Prognostic Analysis And Treatment Of Diffuse Axonal Injury

Background:Diffuse axonal injury is a common primary injury and pathologic type of traumatic brain injury. Adams called the brain injury that was not visible to the naked eyes, but could observe the extensive axonal swelling, fracture and come into the axonal ball in parts of the corpus callosum, brain stem, white matter in the hemispheres under microscope as diffuse axonal injury in1982. From then on, it was used widely.At present, there is no uniform diagnostic standard for diffuse axonal injury, and the clinical manifestation has no obvious characteristic, either. The common manifestations include the head rotation injury by acceleration or deceleration, primary coma after injury, disorder of vital sign, one side or both sides change of pupil, and so on. Therefore, the study of diagnosis for diffuse axonal injury inclined to imaging diagnosis and other auxiliary examinations evidently.Not a little research were made about related factors of the prognosis for diffuse axonal injury, but mostly confined to a single clinical factor or radiographic parameter. It is necessary to establish a more comprehensive multi-factor evaluation system for better assessing the relationship between the clinical risk factors and the prognosis, which could make the progression and the outcome of the disease better understood than before. There are no breakthrough for treating diffuse axonal injury so far yet, because of the ambiguous on the diagnostic standard and the lack of fully knowledge of the disease,. It still used the traditional method, such as oxygen indraft, hyperventilation, hypothermia, dehydration, sedation and surgical decompression treatment. All these methods can’t improve the patients’clinical status and prognosis significantly. With more and more research of pathophysiology for diffuse axonal injury, recent years, therapy more inclined to use the drug aim to the middle link of the secondary axonal fracture in the time window, such as calcium antagonists, excitatory amino acid receptor blockers, free radical scavenger. Moreover, the adjuvant therapy such as hypothermia therapy and hyperbaric oxygen was used to affect the progress of the axonal injury.Calcium ion can effect synergically with varieties of enzymes and proteins, maintain the biochemical function. Calcium, as a second messenger, be play a regulatory role within the cell and involve in the synthesis and release of neurotransmitters. In addition, calcium also involve in the maintenance of membrane fluidity and integrity, cell adhesion, the integrity of chromosome structure. Calcium channels are opened after brain injury, and calcium influx increase. But Na+, K+-ATPase and Ca2+, Mg2+-ATPase are inhibited and calcium outflow decrease. As a result, calcium overload in the cell, and led to a series of pathological effect. Nimodipine, a calcium channel blocker, using early after brain injury, can help to reduce the calcium overload and cell edema and decrease the extent of axonal injury by blocking L-type voltage-sensitive calcium channels.Magnesium ion is an essential trace element for the human body. It is involveed in all the enzyme-related biochemical metabolic processes in the cell and maintains the integrity of the cell membrane. Magnesium ion regulates the excitatory amino acid NMDA (N-methyl D-aspartate) receptor calcium channel on the nerve cell membrane. Therefore, early use of magnesium after diffuse axonal injury, maybe, in this way, collaborate to maintain the integrity of the cell membrane, to block calcium influx and to reduce intracellular calcium overload. Therefore, it could decrease the severity of neuronal and axonal injury.Objective:1. Analysis of the prognostic factors in diffuse axonal injury, and to establish a better system to evaluate the prognosis of this disease in early stage.2. By using the calcium channel blocker (nimodipine) and magnesium sulfate early after injury, analyze their influence on the prognosis of diffuse axonal injury, investigate the therapeutic effect and mechanisms of magnesium sulfate. Therefore, provide basis to find therapeutic method in early treatment of diffuse axonal injury.Methods:1. Study population:A total of99diffuse axonal injury patients from September2006to June2010were brought into this study, including64cases of males and35females. The average age was33.6±9.2years, range17-54years old. The causes of injury were traffic accident, fall injury, hitting hurt and sport injury. All cases accord with the inclusion criteria:1) head rotation history of violence, such as traffic accidents, falling, high-speed violence injury, etc;2) clinical manifestations:disturbance of consciousness occurred immediately after injury with the different duration; may be associated with eye movement disorders and staring paralysis, the disorder of vital signs and hypothalamic symptoms.3) CT or MRI performance was multiple non-placeholder white mass bleeding lesions within cerebral hemispheres, corpus callosum, brain stem, cerebellum or other locations, with the diameter less than2cm. The hemorrhage also can be found in subarachnoid space, ventricle or close to the third ventricle. It may have diffuse brain swelling, or coma maintain more than6hours without CT performance change.4) The increased intracranial pressure was not consisted with the clinical severity of the disease.5) Autopsy or surgical biopsy found evidence of axonal injury.6) CT/MRI found diffuse encephalatrophy in late trauma recovery, and with more nerve damage sequelae.2. Assessments and measurements:The GCS of99patients on admission were as follow:22cases were3scale,3cases were4scale,9cases were5scale,17cases were6scale,20cases were7scale,5cases were8scale,12cases were9scale,7cases were10scale,2cases were11scale,2cases were12scale.44patients had bilateral pupil change, accounting for44.4%. Other cases had not change of pupil. There were26patients with central high fever, accounting for26.3%.73.7%of the patients had no central high fever. CT within24hours after injury, showed0-1lesion in52patients (52.7%).47cases had more than2lesions. Admission in patients with only12cases decline of the serum magnesium concentration,87cases of normal magnesium ion concentration.23patients with admission serum calcium concentration decrease,76cases of normal calcium ion concentration.3. Treatment:99patients were divided into two groups. The experimental group was treated with10ml of250g/L MgSO4injection in100ml normal saline, dripped within15min right after admission and followed by40ml of250g/L MgSO4injection in500ml normal saline dripped continuously in24hr for3consecutive days. The control group was treated without MgSO4.Both groups were treated with nimodipine injection intravenously5-10mg/hr for7consecutive days after admission. The prognoses was followed up to observe the relationship between prognoses and early MgSO4treatment.4. Statistical analysis: All statistical analyses were conducted using SPSS software version17.0(SPSS). GCS at admission and the follow-up of GOS used a linear correlation test. The Kruskal-Waliis H test was used to determine the statistical differences of prognosis in different age. The Wilcoxon rank sum test was applied to assess the relationship between gender, pupil change at admission, the central high fever, the lesion number in CT, the serum concentration of magnesium ions, the serum concentration of calcium ions and GOS in the two groups. A Pearson x2test was used for the mortality and follow up GOS in survival patients of the two groups. Multivariate analysis of prognoses was used the Polytomous logistic regression analysis. P<0.05was considered as statistically significant.Results:The GCS at admission can refect the severity of injury. It was significantly related to the prognosis of GOS. The more serious injury grade of GCS, the worse prognosis of GOS was. Excluding the impact of children and elder, the age of patients was no significant correlation with the prognosis, and the same with gender. The change of pupil and central high fever were often associated with brain stem injury or hypothalamus injury, which led to a worse prognosis. The lesion number in CT suggested its correlation with prognosis by the single factor analysis, but multivariate analysis did not support this correlation. So, it needs to make a further study to confirm the result. Both the serum concentration of magnesium ions and calcium ions at admission were not significantly associated with the prognosis. There was no significant difference of fatality rate between the MgSO4group and the control group, in which patients only treated with nimodipine alone. However, the MgSO4group had a significant higher good recovery and moderate disability than the control group (x2=4.937, v=1, P=0.026)Conclusion:1. The factor of age can not affect the prognosis in diffuse axonal injury. Gender is not an independent prognostic factor either.2. The two leading causes of DAI are traffic accidence and falling from the height. It can not be ignored that sports injury is an important injured factor. With the improving standards of social life and emergence of dangerous sports, it is necessary to enhance the sports security and related education.3. The coma severity by GCS at admission is an important determinant of prognosis and assessment of DAI. Patients with the change of pupil and central high fever often indicate the brain stem injury or hypothalamus injury, which lead to serious consequences and could be considered as independent factors in the prognosis evaluation.4. The lesion number of CT may help determine the prognosis, but multivariate analysis prompted that it is not accurate. CT, as its little time consuming, cheapness and expedience, can be take as a basic and preliminary screening test of DAI. In the circumstances of the patients having poor clinical condition without positive change of CT, it is suitable to have a MRI examination and DTI, SWI, etc further.5. The serum concentration of magnesium and calcium after injury are not significant correlation with the prognosis.6. It had be confirmed that calcium influx after diffuse axonal injury led to axonal intracellular calcium overloading, resulting in a series of pathophysiological changes, made axonal injury severely. It was identified by most of the studies that early application of nimodipine, a calcium channel blocker, can help to reduce calcium overloading and cell edema, decrease the severity of axonal injury.7. This study showed that the early treatment combined with magnesium sulfate (MgSO4) after injury may prevent cell membrane damage and maintain a stable internal environment to alleviate the axonal edema and reduce secondary brain insult. It may also reduce calcium influx and block the toxic effects of glutamate on neurons to protect more neurons from death and restore the brain function, Thus this treatment lowered the severe disability, improved the prognoses of patients and enhanced their life qualities.