Increasing Risk of Dementia Among Patients with Subsequent Epilepsy Within 2 Years Post-Traumatic Brain Injury: A Population-Based Case-Control Study.

Background: Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial. Aim: This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period. Methods: This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression. Results: Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a >3.03 times risk of dementia after correcting for age, sex, and comorbidities. Conclusion: These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.

Association between short-term air pollution exposure and traumatic intracranial hemorrhage: pilot evidence from Taiwan.

Introduction: The detrimental effects of air pollution on the brain are well established. However, few studies have examined the effect of air pollution on traumatic brain injury (TBI). This pilot study evaluated the association between short-term air pollution exposure and traumatic intracranial hemorrhage (TIH). Methods: Hospital data of patients with TBI following road traffic accidents were retrospectively collected from the electronic medical records at five trauma centers in Taiwan between 1 January and 31 December 2017. TIH was employed as an outcome measure. All road accident locations were geocoded, and air quality data were collected from the nearest monitoring stations. Air pollutants were entered into five multivariable models. A sensitivity analysis was performed on patients who are vulnerable to suffering TBI after road accidents, including motorcyclists, bicyclists, and pedestrians. Results: Among 730 patients with TBI, 327 had TIH. The ages of ≥65 [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.85-5.70], 45-64 (OR, 2.61; 95% CI, 1.64-4.15), and 25-44 (OR, 1.79; 95% CI, 1.13-2.84) years were identified as significant risk factors in the multivariable analysis. In the best-fit multivariable model, exposure to higher concentrations of particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) was associated with an elevated TIH risk (OR, 1.50; 95% CI, 1.17-1.94). The concentration of nitrogen oxides (NOX) did not increase the risk of TIH (OR, 0.45; 95% CI, 0.32-0.61). After categorizing the air pollution concentration according to quartile, the trend tests in the multivariate model showed that the concentrations of PM2.5 and NOX were significant (p = 0.017 and p < 0.001, respectively). There was a negative borderline significant association between temperature and TIH risk (OR, 0.75; 95% CI, 0.56-1.00, p = 0.05). Notably, the single-vehicle crash was a significant risk factor (OR, 2.11; 95% CI, 1.30-3.42) for TIH. Discussion: High PM2.5 concentrations and low temperatures are risk factors for TIH in patients with TBI. High NOX concentrations are associated with a lower TIH risk.

Screening for Poor Self-Reported Sleep Quality at 12 Weeks in Post-Mild Traumatic Brain Injury Patients Using the HF-Age-Gender (HAG) Index.

To identify a screening tool for poor self-reported sleep quality at 12 weeks according to non-invasive measurements and patients' characteristics in the first week after mild traumatic brain injury (mTBI), data from 473 mTBI participants were collected and follow-ups were performed at 12 weeks. Patients with previous poor self-reported sleep quality prior to the injury were excluded. Patients were then divided into two groups at 12 weeks according to the Pittsburgh Sleep Quality Index based on whether or not they experienced poor sleep quality. The analysis was performed on personal profiles and heart rate variability (HRV) for 1 week. After analyzing the non-invasive measurements and characteristics of mTBI patients who did not complain of poor sleep quality, several factors were found to be relevant to the delayed onset of poor sleep quality, including age, gender, and HRV measurements. The HRV-age-gender (HAG) index was proposed and found to have 100% sensitivity (cut-off, 7; specificity, 0.537) to predicting whether the patient will experience poor sleep quality after mTBI at the 12-week follow-up. The HAG index helps us to identify patients with mTBI who have no sleep quality complaints but are prone to developing poor self-reported sleep quality. Additional interventions to improve sleep quality would be important for these particular patients in the future.

17ß-estradiol induces temozolomide resistance through NRF2-mediated redox homeostasis in glioblastoma.

Glioblastoma multiforme (GBM) is the most fatal cancer among brain tumors, and the standard treatment of GBM patients is surgical tumor resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. However, tumors always recur due to the developing drug resistance. It has been shown that neurosteroids, including dehydroepiandrosterone and 17ß-estradiol, are synthesized in TMZ-resistant GBM tumors. Therefore, we sought to explore the possible role of 17ß-estradiol in the development of drug resistance in GBM. Bioinformatics analysis revealed that aromatase/cytochrome P450 19A1 expression was gradually increased in the development from normal, astrocytoma to GBM. The level of 17ß-estradiol was significantly increased in TMZ-resistant cells characterized by ultra performance liquid chromatography-tandem mass spectrometry. Furthermore, 17ß-estradiol attenuated TMZ-induced cell death and reduced reactive oxygen species production by mitochondria. In addition, 17ß-estradiol attenuated oxidative stress by increasing the expression of superoxide dismutase 1/2, catalase, and nuclear factor erythroid 2-related factor (NRF) 2. We found that NRF2 expression was essential for the induction of drug resistance by 17ß-estradiol through the reduction of oxidative stress in GBM.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Psychometric Evaluation of Anxiety, Depression, and Sleep Quality after a Mild Traumatic Brain Injury: A Longitudinal Study.

Introduction. Over 1 million mild traumatic brain injury (mTBI) cases are reported annually worldwide and may result in cognitive, physical, and emotional deterioration; depression; anxiety; and sleep problems. However, studies on long-term mTBI effects are limited. This study included 440 patients, and regular follow-ups of psychological assessments were performed for 2 years. Four questionnaires, including the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), Beck's anxiety inventory (BAI), and Beck's depression inventory (BDI), were used to evaluate sleep problems, daytime sleepiness, anxiety, and depression, respectively. Results show that BAI and BDI scores considerably improved at the 6th-week, 1st-year, and 2nd-year follow-ups compared to baseline, yet these remained significantly different. In addition, anxiety and depression were prominent symptoms in a select subgroup of patients with poor initial evaluations, which improved over the 2 years. However, the ESS and PSQI scores fluctuated only mildly over the same time span. In conclusion, the mTBI patients showed a gradual improvement of anxiety and depression over the 2 years following injury. While anxiety and depression levels for mTBI patients in general did not return to premorbid status, improvements were observed. Sleep disorders persisted and were consistent with initial levels of distress.

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury.

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown. Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test. Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01). Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance.

The association between BDNF Val66Met polymorphism and emotional symptoms after mild traumatic brain injury.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the adult brain, and it plays important roles in modulating synaptic plasticity and synaptogenesis. This study attempted to elucidate the role of the BDNF variant rs6265 in emotional symptoms following mild traumatic brain injury (mTBI). METHODS: To investigate the association between BDNF Val66Met polymorphism (rs6265) and emotional symptoms in mTBI patients, we recruited 192 mTBI patients and evaluated their Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scores in the first and sixth week after mTBI. RESULTS: The patients carrying the T allele of rs6265 had significantly higher BAI scores in the first week following mTBI. In addition, the patients carrying the T allele also showed higher scores of BDI in the first week. In the gender-specific subgroup analysis, the male patients carrying the T allele of rs6265 had higher scores of both BAI and BDI in the first and sixth week. Meanwhile, female patients carrying the T allele also had significantly higher scores of BDI in the first week following mTBI. CONCLUSIONS: This study provides evidence for the association between the BDNF variant rs6265 and emotional symptoms following mTBI.

The Association of Apolipoprotein E Allele 4 Polymorphism with the Recovery of Sleep Disturbance after Mild Traumatic Brain Injury.

PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4 polymorphism may affect several physiological states, such as the recovery from mTBI as well as sleep. This study aims to investigate the association between APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012 to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow-up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh Sleep Quality Index (PSQI). APOE genotypes were determined by sequencing the products of polymerase chain reaction from genomic DNA. Statistical analyses were performed using the Wilcox signed-rank or chi-square test. RESULTS: Thirty-five (18.5%) participants were APOE4 carriers. At baseline, the demographic data and the severity of sleep disturbance were similar in both groups. APOE4 carriers demonstrated significant improvement in the overall PSQI score (8.34±3.9 at baseline and 7.43±3.99 at follow-up, p = 0.05) and scores of several PSQI subscales, including sleep disturbance, sleep latency, daytime dysfunction caused by sleepiness, and overall sleep quality, which was similar to APOE4 noncarriers. CONCLUSION: APOE4 is not associated with the recovery of sleep disturbance after mTBI.

Therapeutic Potential of Drugs Targeting Pathophysiology of Intracerebral Hemorrhage: From Animal Models to Clinical Applications.

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most common forms of cerebral hemorrhage, the morbidity and death of ICH is high worldwide. ICH can be spontaneous or caused by hypertension, coagulopathy, angiopathy, head trauma, bleeding disorders, tumors, or drug usage. ICH is the most serious and least treatable form of hemorrhagic stroke, with rapidly increasing hematoma size and often resulting in significant brain injury and long term neurological deficits. Surgical hematoma evacuation remains controversial. The currently therapy is mainly supportive with limited benefit. New therapeutic approaches are desperately needed. METHODS: In this review, we provide an overview of the published literature concerning the pathophysiology leading to the ongoing neurologic damage, Emerging information of the physio-pathologic mechanisms of injury that occur after ICH is available from current animal models. Ideal therapeutic strategies should target on the pathophysiology of ICH. This review summarizes the recent advances in developing pharmaceutical agents in terms of therapeutic targets and effects in pre-clinical and clinical studies. RESULTS: Recent animal and clinical studies have provided important information about the parallel and sequential deleterious mechanisms underlying ICH-induced brain injury and pharmacological agents targeting on these mechanisms. Neuroscientists have paid more attention to novel drug development that target on antioxidants, antiinflammatory, and anti-apoptosis for neuroprotection after ICH. CONCLUSION: Although ICH remains without an approved treatment proven to decrease morbidity and mortality, notable advances in the understanding of ICH pathophysiology and new drug development have been made in the last decade.

Reduced power spectra of heart rate variability are correlated with anxiety in patients with mild traumatic brain injury.

Anxiety is one of the most frequently diagnosed emotional disorders after a mild traumatic brain injury (mTBI); however, predictors of anxiety after an mTBI remain uncertain. Recent research indicated that anxiety is associated with abnormalities in the autonomic nervous system (ANS) which can be evaluated by a power spectral analysis of heart rate variability (HRV). In this study, we investigated whether a frequency-domain analysis of HRV could correlate with the occurrence of anxiety in mTBI patients. We recruited 165 Taiwanese patients diagnosed with an mTBI and 82 volunteer healthy controls from three affiliated hospitals of Taipei Medical University during 2010-2014. The Beck Anxiety Inventory (BAI) was assessed at the 1st, 6th, and 12th weeks. We found that mTBI patients were more vulnerable to anxiety compared to healthy controls. The power spectral density of HRV was significantly lower in mTBI patients than in healthy controls. A correlation analysis indicated that anxiety was negatively significantly correlated with low- and high-frequency power at the 6th week. Our study suggests the clinical usefulness of HRV as a potential noninvasive tool for evaluating later anxiety in mTBI patients.

Early dysautonomia detected by heart rate variability predicts late depression in female patients following mild traumatic brain injury.

Depression is one of the frequent complications following a mild traumatic brain injury (mTBI). Recent research indicated that abnormalities in the autonomic nervous system (ANS) can be evaluated by a noninvasive power spectral analysis of the heart rate variability (HRV). In this study, we investigated whether a frequency-domain analysis of HRV was correlated with late depression in mTBI patients. In total, 181 patients diagnosed with mTBI and 83 volunteers as healthy controls were recruited in 2010-2014. Beck Depression Inventory (BDI) scores were used to evaluate depression in the 1st week of assessment and at 1.5-, 3-, 6-, 12-, and 18-month follow-ups. Correlation and logistic regression analyses of the 1st week HRV parameters with BDI scores at 18 months were performed in individual female mTBI patients. Female mTBI patients were more vulnerable to depression accompanied by reduced HRV compared to healthy controls. Over time, depression was aggravated in female mTBI patients but was alleviated in male mTBI patients. A significantly lower parasympathetic proportion of the ANS was noted at 18 months with respect to the 1st week in female mTBI patients. In addition, depression in female mTBI patients at 18 months after injury was significantly correlated with a decrease in the parasympathetic proportion of the ANS in the 1st week (ρ = -0.411; p < .05). Dysautonomia resulted in higher risks of depression in female mTBI patients. We concluded that early dysautonomia following an mTBI contributes to late depression in female mTBI patients.

Heart rate variability and serum level of insulin-like growth factor-1 are correlated with symptoms of emotional disorders in patients suffering a mild traumatic brain injury.

OBJECTIVE: Patients who have experienced a mild traumatic brain injury (mTBI) are susceptible to symptoms of anxiety or depression. To explore the potential biomarkers for emotional disorders in mTBI patients, we analyzed the frequency domain of heart rate variability (HRV) and serum concentrations of four neurohormones. METHODS: We assessed mTBI patients on their first visit and follow-up. Symptoms were evaluated by the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. Serum levels of adrenocorticotropic hormone (ACTH), melatonin, cortisol, and insulin-like growth factor (IGF)-1 and HRV follow-ups were measured and compared. RESULTS: mTBI patients were more vulnerable to symptoms of anxiety or depression than healthy controls. Reduced HRV was noted in mTBI patients compared to healthy controls. The mTBI patients demonstrated higher serum levels of ACTH, lower IGF-1 compared to healthy controls. In correlation analysis, only IGF-1 was positively correlated with HRV in mTBI patients. Both HRV and IGF-1 were correlated with symptom of depression while only HRV was correlated with symptom of anxiety in mTBI patients. CONCLUSIONS: We infer that HRV may be more significantly correlated with emotional disorders than is IGF-1 in mTBI patients. SIGNIFICANCE: The study is relevant for specific diagnostic markers in mTBI patients.

Risk of death in patients with post-traumatic cerebrospinal fluid leakage--analysis of 1773 cases.

BACKGROUND: Post-traumatic cerebrospinal fluid (CSF) leakage is one of the most troublesome conditions associated with head trauma. CSF fistulae, meningitis/central nervous infection, or even death may accompany it. Few studies have discussed post-traumatic CSF leakage as a risk factor in mortality following head trauma. We conducted this cohort study to examine the issue. METHODS: We reviewed the records in the Taiwan Traumatic Brain Injury (TBI) Registry System between 1993 and 2008. The study group included patients with acute TBI and post-traumatic CSF leakage, and the control group included cases with TBI but without CSF leakage, selected randomly at a 5:1 ratio with respect to the study group. The demographic data, Glasgow Coma Scale, brain computerized tomography, association of skull fractures and intracranial lesions, and 1-year mortality rates between these two cohorts were reviewed meticulously and analyzed statistically. RESULTS: Of 174,236 cases, 1773 with post-traumatic CSF leakage were included in the study group, and 8865 cases in the control group. Of the total 10,638 sampled cases, 406 (3.8%) died during the 1-year follow-up period, 159 (9.0%) cases in the CSF leakages group, and 247 (2.8%) in the control group. The patients with CSF leakage had a significantly higher mortality rate within 1 year (adjusted hazard ratio = 1.44, p < 0.001) than those without. We divided the CSF leakage group into three subgroups: otorrhea (n = 568), rhinorrhea (n = 302), and tension pneumocephalus (n = 903). The mortality rates were 8.5% (48/568) in the otorrhea subgroup, 10.9% (33/302) in the rhinorrhea subgroup, and 8.6% (78/903) in the tension pneumocephalus subgroup. The cases with CSF rhinorrhea had a significantly higher mortality rate than the other two subgroups (p < 0.05). All three subgroups had significantly higher mortality rates than the control group during the 1-year follow-up period (adjusted hazard ratios = 2.29, 1.35, and 1.32 in the rhinorrhea, tension pneumocephalus, and otorrhea subgroups, respectively). CONCLUSION: Post-traumatic CSF leakages had higher mortality rates than those without CSF leakages in TBI cases, and the cases with CSF rhinorrhea had worse outcomes compared with CSF leakages with pneumocephalus or otorrhea.

Increased Risk of Post-Trauma Stroke after Traumatic Brain Injury-Induced Acute Respiratory Distress Syndrome.

This study determines whether acute respiratory distress syndrome (ARDS) is an independent risk factor for an increased risk of post-traumatic brain injury (TBI) stroke during 3-month, 1-year, and 5-year follow-ups, respectively, after adjusting for other covariates. Clinical data for the analysis were from the National Health Insurance Database 2000, which covered a total of 2121 TBI patients and 101 patients with a diagnosis of TBI complicated with ARDS (TBI-ARDS) hospitalized between January 1, 2001 and December 31, 2005. Each patient was tracked for 5 years to record stroke occurrences after discharge from the hospital. The prognostic value of TBI-ARDS was evaluated using a multivariate Cox proportional hazard model. The main outcome found that stroke occurred in nearly 40% of patients with TBI-ARDS, and the hazard ratio for post-TBI stroke increased fourfold during the 5-year follow-up period after adjusting for other covariates. The increased risk of hemorrhagic stroke in the ARDS group was considerably higher than in the TBI-only cohort. This is the first study to report that post-traumatic ARDS yielded an approximate fourfold increased risk of stroke in TBI-only patients. We suggest intensive and appropriate medical management and intensive follow-up of TBI-ARDS patients during the beginning of the hospital discharge.

PERIOD3 polymorphism is associated with sleep quality recovery after a mild traumatic brain injury.

BACKGROUND AND AIM: Mild traumatic brain injury (mTBI) causes transient sleep disorders and circadian dysrhythmia. One of the clock genes, PERIOD3 (PER3), regulates the circadian rhythm and contains a genetic polymorphism, namely a variable-number tandem repeat in the coding area with either four or five repeats. PER3(5) carriers are inclined to have a morning preference and associated with higher risk of bipolar disorder and diabetes. This study investigated the effects of PER3 polymorphism on sleep quality changes after mTBI. MATERIALS AND METHODS: From May 2012 to May 2014, a total of 96 mTBI patients completed the baseline (1 week after mTBI) and follow-up (6 weeks after mTBI) assessments, including the Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression questionnaires. Statistics were analyzed using the Mann-Whitney U test, Wilcox signed-rank test or chi-squared test. RESULTS: Among the 96 patients, 24 were heterozygous PER3(5) carriers (PER3(4/5)), and the rest of 72 were PER3(5) noncarriers (PER3(4/4)). The subscale of PSQI questionnaire results indicated that the PER3(5) allele was associated with significant sleep duration shortening, but improvement in overall sleep quality. Furthermore, analyzing patients with sleep disturbance at the baseline (PSQI >5) revealed that only the PER3(5) noncarriers exhibited a significant improvement in overall PSQI scores. CONCLUSION: PER3(5) carriers exhibited sleep duration shortening and improved daytime function 6 weeks after mTBI compared with the baseline values. On the other hand, among poor sleepers, PER3(5) carriers did not embrace a significant improvement of overall PSQI scores as noncarriers. The underlying mechanisms and clinical significances must be investigated further.

A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients.

The purpose of this study was to compare the effect of PbtO2-guided therapy with traditional intracranial pressure- (ICP-) guided treatment on the management of cerebral variables, therapeutic interventions, survival rates, and neurological outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009 to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6 collaborative hospitals in northern Taiwan, excluding patients with severe systemic injuries, fixed and dilated pupils, and other major diseases. In total, 23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27 patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg) in the neurosurgical intensive care unit (NICU); demographic characteristics were similar across groups. The survival rate in the PbtO2-guided group was also significantly increased at 3 and 6 months after injury. Moreover, there was a significant correlation between the PbtO2 signal and Glasgow outcome scale-extended in patients from 1 to 6 months after injury. This finding demonstrates that therapy directed by PbtO2 monitoring is valuable for the treatment of patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be efficacious for preventing cerebral hypoxic events after brain trauma.