Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury

Primary objective: A comparison of the effects of focal and diffuse axonal injury in mild-to-moderate traumatic brain injury (TBI). Research design: In a prospective longitudinal study of 138 consecutive patients suffering from TBI who were admitted to the Magdeburg University Hospital, 60 could be assessed neuropsychologically 8-31 days after trauma and 18-45 weeks later. Methods and procedures: GCS, CT-analysis, comprehensive neuropsychological assessment. Main results: The initial GCS-score was significantly correlated with outcome impairments of semantic fluency and memory in the Wechsler Similarities and in two clinical scales (Neurobehavioural Rating Scale, Frontal Lobe Score). The presence of CT-signs of DAI corresponded with deficits in tasks of response selection and suppression, the presence of focal contusions with results in the clinical scales, reaching significance for behavioural deficits with frontal contusions. Improvements between first and second assessments were pronounced in patients with signs of DAI. Conclusions: The data indicate that traumatic DAI results in mainly transient neuropsychological deficits. Focal frontal contusions result in more relevant deficits at outcome that affect behaviour and, thus, impair rehabilitation prognosis. It is concluded that even in clinically 'mild' TBI, prognosis and rehabilitation requirements should be established by early imaging and post-acute neuropsychological assessment.     

Acute subdural hematoma and diffuse axonal injury after severe head trauma

The association of acute subdural hematoma (SDH) and diffuse axonal injury has received little attention in the literature. The authors report the clinicopathological findings in six patients who died of severe head injury in whom computerized tomography revealed acute SDH as the predominant lesion. All patients were injured in road traffic accidents and lost consciousness on impact. The mean total contusion index was 17.4 and sever contusions were seen in only two cases. All patients presented histological criteria of intracranial hypertension (pressure necrosis focus in one or both parahippocampal gyri). Hypoxic brain damage was evident in the postmortem examination of three patients. In three cases, macroscopic hematic lesions were observed in the corpus callosum. All patients had widespread axonal retraction balls disseminated in the white brain matter. Three patients who survived for more than 11 days had microglial clusters. In some patients with a head injury, acute SDH may be only an epiphenomenon of a primary impact lesion of variable severity: that is, a diffuse axonal injury. In these cases, the final outcome is fundamentally dependent on the severity of the subjacent diffuse axonal injury.     

异丙酚对大鼠脑弥漫性轴索损伤后的脑保护作用

目的 评价异丙酚对损伤后脑组织的神经保护作用。方法 取健康Ｗｉｓｔａｒ大鼠７２只,采用Ｍａｒｍａｒｏｕ弥漫性颅脑损伤动物模型制备方法,造成大鼠重度颅脑损伤,异丙酚组（Ｐ组）给予１％异丙酚１ｍｇ．ｋｇ＾－１．ｍｉｎ＾－１持续静注３ｈ;对照组（Ｃ组）伤后不作处理;正常组（Ｎ组）不造成颅脑损伤,各组在伤后６、２４、４８和７２ｈ分别取脑组织做电镜观察和血生化指标测定。结果 （１）形态学：Ｃ组各时相显示了典型ＤＡＩ改变过程;Ｐ组在４８和７２ｈ轴索改变、微血管及胶质细胞损伤程度均明显轻于Ｃ组;（２）血生化指标：损伤后ＮＥＳ、ＥＴ和ＭＤＡ值Ｐ组和Ｃ组均较Ｎ组明显升高,但Ｐ组升高程度明显低于Ｃ组,并且随时间延长Ｐ组各值逐渐下降,而Ｃ组仍持续在较高水平。ＭＢＰ与ＮＯ高程度明显低于Ｃ组。并且随时间延长Ｐ组各值逐渐下降,而Ｃ组仍持续     

Diffuse axonal injury and early intracranial sequelae in severe head injury.

The importance of diffuse axonal injury (DAI) and early intracranial sequelae was studied in 107 patients with diffuse and focal brain injuries. Comprehensive neuropathological study was also undertaken in 24 fatal patients. The mortality rate was clearly the highest in traumatic subarachnoid hemorrhage, followed by acute subdural hematoma, cerebral contusion with delayed hematoma formation, traumatic intracerebral hematoma, diffuse cerebral swelling, DAI with classical features, and finally nearly normal on computed tomographic scans. The mean flow velocities in the middle cerebral artery recorded by transcranial Doppler ultrasound were variable in diffuse brain injury, but commonly decreased on the hematoma side depending on increased intracranial pressure and decreased cerebral perfusion pressure in focal brain injury. Deep-seated hemorrhagic lesions did not expand in diffuse brain injury, but sizable hematoma developed within 24 hours in focal brain injury. The platelet count was significantly lower in patients with poor outcomes in focal brain injury. Histological evidence of classical DAI was found in eight (50%) of 16 cases with focal brain injury. DAI of varying severity is the common subjacent lesion in patients with severe head injury, but the final outcome varies greatly with different lesion types.     

Mild traumatic brain injury and diffuse axonal injury in swine

Until recently, mild traumatic brain injury (mTBI) or "concussion" was generally ignored as a major health issue. However, emerging evidence suggests that this injury is by no means mild, considering it induces persisting neurocognitive dysfunction in many individuals. Although little is known about the pathophysiological aspects of mTBI, there is growing opinion that diffuse axonal injury (DAI) may play a key role. To explore this possibility, we adapted a model of head rotational acceleration in swine to produce mTBI by scaling the mechanical loading conditions based on available biomechanical data on concussion thresholds in humans. Using these input parameters, head rotational acceleration was induced in either the axial plane (transverse to the brainstem; n=3), causing a 10- to 35-min loss of consciousness, or coronal plane (circumferential to the brainstem; n=2), which did not produce a sustained loss of consciousness. Seven days following injury, immunohistochemical analyses of the brains revealed that both planes of head rotation induced extensive axonal pathology throughout the white matter, characterized as swollen axonal bulbs or varicosities that were immunoreactive for accumulating neurofilament protein. However, the distribution of the axonal pathology was different between planes of head rotation. In particular, more swollen axonal profiles were observed in the brainstems of animals injured in the axial plane, suggesting an anatomic substrate for prolonged loss of consciousness in mTBI. Overall, these data support DAI as an important pathological feature of mTBI, and demonstrate that surprisingly overt axonal pathology may be present, even in cases without a sustained loss of consciousness.     

Computed tomography in diagnosis of diffuse axonal injury

Diffuse axonal injury (DAI) has been described in instances of prolonged traumatic coma on the basis of the neuropathological findings, but the same findings are also found in patients with cerebral concussion. Experimental studies confirm that the quality of survivors following trauma is directly proportional to the amount of primarily injured-axon. When the injured axon lies in a widespread area of the brain, outcome for the patient is always poor. In a series of 260 severely head-injured patients, based on their poor outcome, 69 (27%) were diagnosed as DAI. Because of their relatively good outcome, eighty-two patients (32%) were classified into non-DAI group. The predominant CT finding of DAI patients was intraparenchymal deep-seated hemorrhagic lesion. This was observed in 28 patients (41%). Normal CT was also observed in 11 patients (16%). On the other hand, 8 of the non-DAI group (10%) manifested deep-seated lesions. Diffuse cerebral swelling (DCS) appeared in both groups in the same incidence. Subarachnoid hematoma in the perimesencephalic cistern (SAH (PMC] and intraventricular hematoma (IVH) were observed in 64% of the DAI group, and in 23% of the non-DAI group. The available evidence indicates that various types of hematoma seen in the deep-seated structures of the brain do not have an absolute diagnostic value, but the frequency of hematoma is thought to increase in proportion to the amount of injured-axon.     

新型弥漫性轴索损伤动物模型的建立

了大鼠DAI模型,且具良好的稳定性和重复性.     

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 (2h,12h,and 24h 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 contene 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 2h post injury,decreased significantly at 12h and continued its decrease at 24h.NF56 and NF52,as the breakdown products of NF68,had a tendency to increase at 2-12h after the injury,and amounted to a significantly higher level at 24h.Microscopically,there were a lot of swelling neuronal axons in the ventral part of the medullar oblongate at 2h after the injury.some axons were disconnected,and axonal retraction balls formed on their proximal end.Conclusions:There is and 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 structural destroy of neurofilaments in DAI.     

重型颅脑损伤中的弥漫性轴索损伤的救治

目的 探讨重型颅脑损伤中弥漫性轴索损伤的诊断与治疗。方法 总结本院近5年救治58例弥漫性轴索损伤患临床资料，并结合献，对重型颅脑损伤中的弥漫性轴索损伤的病因、诊断标准及治疗方法进行讨论。结果 58例弥漫性轴索损伤患诊治正确，31例抢救成功，27例死亡。结论 重型颅脑损伤中的弥漫性轴索损伤的死亡率较高，早期诊治是其抢救成功的关键。     

Diagnosis and treatment of diffuse axonal injury in 169 patients

Diffuse axonal injury (DAI) following brain injuryhas acute and severe clinical manifestations andleads to a very high death rate. At presenttherapies for DAI do not have good effect. Weretrospectively analyzed 169 DAI patients treated in theSecond, Sixth…     

Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain

A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve of the albino guinea pig. Electron microscopy demonstrates axonal swelling, axolemmal blebs, and accumulation of organelles identical to those seen in human and experimental brain injury. Quantitative morphometric studies confirm that 17% of the optic nerve axons are injured without vascular disruption, and horseradish peroxidase (HRP) studies confirm alterations in rapid axoplasmic transport at the sites of injury. Since 95% to 98% of the optic nerve fibers are crossed, studies of the cell bodies and terminal fields of injured axons can be performed in this model. Glucose utilization was increased in the retina following injury, confirming electron microscopic changes of central chromatolysis in the ganglion cells and increased metabolic activity in reaction to axonal injury. Decreased activity at the superior colliculus was demonstrated by delayed HRP arrival after injury. The model is unique because it produces axonal damage that is morphologically identical to that seen in human brain injury and does so by delivering tissue strains of the same type and magnitude that cause axonal damage in the human. The model offers the possibility of improving the understanding of traumatic damage of central nervous system (CNS) axons because it creates reproducible axonal injury in a well-defined anatomical system that obviates many of the difficulties associated with studying the complex morphology of the brain.     

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.     

A clinical and pathological study of diffuse axonal injury

There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Traumatic axonal injury after closed head injury in the neonatal pig

Closed head injury is the leading cause of morbidity and mortality in infants and children, and results in pathologies such as diffuse axonal injury (DAI) and subarachnoid hematoma (SAH). To better understand the mechanical environment associated with closed head injury in the pediatric population, animal models that include salient features of human infant brain must be utilized. Based on detailed information regarding the parallels between brain development in the pig and the human, the 3-5-day-old piglet was used to represent the infant at less than 3 months of age. Anesthetized piglets (n = 7) were subjected to rapid, inertial (nonimpact) rotation of the head about its axial plane and sacrificed at 6 h postinjury. Immediately following injury, five of seven piglets were apneic, with an absence of pupillary and pain reflexes. All piglets exhibited severe coma immediately postinjury, but recovered by sacrifice time. Blood was present on the surface of the frontal lobes, cerebellum, and brainstem, and subarachnoid hemorrhage was evident in the frontal cortex. In six of seven brain-injured piglets, accumulation of the 68-kDa neurofilament protein was evident in contiguous axons (swollen) and occasionally in disconnected axons (axonal bulbs), suggestive of traumatic axonal injury (TAI). Mapping of the regional pattern of TAI revealed injured axons predominantly in central and peripheral white matter tracts in the frontal and temporal lobes and in the midbrain. The number of injured axons was equivalent in both hemispheres, and did not correlate to the load applied to the head. Together, these data demonstrate that rapid rotation of the piglet head without impact results in SAH and TAI, similar to that observed in children following severe brain trauma.