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An in vitro uniaxial stretch model for axonal injury.

We have developed a unique uniaxial stretching device to study axonal injury and neural cell death resulting from brain tissue deformations common in traumatic head injuries. Using displacement control rather than force control, this device is capable of achieving strains >70% and strain rates up to 90 s(-1), well above those currently used for studying axonal injury. We have demonstrated that the deformation of the specimen was uniaxial, uniform and highly reproducible; the prespecified displacement profiles could be realized almost precisely; and adequate cell adhesion could be achieved readily. The entire device can fit into a biological safety cabinet to maintain sterility, and the specimens are convenient for cell culture. This device can be used to investigate a wide range of biomechanical issues involved in diffuse axonal injury.

Animals↗

Metoclopramide-induced raised intracranial pressure after head injury.

We report a case of raised intracranial pressure in a head-injured patient following the intravenous administration of metoclopramide. The patient required admission to an intensive care unit after a road traffic accident. A CT scan of the head was consistent with diffuse axonal injury and supportive management included intracranial pressure monitoring. On the third day after admission, intravenous metoclopramide 10mg was administered to aid gastric emptying during nasogastric feeding. Intracranial pressure increased to 39mmHg from a baseline of 15-20mmHg. The same dose of metoclopramide was repeated the next day during transcranial doppler studies with an increase in ICP to 34mmHg and an associated rise in middle cerebral artery systolic blood velocity from 122cms-1 to 150cms-1. This effect of metoclopramide has not been previously reported.

Accidents, Traffic↗

[FLAIR images of patients with head injuries].

FLAIR (fluid-attenuated inversion recovery) images are MR images obtained with an inversion recovery sequence, which has a long inversion time (TI) and a long echo time (TE). We examined 29 cases (49 graphics) of cerebral contusion, 11 cases (22 graphics) of diffuse axonal injury (DAI) and 11 cases (11 graphics) of traumatic subarachnoid hemorrhage (t-SAH) with FLAIR sequence consisting of a repetitive time (TR) of 6500 msec, TI of 1700 msec and TE of 110 msec, and these graphics were compared with T2-weighted images by spin-echo sequence (TR 2500 msec, TE 90 msec) and computed tomographic (CT) scans. Some lesions of DAI were demonstrated more clearly with FLAIR images than with conventional T2-weighted images. Although contusion could be detected with FLAIR images as well as with conventional T2-weighted images, lesions adjacent to cerebral sulci were better delineated with FLAIR images. Because the cerebrospinal fluid signals in cerebral sulci were low-intensity, FLAIR images were useful in detecting lesions of the cerebral cortex adjacent to cerebral sulci. Although it has been reported that detection of SAH is difficult with standard T1- and T2-weighted images, the presence of t-SAH could be confirmed with FLAIR images as seen in CT scans.

Adult↗

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.

Animals↗

A population-based study of potential brain injuries requiring emergency care.

BACKGROUND: Brain injury is an important health concern, yet there are few population-based analyses on which to base prevention initiatives. This study aimed, first, to calculate rates of potential brain injury within a defined Canadian population and, second, to describe the external causes, natures and disposition from the emergency department of these injuries. METHODS: We studied all cases of blunt head injury that resulted in a visit to an emergency department for all residents of Greater Kingston during 1998. We used data from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) and augmented this by examining all records of emergency or inpatient care received at all hospitals in the area. RESULTS: In 202 (27%) of 760 cases of head injury, there was potential for brain injury. Annual rates of potential brain injury were 16 and 7 per 10,000 population for males and females respectively. CT was performed on 114 (56%) of 202 cases, of which 60 (53%) demonstrated an intracranial pathology, with 11 (10%) showing a diffuse axonal injury pattern on the initial scan. Falls from heights accounted for 14 (47%) of 30 injuries observed in children aged 0-9 years. Individuals aged 10-44 years sustained 32 (63%) of 51 motor vehicle injuries, 15 (88%) of 17 bicycle injuries, 22 (100%) of 22 sports injuries and 8 (89%) of 9 fight-related injuries. Falls accounted for 15 (71%) of 21 injuries among adults aged 65 years or more. INTERPRETATION: The results indicate the relative importance of several external causes of injury. The findings from our geographically distinct population are useful in establishing rational priorities for the prevention of brain injury.

Accidental Falls↗

Delayed diagnosis of concomitant rotator cuff tear and brachial plexopathy in a patient with traumatic brain injury: a case report.

Traumatic brain injury (TBI) is often accompanied by additional trauma that can be obscured by cognitive dysfunction or multiple injuries in the same region of the body. This report describes the case of an unhelmeted motorcycle rider who collided with a telephone pole. He sustained a diffuse subarachnoid hemorrhage, bilateral subdural hematomas (right frontal and left temporal), diffuse axonal injury in the subcortical and periventricular white matter, and a left tibial fracture. After medical and surgical stabilization, he was transferred to a subacute rehabilitation facility and then to a rehabilitation center. He was evaluated for pain and limited range of motion in his right shoulder, where both a rotator cuff tear and a brachial plexopathy were diagnosed. This report discusses concomitant injuries that occur with TBI, and the management of rotator cuff tears and brachial plexopathy.

Brachial Plexus Neuropathies↗

Corpus callosal atrophy following closed head injury: detection with magnetic resonance imaging.

To investigate evidence for diffuse white matter injury and hemispheric disconnection sequelae after severe closed head injury (CHI), this study evaluates the degree of posttraumatic atrophy of the corpus callosum. Corpus callosal atrophy was quantitatively determined using a digitizer to measure sagittal magnetic resonance images of 32 patients with moderate-to-severe CHI and those of 31 control subjects of similar age. In the CHI patients, measurements were significantly reduced for the areas of the anterior four-fifths, the posterior one-fifth, and the total corpus callosum. Moreover, the minimum width of the callosal body was reduced in the CHI patients as compared to that of control individuals. Indices of corpus callosal atrophy were significantly correlated with the chronicity of injury and the degree of lateral ventricular enlargement. There was no difference in callosal measurements between men and women. Magnetic resonance imaging provides an in vivo determination of corpus callosal atrophy which may reflect the severity of diffuse axonal injury and predict the type and severity of hemispheric disconnection effects.

Adolescent↗

Basal ganglia hematomas in severely head injured patients: clinicoradiological analysis of 37 cases.

OBJECT: The authors analyzed the clinicoradiological presentation of traumatic basal ganglia hematomas (TBGHs) in severely head injured (SHI) patients. METHODS: The records of 37 patients (28 male and nine female patients with a mean age of 28 years) in whom computerized tomography (CT) scans revealed TBGHs 2 ml or more in volume were retrospectively reviewed. These cases represented 2.4% of the total series of 1526 SHI patients admitted to the authors' institution between 1979 and 1998. Thirty-five patients (94%) were involved in traffic accidents and only two exhibited a period of lucidity. Associated extracranial injuries were seen in 21 patients (57%) and coagulation disorders in 32 (86%). Skull fracture was present in 10 (43%) of the 23 patients in whom skull x-ray films were obtained. Computerized tomography findings indicated diffuse axonal injury in 27 patients (73%), intraventricular hemorrhage in 22 patients (59%), and subarachnoid hemorrhage in 16 patients (43%). In all but two patients, the TBGHs were visible on the initial CT scan, and in 28 cases (76%) these hematomas were contralateral to the side of impact. Hematoma enlargement over the first few posttraumatic days was noted in 65% of the patients in whom control CT scans had been obtained (22 of 34 patients). Four patients (11%) underwent surgery to remove their TBGHs. Final outcomes were poor: 22 patients (59%) died, two (5%) became vegetative, seven (19%) experienced severe disabilities, and only six patients (16%) made a favorable recovery. CONCLUSIONS: Traumatic basal ganglia hematomas are dynamic lesions that tend to enlarge during the acute posttraumatic period. The overall prognosis in this series was poor. Patients in whom the volume of the hematoma was larger than 25 ml and those in whom hematoma volume enlargement or raised intracranial pressure occurred had the worst outcomes, perhaps indicating the need for a more aggressive surgical treatment.

Adolescent↗

MRI of head injury using FLAIR.

We studied the utility of fluid-attenuated inversion-recovery (FLAIR) MRI in the investigation of head injury. We examined 56 patients with head injuries with T2-weighted spin-echo (SE) and FLAIR sequences. In all cases, the sensitivity of FLAIR images to equal or superior to that of conventional SE images to the traumatic lesions. In 9 cases, central diffuse axonal injury of the fornix and corpus callosum could be seen only on sagittal FLAIR images.

Adult↗

Early versus late lateral ventricular enlargement following closed head injury.

Serial computed tomographic scans in 39 closed head injury patients were measured by planimetry. The ventricle-brain ratio was computed, and the lateral ventricles were considered to be enlarged or normal based on measurements from a control group. Delayed ventricular enlargement was common after head injury producing low Glasgow Coma Scale scores and prolonged coma, whereas subarachnoid/intraventricular haemorrhage was more common with early enlargement. The degree of ventriculomegaly was related to neuropsychological test performance only when enlargement was delayed. It is postulated that diffuse axonal injury and hypoxic-ischaemic insult contributed to late ventricular enlargement, whereas a compensated obstruction of cerebrospinal fluid may be the predominant cause in the early group.

Adolescent↗

Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury.

Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children.

Adolescent↗

Day-of-injury CT as an index to pre-injury brain morphology: degree of post-injury degenerative changes identified by CT and MR neuroimaging.

A detailed case study is presented in which pre-injury CT scan findings are compared and contrasted with post-injury CT and MR results in a case of traumatic brain injury (TBI). The day-of-injury scan represented an adequate estimate of pre-injury morphological status based on cross-sectional area measurements of the ventricular system. By comparing pre-injury CT measurements with those obtained on the day of injury, 2 days post-injury and 16 months post-injury via assessing cross-sectional area of select ventricular regions (e.g. anterior and temporal horns, body and third ventricle) it was demonstrated that the TBI induced over a 50% ventricular expansion. Such ventricular expansions are felt to provide some index into diffuse axonal injury which may provide a means of eventually quantifying the degree of structural damage secondary to TBI. This analysis also demonstrated that there were no significant differences between selected cross-sectional ventricular areas in the 15 day and 16 month post-injury MR scans. This finding suggests that the degenerative effects of TBI have a rapid onset and are becoming readily apparent by 15 days post-injury. Thus, early imaging may provide a good index of long-term morphological outcome in TBI.

Adolescent↗

The rationale for glutamate antagonists in the treatment of traumatic brain injury.

The recent development of potent antagonists for the most widespread neurotransmitter in the mammalian brain has opened up possibilities for many forms of therapy. The excitotoxic hypothesis implicates excessive release of excitatory amino acids (EAAs) as an important cause of brain damage, especially in acute ischemia, and chronic neurodegeneration. Focal ischemic damage and diffuse axonal injury are the major causes of brain damage after traumatic human brain injury. Evidence from animal models has shown that excitatory amino acid-induced events maybe responsible for a proportion of the posttraumatic sequelae and that these effects can be blocked by EAA antagonists. This evidence is reviewed, and the implications for human pathophysiology and treatment are discussed.

Animals↗

Case report of sudden death after a blow to the back of the neck.

A 13-year-old girl experienced a fall during gym class that caused immediate unresponsiveness and death. The lone witness reported that the decedent lost her balance as she approached a hurdle and fell, striking her head on a crossbar of the hurdle near the ground. Autopsy revealed no external injury. Internal injury that could be demonstrated anatomically was confined to a contusion within the right semicapitis muscle at the base of the skull. In the absence of an anatomic cause of death, possible explanations of the death include a cardiac dysrhythmia, a vasovagal stimulus, and diffuse axonal injury caused by a concussive force to the junction of the medulla and spinal cord. Animal studies have shown that severe concussion can cause death via profound autonomic dysfunction without leaving anatomic evidence of injury, and that the essential component of concussion is an element of rotational injury to the brain. The authors believe that the blow to the neck caused this death by the transmission of a concussive force through the reticular activating system. The prompt work of police in distinguishing the lone witness from several people in the area who thought they knew what had happened was essential for diagnosis. On reaching our conclusions, the authors notified first the family, then the superintendent of the school system, and finally the news media. The authors told each party in turn that they would be contacting the others.

Accidental Falls↗

Susceptibility-weighted imaging and proton magnetic resonance spectroscopy in assessment of outcome after pediatric traumatic brain injury.

OBJECTIVE: To assess the role of magnetic resonance imaging, specifically magnetic resonance spectroscopy (MRS) and susceptibility-weighted imaging (SWI), in the evaluation of children with traumatic brain injury (TBI). DATA SOURCES: Literature review and data from our recently published clinical studies. STUDY SELECTION: Children with pediatric TBI who underwent SWI. SWI is a 3-dimensional high-resolution magnetic resonance imaging technique that is more sensitive in detecting hemorrhagic lesions seen with diffuse axonal injury (DAI) than conventional imaging. MRS acquires metabolite information that reflects neuronal integrity and function from multiple brain regions and offers early prognostic information regarding outcome. DATA EXTRACTION: Literature review. DATA SYNTHESIS: Literature review and review of recently published data from our institution. CONCLUSIONS: The data suggest that more sensitive imaging techniques that provide early evidence of injury and that are better predictors of outcome are needed to identify children at risk for such deficits. Specifically, the number and volume of hemorrhagic DAI lesions as well as changes in spectral metabolites such as reduced N-acetylaspartate or elevations in choline-related compounds correlate with neurologic disability and impairments of global intelligence, memory, and attention.

Aspartic Acid↗

Head injury and posttraumatic movement disorders.

WE REVIEW THE phenomenology, pathophysiology, pathological anatomy, and therapy of posttraumatic movement disorders with special emphasis on neurosurgical treatment options. We also explore possible links between craniocerebral trauma and parkinsonism. The cause-effect relationship between head injury and subsequent movement disorder is not fully appreciated. This may be related partially to the delayed appearance of the movement disorder. Movement disorders after severe head injury have been reported in 13 to 66% of patients. Although movement disorders after mild or moderate head injury are frequently transient and, in general, do not result in additional disability, kinetic tremors and dystonia may be a source of marked disability in survivors of severe head injury. Functional stereotactic surgery provides long-term symptomatic and functional benefits in the majority of patients. Thalamic radiofrequency lesioning, although beneficial in some patients, frequently is associated with side effects such as increased dysarthria or gait disturbance, particularly in patients with kinetic tremor secondary to diffuse axonal injury. Deep brain stimulation is used increasingly as an option in such patients. It remains unclear whether pallidal or thalamic targets are more beneficial for treatment of posttraumatic dystonia. Trauma to the central nervous system is an important causative factor in a variety of movement disorders. The mediation of the effects of trauma and the pathophysiology of the development of posttraumatic movement disorders require further study. Functional stereotactic surgery should be considered in patients with disabling movement disorders refractory to medical treatment.

Craniocerebral Trauma↗

Temporal changes in intracranial pressure in a modified experimental model of closed head injury.

OBJECT: The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures. METHODS: Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague-Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p < 0.001, R2=0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7+/-2.8 mm Hg, p=0.004; 24 hours: 21.8+/-1.1 mm Hg, p=0.002; 72 hours: 11.9+/-2.5 mm Hg, p=0.009). Comparison of the rise in ICP between moderate and severe impact-acceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p=0.008; 24 hours: p=0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema. CONCLUSIONS: This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.

Animals↗

Magnetization transfer imaging and proton MR spectroscopy in the evaluation of axonal injury: correlation with clinical outcome after traumatic brain injury.

BACKGROUND AND PURPOSE: Current imaging does not permit quantification of neural injury after traumatic brain injury (TBI) and therefore limits both the development of new treatments and the appropriate counseling of patients concerning prognosis. We evaluated the utility of magnetization transfer ratio (MTR) and proton MR spectroscopy in identifying patients with neuronal injury after TBI. METHODS: Thirty patients with TBI (21-77 years old; mean age, 42 years; admission Glasgow Coma Scale (GOS) scores 3-15; mean score, 11) were studied on a 1.5-T system with magnetization transfer imaging and MR spectroscopy of the splenium. Magnetization transfer imaging was also performed in the brain stem in all patients, and other areas of the brain were sampled in one patient. The splenium of the corpus callosum and brain stem were studied because these are often affected by diffuse axonal injury. Scans were obtained 2 to 1129 days after injury (median, 41 days). MTR was considered abnormal if it was more than 2 SD below normal. Proton MR spectroscopy was used to calculate the N-acetylaspartate (NAA)/creatine (Cr) ratio. GOS was determined at least 3 months after injury. RESULTS: In 10 patients with a GOS of 1 to 4, the mean NAA/Cr was 1.24 +/- 0.28; two of these patients had abnormal MTR in normal-appearing white matter (NAWM). In 20 patients with a GOS of 5, the mean NAA/Cr was 1.53 +/- 0.37 (P < .05); four of these patients had abnormal MTR in NAWM. MTR abnormalities in NAWM were identified in six patients, but these changes did not correlate with GOS or MR spectroscopy changes. CONCLUSION: MTR and MR spectroscopy can quantify damage after TBI, and NAA levels may be a sensitive indicator of the neuronal damage that results in a worse clinical outcome.

Aspartic Acid↗