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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.

Accidents, Traffic↗

[Significance of magnetic resonance imaging in diffuse axonal injury].

Advantages of magnetic resonance imaging (MRI) to computed tomography (CT) on a diagnosis of diffuse axonal injury (DAI) were discussed. Sixteen patients diagnosed as DAI defined by the criteria of Gennarelli were studied with CT and MRI. Lesions were demonstrated as high intensity areas on MRI of T2 weighted imaging (SE 2000/111) in all of the patients. These lesions were located only in a cerebral white matter in the cases of mild DAI, whereas in the cases of severe DAI located in a basal ganglia, corpus callosum, dorsal part of the brain stem as well as in the cerebral white matter. As for the findings of CT, these parenchymal lesions were not visualized in nine cases including six cases without any pathological findings. Our series suggest that MRI is superior to CT on the diagnosis of DAI and provides some information to evaluate the severity of DAI.

Adolescent↗

Acute subdural hematoma and diffuse axonal injury in fatal road traffic accident victims: a clinico-pathological study of 15 patients.

OBJECTIVE: Although acute subdural hematoma (ASDH) and diffuse axonal injury (DAI) are commonly associated in victims of head injury due to road traffic accidents, there are only two clinico-pathological studies of this association. We report a clinical and pathological study of 15 patients with ASDH associated with DAI. METHOD: The patients were victims of road traffic accidents and were randomly chosen. The state of consciousness on hospital admission was evaluated by the Glasgow coma scale. For the identification of axons the histological sections of the brain were stained with anti-neurofilament proteins. RESULTS: Twelve of the 15 patients were admitted to hospital in a state of coma; in three patients, the level of consciousness was not evaluated, as they died before hospital admission. CONCLUSION: The poorer prognosis in patients with ASDH who lapse into coma immediately after sustaining a head injury, as described by several authors, can be explained by the almost constant association between ASDH and DAI in victims of fatal road traffic accidents.

Accidents, Traffic↗

The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.

The immunolocalization of tumor necrosis factor-alpha (TNF alpha) after diffuse axonal injury (DAI) is demonstrated using a midline fluid percussion rat model (moderate brain injury of 1000 mm Hg was generated) and the effects of TNF alpha on the axolemmal permeability using horseradish peroxidase as a tracer. In addition, the accumulation of beta-amyloid precursor protein (beta-APP) was investigated, which has recently been shown to be a reliable marker for the diagnosis of DAI in cases with fatal head injury. TNF alpha levels in brain tissues from the impact site and the cortex including the corpus callosum, gradually increased during the first 1 h, rose to a maximal elevation at 3 h, gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15 min after impact but rapidly recovered and that 1 h after impact, secondary axonal damage occurred in the corpus callosum and the brain stem. By immunoelectron microscopy it was seen that beta-APP accumulated in the axon from 1 h after impact demonstrating that there was functional axonal damage. TNF alpha reactions were detected in the lysosomes of microglia 30 min after impact and 1 h after impact these reactions were mainly detected in the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is generally accepted that TNF alpha directly induces primary demyelination and oligodendrocyte apoptosis. Therefore, TNF alpha conveyed from the microglial cells is one cofactor contributing to the formation of the delayed axonal damage observed at these sites. The present study suggests that TNF alpha conveyed from the glial cells may contribute to the pathogenic mechanism of DAI formation following fluid percussive brain injury.

Amyloid beta-Protein Precursor↗

[An infant with diffuse axonal injury].

Development of MRI enabled accurate and rapid diagnosis of head traumas which had been impossible with the conventional CT. The diagnosis of posttraumatic diffuse axonal injury (DAI) is a typical example. Most of the reported cases of DAI in childhood are of relatively older age, and DAI is rare in infancy. We report here a 1-year-9-month-old infant with DAI. After falling from two meters in height, he presented consciousness disturbance and a seizure that necessitated artificial respiration for half a day. He recovered completely without sequelae. Brain CT on arrival to the ER department was unremarkable, but MRI scans shortly thereafter showed typical findings of DAI. In childhood, DAI tends to be milder than in adult-hood, which may be explained by the age-dependent frequency of traffic accidents, and by anatomical and functional factors of a infant's brain. A large number of infantile cases should be accumulated to draw a more clearcut conclusion.

Brain↗

Evaluation of learning and memory dysfunction and histological findings in rats with chronic stage contusion and diffuse axonal injury.

We previously reported a modified fluid percussion device capable of consistently producing experimental cortical contusion (CC) and diffuse axonal injury (DAI) in separate groups of rats by lateral and midline fluid percussion, respectively. The purpose of the present study was to compare the differences in learning acquisition and memory retention impairments between these two types of injured rats in the chronic stage using the Morris water maze technique. We also compared the histological differences between these two different types of traumatic brain injury. The results showed a statistically significant difference in learning acquisition impairment between the sham and CC rats and also between the sham and DAI rats. However, a significant difference in memory retention impairment was observed only between the sham and DAI rats. Histologically, the neuronal cell loss of CA3 pyramidal cells in the hippocampus was observed on the ipsilateral side in the CC and bilaterally in DAI. The neuronal cell loss was seen in bilateral entorhinal cortex layer II in DAI, but it was not seen in CC. From these results, we speculate that the marked cell loss in the hippocampus CA3 region in both CC and DAI rats was related to the impairment of spatial learning acquisition. The marked cell loss in entorhinal cortex layer II in DAI rats may be one of the important factors in the impairment of spatial memory retention.

Animals↗

Simulation of acute subdural hematoma and diffuse axonal injury in coronal head impact.

Coronal head impacts were simulated in a physical model, based on the hypothesis that acute subdural hematoma (ASDH) is related to cerebral vertex displacement and diffuse axonal injury (DAI) to local Green-Lagrange strain. The geometry of the 2D model was based on anatomical measurements taken from the MRI scans of 10 adult males. Silicone gel modelled the cerebrum, paraffin the CSF and elastic membranes the trabeculae of the sulci. Pendulum impacts gave peak angular acceleration of 7800 rad s(-2) in models with and without sulci. The motion of the gel and Green-Lagrange strain were calculated from tracked coordinates of Patrick markers. Worst-case bridging vein strains are produced on the contrecoup side and are approximately doubled by adding sulci. Given that axons in the corpus callosum are highly oriented, Green-Lagrange strain was resolved in the fibre direction. It is found to be close to the minimum principal strain, indicating a degree of natural, teleological protection for the axons. The data support the use of delta0peak as a suitable descriptor for the risk of DAI but not for ASDH.

Adult↗

The pathological spectrum of diffuse axonal injury in blunt head trauma: assessment with axon and myelin strains.

Although diffuse axonal injury (DAI) has been described as a major form of primary damage to the brain in blunt head injury, there has been no systematic study of the pathological changes in different regions of the brain. In this study, 22 cases of DAI were comprehensively examined histologically in the following areas: corpus callosum, internal capsule, superior cerebellar peduncles, cerebral white matter, fornix, rostral brain stem and globus pallidus, with a total of 17 standard blocks in each case. Sections were stained for axons with Glees and Marsland and neurofilament immunostaining and myelin with luxol fast blue and myelin basic protein immunostaining, and axonal retraction balls and myelin globoids were counted. Neurofilament immunostaining was superior to Glees and Marsland in both the positivity rates and the actual scores. Small myelin globoids were identified by the myelin stains, probably as a form of myelin damage secondary to axonal disruption. Such acute myelin damage was previously undescribed. There was no significant difference in both positivity rates and the scores obtained for luxol fast blue and myelin basic protein. Of all the regions of the brain examined, the internal capsule, corpus callosum and superior cerebellar peduncles yielded the highest counts of axonal balls as well as the highest incidences. It is recommended that in cases of DAI, these three regions of the brain should be examined most profitably with neurofilament immunostaining supplemented with a myelin stain.

Adolescent↗

Content change of neurofilament protein subunits in experimental brain diffuse axonal injury by lateral head rotation.

OBJECTIVE: To explore the content change of neurofilament (NF) protein subunits in the experimental brain diffuse axonal injury (DAI) by lateral head rotation. METHODS: Twenty-four Sprague Dawley (SD) rats were equally divided into three injury groups (2 h, 12 h, and 24 h post injury) and one control group. The models of DAI were made in the injury groups by lateral head rotation. Western blotting technique was used to measure the content of NF68 (a kind of NF protein subunit) in the brainstem tissues among all the injured and control rats. The NF68 immunohistochemical staining was used in another six SD rats in order to observe the morphological changes in DAI. RESULTS: The NF68 content in the brainstem tended to decrease at 2 h post injury, decreased significantly at 12 h and continued its decrease at 24 h. NF56 and NF52, as the breakdown products of NF68, had a tendency to increase at 2-12 h after the injury, and amounted to a significantly higher level at 24 h. Microscopically, there were a lot of swelling neuronal axons in the ventral part of the medullar oblongata at 2 h after the injury. Some axons were disconnected, and axonal retraction balls formed on their proximal end. CONCLUSIONS: There is an occurrence of phosphorolysis within the brainstem in DAI by lateral head rotation. These reactions cause the breakdown of NF68, which results in the decrease of NF68 in content. It suggests that the breakdown of neurofilament protein subunits is an important reason for structur al destroy of neurofilaments in DAI.

Journal Article↗

Ubiquitin marks the reactive swellings of diffuse axonal injury.

Ubiquitin is a protein that targets proteins for non-lysosomal degradation. It has been found to be present in a number of inclusions characteristic of neurodegenerative diseases. Using the fluid percussion model of closed head injury in the cat, a well-established model of diffuse axonal injury (DAI), we now report that the reactive axonal swellings and the retraction balls produced in this model stain positively with anti-ubiquitin immunohistochemistry. Furthermore, the affected axons become ubiquitin positive quickly (within the first 6 h after injury). Anti-ubiquitin immunohistochemistry compares well with the recently reported ability of antibodies to low molecular weight neurofilament proteins to demonstrate reactive axonal change in DAI, and it could provide additional clues to the pathogenesis of axonal transection.

Animals↗

[Clinical study of intracranial pressure and auditory brain stem response in the cases of diffuse axonal injury].

The course of intracranial pressure (ICP) and the finding of auditory brain stem response (ABR) was discussed in the cases diagnosed as diffuse axonal injury (DAI) established by Gennarelli. ICP was measured in twenty-six cases which were divided into three groups according to the course of ICP: Group (1), in which ICP remained below 20 mmHg (group I, 9 cases). Group (2), in which ICP rose above 20 mmHg but was controlled by therapy (group II, 8 cases). Group (3), in which ICP rose above 20 mmHg and could not be controlled by any therapies (group III, 9 cases). Glasgow outcome scale 3 months after the injury in the cases of group I and II was severe disability (SD) and/or persistent vegetative state (PVS), but all of the cases in group III died. The findings of serial ABR were divided into 3 groups. These were group A (2 cases) which showed normal record, group B (5 cases) which showed elongation of latencies between the first and fifth waves, and group C (5 cases) in which there was no response in ABR. GOS in group A or B was SD and/or PVS, but all of the cases in group C were shown to be dead in GOS. Our studies suggest that the level of ICP in DAI is rather higher than that published in previous reports, and the continuous measurements of ICP and serial records of ABR are useful for evaluating the outcome of DAI.

Adolescent↗

Freeze-fracture studies of reactive myelinated nerve fibres after diffuse axonal injury.

We have studied the axonal and myelin sheath response in diffuse axonal injury after angular acceleration using the freeze-fracture and thin section techniques. It was found that the glial-axonal junction was intact until 1 h after injury. But upon loss of the nodal axolemma specialisations, after 3 to 4 h, the dimeric particles of the glial-axonal junction (GAJ) were lost and, by 6 h, the myelin lamellae became separated from the axonal remnant. There was a correlated loss of glial membrane specialisations of the GAJ during this separation. In the internodal region a suggestion of membrane damage occurred after 20 min but discrete myelin dislocations (particle-free areas) were not found until 1-h survival and were extensive by 6 h. Areas of loosely organised myelin occurred between intact axons at 7-28 days after injury. No evidence for growth cone formation was obtained.

Animals↗

Hemorrhagic shearing lesions in children and adolescents with posttraumatic diffuse axonal injury: improved detection and initial results.

PURPOSE: To compare the effectiveness of a high-spatial-resolution susceptibility-weighted (SW) magnetic resonance (MR) imaging technique with that of a conventional gradient-recalled-echo (GRE) MR imaging technique for detection of hemorrhage in children and adolescents with diffuse axonal injury (DAI). MATERIALS AND METHODS: Seven young patients with a mean Glasgow Coma Scale score of 7 +/- 4 (SD) at admission were imaged a mean of 5 days +/- 3 after injury. High-spatial-resolution three-dimensional GRE imaging performed with postprocessing by using a normalized phase mask was compared with conventional GRE MR imaging. The total and mean values of lesion number and apparent hemorrhage volume load determined with both examinations were compared. Mean values were compared by using paired t test analysis. Differences were considered to be significant at P < or =.05. RESULTS: Hemorrhagic lesions were much more visible on SW MR images than on conventional GRE MR images. SW MR imaging depicted 1,038 hemorrhagic DAI lesions with an apparent total hemorrhage volume of 57,946 mm3. GRE MR imaging depicted 162 lesions with an apparent total hemorrhage volume of 28,893 mm3. SW MR imaging depicted a significantly higher mean number of lesions in all patients than did GRE MR imaging, according to results of visual (P =.004) and computer (P =.004) counting analyses. The mean hemorrhage volume load for all patients also was significantly greater (P =.014) by using SW MR imaging according to computer analysis. SW MR imaging appeared to depict much smaller hemorrhagic lesions than GRE MR imaging. The majority (59%) of individual hemorrhagic DAI lesions seen on SW MR images were small in area (<10 mm(2)), whereas the majority (43%) of lesions seen on GRE images were larger in area (10-20 mm(2)). CONCLUSION: SW MR imaging depicts significantly more small hemorrhagic lesions than does conventional GRE MR imaging and therefore has the potential to improve diagnosis of DAI.

Adolescent↗

Hypoflow and hyperflow in diffuse axonal injury. Prognostic and therapeutic implications of transcranial Doppler sonography evaluation.

BACKGROUND: In the present report we describe the results of a study aimed at evaluating the cerebral haemodynamics and the neuroradiological findings observ-ed in 7 consecutive patients, 4 adults and 3 children (6, 8 and 10 years old), affected by diffuse axonal injury (DAI). METHODS: All the patients were admitted to the Paediatric or Adult Intensive Care Unit with GCS scores less than 8 after a severe brain injury. Serial head CT scan and trans-cranial Doppler sonography (TCD) examinations were carried out in all patients; MRI was carried out in the paediatric patients only. TCD of the middle cerebral arteries was performed through the temporal bone window. In 6 cases (2 paediatric) diuretic osmotic therapy was immediately administered and in 6 cases (3 paediatric) barbiturates and hyperventilation were also used. RESULTS: Hyperflow, variably responsive to barbiturate therapy of vasoparalysis, was observed in all paediatric patients and in 3 adult subjects (85.7%: 6 out of 7 pa-tients) by means of TCD. CONCLUSIONS: Observation of these phenomena allowed us to modify the pharmacological treatment and/or perform external cerebrospinal fluid (CSF) drainage (4 cases). Compartimental hyperflow TCD pattern was evident in 1 patient. Although the limited number of patients in our series does not allow definitive conclusions, we strongly believe that TCD monitoring is an useful tool in planning surgical strategy in patients with DAI.

Accidents, Traffic↗

The expression and changes of heat shock protein 70, MDA and haemorheology in rat cortex after diffuse axonal injury with secondary insults.

In the present study the role of heat shock protein 70 (HSP70) expression, changes of malonyldialdehyde (MDA) in rat cortex and haemorheology with time after diffuse axonal injury (DAI) only and DAI with secondary insults (SI) were studied. The rat DAI and DAI with SI model were made according to our previous work and animals were divided into a control and another five injury groups with time after injury. Immunohistochemical assay was used to detect the neuronal expression of HSP70 at 0.5h, 3h, 12h, 24h, 72h after DAI or DAI with SI. In the meantime, the high (etah ) and low whole blood viscosity (etaL ), haematocrit (HCT) and RBC aggregation index (AI = etaL/etah ) were also detected and calculated. MDA in the homogenised brain tissue was assayed by thiobarbituric acid (TBA) reaction. The results showed that HSP70 positive neurons were not detected at 30 minutes, but the number of HSP70 positive neurons begin to increase obviously at 3 hours, reach a peak at 24 hours (P< 0.01), and decrease at 72 hours (P= 0.05) after brain injury. The trend of expression of HSP70 was alike for both DAI only or DAI with SI. Meanwhile, MDA, etah, etaL, HCT and AI changes showed the same tendency. Compared with DAI only group, MDA and blood viscosity indexes in DAI with SI were significantly higher at respective time points (P< 0.01). It is concluded that HSP70 expression, MDA and haemorheology indices increased after brain injury and brain injury with SI. Free radicals and haemorheological changes play an important role in the aggravation of brain damage and HSP70 expression upregulation.

Animals↗

Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase.

BACKGROUND: To compare the magnetic resonance imaging (MRI) findings in the acute phase with outcome in patients with diffuse axonal injury (DAI). METHODS: A group of 33 patients with closed head injury and discrepancy between the apparently normal computed tomographic scan findings and their neurologic statuses were studied with MRI during the first 48 hours. Among them, 24 were found to suffer from DAI-type lesions. According to the Glasgow Coma Scale (GCS), 19 patients suffered from severe head injury (GCS score <8) and 5 patients had moderate head injury (GCS score of 9-12). Four MRI sequences in various planes were applied. Patients were divided into three groups, according to staging described in the literature. RESULTS: In five patients, MRI demonstrated nonhemorrhagic DAI lesions stage 1. In 11 patients, findings were consistent with DAI lesions stage 2, eight nonhemorrhagic and three hemorrhagic. Eight patients showed DAI lesions stage 3, six of which were nonhemorrhagic. CONCLUSIONS: MRI is more sensitive compared with computed tomography in the detection of traumatic brain lesions, especially the nonhemorrhagic DAI. The presence of hemorrhage in DAI-type lesions and the association with traumatic space-occupying lesions is a poor prognostic sign. Isolated nonhemorrhagic DAI-type lesions are not associated with poor clinical outcome.

Adolescent↗

Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation.

PURPOSE: Our goal was to evaluate the use of the magnetization transfer ratio (MTR) in the detection of diffuse axonal injury (DAI) resulting from traumatic brain injury in a swine model. METHOD: DAI was created by applying a nonimpact, coronal plane, rotational acceleration to the heads of miniature swine (n = 4). GE imaging was performed with and without off-resonance MT saturation. Histologic correlation of axonal injury with MRI was performed 7 days postinjury. Thirty-one subcortical white matter regions and 10 deep white matter regions were selected for the direct comparison of histologic data and MTR measurements. RESULTS: Nineteen of 41 examined locations exhibited histologic evidence of axonal injury. The mean MTR in regions with axonal damage was significantly less than in regions without axonal damage. These changes were observed both in regions demonstrating high signal intensity on T2-weighted images (T2WI) (p <0.0001, n = 6) and in regions with no signal intensity change on T2WI (p < 0.05, n = 13). CONCLUSION: These results suggest that the measurement of MTR may have the potential for evaluation axonal damage in DAI following traumatic brain injury even when conventional T2WI does not demonstrate the lesion.

Animals↗