<Emphasis Type="Italic">DRD2 C957T</Emphasis> polymorphism is associated with improved 6-month verbal learning following traumatic brain injury

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI—California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1–5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.     

ENIGMA brain injury: Framework,challenges, and opportunities

Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury-related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes. Additionally, development of reliable biomarkers of mild TBI or repeated subconcussive impacts has been slow, likely due, in part, to subtle effects of injury and the aforementioned variability. The ENIGMA Consortium has established a framework for global collaboration that has resulted in the largest-ever neuroimaging studies of multiple psychiatric and neurological disorders. Here we describe the organization, recent progress, and future goals of the Brain Injury working group.     

Outcomes of traumatic brain injury in Hong Kong: Validation with the TRISS,CRASH, and IMPACT models

We aimed to test prognostic models (the Trauma Injury Severity Score, International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury, and Corticosteroid Randomisation After Significant Head Injury models) for 14-day mortality, 6-month mortality, and 6-month unfavorable outcome in a cohort of trauma patients with traumatic brain injury (TBI) in Hong Kong. We analyzed 661 patients with significant TBI treated in a regional trauma centre in Hong Kong over a 3-year period. The discriminatory power of the models was assessed as the area under the receiver operating characteristic curve. One-sample t-tests were used to compare actual outcomes in the cohort against predicted outcomes. All three prognostic models were shown to have good discriminatory power and no significant systemic over-estimation or under-estimation. In conclusion, all three predictive models are applicable to eligible TBI patients in Hong Kong. These predictive models can be utilized to audit TBI management outcomes for trauma service development in the future.     

Decision making and somatic markers in conversation after traumatic brain injury

Background: Social decision making has been investigated in a range of client groups, resulting in the identification of the ventromedial prefrontal cortex (VMPC) as a significant structure in social decision making and the formulation of the somatic marker hypothesis (Damasio, 1994 Damasio, A. R. 1994. Descartes' error: Emotion, reason, and the human brain, New York: Putnam.  [Google Scholar]) to explain some of the mechanisms involved. The vulnerability of the VMPC following traumatic brain injury (TBI) suggests a potential degree of overlap between decision‐making research and behaviour observed following TBI. Despite this, relatively little awareness of these concepts is evident in research on TBI in general and on communication after TBI in particular.

Aims: To review the literature on decision making and the mechanisms thought to mediate it. To examine the potential application of decision‐making theory to conversational behaviour following TBI.

Main Contribution: The article will highlight the potential role of decision making in conversation, together with the mechanisms that support it, thereby raising awareness among clinicians and researchers of a potentially important contributor to communication after TBI.

Conclusions: Social decision making and the somatic marker hypothesis are important constructs for our understanding of behaviours associated with TBI, including conversation.     

The FOUR Score Predicts Mortality,Endotracheal Intubation and ICU Length of Stay After Traumatic Brain Injury

Background

The Glasgow Coma Scale (GCS) is the most widely accepted scale for assessing levels of consciousness, clinical status, as well as prognosis of traumatic brain injury (TBI) patients. The Full Outline of UnResponsiveness (FOUR) score is a new coma scale developed addressing the limitations of the GCS. The aim of this prospective cohort study was to compare the performance of the FOUR score vs. the GCS in predicting TBI outcomes.

Methods

From April to July 2011, 60 consecutive adult patients with TBI admitted to the Alexandria Main University Hospital intensive care units (ICU) were enrolled in the study. GCS and FOUR score were documented on arrival to emergency room. Outcomes were in-hospital mortality, unfavorable outcome [Glasgow outcome scale extended (GOSE) 1–4], endotracheal intubation, and ICU length of stay (LOS).

Results

Fifteen (25 %) patients died and 35 (58 %) had unfavorable outcome. When predicting mortality, the FOUR score showed significantly higher area under receiver operating characteristic curve (AUC) than the GCS score (0.850 vs. 0.796, p = 0.025). The FOUR score and the GCS score were not different in predicting unfavorable outcome (AUC 0.813 vs. 0.779, p = 0.136) and endotracheal intubation (AUC 0.961 vs. 0.982, p = 0.06). Both scores were good predictors of ICU LOS (r ² = 0.40 [FOUR score] vs. 0.41 [GCS score]).

Conclusions

The FOUR score was superior to the GCS in predicting in-hospital mortality in TBI patients. There was no difference between both scores in predicting unfavorable outcome, endotracheal intubation, and ICU LOS.     

Novel mGluR5 Positive Allosteric Modulator Improves Functional Recovery,Attenuates Neurodegeneration,and Alters Microglial Polarization after Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) causes microglial activation and related neurotoxicity that contributes to chronic neurodegeneration and loss of neurological function. Selective activation of metabotropic glutamate receptor 5 (mGluR5) by the orthosteric agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), is neuroprotective in experimental models of TBI, and has potent anti-inflammatory effects in vitro. However, the therapeutic potential of CHPG is limited due to its relatively weak potency and brain permeability. Highly potent, selective and brain penetrant mGluR5 positive allosteric modulators (PAMs) have been developed and show promise as therapeutic agents. We evaluated the therapeutic potential of a novel mGluR5 PAM, VU0360172, after controlled cortical impact (CCI) in mice. Vehicle, VU0360172, or VU0360172 plus mGluR5 antagonist (MTEP), were administered systemically to CCI mice at 3 h post-injury; lesion volume, hippocampal neurodegeneration, microglial activation, and functional recovery were assessed through 28 days post-injury. Anti-inflammatory effects of VU0360172 were also examined in vitro using BV2 and primary microglia. VU0360172 treatment significantly reduced the lesion, attenuated hippocampal neurodegeneration, and improved motor function recovery after CCI. Effects were mediated by mGluR5 as co-administration of MTEP blocked the protective effects of VU0360172. VU0360172 significantly reduced CD68 and NOX2 expression in activated microglia in the cortex at 28 days post-injury, and also suppressed pro-inflammatory signaling pathways in BV2 and primary microglia. In addition, VU0360172 treatment shifted the balance between M1/M2 microglial activation states towards an M2 pro-repair phenotype. This study demonstrates that VU0360172 confers neuroprotection after experimental TBI, and suggests that mGluR5 PAMs may be promising therapeutic agents for head injury.     

Prevalence and Risk Factors for Early Seizure in Patients with Traumatic Brain Injury: Analysis from National Trauma Data Bank

Background

Traumatic brain injury (TBI) is a well-known risk factor for seizures. We aimed to identify the frequency and risk factors for seizure occurrence during hospitalization for TBI.

Methods

We used ICD-9-CM codes to identify patients 18 years of age or older from the National Trauma Data Bank who were admitted with TBI. We also used ICD-9-CM codes to identify the subset who had seizures during hospitalization. Patient demographics, comorbidities, Glasgow Coma Scale (GCS) score, Injury Severity Score Abbreviated Injury Scale (ISSAIS), in-hospital complications, and discharge disposition were compared in the seizure group (SG) and no-seizure group (NSG).

Results

A total of 1559 patients had in-hospital seizures, comprising 0.4% of all patients admitted with TBI. The mean age of SG was 3 years older than NSG [51 vs. 48; p < 0.0001]. African-American ethnicity (20 vs. 12%, p < 0.0001) and moderate TBI (8 vs. 4%, p < 0.0001) were more common in SG. History of alcohol dependence was more common in the SG (25 vs. 11%, p < 0.0001). Fall was the most common mechanism of injury in SG (56 vs. 36% in NSG; p < 0.0001). Subdural hematoma was more common in SG (31 vs. 21%, p < 0.0001). SG had higher rates of pneumonia, ARDS, acute kidney injury, and increased ICP. The average length of hospital stay was significantly higher in SG (10 vs. 6 days, p < 0.0001), and these patients had higher rate of discharge to nursing facility (32 vs. 25%, p < 0.0001).

Conclusion

In-hospital seizures occur in 0.4% of all TBI patients. Although infrequent, seizure occurrence is associated with higher rates of hospital complications such as pneumonia and ARDS and is an independent predictor of longer hospital stay and worse hospital outcome.

     

Microbleeds on susceptibility-weighted MRI in depressive and non-depressive patients after mild traumatic brain injury

The aim of this study was to explore the relationship between abnormality on susceptibility-weighted imaging (SWI) and newly-developed depression after mild traumatic brain injury. The study registered 200 patients with closed TBI and normal finding at CT and conventional MRI. All patients underwent MRI including conventional MR sequences and SWI. The number and volume of microbleed lesions were semi-automatically outlined and manually counted. All patients were followed up with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-IV) within 1 year after TBI. The difference in microbleed lesions on SWI was compared between the depressive and non-depressive groups. The depressive group had a higher rate of abnormality on SWI than did the non-depressive group (p < 0.001). Among patients that had exhibited microbleed lesions, the number and volume of lesions were greater in the depressive group than the non-depressive group (both p < 0.001). These differences in numbers and volume of lesions were found only at the frontal, parietal and temporal lobes (all p < 0.001). Among patients that had exhibited microbleed lesions, the number and volume of lesions in other areas were not significantly different between the depressive and non-depressive groups (all p > 0.05). In conclusion, SWI was useful to identify the microbleed lesions after mild TBI. The distribution range and location of microbleed lesions were correlated with depression after TBI.     

Neuritin provides neuroprotection against experimental traumatic brain injury in rats

Objectives: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Neuritin is a neurotrophic factor that regulates neural growth and development. However, the role of neuritin in alleviating TBI has not been investigated.

Methods: In this study, Sprague Dawley rats (n = 144) weighing 300 ± 50 g were categorized into control, sham, TBI and TBI + neuritin groups. The neurological scores and the ultrastructure of cortical neurons, apoptotic cells and caspase-3 were measured by using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Western blot analysis and real-time RT-PCR at various time points post-TBI.

Conclusions: Our findings indicated that neuritin plays a protective role in TBI by improving neurological scores, repairing injured neurons and protecting the cortical neurons against apoptosis through inhibition of caspase-3 expression. Further investigation of the molecular mechanisms underlying caspase-3 inhibition by neuritin will provide a research avenue for potential TBI therapeutics.     

Awareness of deficit following traumatic brain injury: A systematic review of current methods of assessment

ABSTRACT

Background: Awareness of deficit plays an important role in adjustment following a brain injury and has been noted to impact on engagement with and outcome of rehabilitation. However, there are challenges associated with the assessment of awareness.

Aim: To systematically review all instruments used to assess intellectual awareness of deficits following Traumatic Brain Injury (TBI) in adults, and evaluate instrument characteristics (e.g., the format and focus of measures of awareness) and assessment methods adopted.

Results: Thirty-four studies, all rated as fair to good quality, were identified and within these twenty-three different assessment tools were adopted. The most common method of assessment was patient-proxy discrepancy, with three frequently used instruments employed in a total of 22 of the 34 studies. Across studies, variability was noted regarding the type of assessment method dependent on various sample demographics (e.g., age of sample) and injury characteristics (e.g., time post injury).

Conclusions: There is no consensus on the preferred instrument to assess intellectual awareness of deficits after TBI. Continued instrument development should attempt to incorporate multiple perspectives and assessment should take into account demographic and injury-related factors. An insightful avenue for future research would be to determine which factors are likely to impact awareness measurement.     

Neuroinflammation and blood–brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets

Traumatic Brain Injury (TBI) is the most frequent cause of death and disability in young adults and children in the developed world, occurring in over 1.7 million persons and resulting in 50,000 deaths in the United States alone. The Centers for Disease Control and Prevention estimate that between 3.2 and 5.3 million persons in the United States live with a TBI-related disability, including several neurocognitive disorders and functional limitations. Following the primary mechanical injury in TBI, literature suggests the presence of a delayed secondary injury involving a variety of neuroinflammatory changes. In the hours to days following a TBI, several signaling molecules and metabolic derangements result in disruption of the blood–brain barrier, leading to an extravasation of immune cells and cerebral edema. The primary, sudden injury in TBI occurs as a direct result of impact and therefore cannot be treated, but the timeline and pathophysiology of the delayed, secondary injury allows for a window of possible therapeutic options. The goal of this review is to discuss the pathophysiology of the primary and delayed injury in TBI as well as present several preclinical studies that identify molecular targets in the potential treatment of TBI. Additionally, certain recent clinical trials are briefly discussed to demonstrate the current state of TBI investigation.     

Emergency Neurological Life Support: Traumatic Brain Injury

Traumatic Brain Injury (TBI) was chosen as an Emergency Neurological Life Support topic due to its frequency, the impact of early intervention on outcomes for patients with TBI, and the need for an organized approach to the care of such patients within the emergency setting. This protocol was designed to enumerate the practice steps that should be considered within the first critical hour of neurological injury.     

PACAP38 Suppresses Cortical Damage in Mice with Traumatic Brain Injury by Enhancing Antioxidant Activity

The production of reactive oxygen species (ROS) and the resulting oxidative stress in mice in response to a controlled cortical impact (CCI) are typical exacerbating factors associated with traumatic brain injury (TBI). Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a multifunctional peptide that has been shown to exhibit neuroprotective effects in response to a diverse range of injuries to neuronal cells. We recently reported that PACAP38 might regulate oxidative stress in mice. The aim of the present study was to determine whether PACAP38 exerts neuroprotective effects by regulating oxidative stress in mice with TBI. Reactive oxidative metabolites (ROMs) and biological antioxidant potential (BAP) were measured in male C57Bl/6 mice before and 3, 4, and 24 h after CCI. PACAP38 was administered intravenously immediately following CCI, and immunostaining for the oxidative stress indicator nitrotyrosine (NT), and for neuronal death as an indicator of the area affected by TBI, was measured 24 h later. Western blot experiments to determine antioxidant activity [as indicated by superoxide dismutase-2 (SOD-2) and glutathione peroxidase 1 (GPx-1)] in the neocortical region were also performed 3 h post-CCI. Results showed that plasma BAP and ROM levels were dramatically increased 3 h after CCI. PACAP38 suppressed the extent of TBI and NT-positive regions 24 h after CCI, and increased SOD-2 and GPx-1 levels in both hemispheres. Taken together, these results suggest that increasing antioxidant might be involving in the neuroprotective effect of PACAP38 in mice subjected to a CCI.     

COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury

Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val¹⁵⁸Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist – Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met¹⁵⁸ allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09–0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20–6.86]) 6-months following injury. The COMT Val¹⁵⁸Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10–0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11–0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03–0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69–4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.     

Measuring recovery in new learning and memory following traumatic brain injury: a mixed-effects modeling approach

Patterns of recovery from traumatic brain injury (TBI) vary greatly across individuals. Using archival data from the Traumatic Brain Injury Model Systems, recovery of memory following TBI as measured by scores on the Rey Auditory Verbal Learning Test (RAVLT) through 5 years postinjury was examined via mixed-effects modeling. Individual-level variables of age and posttraumatic amnesia duration were significant predictors of 1-year RAVLT total score. None of the variables examined predicted the trajectory of memory recovery after 1 year. Mixed-effects analyses can be helpful in determining the effect of intervention while allowing for missing data across time points.     

Fluid markers of traumatic brain injury

Traumatic brain injury (TBI) occurs when an external force traumatically injures the brain. Whereas severe TBI can be diagnosed using a combination of clinical signs and standard neuroimaging techniques, mild TBI (also called concussion) is more difficult to detect. This is where fluid markers of injury to different cell types and subcellular compartments in the central nervous system come into play. These markers are often proteins, peptides or other molecules with selective or high expression in the brain, which can be measured in the cerebrospinal fluid or blood as they leak out or get secreted in response to the injury. Here, we review the literature on fluid markers of neuronal, axonal and astroglial injury to diagnose mild TBI and to predict clinical outcome in patients with head trauma. We also discuss chronic traumatic encephalopathy, a progressive neurodegenerative disease in individuals with a history of multiple mild TBIs in a biomarker context. This article is part of a Special Issue entitled ‘Traumatic Brain Injury’.     

Influence of ATP-Binding Cassette Polymorphisms on Neurological Outcome After Traumatic Brain Injury

Background

As important mediators of solute transport at the blood–brain and blood–cerebrospinal fluid barriers, ATP-binding cassette (ABC) transporters (including ABCB1, ABCC1, and ABCC2), impact the bioavailability of drugs and endogenous substrates in the brain. While several ABCB1, ABCC1, and ABCC2 single nucleotide polymorphisms (SNPs) have been identified, their impact on outcome after traumatic brain injury (TBI) is unknown.

Hypothesis

ABCB1, ABCC1, and ABCC2 SNPs are associated with Glasgow Outcome Scale (GOS) score after TBI.

Methods

DNA samples from 305 adult patients with severe TBI (Glasgow Coma Scale, GCS score ≤ 8) were genotyped for tagging SNPs of ABCB1 (rs1045642; rs1128503), ABCC1 (rs212093; rs35621; rs4148382), and ABCC2 (rs2273697). For each SNP, patients were dichotomized based on presence of variant allele for multivariate analysis to determine associations with GOS assigned at 6 months adjusting for GCS, Injury Severity score, age, and patient sex.

Results

For ABCB1 rs1045642, patients homozygous for the T allele were less likely to be assigned poor outcome versus those possessing the C allele [CT/CC; odds of unfavorable GOS = 0.71(0.55–0.92)]. For ABCC1 rs4148382, patients homozygous for the G allele were less likely to be assigned poor outcome versus those possessing the A allele [AG/AA; odds of unfavorable GOS = 0.73(0.55–0.98)].

Conclusions

In this single-center study, patients homozygous for the T allele of ABCB1 rs1045642 or the G allele of ABCC1 rs4148382 were found to have better outcome after severe TBI. Further study is necessary to replicate these very preliminary findings and to determine whether these associations are due to central nervous system bioavailability of ABC transporter drug substrates commonly used in the management of TBI, brain efflux of endogenous solutes, or both.     

Severe Leukoaraiosis Portends a Poor Outcome After Traumatic Brain Injury

Background and Purpose

It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI.

Methods

We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0–4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively.

Results

After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3–6 and GOS 1–3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) ≤12; p = 0.001], or had mild TBI (GCS 13–15; p = 0.002), respectively.

Conclusion

We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization.

     

轻、中度颅脑创伤患者早期症状群的分析研究

目的调查并分析轻中度颅脑创伤患者早期症状群的发生及分布情况。方法采用成人颅脑创伤症状自评量表以及90项症状自评量表(SCL-90)分别对颅脑创伤急性期治愈后拟出院患者及仅门诊就诊患者进行调查。使用主成分分析法(PCA)对全部颅脑创伤症状进行检验。结果自2012年9月至2013年9共收集到符合纳入标准病例132例,成人颅脑创伤症状自评量表经PCA分析显示存在4个症状群,分别命名为躯体化症状群,睡眠-情绪-认知症状群,神经行为症状群以及精力下降型症状群;SCL-90中颅脑创伤相关症状亚量表(BIS)经PCA分析后显示存在3个症状群,分别命名为躯体化症状群、精力下降型症状群以及情绪性症状群。其中稳定成群的症状有:头痛、头晕与注意力障碍;动力缺乏与思维迟缓。结论颅脑创伤后早期亦存在症状聚集成群的情况,颅脑创伤早期症状群的研究有助于理解症状的病理生理学特征,并能有针对性改善颅脑创伤后患者生活质量。