Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

Traumatic brain injury(TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1(Ang-1), vascular endothelial growth factor(VEGF), and granulocyte-colony stimulating factor(G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended(GOSE). Patients having a GOSE score of 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1–5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI(within 7 days). This study was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800018251) on September 7, 2018.     

Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury

Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In this study, 96 adult patients with TBI(enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group(36 males and 25 females, aged 38 ± 13 years) and severe TBI group(22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls(15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.     

Evaluating the prognosis and degree of brain injury by combined S-100 protein and neuron specific enolase determination

BACKGROUND: S-100 and neuron specific enolase (NSE) possess the characteristics of specific distribution in brain and relative stable content. Some studies suggest that combined detection of the both is of very importance for evaluating the degree of brain injury. OBJECTIVE: To observe the changes of S-100 protein and NSE levels at different time points after acute brain injury, and evaluate the values of combined detection of the both for different injury degrees, pathological changes and prognosis. DESIGN: Case-control observation. SETTING: Department of Neurosurgery, Second Affiliated Hospital, Lanzhou University. PARTICIPANTS: Thirty-four inpatients with brain injury, 19 males and 15 females, aged 15 to 73 years, who received treatment between September 2005 and May 2006 in the Department of Neurosurgery, Second Affiliated Hospital, Lanzhou University, were recruited. The patients were admitted to hospital at 24 hours after brain injury. After admission, skull CT confirmed that they suffered from brain injury. Following Glasgow coma score (GCS) on admission, the patients were assigned into 3 groups: severe group (GCS 3 to 8 points, n =15), moderate group (GCS 9 to 12 points, n =8) and mild group (GCS 13 to 15 points, n =11). Following Glasgow outcome scale (GOS) at 3 months after brain injury, the patients were assigned into good outcome group (GOS 4 to 5 points, good recovery and moderate disability included, n =19) and poor outcome group (GOS 1 to 3 points, severe disability, vegetative state and death, n =15). Ten subjects who received health examination concurrently were chosen as normal control group , including 6 males and 4 females , aged （45.4±14.3）years. In our laboratory, the normal level of NSE was ≤15.2 ng/L, and that of S100 was ≤ 0.105 μg/L. METHODS: ①Blood samples of control group were collected when the subjects received health examination. Blood samples of patients with brain injury were collected at 24 hours, 3, 7 and 14 days after injury. According to the instructions of NSE and S-100 kits purchased from Roche Company, serum NSE and S-100 levels were determined by electrochemiluminescence immunoassay (ECLIA). ②Analysis of variance was used for intergroup comparison, Spearman correlative analysis for comparison of different GCS and GOS, and linear regression analysis for comparison of correlation of two factors. MAIN OUTCOME MEASURES: ①The dynamic changes of NSE and S-100 of patients with different brain injuries and their correlations with GCS. ② The dynamic changes of NSE and S-100 of patients with different outcomes and their correlations with GOS. RESULTS: Thirty-four patients with brain injury and ten healthy persons were involved in the result analysis. ①Overall change rule of NSE and S100 after brain injury: NSE of patients with brain injury reached its peak at 24 hours after injury, then was gradually decreased with time and was below normal level in the 2nd week. The overall tendency of S-100 was the same as that of NSE in patients with brain injury. ② The dynamic changes of NSE and S100 of patients with different brain injuries and their correlations with GCS: NSE and S-100 levels at 24 hours after injury were significantly negatively correlated with those on admission （r = －0.537,－0.731, P < 0.05）. At 24 hours after injury, serum NSE and S-100 levels of patients with mild, moderate and severe brain injuries were significantly higher than those of control group (P < 0.05); At 14 days after brain injury, serum NSE and S-100 levels of patients with mild and severe brain injury were close to those of control group (P > 0.05); While at 24 hours, 3, 7 and 14 days after brain injury, the serum NSE and S-100 levels of patients with severe brain injury were significantly higher than those of control group (all P < 0.05). NSE level of patients with mild brain injury was decreased to normal level at 7 days after injury and that of patients with moderate brain injury at 14 days after injury. S-100 level of patients with mild and moderate brain injury was decreased to normal level at 14 days after injury. Serum NSE and S-100 levels of patients with severe brain injury always kept over normal level and those of patients with mild brain injury reached peak value at 3 days after injury. ③ The dynamic changes of NSE and S-100 levels of patients with different outcomes and their correlations with GOS: serum NSE and S-100 levels at 24 hours after injury were significantly negatively correlated with GOS （r =－0.573,－0.756, P < 0.05）. It suggested that the severer the injury was, the lower the GOS was. At 24 hours, 3, 7 and 14 days after injury, serum NSE and S-100 levels of patients in good outcome group were significantly lower than those of poor outcome group (P < 0.05). CONCLUSION: The injury degree and prognosis of patients with brain injury are correlated with serum NSE and S-100 levels. The detection of serum S-100 and NSE levels after injury can be used for evaluating injury and prognosis of brain injury     

Association between serum malondialdehyde levels and mortality in patients with severe brain trauma injury

There is a hyperoxidative state in patients with trauma brain injury （TBI）. Malondialdehyde （MDA） is an end-product formed during oxidative stress, concretely lipid peroxidation. In small studies （ highest sample size 50 patients）, higher levels of MDA have been found in non-surviving than surviving TBI patients. However, an association between serum MDA levels and mortality in patients with TBI has not been reported. Thus, the objective of this prospective, observational, muhicenter study, carried out in six Spanish Intensive Care Units, was to determine whether MDA serum levels are associated with early mortality in a large series of patients with severe TBI. Serum MDA levels were measured in 100 patients with severe TBI on day 1 and in 75 healthy controls. The end-point of the study was 30-day mortality. We found higher serum MDA levels in patients with severe TBI than in healthy controls （P 〈 0. 001 ）. Non-surviving TBI patients （ N = 27） showed higher serum MDA levels （P 〈 0. 001 ） than survivors （ N = 73）. Logistic regression analysis showed that serum MDA levels were associated with 30-day mortality （ OR = 4. 662 ; 95% CI = 1. 466 - 14. 824 ; P = 0. 01 ）, controlling for Glasgow coma score, age and computed tomography findings. Survival analysis showed that patients with serum MDA levels higher than 1.96 nmol/mL presented increased 30-day mortality than patients with lower levels （Hazard ratio = 3. 5 ; 95% CI = 1.43 - 8. 47; P 〈 0. 001 ）. Thus, the most relevant new finding of our study, the largest to date on serum MDA levels in patients with severe TBI, was an association between serum MDA levels and early mortality.     

Prognosis in prolonged coma patients with diffuse axonal injury assessed by somatosensory evoked potential

A total of 43 prolonged coma patients with diffuse axonal injury received the somatosensory evoked potential examination one month after injury in the First Affiliated Hospital, School of Medicine, Zhejiang University in China. Somatosensory evoked potentials were graded as normal, abnormal or absent (grades Ⅰ-Ⅲ) according to N20 amplitude and central conduction time. The outcome in patients with grade Ⅲ somatosensory evoked potential was in each case unfavorable. The prognostic accuracy of grade Ⅲ somatosensory evoked potential for unfavorable and non-awakening outcome was 100% and 80%, respectively. The prognostic accuracy of grade Ⅰ somatosensory evoked potential for favorable and wakening outcome was 86% and 100%, respectively. These results suggest that somatosensory evoked potential grade is closely correlated with coma severity and degree of recovery. Somatosensory evoked potential is a valuable diagnostic tool to assess prognosis in prolonged coma patients with diffuse axonal injury.     

Changes in circulating inflammatory cells and the relationship to secondary brain injury in patients with craniocerebral injury★

BACKGROUND: Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING: A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS: Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS: WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES: The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS: WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury (P < 0.01). These measures negatively correlated to the Glasgow coma scale (r = -0.657, -0.541, respectively, P < 0.05). In patients with Glasgow coma sale < 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 (P < 0.05). Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size (P < 0.05). CONCLUSION: WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale. Key Words: craniocerebral injury; inflammatory cells; secondary brain injury     

Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury

Fifty-one patients with mild(n = 14),moderate(n = 10) and severe traumatic brain injury(n = 27) received early rehabilitation.Level of consciousness was evaluated using the Glasgow Coma Score.Functional level was determined using the Glasgow Outcome Score,whilst mobility was evaluated using the Mobility Scale for Acute Stroke.Activities of daily living were assessed using the Barthel Index.Following Bobath neurodevelopmental therapy,the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury,but was not greatly influenced in patients with mild traumatic brain injury.Mobility and functional level were significantly improved in patients with mild,moderate and severe traumatic brain injury.Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury.Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury.Nevertheless,complete recovery was not acquired at discharge.Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury.     

Pre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from immunogenic and oncogenic perspectives

Stem cell therapy is a promising strategy for the treatment of traumatic brain injury(TBI). However, animal experiments are needed to evaluate safety;in particular, to examine the immunogenicity and tumorigenicity of human umbilical cord mesenchymal stem cells(hu MSCs) before clinical application. In this study, hu MSCs were harvested from human amniotic membrane and umbilical cord vascular tissue. A rat model of TBI was established using the controlled cortical impact method. Starting from the third day after injury, the rats were injected with 10 μL of 5 × 10⁶/m L hu MSCs by cerebral stereotaxis or with 500 μL of 1 × 10⁶/m L hu MSCs via the tail vein for 3 successive days. hu MSC transplantation decreased the serum levels of proinflammatory cytokines in rats with TBI and increased the serum levels of anti-inflammatory cytokines, thereby exhibiting good immunoregulatory function. The transplanted hu MSCs were distributed in the liver, lung and brain injury sites. No abnormal proliferation or tumorigenesis was found in these organs up to 12 months after transplantation. The transplanted hu MSCs negligibly proliferated in vivo, and apoptosis was gradually observed at later stages. These findings suggest that hu MSC transplantation for the treatment of traumatic brain injury displays good safety. In addition, hu MSCs exhibit good immunoregulatory function, which can help prevent and reduce secondary brain injury caused by the rapid release of inflammatory factors after TBI. This study was approved by the Ethics Committee of Wuhan General Hospital of PLA(approval No. 20160054) on November 1, 2016.     

Serum alkaline phosphatase and γ-glutamyl transpeptidase levels in patients with neuromyelitis optica and multiple sclerosis

Objective To investigate the serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS).Methods Serum ALP and GGT levels in patients with NMO and MS from the database of demyelinating diseases in our hospital were analyzed.Eighty-five healthy controls were chosen.The differences of serum ALP and GGT levels in patient groups and controls were compared, and the correlations between clinical features (age of the subjects, course of disease, times of relapse and scores of EDSS) and both ALP and GGT levels were analyzed. Results The serum ALP and GGT levels in patients with NMO were significantly higher than those in patients with MS and the controls (P<0.05).Patients with NMO still had significantly higher serum ALP level in acute phase than patients with MS,and the serum ALP levels in male patients with NMO and the serum GGT levels in female patients with NMO were, respectively,statistically higher than that of male patients with MS and female patients with MS (P<0.05). In patients with NMO, significantly positive correlations between serum GGT level and both age and times of relapse were noted (P<0.05). Conclusion Serum ALP and GGT levels differ in patients with NMO and MS, indicating their differential diagnostic value in NMO and MS to certain extent.     

Serum alkaline phosphatase and γ-glutamyl transpeptidase levels in patients with neuromyelitis optica and multiple sclerosis

Objective To investigate the serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS).Methods Serum ALP and GGT levels in patients with NMO and MS from the database of demyelinating diseases in our hospital were analyzed.Eighty-five healthy controls were chosen.The differences of serum ALP and GGT levels in patient groups and controls were compared, and the correlations between clinical features (age of the subjects, course of disease, times of relapse and scores of EDSS) and both ALP and GGT levels were analyzed. Results The serum ALP and GGT levels in patients with NMO were significantly higher than those in patients with MS and the controls (P<0.05).Patients with NMO still had significantly higher serum ALP level in acute phase than patients with MS,and the serum ALP levels in male patients with NMO and the serum GGT levels in female patients with NMO were, respectively,statistically higher than that of male patients with MS and female patients with MS (P<0.05). In patients with NMO, significantly positive correlations between serum GGT level and both age and times of relapse were noted (P<0.05). Conclusion Serum ALP and GGT levels differ in patients with NMO and MS, indicating their differential diagnostic value in NMO and MS to certain extent.     

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND: Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE: To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN: Case analysis. SETTING: Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS: A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5–108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS: Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187–1 059 ng/L and normal value of serum homocysteine was 5–15 μmol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES: ① Levels of blood routine, serum vitamin B12 and homocysteine; ② results of neuroelectrophysiological examination; ③ results of MRI examination of spinal cord; ④ prognosis. RESULTS: Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. ① Clinical manifestations: All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs (5 cases), unstable gait (3 cases), limb asthenia (4 cases), limb numbness combined with light asthenia (5 cases), limb numbness combined with unskillful activity (3 cases), and limb numbness combined with unstable gait (1 case). ② Experimental results: Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of homocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. ③ Results of neuroelectrophysiological examination: Among all patients, 95% (20/21) patients had abnormal sensory-evoked potential, 89% (8/9) patients had abnormal motor evoked potential, 67% (10/15) patients had abnormal nerve conduction, 13% (2/15) patients had neurogenic muscle injury showed by electromyography (EMG), 70% (7/10) patients had abnormal brain-stem auditory evoked potential, and 40% (4/10) patients had abnormal visual evoked potential. ④ Results of MRI examination of spinal cord: MRI examination demonstrated that 40% (6/15) patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B12 therapy. CONCLUSION: Nervous system lesion caused by vitamin B12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin B12. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.     

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury：not by immediately improving cerebral oxygen saturation and oxygen partial pressure

Although hyperbaric oxygen (HBO) therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury (TBI), the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation (rSO2) and oxygen partial pressure (PaO2). To test this idea, we compared two groups:a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO2 were measured. The controls were also examined for rSO2 and PaO2, but received no treatment. rSO2 levels in the patients did not differ signiifcantly after treatment, but levels before and after treatment were signiifcantly lower than those in the control group. PaO2 levels were signiifcantly decreased after the 30-minute HBO treatment. Our ifndings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.     

Prognostic value of dynamic electroencephalogram in comatose patients with different diseased regions

BACKGROUND: It has proved that dynamic electroencephalogram (EEG) is definite in judging the outcome of ischemic hypoxic comatose patients, EEG is more sensitive to the cortical affection, but not sensitive to the subcortical and brainstem affections, thus it is necessary to clarify the indications of this technique in the clinical application. OBJECTIVE: To observe and compare the prognostic value of dynamic EEG and Glasgow coma score in comatose patients with different diseased region. DESIGN: A clinical case-controlled observation. SETTING: Union Hospital of Fujian Medical University. PARTICIPANTS: Sixty-eight comatose patients were selected from the Union Hospital affiliated to Fujian Medical University from June 1998 to January 2005. The diseased regions were identified using cranial CT (n =43) or MR (n =25). According to different primarily diseased regions, the comatose patients were divided into two groups: ① brainstem affection group (n =23): 13 males and 10 females, 14–62 years of age; ② diffuse cortical affection group (n =45): 28 males and 17 females, 23–75 years of age. METHODS: The dynamic EEG and Glasgow coma score were examined in the 45 comatose patients with primarily cortical affection and 22 comatose patients with primarily brainstem affection at acute phase. The patients were followed-up for 3 months to observe the outcome, The termination of outcome judgment was 3 months after attack or the death. The clinical outcome was classified as complete rehabilitation, survived with disability, death or vegetative state. Correlations of dynamic EEG and Glasgow coma score with the outcome of patients were analyzed. The correlations of dynamic EEG grades and Glasgow coma scores with the outcome were analyzed, and the prognostic value of dynamic EEG grades was compared between the two groups. MAIN OUTCOME MEASURES: ① Correlations of dynamic EEG and Glasgow coma score with the outcome of patients; ② Comparison of the prognostic value of dynamic EEG grades between the two groups. RESULTS: All the 68 patients were involved in the analysis of results. ① Correlations of dynamic EEG grades and Glasgow scores and their correlation analysis: EEG grades had significant negative correlation with Glasgow coma scores in both the cortical affection group and brainstem affection group (r =–0.743, –0.564, P < 0.01, 0.05). In the cortical affection group, the Glasgow coma scores and dynamic EEG grades in the patients with the outcome of death or vegetative state were significantly different from those with the outcome of rehabilitation (P < 0.05–0.01). In the brainstem affection group, the Glasgow coma scores were only significantly different between the patients with outcome of rehabilitation and death (P < 0.05), and there was no significant difference in dynamic EEG grades among the three prognostic states (P > 0.05). ② Comparison of the prognostic value of dynamic EEG grades between comatose patients with cortical affection and brainstem affection: The sensitivity, specificity and accuracy were all higher (P < 0.05), while the error rate was lower (P < 0.05) in the cortical affection group than in the brainstem affection group. CONCLUSION: Dynamic EEG was valuable in predicting the outcome of comatose patients with primarily cortical affection, but it was not certainly valuable in those with primarily brainstem affection.     

血浆游离DNA水平增高可作为预测重型颅脑损伤患者死亡率的独立指标(英文)

Trauma is the leading cause of death under 45 years worldwide and up to 50% of trauma fatalities are due to brain injury.Prediction of outcome is one of the major problems associated with severe TBI and research efforts have focused on the investigation of biomarkers with prognostic value following TBI. Therefore,our aim was to investigate whether cell-free DNA concentrations correlated to short-term primary outcome( survivor or death) and GCS scores following severe TBI. A total of 188 victims of severe TBI were enrolled in this prospective study,outcome variables comprised: survival and neurological assessment using the GCS at ICU discharge. Control blood samples were obtained from 25 healthy volunteers. Peripheral venous blood was collected at admission in the ICU. Plasma DNA was measured using a real-time quantitative PCR assay for the β-globin gene. There was correlation between higher DNA levels and both fatal outcome and lower hospital admission GCS scores. Plasma DNA concentrations at the chosen cut- off point( ≥171,381 kilogenomesequivalents /L) predicted mortality with a specificity of 90% and a sensitivity of 43%. Logistic regression analysis showed that elevated plasma DNA levels were independently associated with death( P 0. 001). In conclusion,high cell-free DNA concentration was a predictor of short-term mortality following severe TBI.     

Changes in T lymphocyte subsets after severe traumatic brain injury

BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN: A comparative observation. SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16–62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14–15 points), including 18 males and 12 females, aging 15–58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury. Informed consents were obtained from all the patients or their relatives. METHODS: ① The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at 1, 3, 7 and 14 days after injury in both groups. ② The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1–14 days after severe and mild or moderate traumatic injury. RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. ① Changes of T lymphocyte subsets: At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77–3.26, P < 0.01), and began to recover at 7 days, which were significantly different from those in the control group (t = 2.06–2.24, P < 0.05), and generally recovered to the normal levels at 14 days (P > 0.05). ② Conditions of pulmonary infections: At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% (22/30), 0, χ2=37.29, P < 0.01]. CONCLUSION: Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period (within 7 days), and they are easily to be accompanied by pulmonary infections.     

Changes in T .lymphocyte subsets after severe traumatic brain inJury

BACKGROUND： Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE： To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN： A comparative observation. SETTINGS： Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS： All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score （GCS） was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group （GCS ranged 14- 15 points）, including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS： （1） The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. （2） The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES： Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS： Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. （1） Changes of T lymphocyte subsets： At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group （t =2.77 - 3.26, P 〈 0.01）, and began to recover at 7 days, which were significantly different from those in the control group （t = 2.06 - 2.24, P 〈 0.05）, and generally recovered to the normal levels at 14 days （P 〉 0.05）. （2） Conditions of pulmonary infections： At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% （22/30）, 0, x2=37.29, P 〈 0.01]. CONCLUSION： Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period （within 7 days）, and they are easily to be accompanied by pulmonary infections.     

Traumatic brain injury and palliative care: a retrospective analysis of 49 patients receiving palliative care during 2013–2016 in Turkey

Traumatic brain injury(TBI),which is seen more in young adults,affects both patients and their families.The need for palliative care in TBI and the limits of the care requirement are not clear.The aim of this study was to investigate the length of stay in the palliative care center(PCC),Turkey,the status of patients at discharge,and the need for palliative care in patients with TBI.The medical records of 49 patients with TBI receiving palliative care in PCC during 2013–2016 were retrospectively collected,including age and gender of patients,the length of stay in PCC,the cause of TBI,diagnosis,Glasgow Coma Scale score,Glas gow Outcome Scale score,Karnofsky Performance Status score,mobilization status,nutrition route(oral,percutaneous endoscopic gastrostomy),pressure ulcers,and discharge status.These patients were aged 45.4 ± 20.2 years.The median length of stay in the PCC was 34.0 days.These included TBI patients had a Glasg ow Coma Scale score ≤ 8,were not mobilized,received tracheostomy and percutaneous endoscopic gastrostomy nutrition,and had pressure ulcers.No difference was found between those who were discharged to their home or other places(rehabilitation centre,intensive care unit and death) in respect of mobilization,percutaneous endoscopic gastrostomy,tracheostomy and pressure ulcers.TBI patients who were followed up in PCC were determined to be relatively young patients(45.4 ± 20.2 years) with mobilization and nutrition problems and pressure ulcer formation.As TBI patients have complex health conditions that require palliative care from the time of admittance to intensive care unit,provision of palliative care services should be integrated with clinical applications.     

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord： Analysis of 21 cases

BACKGROUND： Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE： To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN： Case analysis. SETTING： Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS： A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5 - 108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS： Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187 - 1 059 ng/L and normal value of serum homocysteine was 5 - 15μ mol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES： （1） Levels of blood routine, serum vitamin B12 and homocysteine; （2） results of neuroelectrophysiological examination; （3） results of MRI examination of spinal cord; （4） prognosis. RESULTS： Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. （1） Clinical manifestations： All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs （5 cases）, unstable gait （3 cases）, limb asthenia （4 cases）, limb numbness combined with light asthenia （5 cases）, limb numbness combined with unskillful activity （3 cases）, and limb numbness combined with unstable gait （1 case）. （2） Experimental results： Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of bomocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. （3） Results of neuroelectrophysiological examination： Among all patients, 95% （20/21） patients had abnormal sensory-evoked potential, 89% （8/9） patients had abnormal motor evoked potential, 67% （10/15） patients had abnormal nerve conduction, 13% （2/15） patients had neurogenic muscle injury showed by electromyography （EMG）, 70% （7/10） patients had abnormal brain-stem auditory evoked potential, and 40% （4/10） patients had abnormal visual evoked potential. （4） Results of MRI examination of spinal cord： MRI examination demonstrated that 40% （6/15） patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B I2 therapy. CONCLUSION： Nervous system lesion caused by vitamin B 12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin BI2. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.     

Elevated cell-free plasma DNA level as an independent predictor of mortality in patients with severe traumatic brain injury

Trauma is the leading cause of death under 45 years worldwide and up to 50% of trauma fatalities are due to brain injury. Prediction of outcome is one of the major problems associated with severe TBI and research efforts have focused on the investigation of biomarkers with prognostic value following TBI. Therefore, our aim was to investigate whether cell-free DNA concentrations correlated to short-term primary outcome （survivor or death） and GCS scores following severe TBI. A total of 188 victims of severe TBI were enrolled in this prospective study, outcome variables comprised： survival and neurological assessment using the GCS at ICU discharge.     

亚低温对重型颅脑创伤患者血清抗脑抗体含量的影响

目的 研究重型颅脑创伤(sTBI)后患者血清抗脑抗体(ABAb)浓度变化及亚低温治疗对血清ABAb浓度的影响,探讨亚低温脑保护机制.方法 选择80例sTBI住院患者,随机分成常温治疗(NT)组和亚低温治疗(HT)组各40例,分别予以常温治疗和亚低温治疗,于伤后第1、3、5、7、14天采血.用酶联免疫吸附(ELISA)法测定血清ABAb浓度,观察各时间点血清ABAb浓度的变化,分析各时间点两组血清ABAb浓度与格拉斯哥预后评分(GOS)的相关性.另取20例健康体检者作为对照组.结果 (1)所有sTBI患者在伤后各时间点血清ABAb浓度高于正常对照组(P＜0.01).(2)HT组于伤后各时间点血清ABAb浓度低于NT组,且差异有统计学意义(P＜0.01).(3)NT组于伤后各时间点血清ABAb浓度与GOS评分呈负相关,出院时HT组预后也较NT组为佳.结论 HT能够降低sTBI患者血清ABAb含量,具有脑保护作用,其脑保护机制可能与HT能减轻血清ABAb介导的损伤性脑细胞炎性反应有关.

Abstract：

Objective To disclose the Probably protective mechanism of mild hypothermia protecting brain through investigating the contents charges of Antibrain-Antibody(ABAb)in serum in patients with severe traumatic brain injury(sTBI) and the influence of mild hypothermia on serum levels of ABAb.Methods A total of 80 cases with sTBI were treated with normothennia - treated (NT) (NT group, re =40)and mild hypothermia( HT) (HT group, n =40) respectively. ELISA was used to measure serum levels of ABAb. Groups at 1、3、5、7 and 14 days after injury to observe the contents changes of ABAb in serum and the influence of mild hypothermia. Simultaneous analysis two groups at each time point of serum ABAb concentration and Glasgow outcome scale (GOS) of relevance was performed Contrast analysis of clinical prognosis for patients in the two groups was carried out to reveal the protective mechanism of mild hypothermia protecting on patients with sTBL 20 serum specimens of normal persons were used as control group. Results (1) All sTBI patients at each time point after injury, serum ABAb levels were higher than the normal control group ( P ＜0.01). (2) Concentration of antibodies in the serum ABAb levels in HT group at each time point was lower than in NT group( P＜0.01). (3) Concentration of serum ABAb levels in NT group at each time point of injury was negatively correlated with the GOS score; prognosis at discharge in HT group was better than in NT group. Conclusions HT can reduce the serum ABAb levels in sTBI patients, improve the prognosis, have brain protective effect The brain protective mechanisms may be related to the mild hypothermia which reduce the serum ABAb - mediated inflammatory damage on brain cells.