Case of a Hypertensive Crisis in Diffuse Axonal Injury.

This case considers underdosing of analgesics as a prime contributor to hypertension in diffuse axonal injury (DAI) patients who are being mechanically ventilated. In the air medical environment, obtunded patients' hemodynamic parameters are the primary tools available in diagnosing complex disorders such as an acute rise in intracranial pressure (ICP) when invasive ICP monitoring is not available. Therefore, differential diagnoses must follow a continuum, from most severe to least, in order to deal with sudden-onset hypertension rapidly. Not until all critical differentials have been eliminated is analgesia considered. Mimicking the signs of ICP, a compensatory rise in the mean arterial pressure (MAP) is displayed in an acute pain response for mechanically ventilated patients. Therefore, poor analgesic coverage should be considered early in DAI patients who are being ventilated, especially when an increased metabolic drive may be occurring, forcing the therapeutic dosing intervals to be increased. This patient was transferred from Europe back to North America via a fixed wing aircraft, a 16-hour transport time.

Does progesterone improve outcome in diffuse axonal injury?

BACKGROUND AND OBJECTIVE: The benefits of progesterone have been demonstrated in the animal models of traumatic brain injury (TBI). However, the results of clinical studies are conflicting. Considering the heterogenic nature of TBI, the effect of progesterone in patients with diffuse axonal injury (DAI) was investigated in a clinical trial. METHODS: In this study, 48 patients with DAI and Glasgow Coma Scale of 3-12, admitted within 4 hours after injury, were randomly assigned to the progesterone or control group. The dose of progesterone administration was 1 mg kg-1 per 12 hours for 5 days. The effect of progesterone was investigated using extended-Glasgow Outcome Scale (GOS-E), functional independence measure (FIM) scores and also mortality within the follow-up period. RESULTS: The progesterone group exhibited higher GOS-E and FIM scores in comparison to the control group at 6 months post-injury (p < 0.01 and p < 0.05, respectively). Mortality was also found in the control group (p < 0.05). The adverse events attributed to the progesterone administration were not found throughout the study. CONCLUSIONS: Findings of this study suggest that progesterone may be neuroprotective in patients with DAI. However, large clinical trials are needed to assess progesterone as a promising drug in DAI.

Subarachnoid hemorrhage prevalence and its association with short-term outcome in pediatric severe traumatic brain injury.

BACKGROUND: Subarachnoid hemorrhage (SAH) is an independent prognostic indicator of outcome in adult severe traumatic brain injury (sTBI). There is a paucity of investigations on SAH in pediatric sTBI. The goal of this study was to determine in pediatric sTBI patients SAH prevalence, associated factors, and its relationship to short-term outcome. METHODS: We retrospectively analyzed 171 sTBI patients (pre-sedation GCS ≤8 and head MAIS ≥4) who underwent CT head imaging within the first 24 h of hospital admission. Data were analyzed with both univariate and multivariate techniques. RESULTS: SAH was found in 42 % of sTBI patients (n = 71/171), and it was more frequently associated with skull fractures, cerebral edema, diffuse axonal injury, contusion, and intraventricular hemorrhage (p < 0.05). Patients with SAH had higher Injury Severity Scores (p = 0.032) and a greater frequency of fixed pupil(s) on admission (p = 0.001). There were no significant differences in etiologies between sTBI patients with and without SAH. Worse disposition occurred in sTBI patients with SAH, including increased mortality (p = 0.009), increased episodes of central diabetes insipidus (p = 0.002), greater infection rates (p = 0.002), and fewer ventilator-free days (p = 0.001). In sTBI survivors, SAH was associated with increased lengths of stay (p < 0.001) and a higher level of care required on discharge (p = 0.004). Despite evidence that SAH is linked to poorer outcomes on univariate analyses, multivariate analysis failed to demonstrate an independent association between SAH and mortality (p = 0.969). CONCLUSION: SAH was present in almost half of pediatric sTBI patients, and it was indicative of TBI severity and a higher level of care on discharge. SAH in pediatric patients was not independently associated with increased risk of mortality.

Predicting Outcomes in Patients with Diffuse Axonal Injury: External Validation of the Widely Used Prognostic Instruments.

AIM: Accurate prognosis of diffuse axonal injury (DAI) is important in directing clinical care, allocating resources appropriately, and communicating with families and surrogate decision-makers. METHODS: A study was conducted on patients with clinical DAI due to closed-head traumatic brain injury treated at a trauma center in Brazil from July 2013 to September 2015.  The objective efficacy of the Glasgow Coma Scale (GCS), Trauma and Injury Severity Scoring system (TRISS), New Trauma and Injury Severity Scoring system (NTRISS), Abbreviated Injury Scale (AIS)/head, Corticosteroid Randomization After Significant Head Injury (CRASH), and International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) models in the prediction of mortality at 14 days and 6-months and unfavorable outcomes at 6 months was tested. RESULTS: Our cohort comprised 95 prospectively recruited adults (85 males, 10 females, mean age 30.3 ± 10.9 years) admitted with DAI. Model efficacy was assessed through discrimination (area under the curve [AUC]), and Cox calibration. The AIS/head, TRISS, NTRISS, CRASH, and IMPACT models were able to discriminate both mortality and unfavorable outcomes (AUC 0.78-0.87). IMPACT models resulted in a statistically perfect calibration for both 6-month outcome variables; mortality and 6-month unfavorable outcome. Calibration also revealed that TRISS, NTRISS, and CRASH systematically overpredicted both outcomes, except for 6-month unfavorable outcome with TRISS. CONCLUSIONS: The results of this study suggest that TRISS, NTRISS, CRASH, and IMPACT models satisfactorily discriminate between mortality and unfavorable outcomes. However, only the TRISS and IMPACT models showed accurate calibration when predicting 6-month unfavorable outcome.

Genu of corpus callosum in diffuse axonal injury induces a worse 1-year outcome in patients with traumatic brain injury.

BACKGROUND: Previous studies have shown a relationship between diffuse axonal injury (DAI) and unfavorable clinical outcome in patients with traumatic brain injury (TBI), but it remains unclear whether the type of DAI lesion influences outcome after TBI. The aim of the present study was to investigate whether 1-year outcome after TBI differed between patients with different types of lesions. METHODS: A retrospective, single-institution study involving 261 patients with TBI was carried out between April 2003 and December 2009. Outcome was measured using the Glasgow Outcome Scale (GOS) 1 year after TBI. DAI lesions occurred in the lobar region, corpus callosum (CC), and brainstem. CC lesions were subdivided into three types: genu, body, and splenium. Univariate and multivariate logistic regression analyses were performed to evaluate the relationships between clinical characteristics and outcome for each type of DAI lesion and each type of CC lesion in patients with TBI. FINDINGS: Sixty-nine patients had DAI lesions: 34 in the lobar region, 30 in the CC, and five in the brainstem. Of the 30 patients with CC lesions, ten each were found in the genu, body, and splenium. Each DAI, CC, and genu lesion was significantly associated with unfavorable outcome 1 year after TBI by multivariate analysis using variables that were significantly associated with unfavorable outcome as determined by univariate analysis after adjustment for age. CONCLUSIONS: CC lesions, especially those in the genu, were related to unfavorable 1-year outcome in patients with TBI.

Severe traumatic brain injury: outcome in patients with diffuse axonal injury managed conservatively in Hospital Sultanah Aminah, Johor Bahru--an observational study.

Patients with isolated severe head injury with diffuse axonal injury and without any surgical lesion may be treated safely without cerebral resuscitation and intracranial pressure (ICP) monitoring. Seventy two patients were divided into three groups of patients receiving treatment based on ICP-CPP-targeted, or conservative methods either with or without ventilation support. The characteristics of these three groups were compared based on age, gender, Glasgow Coma Scale (GCS), pupillary reaction to light, computerized tomography scanning according to the Marshall classification, duration of intensive care unit (ICU) stays, Glasgow Outcome Score (GOS) and possible complications. There were higher risk of mortality (p < 0.001), worse GCS improvement upon discharge (p < 0.001) and longer ICU stays (p = 0.016) in ICP group compared to Intubation group. There were no significant statistical differences of GOS at 3rd and 6th months between all three groups.

Early predictors of unfavourable outcome in subjects with moderate head injury in the emergency department.

BACKGROUND: Subjects with moderate head injury are a particular challenge for the emergency physician. They represent a heterogeneous population of subjects with large variability in injury severity, clinical course and outcome. We aimed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department (ED) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre. PATIENTS AND METHODS: We reviewed, prospectively, 12,675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury. A total of 309 cases (2.4%) with an admission Glasgow Coma Scale (GCS) 9-13 were identified as having moderate head injury. The main outcome measure was an unfavourable outcome at 6 months after injury. The predictive value of a model based on main entry variables was evaluated by logistic regression analysis. FINDINGS: 64.7% of subjects had a computed tomographic scan that was positive for intracranial injury, 16.5% needed a neurosurgical intervention, 14.6% had an unfavourable outcome at 6 months (death, permanent vegetative state, permanent severe disability). Six variables (basal skull fracture, subarachnoid haemorrhage, coagulopathy, subdural haematoma, modified Marshall category and GCS) predicted an unfavourable outcome at 6 months. This combination of variables predicts the 6-month outcome with high sensitivity (95.6%) and specificity (86.0%). INTERPRETATION: A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months, when applied to subjects admitted to an ED of a General Hospital with moderate head injury.

Value of repeat cranial computed tomography in pediatric patients sustaining moderate to severe traumatic brain injury.

BACKGROUND: Repeat head computed tomography (CT) is standard practice for traumatic brain injury (TBI) at many centers. The few studies available in children remain unclear over the value of repeat CT within 24 hours to 48 hours of lesion in such patients. The purpose of the present study was to assess the value of repeat cranial CT in children presenting moderate or severe TBI. METHODS: A retrospective study performed within a pediatric intensive care unit between January 2000 and December 2006. All patients with moderate and severe TBI who survived the first 24 hours after admission were included. Clinical data collected included age, lesion mechanism, time between first and second CTs, disease severity score at admission, and Glasgow Coma Scale (GCS) both at admission and day of repeat CT. RESULTS: A total of 63 children were assessed whose mean age was 72 months (48-112). The time between the first and the second CT scans averaged 25.78 hours +/- 13.75 hours (range, 6-48 hours). The reasons for ordering repeat CT scans were divided as follows: follow-up (78%), neurologic deterioration (20.4%), and increased intracranial pressure (1.6%). The change on the follow-up CT scan was compared with the GCS score. The GCS score was improved in 66.6% of patients, remained the same in 15.9%, and worsened in 17.5%. The appearance on the CT scans was better, the same or worse in 41.3%, 34.9%, and 23.8% of patients, respectively. There was a significant association between GCS and changes in findings on repeat CT (OR = 34.5, confidence interval [5.98-199.04], p = 0.000009). The positive and negative predictive values were 82% and 89%, respectively. One patient with a worsened GCS required surgical intervention based on the repeat CT scan. CONCLUSION: An unchanged or improving neurologic examination in children sustaining moderate or severe TBI who are appropriately monitored may be adequate to exclude the possibility of neurosurgical intervention and, hence, repeat head CT scan.

Prognosis of diffuse axonal injury with traumatic brain injury.

BACKGROUND: Determine the prognostic impact of magnetic resonance imaging (MRI)-defined diffuse axonal injury (DAI) after traumatic brain injury (TBI) on functional outcomes, quality of life, and 3-year mortality. METHODS: This retrospective single center cohort included adult trauma patients (age > 17 years) admitted from 2006 to 2012 with TBI. Inclusion criteria were positive head computed tomography with brain MRI within 2 weeks of admission. Exclusion criteria included penetrating TBI or prior neurologic condition. Separate ordinal logistic models assessed DAI's prognostic value for the following scores: (1) hospital-discharge Functional Independence Measure, (2) long-term Glasgow Outcome Scale-Extended, and (3) long-term Quality of Life after Brain Injury-Overall Scale. Cox proportional hazards modeling assessed DAI's prognostic value for 3-year survival. Covariates included age, sex, race, insurance status, Injury Severity Score, admission Glasgow Coma Scale Score, Marshall Head computed tomography Class, clinical DAI on MRI (Y/N), research-level anatomic DAI Grades I-III (I, cortical; II, corpus callosum; III, brainstem), ventilator days, time to follow commands, and time to long-term follow-up (for logistic models). RESULTS: Eligibility criteria was met by 311 patients, who had a median age of 40 years (interquartile range [IQR], 23-57 years), Injury Severity Score of 29 (IQR, 22-38), intensive care unit stay of 6 days (IQR, 2-11 days), and follow-up of 5 years (IQR, 3-6 years). Clinical DAI was present on 47% of MRIs. Among 300 readable MRIs, 56% of MRIs had anatomic DAI (25% Grade I, 18% Grade II, 13% Grade III). On regression, only clinical (not anatomic) DAI was predictive of a lower Functional Independence Measure score (odds ratio, 2.5; 95% confidence interval, 1.28-4.76], p = 0.007). Neither clinical nor anatomic DAI were related to survival, Glasgow Outcome Scale-Extended, or Quality of Life after Brain Injury-Overall Scale scores. CONCLUSION: In this longitudinal cohort, clinical evidence of DAI on MRI may only be useful for predicting short-term in-hospital functional outcome. Given no association of DAI and long-term TBI outcomes, providers should be cautious in attributing DAI to future neurologic function, quality of life, and/or survival. LEVEL OF EVIDENCE: Epidemiological, level III; Therapeutic, level IV.

"Don't lose hope early": Hemorrhagic diffuse axonal injury on head computed tomography is not associated with poor outcome in moderate to severe traumatic brain injury patients.

BACKGROUND: Diffuse axonal injury (DAI) on magnetic resonance imaging has been associated with poor functional outcome after moderate-severe traumatic brain injury (msTBI). Yet, DAI assessment with highly sensitive magnetic resonance imaging techniques is unfeasible in the acute trauma setting, and computed tomography (CT) remains the key diagnostic modality despite its lower sensitivity. We sought to determine whether CT-defined hemorrhagic DAI (hDAI) is associated with discharge and favorable 3- and 12-month functional outcome (Glasgow Coma Scale score ≥4) after msTBI. METHODS: We analyzed 361 msTBI patients from the single-center longitudinal Outcome Prognostication in Traumatic Brain Injury study collected over 6 years (November 2009 to November 2015) with prospective outcome assessments at 3 months and 12 months. Patients with microhemorrhages on CT were designated "CT-hDAI-positive" and those without as "CT-hDAI-negative." For secondary analyses "CT-hDAI-positive" was stratified into two phenotypes according to presence ("associated") versus absence ("predominant") of concomitant large acute traumatic lesions to determine whether presence versus absence of additional focal mass lesions portends a different prognosis. RESULTS: Seventy (19%) patients were CT-hDAI-positive (n = 36 predominant; n = 34 associated hDAI). In univariate analyses, CT-hDAI-positive status was associated with discharge survival (p = 0.004) and favorable outcome at 3 months (p = 0.003) and 12 months (p = 0.005). After multivariable adjustment, CT-hDAI positivity was no longer associated with discharge survival and functional outcome (all ps > 0.05). Stratified by hDAI phenotype, predominant hDAI patients had worse trauma severity, longer intensive care unit stays, and more systemic medical complications. Predominant hDAI, but not associated hDAI, was an independent predictor of discharge survival (adjusted odds ratio, 24.7; 95% confidence interval [CI], 3.2-192.6; p = 0.002) and favorable 12-month outcome (adjusted odds ratio, 4.7; 95% CI, 1.5-15.2; p = 0.01). Sensitivity analyses using Cox regression confirmed this finding for 1-year survival (adjusted hazard ratio, 5.6; 95% CI, 1.3-23; p = 0.048). CONCLUSION: The CT-defined hDAI was not an independent predictor of unfavorable short- and long-term outcomes and should not be used for acute prognostication in msTBI patients. Predominant hDAI patients had good clinical outcomes when supported to intensive care unit discharge and beyond. LEVEL OF EVIDENCE: Prognostic study, level III.

Brain damage and axonal injury in a Scottish cohort of neonatal deaths.

Despite the clinical and medicolegal significance attached to perinatal asphyxia, the neuropathological basis of this condition remains obscure. There are very few studies in the literature which correlate the pathological findings in neonatal brains with detailed epidemiological data, and none which are population based. In a Scotland-wide study of neonatal deaths, 70 brains have been examined. On the basis of glial and macrophage reactions, we previously identified infants with putative antepartum brain damage in this cohort and have related these reactions to signs of birth asphyxia. The present study explores the extent of neuronal/axonal injury in these infants since this is likely to be the basis for neurological deficits in surviving infants. We have also investigated these brains for beta-amyloid precursor protein (betaAPP) positivity to determine whether this is a useful marker of neuronal injury in neonates. Neuronal eosinophilia and karyorrhexes were detected in 43% and 27% of the cohort, respectively; maximally in the subiculum and ventral pons, but often present elsewhere. White matter damage was detected in 24% of cases but without classic cystic lesions of periventricular leucomalacia. betaAPP positivity was present in neuronal soma in 52% of cases and, in axons, in 27% of cases, and was seen from as early as 25-weeks gestation. Axonal bulbs were clearly delineated by betaAPP positivity and were usually located in the cerebral white matter and internal capsule, and infrequently in the brain stem. Although white matter damage and betaAPP axonal positivity were often detected in the same cases (P = 0.034), these features also occurred independently of each other. Both neuronal karyorrhexes and white matter betaAPP positivity were significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both betaAPP and glial fibrillary acidic protein proved useful in detecting neuropathological features which escaped detection on routine examination, particularly in preterm infants. The presence together of recent and older damage in individual brains suggests that there is an ongoing neuronal response to cerebral insults. We find that betaAPP is a useful marker of white matter damage in the neonatal brain. Immunopositivity for betaAPP in these circumstances is not attributable to inflicted or accidental trauma. While birth-related trauma cannot be ruled out, hypoxia/ischaemia is a likely cause in these infants. However, the exact pathogenesis of neuronal/axonal injury in the neonatal brain remains unclear.

Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury.

BACKGROUND AND PURPOSE: Multiple biomarkers are used to quantify the severity of traumatic brain injury (TBI) and to predict outcome. Few are satisfactory. CT and conventional MR imaging underestimate injury and correlate poorly with outcome. New MR imaging techniques, including diffusion tensor imaging (DTI), can provide information about brain ultrastructure by quantifying isotropic and anisotropic water diffusion. Our objective was to determine if changes in anisotropic diffusion in TBI correlate with acute Glasgow coma scale (GCS) and/or Rankin scores at discharge. METHODS: Twenty patients (15 male, five Female; mean age, 31 years) were evaluated. Apparent diffusion coefficients (ADCs) and fractional anisotropy (FA) values were measured at multiple locations and correlated with clinical scores. Results were compared with those of 15 healthy control subjects. RESULTS: ADC values were significantly reduced within the splenium (Delta18%, P =.001). FA values were significantly reduced in the internal capsule (Delta14%; P <.001) and splenium (Delta16%; P =.002). FA values were significantly correlated with GCS (r = 0.65-0.74; P <.001) and Rankin (r = 0.68-0.71; P <.001) scores for the internal capsule and splenium. The correlation between FA and clinical markers was better than for the corresponding ADC values. No correlation was found between ADC of the internal capsule and GCS/Rankin scores. CONCLUSION: DTI reveals changes in the white matter that are correlated with both acute GCS and Rankin scores at discharge. DTI may be a valuable biomarker for the severity of tissue injury and a predictor for outcome.

Diffuse axonal injury with or without an evacuated intracranial hematoma in head injured patients. Are they different lesions?

The general classification of head injury proposed by Marshall et al., based on admission CT scan findings, might mask a group of patients who have Diffuse Brain Injury (DI) in addition to intracranial haematomas. The aim of this study was to assess possible differences in outcome with respect to the level of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) between a group of patients with DI: III-IV (Marshall's classification) after the evacuation of an intracranial haematoma (group A) and another group with DI: III-IV in the absence of a mass lesion (group B). We prospectively studied 129 patients with isolated and closed severe head injury (GCS < 9). In group A (n = 61), the median percentage of hours with ICP > 20 mmHg and CPP < 70 mmHg was 42.8 and 18, respectively and 17 (28%) survived with GOS 4-5. In group B (n = 68), median values of 20 and 5.5 hours were obtained for ICP > 20 and CPP < 70 respectively, whilst 39 (57.3%) survived with favourable outcomes. When we analysed the effects of the DI: III-IV in both groups of patients, we found that the differences in percentage of time with ICP > 20 and CPP < 70 were statistically significant (p < 0.01) and patients in group A had a higher morbidity and mortality (p < 0.05). This study has demonstrated that the levels of ICP, morbidity and mortality in patients with DI: III-IV and an evacuated mass lesion were higher than in patients with DI: III-IV without a mass lesion.

The conformation of the brain plays an important role in the distribution of diffuse axonal injury in fatal road traffic accident.

OBJECTIVE: A study was made of the brain lesions in 120 random victims of fatal road traffic accidents to determine the frequency and topographic distribution of diffuse axonal damage (DAI) in relation to the midline brain structures. METHOD: The identification of axons was carried out with a mouse antibody anti-neurofilament proteins 70-, 160-, and 210-kD. RESULTS: DAI was identified in 96 (80%) brains and classified as Grade 1 in 21.9%, as Grade 2 in 51%, and as Grade 3 in 27.1% of the patients. In spite of the diffuse distribution that is characteristic of DAI, damage occurred preferentially in the interhemispheric formations (corpus callosum and fornix) and rostral portion of the brainstem, usually to one side of the midline. CONCLUSION: From a mechanical point of view, the interhemispheric formations and the rostral portion of the brainstem act as fixating structures for the cerebral hemispheres during rotational acceleration of the head. It is known that the motion of the cerebral hemispheres is delayed at the points of fixation, where greater stress would be produced, particularly on the side subjected to greater displacement. The frequent involvement by DAI of deep, center-medial brain structures, usually to one side of the midline, supports the mechanism proposed above.

Traumatic brain injury, axonal injury and shaking in New Zealand sea lion pups.

Trauma is a common cause of death in neonatal New Zealand sea lion pups, and subadult male sea lions have been observed picking up and violently shaking some pups. In humans, axonal injury is a common result of traumatic brain injury, and can be due to direct trauma to axons or to ischaemic damage secondary to trauma. 'Shaken baby syndrome', which has been described in human infants, is characterised by retinal and intracranial subdural haemorrhages, and has been associated with axonal injury to the brain, spinal cord and optic nerve. This study identifies mechanisms of traumatic brain injury in New Zealand sea lion pups, including impact injuries and shaking-type injuries, and identifies gross lesions of head trauma in 22/36 sea lion pups found dead at a breeding site in the Auckland Islands. Despite the high frequency of such gross lesions, only three of the pups had died of traumatic brain injury. Observational studies confirmed that shaking of pups occurred, but none were shown to die as a direct result of these shaking events. Axonal injury was evaluated in all 36 pup brains using ß-amyloid precursor protein immunohistochemistry. Immunoreactive axons were present in the brains of all pups examined including seven with vascular axonal injury and two with diffuse axonal injury, but the severity and pattern of injury was not reliably associated with death due to traumatic brain injury. No dead pups had the typical combination of gross lesions and immunohistochemical findings that would conform to descriptions of 'shaken baby syndrome'. Axonal injury was present in the optic nerves of most pups, irrespective of cause of death, but was associated with ischaemia rather than trauma.

Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma.

OBJECTIVE: Severe traumatic brain injury (TBI) has a major role in mortality rate among the other types of trauma. The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with acute severe TBI. METHODS: A total of 76 patients who had arrived within 8h of injury with a Glasgow Coma Score≤8 were enrolled in the study. In a randomized style 38 received progesterone (1mg/kg per 12h for 5 days) and 38 did not. RESULTS: There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03). CONCLUSION: The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5≤GCS≤8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.

Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury.

BACKGROUND: Diffuse axonal injury (DAI) is a common type of traumatic brain injury, mostly associated with mild changes on computed tomography (CT) scan. Serum biomarkers might be used in the diagnosis and prognosis of this injury type. Our purpose was to determine temporal profile and predictive values of serum concentrations of protein S100BB and neuron-specific enolase (NSE) after DAI. METHODS: Twenty-eight isolated severe DAI patients (Glasgow Coma Scale score ≤ 8) with normal CT were enrolled in the study. Serum levels of S100BB and NSE were determined at 6 hours, 24 hours, 48 hours, and 72 hours after injury, using enzyme-linked immunosorbent assay. Clinical outcome variables of DAI comprised survival at discharge and Glasgow Outcome scale (GOS) after 3 months and also 2 years. RESULTS: S100BB concentration was maximum in 6 hours after injury (median = 280.75 ng/L) followed by a quick drop. Its value was significantly higher on third day in patients with unfavorable outcome (GOS score = 1-3) versus favorable outcome (GOS score = 4, 5) (p < 0.0001). The values of NSE had mild changes during 3 days; however, these measured values at 72 hours after trauma manifested higher in unfavorable outcome (p < 0.05). CONCLUSIONS: Increased serum concentrations of NSE and S100BB within first 3 days after DAI are associated with poor outcome despite mild CT findings. S100BB level at 72 hours after injury can predict late outcome in DAI patients. LEVEL OF EVIDENCE: Prognostic study, level III.

Extradural haematoma and diffuse axonal injury in victims of fatal road traffic accidents.

Seven cases of victims of road traffic accidents with extradural haematoma (EH) and diffuse axonal injury (DAI) are reported. Such cases are part of a total of 120 victims of fatal road traffic accidents that were subjected to pathological study. The association of the two lesions occurred in 5.8% of the patients and all cases of EH were associated with DAI. The latter explains the immediate coma (absence of lucid interval) and the grave prognosis for all seven patients. It was noted that EH is relatively infrequent in road traffic accidents, but in such cases it is more severe since it is frequently associated with DAI and immediate coma.

Incidence of axonal injury in human brain tissue.

Diffuse axonal injury (DAI) is considered to be the morphological correlate of traumatic brain injury as seen in acceleration/deceleration trauma and is believed to be the main cause for a poor clinical outcome in the absence of detectable intracranial lesions. To estimate the overall incidence of DAI, and since most changes are only seen microscopically to rule out whether there is a high number of undetected cases, 450 non-selected human brains were examined. Samples from two brain areas (pons and cerebrum) were immunostained for beta-amyloid-precursor-protein (betaAPP), and axonal damage was assessed microscopically. Axonal injury was detected in 12% of all cases, but only one third had a history of traumatic brain injury. The majority of the positive cases were associated with drug intoxication, chiefly due to opiates. betaAPP staining was positive in both pons and cerebrum to a much higher extent in intoxication than in trauma cases; the latter showing axonal damage mainly in the pons area. This may reflect a more generalized pathomechanism in the intoxication group as compared to more biomechanical mechanisms in the trauma group. The findings also show that various causes may produce diffuse axonal injury and suggest that traumatic brain injury is not the only and probably not even the main cause of the observed neuropathological changes. A correlation between axonal damage and age-related processes could not be shown.