Kuo Hsing Liao

Clinical practice guidelines in severe traumatic brain injury in Taiwan

BACKGROUND Severe TBIs are major causes of disability and death in accidents. The Brain Trauma Foundation supported the first edition of the Guidelines for the Management of Severe Traumatic Brain Injury in 1995 and revised it in 2000. The recommendations in these guidelines are well accepted in the world. There are still some different views on trauma mechanisms, pathogenesis, and managements in different areas. Individualized guidelines for different countries would be necessary, and Taiwan is no exception. METHODS In November 2005, we organized the severe TBI guidelines committee and selected 9 topics, including ER treatment, ICP monitoring, CPP, fluid therapy, use of sedatives, nutrition, intracranial hypertension, seizure prophylaxis, and second-tier therapy. We have since searched key questions in these topics on Medline. References are classified into 8 levels of evidence: 1++, 1+, 1-, 2++, 2+, 2-, 3, and 4 based on the criteria of the SIGN. RESULTS Recommendations are formed and graded as A, B, C, and D. Grade A means that at least one piece of evidence is rated as 1++, whereas grade B means inclusion of studies rated as 2++. Grade C means inclusion of references rated as 2+, and grade D means levels of evidence rated as 3 or 4. Overall, 42 recommendations are formed. Three of these are rated as grade A, 13 as grade B, 21 as grade C, and 5 as grade D. CONCLUSIONS We have completed the first evidence-based, clinical practice guidelines for severe TBIs. It is hoped that the guidelines will provide concepts and recommendations to promote the quality of care for severe TBIs in Taiwan.

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.

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.

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.

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

BackgroundBrain-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).MethodsTo 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.ResultsThe 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.ConclusionsThis study provides evidence for the association between the BDNF variant rs6265 and emotional symptoms following mTBI.

Novel Consensus of Management Guidelines for Severe Traumatic Brain Injury in Asia

Management guidelines for severe traumatic brain injury (STBI) (Brain Trauma Foundation, 1996) have been in place in the United States since 1995. Since that time, the Society of Neurosurgery in Taiwan has made efforts to educate neurosurgeons in Taiwan about these guidelines, encourage integration of these concepts into clinical practice, and to lobby the National Health Institute to pay for STBI treatment. Due to differences in cultural background and traditional practice customs, we found several discrepancies during this period of transition to widespread use of the guidelines in Taiwan, and thus saw a need for locally developed guidelines for use in Asia. In July 2008, more than 300 neuroscience experts in Asia participated in the first Asia-Oceania Neurotrauma Society (AONTS) congress. Specialists discussed differences in the management of STBI and differences among the guidelines published in China, Korea, Japan, and Taiwan. Novel consensus agreements were proposed for four key topics, including the management of intracranial pressure (ICP) (Bratton et al., 2007) and cerebral perfusion pressure (CPP) (Chang et al., 2009; Lin et al., 2008; Sviri et al., 2009), and the use of decompressive craniectomy (DC) (Howard et al., 2008; Timofeev et al., 2008) and sedatives (Chiu et al. 2006). New consensus guidelines recommend that ICP should be considered as a treatment concept rather than just a monitoring tool. For those patients indicated for ICP monitoring, external ventriculostomies are the best choice for the most accurate and cost-effective management. They also allow the dual functions of monitoring and cerebrospinal fluid (CSF) drainage. In addition, ICP data as measured by ventriculostomy are more representative of the overall intracranial condition than intraparenchymal, subdural, or extradural insertion (Bratton et al., 2007). The consensus recommendation for CPP is that it should be maintained at 60 mm Hg for most patients. However, it is advisable to maintain CPP > 70 mm Hg for extremely severe TBI patients, such as patients with Glasgow Coma Scale (GCS) scores of 3–5 (Lin et al., 2008), despite the high complication rates associated with the inotropic drugs used to maintain CPP. In this subgroup, the recovery of cerebral autoregulation is also poor compared to patients with GCS scores 6 (Sviri et al., 2009). Maintaining these higher CPP values provides improved survival rates and long-term prognosis for these patients. Decompressive craniectomies are thought to be clinically effective in lowering ICP in those with refractory intracranial hypertension (Timofeev et al., 2008), and prophylactic DC may also be useful in those requiring urgent evacuation of intracranial hemorrhage and other conditions. Thus DCs should be considered and used soon after primary therapy is complete, and in some cases sooner (Howard et al., 2008). The guidelines for the use of sedatives recommend the use of short-term sedation, and analgesics are indicated for acute and ventilated STBI patients with adequate monitoring. We plan to build on these initial four consensus guidelines proposed by the first AONTS congress, and more advanced prospective studies of STBI will be conducted in Asia to help refine them.

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.

Significance of Balance Test in Assessing Emotional Aspect of Dizziness in Mild Traumatic Brain Injury Patients

Background: Mild traumatic brain injury (mTBI) is the major cause of neurobehavioral disorder. It often causes persistent and progressive symptoms, such as mental disorder, dizziness and balance problems. The relationship between subjective measurement of balance and the objective instrument of dizziness remains unclear. Methods and findings: We enrolled 210 mTBI patients, including 94 patients with dizziness problems and 116 patients without dizziness problems. The participants completed the dizziness handicap inventory (DHI) and stability and sway indices through the Biodex stability System. A Box-Cox transformation for each index was performed to assess the linear regression relationship with all aspects (physical, emotional, and functional) of the DHI. After a propensity score adjustment, gender and age were significant predictors for all stability and sway indices. In addition, body height was a significant factor in balance test results when eyes were open. Furthermore, the emotional aspect of the DHI significantly correlated with stability and sway indices, except the mediolateral stability index (MLSI). Conclusion: The three aspects of the subjective instrument of dizziness were significantly related with anxiety, depression and sleep problems. For mTBI patients, the objective changes in balance were associated with the emotional aspect of DHI.