the first 48 hours following acute head injury. Factors such as hypocapnia and cerebral hypoperfusion that primarily reduce cerebral blood flow are predominant.

Comparison between acute- and delayed-onset depression following traumatic brain injury

Sixty-six patients admitted for the treatment of acute closed head injury were assessed for the presence of mood disorders during the in-hospital period and at 3-, 6-, and 12-month follow-ups. Diagnosis was made using a structured psychiatric interview and DSM-III criteria. A total of 28 patients had major depression at some time during the study: 17 had acute-onset depression and 11 had delayed-onset depression. Acute-onset depressions are related to lesion location and may have their etiology in biological responses of the injured brain, whereas delayed depressions may be mediated by psychosocial factors, suggesting psychological reaction as a possible mechanism.

47. Is 99Tcm-HMPAO brain SPET of prognostic value in acute closed head injury?

47. Is 99Tcm-HMPAO brain SPET of prognostic value in acute closed head injury?

Role of auditory brainstem responses in the prognosis of coma due to severe acute closed head injury

Role of auditory brainstem responses in the prognosis of coma due to severe acute closed head injury

Multimodality evoked potential testing in acute mild closed head injury.

Multimodality evoked potential (MEP) testing, including brainstem auditory, visual, and somatosensory evoked potentials, have been reported to be useful in predicting outcome in severe closed head injury. Brainstem auditory evoked potentials have been demonstrated to be abnormal in 10% to 40% of acute mild head injury. A prospective study of 18 patients with mild closed head injury was undertaken to determine the usefulness of MEP screening within two weeks of the acute event. Long latency event-related potentials (P300s), in response to auditory stimuli with an oddball paradigm, were included in the screening. The subjects had several symptoms consistent with the postconcussive syndrome at the time of the evoked potential testing. Only one patient had an abnormal evoked potential response (greater than three standard deviations from the mean) from all the testing done. The standard methods of MEP testing were insensitive to quantifying the possible physiologic changes that are associated with memory deficits, lethargy, and emotional irritability after mild closed head injury.

Closed Head Injuries in Athletes

Nervous system sports-related injuries constitute a major source of serious morbidity and mortality in athletes. In particular, acute closed head injuries account for some 6000 potentially preventable deaths and literally millions of episodes of less severe head injuries each year. The long-term significance of chronic head injuries resulting from repetitive blows to the brain is only now being fully appreciated. Similarly subtle neuropsychological changes are being increasingly recognized resulting from milder head injuries. Although head injuries are almost inevitable and unavoidable sequelae of most contact and competitive sports, much can and should be done to reduce the serious acute and chronic neurologic complications inherent in these activities. Prevention of catastrophic sports injuries by careful preseason examination, education, training, and conditioning, and ongoing counseling of the athlete is of paramount importance. The use of carefully fitted protective headgear, and avoidance of maneuvers that may directly result in serious head injuries are also key. The immediate evaluation, evacuation, and triage of the injured athlete must take place carefully and expeditiously. Skillful, experienced, and compassionate definitive care must then ensue. In the long term, the complications and analysis of accurate statistical data on the magnitude of sports injuries in general, and nervous system involvement in particular, must be studied. Presently, only a few sports have accumulated such data, such as in the National Football Head and Neck Injury Registry. In the final analysis, it is the cooperative responsibility of the medical and athletic communities to strive to reduce these tragic injuries.

Auditory brain stem responses (ABR) in patients with acute severe closed head injuries. The use of a grading system.

ABR were recorded in 68 cases suffering from severe acute closed head injuries. Abnormal recordings were observed in 60 per cent of patients, and the abnormalities ranged from prolongation of the interpeak latency intervals to complete absence of auditory brain stem activity. Based on the results obtained, a grading system was developed and correlated with the neurological outcome. It was concluded that ABR is a useful diagnostic and prognostic tool which can provide valuable information about the function of the brain stem in these patients. Inclusion of ABR studies in the head injury management protocol is strongly recommended.