[Progress in application of adult endogenous neurogenesis in brain injury repair].

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Tranexamic Acid Inhibits Hematoma Expansion in Intracerebral Hemorrhage and Traumatic Brain Injury. Does Blood Pressure Play a Potential Role? A Meta-Analysis from Randmized Controlled Trials.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Many studies focus on the effect of TXA on cerebral hemorrhage, however, whether TXA can inhibit hematoma expansion is still controversial. Our meta-analysis performed a quantitative analysis to evaluate the efficacy of TXA for the hematoma expansion in spontaneous and traumatic intracranial hematoma. METHOD: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to May 2020 for randomized controlled trials (RCTs). RESULT: We pooled 3102 patients from 7 RCTs to evaluate the efficacy of TXA for hematoma expansion. Hematoma expansion (HE) rate and hematoma volume (HV) change from baseline were used to analyze. We found that TXA led to a significant reduction in HE rate (P = 0.002) and HV change (P = 0.03) compared with the placebo. Patients with moderate or serious hypertension benefit more from TXA. (HE rate: P = 0.02, HV change: P = 0.04) TXA tends to have a better efficacy on HV change in intracerebral hemorrhage (ICH). (P = 0.06) CONCLUSIONS: TXA showed good efficacy for hematoma expansion in spontaneous and traumatic intracranial hemorrhage. Patients with moderate/severe hypertension and ICH may be more suitable for TXA administration in inhibiting hematoma expansion .

Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

BACKGROUND: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. DESIGN: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI). RESULTS: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy. CONCLUSIONS AND RELEVANCE: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Clinical outcomes following early versus late pharmacologic thromboprophylaxis in patients with traumatic intracranial hemorrhage: a systematic review and meta-analysis.

Venous thromboembolism (VTE) after traumatic brain injury (TBI) with intracranial hemorrhage (ICH) presents a serious yet manageable morbidity and mortality risk. This systematic review and meta-analysis aimed to pool the current literature to evaluate whether or not pharmacologic thromboprophylaxis (PTP) administered early after traumatic ICH significantly changes incidence of VTE or hemorrhagic progression when compared to late administration. Systematic searches of seven electronic databases from their inception to July 2018 were conducted following the appropriate guidelines. One thousand four hundred ninety articles were identified for screening. Outcomes of interest were pooled as odd ratios (ORs) and analyzed using a random-effects model. Eleven comparative studies satisfied selection criteria, yielding a total of 5036 cases. Overall, mean age was 47.6 years and 36% patients were female. PTP was administered early (≤ 72 h from admission) in 2106 (42%) patients and late (> 72 h from admission) in 2922 (58%) cases. There was no statistically significant difference in the incidence of hemorrhagic progression (OR, 0.86; P = 0.450) or all-cause mortality (OR, 0.83; P = 0.347) between the early versus late PTP patient groups. However, incidence of VTE was significantly less in the early PTP patient group (OR, 0.58; P = 0.008). The early administration of PTP after traumatic ICH does not appear to confer a worse prognosis in terms of hemorrhagic progression. However, it seems to confer superior VTE prophylaxis, when compared to late PTP administration. We suggest that early PTP should not be prematurely discounted for patients with ICH in TBI on the assumption of aggravating hemorrhagic progression alone.

Ability of Fibrin Monomers to Predict Progressive Hemorrhagic Injury in Patients with Severe Traumatic Brain Injury.

BACKGROUND: Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with poor outcomes. TBI-associated coagulopathy is frequent and has been described as risk factor for PHI. This coagulopathy is a dynamic process involving hypercoagulable and hypocoagulable states either one after the other either concomitant. Fibrin monomers (FMs) are a direct marker of thrombin action and thus reflect coagulation activation. This study sought to determine the ability of FM to predict PHI after severe TBI. METHODS: We conducted a prospective, observational study including all severe TBI patients admitted in the trauma center. Between September 2011 and September 2016, we enrolled patients with severe TBI into the derivation cohort. Between October 2016 and December 2018, we recruited the validation cohort on the same basis. Study protocol included FM measurements and standard coagulation test at admission and two computed tomography (CT) scans (upon arrival and at least 6 h thereafter). A PHI was defined by an increment in size of initial lesion (25% or more) or the development of a new hemorrhage in the follow-up CT scan. Multivariate logistic regression analysis was applied to identify predictors of PHI. RESULTS: Overall, 106 patients were included in the derivation cohort. Fifty-four (50.9%) experienced PHI. FM values were higher in these patients (151 [136.8-151] vs. 120.5 [53.3-151], p < 0.0001). The ROC curve demonstrated that FM had a fair accuracy to predict the occurrence of PHI with an area under curve of 0.7 (95% CI [0.6-0.79]). The best threshold was determined at 131.7 µg/ml. In the validation cohort of 54 patients, this threshold had a negative predictive value of 94% (95% CI [71-100]) and a positive predictive value of 49% (95% CI [32-66]). The multivariate logistic regression analysis identified 2 parameters associated with PHI: FM ≥ 131.7 (OR 6.8; 95% CI [2.8-18.1]) and Marshall category (OR 1.7; 95% CI [1.3-2.2]). Coagulopathy was not associated with PHI (OR 1.3; 95% CI [0.5-3.0]). The proportion of patients with an unfavorable functional neurologic outcome at 6-months follow-up was higher in patients with positive FM: 59 (62.1%) versus 16 (29.1%), p < 0.0001. CONCLUSIONS: FM levels at admission had a fair accuracy to predict PHI in patients with severe TBI. FM values ≥ 131.7 µg/ml are independently associated with the occurrence of PHI.

Early tranexamic acid in traumatic brain injury: Evidence for an effective therapy.

The guidelines for management of traumatic brain injury (TBI) are based largely on measures to maintain an optimum internal milieu for prevention of secondary brain injury and enhancing recovery. One of the most common reasons for worsening outcomes following TBI is expanding intracranial haematoma which is compounded by the fibrinolytic physiology that follows TBI. Tranexamic acid (TXA) has a time tested role in preventing poor outcomes linked to excessive haemorrhage in trauma patients. Historically, patients with isolated head trauma were excluded from TXA use due to a theoretical increased risk of thrombosis. Recent evidence that redefines the beneficial role of early TXA administration in preventing mortality amongst patients with TBI is now at hand and offers a real prospect of a pharmacological intervention that would be adopted as a recommendation based on Class l evidence.

Permanent isolated micrographia from traumatic basal ganglia injury.

Micrographia is a rare neurological finding in isolation. Most cases of isolated micrographia have been found in association with focal ischemia of the left basal ganglia. Here, we present a case of post-traumatic micrographia stemming from contusion to the left basal ganglia.

Description of the predictors of persistent post-concussion symptoms and disability after mild traumatic brain injury: the SHEFBIT cohort.

Introduction: Several patients who suffer Mild Traumatic Brain Injury (mTBI) develop Persistent Post-Concussion Symptoms (PPCS) and long-term disability. Current prognostic models for mTBI have a large unexplained variance, which limits their use in a clinical setting. Aim: This study aimed to identify background demographics and mTBI details that are associated with PPCS and long-term disability. Methods: Patients from the SHEFfield Brain Injury after Trauma (SHEFBIT) cohort with mTBI in the Emergency Department (ED) were analysed as part of the study. PPCS and long-term disability were measured using the Rivermead Post-Concussion Questionnaire and the Rivermead Post-Injury Follow-up Questionnaire respectively, during follow up brain injury clinics. Results: A representative mTBI sample of 647 patients was recruited with a follow-up rate of 89%. Non-attenders were older (p < 0.001), a greater proportion were retired (p < 0.001) and had a greater burden of comorbidity (p = 0.009). Multivariate analysis identified that female gender, previous psychiatric history, GCS <15, aetiology of assault and alcohol intoxication, were associated with worse recovery. Conclusion: These findings will support and add to current understanding of MBTI recovery in pursuit of developing a validated prognostic model. This will allow for more accurate prognostication and eventual improved treatment for sufferers of this complex disorder.

A risk score based on admission characteristics to predict progressive hemorrhagic injury from traumatic brain injury in children.

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children, and progressive hemorrhagic injury (PHI) post TBI is associated with poor outcomes. Therefore, the objective of this study was to develop and validate a prognostic model that uses the information available at admission to determine the likelihood of PHI occurrence after TBI in children. The identified demographic data, cause of injury, clinical predictors on admission, computed tomography scan characteristics, and routine laboratory parameters were collected and used to develop a PHI prognostic model with logistic regression analysis, and the prediction model was validated in 68 children. Eight independent prognostic factors were identified: lower Glasgow coma scale score (3 ~ 8) (6 points), intra-axial bleeding/brain contusion (4 points), midline shift ≥5 mm (9 points), platelets <100 × 109/L (11 points), prothrombin time >14 s (6 points), international normalized ratio >1.25 (7 points), D-dimer ≥5 mg/L (14 points), and glucose ≧10 mmol/L (11 points). We calculated risk scores for each child and defined three risk groups: low risk (0-16 points), intermediate risk (17-36 points), and high risk (37-68 points). In the development cohort, the PHI rates after TBI for the low-, intermediate-, and high-risk groups were 10.1, 47.9, and 84.2%, respectively. In the validation cohort, the corresponding PHI rates were 10.9, 47.5, and 85.4%, respectively. The C-statistic for the point system was 0.873 (p = 0.586 by the Hosmer-Lemeshow test) in the development cohort and 0.877 (p = 0.524 by the Hosmer-Lemeshow test) in the validation cohort. CONCLUSION: Using admission predictors, we developed a relatively simple risk score that accurately predicted the risk of PHI after TBI in children. What is Known: • TBI is one of the leading causes of death and disability in children, and PHI post TBI is associated with poor outcomes. •Prediction of patients at low risk of PHI could help reduce treatment costs, whereas identification of patients at high risk of PHI could direct early medical intervention to improve outcomes. What is New: • This study firstly developed a risk score system by assessing the admission information that could provide an earlier prediction of the occurrence of PHI after acute TBI in children.

A Survey of Clinicians Working in Brain Injury Rehabilitation: Are Social Cognition Impairments on the Radar?

OBJECTIVES: To examine the social cognition assessment practices of clinicians working with children and adults with traumatic brain injury. MAIN MEASURES: Online survey addressing frequency of social cognition impairments, how these are assessed and obstacles to same, and treatment practices. PARTICIPANTS: A total of 443 clinicians worldwide working in inpatient and outpatient settings. RESULTS: While 84% of clinicians reported that more than half of their clients with severe traumatic brain injury had social cognition impairments, 78% of these reported that they infrequently or never assessed these domains using a formal assessment tool. Lack of reliable tests was most frequently (33% of respondents) cited as the greatest barrier to undertaking social cognition assessment. CONCLUSIONS AND IMPLICATIONS: Improvements are needed in the development and norming of instruments capable of detecting social cognition impairments in the traumatic brain injury population. Additional training and education is needed in the use of social cognition assessment tools.