Association between elevated brain tissue glycerol levels and poor outcome following severe traumatic brain injury

OBJECT: Glycerol is considered to be a marker of cell membrane degradation and thus cellular lysis. Recently, it has become feasible to measure via microdialysis cerebral extracellular fluid (ECF) glycerol concentrations at the patient's bedside. Therefore the aim of this study was to investigate the ECF concentration and time course of glycerol after severe traumatic brain injury (TBI) and its relationship to patient outcome and other monitoring parameters. METHODS: As soon as possible after injury for up to 4 days, 76 severely head-injured patients were monitored using a microdialysis probe (cerebral glycerol) and a Neurotrend sensor (brain tissue PO2) in uninjured brain tissue confirmed by computerized tomography scanning. The mean brain tissue glycerol concentration in all monitored patients decreased significantly from 206 +/- 31 micromol/L on Day 1 to 9 +/- 3 micromol/L on Day 4 after injury (p < 0.0001). Note, however, that there was no significant difference in the time course between patients with a favorable outcome (Glasgow Outcome Scale [GOS] Scores 4 and 5) and those with an unfavorable outcome (GOS Scores 1-3). Significantly increased glycerol concentrations were observed when brain tissue PO2 was less than 10 mm Hg or when cerebral perfusion pressure was less than 70 mm Hg. CONCLUSIONS: Based on results in the present study one can infer that microdialysate glycerol is a marker of severe tissue damage, as seen immediately after brain injury or during profound tissue hypoxia. Given that brain tissue glycerol levels do not yet add new clinically significant information, however, routine monitoring of this parameter following traumatic brain injury needs further validation.     

Hybrid outcome prediction model for severe traumatic brain injury

Numerous studies addressing different methods of head injury prognostication have been published. Unfortunately, these studies often incorporate different head injury prognostication models and study populations, thus making direct comparison difficult, if not impossible. Furthermore, newer artificial intelligence tools such as machine learning methods have evolved in the field of data analysis, alongside more traditional methods of analysis. This study targets the development of a set of integrated prognostication model combining different classes of outcome and prognostic factors. Methodologies such as discriminant analysis, logistic regression, decision tree, Bayesian network, and neural network were employed in the study. Several prognostication models were developed using prospectively collected data from 513 severe closed head-injured patients admitted to the Neurocritical Unit at National Neuroscience Institute of Singapore, from April 1999 to February 2003. The correlation between prognostic factors at admission and outcome at 6 months following injury was studied. Overfitting error, which may falsely distinguish different outcomes, was compared graphically. Tenfold cross-validation technique, which reduces overfitting error, was used to validate outcome prediction accuracy. The overall prediction accuracy achieved ranged from 49.79% to 81.49%. Consistently high outcome prediction accuracy was seen with logistic regression and decision tree. Combining both logistic regression and decision tree models, a hybrid prediction model was then developed. This hybrid model would more accurately predict the 6-month post-severe head injury outcome using baseline admission parameters.     

Vocational outcome of aphasic patients following severe traumatic brain injury

The incidence and course of aphasia, and its impact on vocational outcome, were determined in a group of 351 patients with severe traumatic brain injury TBI . Aphasia was found in 111 , the common forms being amnestic 56 , 22 39 , expressive 10 3 , 4 39 and receptive 10 5 , 8 39 , as found on the first language assessment. No age difference was found between the aphasic and nonaphasic patients. Coma was more common in the aphasics than the non-aphasics 95 and 82 , respectively , although its mean duration was shorter. Aphasics had more severe locomotor deficits p 0 01, Fisher test and tended towards more severe cognitive disorders p 0 07, Fisher test . There was no difference between the groups in incidence of behavioural disturbances or occupational outcome. Most of the aphasic patients improved after therapy, and two recovered completely. The presence of aphasia did not have negative prognostic implications for occupational outcome.     

Blood pressure and outcome after severe pediatric traumatic brain injury

BACKGROUND: The relationship between systolic blood pressure and outcome in children after severe traumatic brain injury (TBI) is unclear. We examined the relationship between age-appropriate systolic blood pressure (AASBP) percentile and outcome after severe pediatric TBI. METHODS: We examined the association between AASBP percentiles and outcome in 172 children younger than 14 years of age with a Glasgow Coma Scale score < 9. Outcome was evaluated using discharge Glasgow Outcome Scale score. Poor outcome was defined as a Glasgow Outcome Scale score < 4. RESULTS: Poor outcome was associated with AASBP < 75th percentile (odds ratio, 4.2; 95% confidence interval, 2.1-8.3). Patients with systolic blood pressure (SBP) > or = 90 mm Hg and AASBP < 75th percentile had a higher odds for poor outcome compared with patients with SBP > or = 90 mm Hg and AASBP > or = 75th percentile (odds ratio, 3.5; 95% confidence interval, 1.7-7.3). CONCLUSION AASBP < 75th percentile was associated with poor outcome after severe pediatric TBI, even when SBP was > or = 90 mm Hg.     

Interleukin-6 and nerve growth factor upregulation correlates with improved outcome in children with severe traumatic brain injury

Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.     

Time of hypotension and discharge outcome in children with severe traumatic brain injury

We performed a retrospective study at a level I pediatric trauma center of patients admitted between 1998 and 2005 to determine the time after severe pediatric traumatic brain injury (TBI) that hypotension (systolic blood pressure [SBP] of <5th percentile) is most strongly associated with poor outcome. One hundred forty-six patients of <18 years of age with TBI, head Abbreviated Injury Score (AIS) of >or=3, and PICU admission Glasgow Coma Scale (GCS) score of <9 formed the analytic sample. Available SBP readings through the first 72 h after severe TBI were collected. SBP of <5th percentile was defined as hypotension. Discharge Glasgow Outcome Scale (GOS) score of <4 defined poor outcome. Of 146, 59 (40%) patients had discharge GOS of <4 and 12% died. The adjusted risk of poor outcome associated with hypotension stabilized by 8 h (adjusted risk ratio [RR] 1.7; 95% confidence interval [CI] 1.1-2.6) after injury. The risk of poor outcome peaked with hypotension occurring within the first 6 h after injury (RR 2.0, 95% CI 1.3-3.3). Poor discharge GOS was predicted by hypotension occurring during the first 6 h after injury. SBP data beyond the first 6 h did not improve our ability to predict poor discharge GOS. The first 6 h after severe pediatric TBI may represent a critical time period for either predicting or improving outcome.     

One-year outcome and course of recovery after severe traumatic brain injury

Goal  

To describe the outcome of patients with severe traumatic brain injury (TBI) 3, 6 and 12 months after trauma.     

Gender differences in outcome in patients with hypotension and severe traumatic brain injury

BACKGROUND: Animal studies have identified hormonal influences on responses to injury and recovery, creating a potential gender effect on outcome. Progesterone and oestrogen are thought to afford protection in the immediate post-injury period, suggesting females have an advantage, although there has been limited evidence of this in human outcome studies. METHODS: This study examined the influence of gender on outcome in 229 adults (151 males), aged >17 years, with severe blunt head trauma, initial GCS <9 and hypotension, recruited into a randomised controlled trial of pre-hospital hypertonic saline resuscitation versus conventional fluid management. Outcome was measured by survival and Glasgow Outcome Scale-Extended version (GOS-E) scores at 6 months post-injury. RESULTS: Females recruited into the study had a higher mean age. Females were more likely to be injured as passengers and pedestrians and males as drivers or motorcyclists. There were no gender differences in GCS or injury severity scores, ICP, cerebral perfusion pressure, gas exchange (PaO2/FiO2 ratio), or duration of mechanical ventilation. After controlling for GCS, age and cause of injury, females had a lower rate of survival. They also showed a lower rate of good outcome (GOS-E score >4) at 6 months, but this appeared to reflect the lower rate of initial survival. Those females surviving had similar outcomes to males. CONCLUSIONS: The study provides no evidence that females fare better than males following severe TBI, suggesting rather that females may fare worse.     

重型颅脑损伤后高血糖的临床意义分析

目的探讨重型颅脑损伤（SBI）后高血糖的临床意义。方法回顾性收集了128例重型闭合性颅脑损伤（GCS≤8分）患者的临床资料,应用统计学方法分析不同颅脑损伤损伤类型、入院时GCS水平、瞳孔光反应、近期预后与术后24小时内血糖水平的关系。颅脑损伤类型分为硬膜外血肿、硬膜下血肿、脑内血肿/脑挫裂伤3组;入院时GCS水平分成3-4分组、5-6分组、7-8分组;瞳孔对光反应情况分成双侧瞳孔光反应存在、单侧瞳孔光反应消失、双侧瞳孔光反应消失3组。近期预后分为预后良好和预后不良2组。结果重型颅脑损伤组血糖水平明显高于中型颅脑损伤组（P〈0.05）,3-4分组血糖水平（16.11±2.85）mmol/L明显高于7-8分组（12.33±2.23）mmol/L和5-6分组（14.11±2.85）mmol/L,而5-6分组血糖水平也明显高于7-8分组,各组间差异均有统计学意义（P〈0.05）;双侧瞳孔光反应消失组术后24小时内血糖水平（19.29±3.87）mmol/L,明显高于双侧瞳孔光反应存在组（15.69±2.83）mmol/L和单侧瞳孔光反应消失组（17.84±3.89）mmol/L,单侧瞳孔光反应消失组血糖水平明显高于双侧瞳孔光反应存在组,各组间差异均有统计学意义（P〈0.05）;预后不良组术后24小时内血糖水平明显高于预后良好组（P〈0.05）。血糖16.7mmol/L组的预后明显差于≤16.7mmol/L组（P〈0.05）。结论重型颅脑损伤后血糖水平明显增高。颅脑损伤伤情越重,血糖水平越高。高血糖是严重影响重型颅脑损伤预后的重要指标。     

Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats

Previous animal research suggests that progesterone may have powerful neuroprotective effects in traumatic brain injury (TBI). This experiment tested the hypothesis that progesterone levels correlate with decreased cerebral edema in male rats with bilateral medial frontal cortex injuries. Three groups of male Sprague-Dawley rats were used: injured given progesterone (4 mg/kg), injured given vehicle (oil), and uninjured controls given vehicle. Progesterone or vehicle was administered intraperitoneally at 1, 6, and 24 h postinjury. At 48 h postinjury, the rats were killed, brains extracted, and assayed for edema. Percent difference in water content of the area surrounding the lesion was compared to posterior cortex. A strong inverse relationship was found between serum progesterone levels and percent cerebral edema; the higher the progesterone levels, the lower the percent edema. Both progesterone and oil-treated animals had some edema compared to sham-operated controls. The brains of the injured animals given control solution were higher in water content than either the uninjured group or injured progesterone-treated rats 48 h postinjury. These findings confirm that progesterone significantly decreases cerebral edema after TBI in adult male subjects.     

Clinical predictors and neuropsychological outcome in severe traumatic brain injury patients

Summary Background. The aim of the study was to evaluate the possible significant role of some clinical factors in predicting cognitive outcome in a group of severe traumatic brain injury (TBI) patients, with Glasgow Coma Scale (GCS) lower than 8 and duration of unconsciousness for at least 15 days (prolonged coma).Method. A consecutive sample of 25 survivors of severe TBI attending the Physical and Cognitive Rehabilitation program participated in this study. The neuropsychological test battery included: Word-list Learning, Prose recall, Rey Figure Delayed recall, Word fluency, Ravens Progressive Matrices 47. The clinical variables evaluated in correlation with the neuropsychological outcome were the following: age, duration of unconsciousness, duration of post-traumatic amnesia, interval from head trauma to neuropsychological evaluation, interval from head trauma to recovery of oral feeding, and finally interval from head trauma to first verbal communication.Findings. The clinical variable with a significant predictive value on most neuropsychological scores was the interval from head trauma to the recovery of oral feeding.Conclusions. If this result is confirmed in larger samples, time interval of oral feeding recovery from head trauma should be considered as a possible predictor of neuropsychological outcome in TBI patients with prolonged coma.     

Serum and cerebrospinal fluid magnesium in severe traumatic brain injury outcome

Serum magnesium concentration has a neuroprotective effect in experimental models of traumatic brain injury (TBI). This study was designed to assess the relationship between initial serum magnesium, cerebrospinal fluid (CSF) magnesium, neurological outcome and the efficacy of magnesium replacement therapy (MgSO4). A retrospective analysis was performed on a prospectively collected dataset from 216 patients admitted during 1996-2006 to the University of Pittsburgh Medical Center with severe TBI. Admission serum and CSF magnesium were dichotomized into low and normal magnesium concentration groups for serum and normal and high concentration groups for CSF. A logistic-regression analysis was performed with 6-month Glasgow Outcome Scale (GOS) scores as outcome variable. The outcome of a subset of 31 patients who presented with low serum magnesium and who were rapidly corrected within 24 h of admission was also analyzed. Low initial serum magnesium was measured in 56.67% of all patients. Patients with an initial serum magnesium of <1.3 mEq/L were 2.37 times more likely to have a poor outcome (CI: 1.18-4.78, p = 0.016). The prognostic significance of depressed serum magnesium remained, even in patients whose serum magnesium levels were corrected within 24 h (OR = 11.03, CI: 1.87-68.14, p = 0.008). Patients with an initial high CSF magnesium were 7.63 more likely to have a poor outcome (p = 0.05). Elevated CSF magnesium correlated with depressed serum magnesium only in patients with poor outcome (p = 0.013). Patients with low serum magnesium and high CSF magnesium are most likely to have poor outcome after severe TBI. Rapid correction of serum magnesium levels does not reverse the prognostic value of these markers.     

Cognitive and psychosocial outcome following moderate or severe traumatic brain injury

The outcome of 96 consecutive adult patients with moderate to severe head injury was sequentially measured at 6, 12 and 24 months post-injury. In addition to global outcome using the Glasgow Outcome Scale (GOS) and a battery of neuropsychological tests of cognitive function, the Head Injury Symptom Checklist (HISC) and Relative's Questionnaire (RQ) were used. Although poorer GOS scores and severe cognitive impairments were typically associated with greater severity of initial injury, relatives reported similar functional problems irrespective of injury severity. This illustrates the legacy of moderate head injury in influencing many aspects of everyday life, supporting the argument that the needs of this group should not be overlooked.     

Clinical features of fever associated with poor outcome in severe pediatric traumatic brain injury

We describe the incidence and etiology of fever and the relationship between fever characteristics and outcome in children with severe traumatic brain injury (TBI). We conducted a retrospective study of children <14 years and with Glasgow Coma Scale (GCS) score of <9 admitted to a level I pediatric trauma center intensive care unit (PICU) between 1998 and 2003. We examined whether fever characteristics were associated with poor outcome (hospital discharge GCS score <13 and discharge disposition of either death or discharge to a skilled nursing facility). PICU length of stay (LOS) and hospital LOS were also examined. Data are presented as means and medians (SD), and P < 0.05 reflects significance. Ninety-three records were reviewed. Patients were 5.7 (SD 4.1) years old, 70% were male, and the average admission GCS score was 5. Mortality rate was 14%. Forty-eight (52%) patients had fever, and 23 (48%) of those patients had infectious fever. Each additional febrile episode was associated with a twofold higher risk of patients having a hospital discharge GCS score of <13 (odds ratio 2.4, 95% confidence interval 1.2-5.0) and having a 0.4-day longer PICU LOS (P < 0.001). Patients with infectious fever had a 0.9-day longer PICU LOS (P < 0.001). Patients with any fever in the PICU had an increased HLOS (0.9 days; P < 0.001). Our data suggest that in severe pediatric TBI, both fever and infection were common, and both were associated with longer LOS. Patients with higher fever burden had poor hospital discharge GCS score.     

Management of severe traumatic brain injury

Severe brain injuries, most often occurring in young subjects, are a major source of lost work years. These injuries are medical and surgical emergencies. Prehospital management of severe brain injuries requires intubation and mechanical ventilation aimed at normal arterial carbon dioxide pressure. Signs of transtentorial herniation: Uni- or bilateral mydriasis requires immediate perfusion of 20% mannitol or hypertonic sodium chloride. Neurological disorders after head injury justify emergency cerebral computed tomography. The presence of a mass syndrome or signs of transtentorial herniation are in principle indications for surgery. Specialized hospital management is essential. In the case of refractory intracranial hypertension, the cerebral perfusion pressure and osmotherapy should be adapted to the volume of the cerebral contusion. The use of deep hypothermia and barbiturates should be minimized as much as possible. Magnetic resonance imaging makes it possible to identify the cerebral lesions.