Early Pharmacologic Therapy in Patients With Blunt Cerebrovascular Injury and TBI: Is it Safe and Effective? An EAST Multicenter Study.

BACKGROUND: Blunt cerebrovascular injury (BCVI) with concurrent traumatic brain injury (TBI) presents increased risk of both ischemic stroke and bleeding. This study investigated the safety and survival benefit of BCVI treatment (antithrombotic and/or anticoagulant therapy) in this population. We hypothesized that treatment would be associated with fewer and later strokes in patients with BCVI and TBI without increasing bleeding complications. METHODS: Patients with head AIS >0 were selected from a database of BCVI patients previously obtained for an observational trial. A Kaplan-Meier analysis compared stroke survival in patients who received BCVI treatment to those who did not. Logistic regression was used to evaluate for confounding variables. RESULTS: Of 488 patients, 347 (71.1%) received BCVI treatment and 141 (28.9%) did not. BCVI treatment was given at a median of 31 h post-admission. BCVI treatment was associated with lower stroke rate (4.9% vs 24.1%, P < .001 and longer stroke-free survival (P < .001), but also less severe systemic injury. Logistic regression identified motor GCS and BCVI treatment as the only predictors of stroke. No patients experienced worsening TBI because of treatment. DISCUSSION: Patients with BCVI and TBI who did not receive BCVI treatment had an increased rate of stroke early in their hospital stay, though this effect may be confounded by worse motor deficits and systemic injuries. BCVI treatment within 2-3 days of admission may be safe for patients with mean head AIS of 2.6. Future prospective trials are needed to confirm these findings and determine optimal timing of BCVI treatment in TBI patients with BCVI.

Efficacy of Antithrombotic Therapy and Risk of Hemorrhagic Complication in Blunt Cerebrovascular Injury Patients with Concomitant Injury: A Systematic Review.

BACKGROUND: The risk-benefit balance of antithrombotic therapy administration for blunt cerebrovascular injuries (BCVI) patients with concomitant injuries at high risk for bleeding is an ongoing therapeutic conundrum for trauma clinicians. We performed a systematic review to assess the reported efficacy and safety of treatment in this population with respect to prevention of ischemic stroke and risk of hemorrhagic complications. STUDY DESIGN: A systematic electronic literature search of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was performed from January 1, 1996 to December 31, 2021. Studies were included if they reported treatment-stratified clinical outcomes after antithrombotic therapy in BCVI patients with concomitant injuries at high risk of bleeding into a critical site. Data were extracted from selected studies by two independent reviewers, including the main outcomes of interest were BCVI-related ischemic stroke rates and rates of hemorrhagic complications. RESULTS: Of the 5,999 studies reviewed, 10 reported on the effects of treating BCVI patients with concurrent traumatic injuries and were included for review. In the pooled data, among patients with BCVI and concomitant injury who received any form of antithrombotic therapy, the BCVI-related stroke rate was 7.6%. The subgroup of patients who did not receive therapy had an overall BCVI-related stroke rate of 34%. The total rate of hemorrhagic complications in the treated population was 3.4%. CONCLUSIONS: In BCVI patients with concomitant injuries at high risk for bleeding, antithrombotic use reduces the risk of ischemic strokes with a low reported risk of serious hemorrhagic complications.

Timing of anticoagulation for venous thromboembolism after recent traumatic and vascular brain Injury.

Currently, there is no consensus guideline for initiating anticoagulation in patients with a traumatic or vascular brain injury. Initiating anticoagulation for management of venous thromboembolism (VTE) can vary significantly from 72 hours to 30 weeks due to the risk of hemorrhagic complications. The purpose of this study is to compare clinical outcomes using modified Rankin Score (mRS) in a patient population with early (≤ 3 days) versus late (> 3 days) initiation of therapeutic anticoagulation from the time VTE was diagnosed. This retrospective study included patients with a traumatic or vascular brain injury who developed either deep vein thrombosis (DVT) or pulmonary embolism (PE). Use of anticoagulation prior to admission, diagnosis with VTE on admission, or patients with a non-brain injury were exclusion criteria. Secondary outcomes measured were all-cause mortality, length of stay, and reasons for early interruption of anticoagulation. Therapeutic anticoagulation was started early in 76 (74%) patients compared to late initiation in 27 (26%) patients. Baseline characteristics were similar between the two groups. The mRS score 0-3 versus 4-6 was similar in patients who received early anticoagulation versus those who received it later. However, there was a trend favoring better outcomes in the early group [mRS 4-6; 78% vs. 93%; p = 0.085] and in subgroup analysis of patients with VTE diagnosed 4-7 days [mRS 4-6; 26% vs. 56%; p = 0.006] compared to the late group. In univariate and multivariable logistic regression, only age was associated with a significant worse outcome (median, IQR) 36 years (24-50) vs. 58 years (44-65) OR 1.07 (1.03-1.12); p < 0.001. In this study, early initiation of anticoagulation did not worsen clinical outcomes.

Antithrombotic choice in blunt cerebrovascular injuries: Experience at a tertiary trauma center, systematic review, and meta-analysis.

BACKGROUND: Blunt cerebrovascular injuries (BCVIs) may occur following trauma and lead to ischemic stroke if untreated. Antithrombotic therapy decreases this risk; however, the optimal agent has yet to be determined in this population. The aim of this study was to compare the risk-benefit profile of antiplatelet (AP) versus anticoagulant (AC) therapy in rates of ischemic stroke and hemorrhagic complications in BCVI patients. METHODS: We performed a retrospective review of BCVI patients at our tertiary care Trauma hospital from 2010 to 2015, and a systematic review and meta-analysis of the literature. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to September 16, 2019. References of included publications were searched manually for other relevant articles. The search was limited to articles in humans, in patients 18 years or older, and in English. Studies that reported treatment-stratified clinical outcomes following AP or AC treatment in BCVI patients were included. Exclusion criteria included case reports, case series with n < 5, review articles, conference abstracts, animal studies, and non-peer-reviewed publications. Data were extracted from each study independently by two reviewers, including study design, country of origin, sex and age of patients, Injury Severity Score, Biffl grade, type of treatment, ischemic stroke rate, and hemorrhage rate. Pooled estimates using odds ratio (OR) were combined using a random-effects model using a Mantel-Hanzel weighting. The main outcome of interest was rate of ischemic stroke due to BCVI, and the secondary outcome was hemorrhage rate based on AC or AP treatment. RESULTS: In total, there were 2044 BCVI patients, as reported in the 22 studies in combination with our institutional data. The stroke rate was not significantly different between the two treatment groups (OR, 1.27; 95% confidence interval, 0.40-3.99); however, the hemorrhage rate was decreased in AP versus AC treated groups (OR, 0.38; 95% confidence interval, 0.15-1.00). CONCLUSION: Based on this meta-analysis, both AC and AP seem similarly effective in preventing ischemic stroke, but AP is better tolerated in the trauma population. This suggests that AP therapy may be preferred, but this should be further assessed with prospective randomized trials. LEVEL OF EVIDENCE: Review article, level II.

Treatment of blunt cerebrovascular injuries: Anticoagulants or antiplatelet agents?

BACKGROUND: Blunt cerebrovascular injury (BCVI) is associated with cerebrovascular accidents (CVA). Early therapy with antiplatelet agents or anticoagulants is recommended. There are limited data comparing the effectiveness of these treatments. The aim of our study was to compare outcomes between BCVI patients who received anticoagulants versus those who received antiplatelet agents. METHODS: We performed an (2011-2015) analysis of the Nationwide Readmission Database and included all adult trauma patients 18 years or older who had an isolated BCVI (other body regions Abbreviated Injury Scale [AIS] < 3). Head injury patients or those who developed a CVA during the index admission were excluded. Patients were stratified into anticoagulants and antiplatelet agents. Propensity score matching was performed (1:1 ratio) to control for demographics, comorbidities, BCVI grade, distribution, and severity of injuries. Outcomes were readmission with CVA and mortality within 6 months. RESULTS: A total of 725 BCVI patients were identified. A matched cohort of 370 patients (antiplatelet agents, 185; anticoagulants, 185) was obtained. Mean age was 50 ± 15 years, neck AIS was 3 (3,4), and Injury Severity Score was 12 (9-17). The majority of the patients (69%) had high-grade BCVI (AIS ≥ 3). Overall, 3.7% were readmitted with CVA and 3% died within 6 months. Patients who received anticoagulants had a lower rate of readmission with CVA (1.8% vs. 5.72%; p = 0.03), and a lower rate of 6-month mortality (1.3% vs. 4.9%; p = 0.03). There was no significant difference between the two groups reading the median time to stroke (9 days vs. 6 days; p = 0.12). CONCLUSION: The BCVI patients on CVA prophylaxis for BCVI have a 3.7% rate of stroke after discharge. Compared with antiplatelet agents, anticoagulants are associated with lower rates of CVA in the first 6-month postdischarge. Further studies are required to identify the optimal agent to prevent CVA in this high-risk subset of trauma patients. LEVEL OF EVIDENCE: Therapeutic, level IV.

Management of Extracranial Blunt Cerebrovascular Injuries: Experience with an Aspirin-Based Approach.

BACKGROUND: Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. METHODS: Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. RESULTS: Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. CONCLUSIONS: An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.

Simvastatin improves cerebrovascular injury caused by ischemia­reperfusion through NF­κB­mediated apoptosis via MyD88/TRIF signaling.

Cerebrovascular injury is the most prevalent human cerebrovascular disease and frequently results in ischemic stroke. Simvastatin may be a potential therapeutic agent for the treatment of patients with cerebrovascular injury. The present study aimed to investigate the efficacy of and the potential mechanisms regulated by simvastatin in a rat model of ischemia­reperfusion (I/R)­induced cerebrovascular injury. Cerebrovascular injury model rats were established and were subsequently treated with simvastatin or a vehicle control following I/R injury. Cell damage, neurological functions and neuronal apoptosis were examined, as well as the nuclear factor (NF)­κB­mediated myeloid differentiation primary response protein 88 (MyD88)/toll­interleukin­1 receptor domain­containing adapter molecule 1 (TRIF) signaling pathway following simvastatin treatment. The results of the present study demonstrated that simvastatin treatment led to a reduction in cell damage, improvement of neurological functions and decreased neuronal apoptosis compared with vehicle­treated I/R model rats, 14 days post­treatment. In addition, simvastatin treatment reduced cerebral water content and blood­brain barrier disruption in cerebrovascular injury induced by I/R. The results also revealed that simvastatin treatment inhibited neuronal apoptosis via the NF­κB­mediated MyD88/TRIF signaling pathway. In conclusion, simvastatin treatment may reduce I/R­induced neuronal apoptosis via inhibition of the NF­κB­mediated MyD88/TRIF signaling pathway.

Management of blunt cerebrovascular injury (BCVI) in the multisystem injury patient with contraindications to immediate anti-thrombotic therapy.

INTRODUCTION: Practice management guidelines for screening and treatment of patients with blunt cerebrovascular injury (BCVI) have been associated with a decreased risk of ischemic stroke. TREATMENT: of patients with BCVI and multisystem injuries that delays immediate antithrombotic therapy remains controversial. The purpose of this study was to determine the timing of BCVI treatment initiation, the incidence of stroke, and bleeding complications as a result of antithrombotic therapy in patients with isolated BCVI in comparison to those with BCVI complicated by multisystem injuries. MATERIALS AND METHODS: This study was a retrospective review of all adult blunt trauma patients admitted to a level 1 trauma center from 2009 to 2014 with a diagnosis of BCVI. RESULTS: A total of 28,305 blunt trauma patients were admitted during the study period. Of these, 323 (1.1%) had 481 BCEVIs and were separated into two groups. Isolated BCVI was reported in 111 (34.4%) patients and 212 (65.6%) patients had accompanying multisystem injuries (traumatic brain injury (TBI), solid organ injury, or spinal cord injury) that contraindicated immediate antithrombotic therapy. TREATMENT: started in patients with isolated BCVI at a median time of 30.3 (15, 52) hours after injury in contrast to 62.4 (38, 97) hours for those with multisystem injuries (p<0.001). The incidence of stroke was identical (9.9%) between groups and no bleeding complications related to antithrombotic therapy were identified. CONCLUSION: The lack of bleeding complications and equivalent stroke rates between groups suggests that the presence of TBI, solid organ injury, and spinal cord injury are not contraindications to anti-thrombotic therapy for stroke prevention in patients with BCVI.

Symptomatogenic acute cervical artery dissection following dental procedure - Case series.

INTRODUCTION: Cervical artery dissection (CAD) is an important cause of ischemic stroke which may occur following minor traumatic neck manipulations or hyperextension. This paper describes four cases of CAD secondary to dental procedures. CASES: Four patients were admitted to the neurology department due to various neurological deficits, which developed subsequently to dental procedure. CT angiography demonstrated CAD in all patients. No predisposing background disease or other neck manipulations were found. DISCUSSION: We describe four cases of dental procedure induced CAD. Since dental procedures are very common, CAD incidence may be higher than recognized. High clinical suspicion is crucial for promoting vascular imaging and diagnosis, especially among patients with non-neurologically symptomatic CAD. We suggest avoiding prolonged neck hyperextension during dental procedures, especially under general anesthesia, in order to prevent this rare but dramatic complication.

Early antithrombotic therapy is safe and effective in patients with blunt cerebrovascular injury and solid organ injury or traumatic brain injury.

BACKGROUND: Early antithrombotic therapy (AT) is the mainstay of treatment in the management of blunt cerebrovascular injury (BCVI). Despite this, optimal timing of initiation of AT in patients with BCVI in the presence of concomitant traumatic brain injury (TBI) or solid organ injury (SOI) remains controversial. The purpose of this study was to evaluate the impact of early initiation of AT on outcomes in patients with BCVI and TBI and/or SOI. METHODS: Patients with BCVI and concomitant TBI and/or SOI over 6 years were identified. Aspirin and/or clopidogrel or low-intensity heparin infusion (AT) was instituted in all patients immediately upon diagnosis of BCVI. Cessation of AT, worsening TBI, the need for delayed operative intervention, ischemic stroke, and mortality were reviewed and compared. Worsening of TBI or delayed operative intervention for SOI were compared with those of patients without BCVI treated at the same institution during the study period. RESULTS: A total of 119 patients (74 with TBI, 26 with SOI, and 19 with both) were identified. Seventy-one percent were treated with heparin infusion (goal activated partial thromboplastin time, 45-60 seconds), and 29% received antiplatelet therapy alone. When compared with patients without BCVI, there was no difference in worsening of TBI (9% vs. 10% with no BCVI, p = 0.75) or need for delayed operative intervention for SOI (7% vs. 5% with no BCVI, p = 0.61). No patients required cessation of AT. A total of 11 patients (9%) experienced a BCVI-related stroke. CONCLUSION: Initiation of early AT for patients with BCVI and concomitant TBI or SOI does not increase risk of worsening TBI or SOI above baseline. Close monitoring is required, but our results suggest that appropriate antiplatelet or heparin therapy should not be withheld in patients with BCVI and concomitant TBI or SOI. In fact, prompt treatment with either antiplatelet or heparin therapy remains the mainstay for prevention of stroke-related morbidity and mortality in these patients. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

Angiopoietin-1 and C16 Peptide Attenuate Vascular and Inflammatory Responses in Experimental Allergic Encephalomyelitis.

Breakdown of normal blood-brain barrier function and accompanying vascular leakage are fundamental stages in the onset of multiple sclerosis and its animal counterpart, experimental allergic encephalomyelitis. In the present study, angiopoietin-1, an endothelial growth factor well known for its role in establishing and maintaining vascular integrity, and C16, a peptide that competitively binds to integrin αvß3 expressed on endothelial cells, were used to treat acute experimental allergic encephalomyelitis in Lewis rats. Angiopoietin-1 was more effective than C16 for reducing inflammation-induced vascular leakage. Moreover, treatment with a combination of angiopoietin-1 and C16 resulted in greater effects, not only in alleviating inflammation and reducing axonal loss/demyelination but also in down-regulating pro-inflammatory cytokine expression and improving electrophysiological dysfunction, than treatment with either angiopoietin-1 or C16 alone. Different protective effects were observed with angiopoietin-1 and C16 treatment suggesting that these proteins target specific receptors to act through different pathways. Furthermore, angiopoietin-1 and C16 may form the basis of a promising therapeutic strategy for experimental allergic encephalomyelitis and multiple sclerosis.

Propuesta de tratamiento de la enfermedad cerebrovascular en los niños / Treatment proposal for cerebrovascular disease present in children

Consideramos útil al tratar de protocolizar el manejo de los ictus infantiles en nuestro país, comenzar por realizar acciones educativas tanto en la población en general, como en los propios médicos y enfermeras de la atención primaria, así como en los pediatras de cualquiera de los niveles de atención de nuestro sistema de salud. El conocer que existe la ECV tanto en adultos como en niños, el saber que un niño puede mostrar síntomas y signos expresión de un ictus isquémico o hemorrágico o en relación con una malformación cerebrovascular, sería el primer paso, posiblemente uno de los más importantes, en el proceso del diagnóstico y manejo oportuno de este conjunto de entidades neurológicas que son causa de muerte o de discapacidades en la infancia. El identificar tempranamente uno de estos síndromes permite actuar rápidamente, bien ante la sospecha diagnóstica de una malformación cerebrovascular o con el tratamiento de urgencia y el posterior traslado a un centro asistencial, donde existan profesionales con experiencia y recursos para el tratamiento de los síndromes cerebrovasculares de los niños...

Propuesta de tratamiento de la enfermedad cerebrovascular en los niños / Treatment proposal for cerebrovascular disease present in children

Consideramos útil al tratar de protocolizar el manejo de los ictus infantiles en nuestro país, comenzar por realizar acciones educativas tanto en la población en general, como en los propios médicos y enfermeras de la atención primaria, así como en los pediatras de cualquiera de los niveles de atención de nuestro sistema de salud. El conocer que existe la ECV tanto en adultos como en niños, el saber que un niño puede mostrar síntomas y signos expresión de un ictus isquémico o hemorrágico o en relación con una malformación cerebrovascular, sería el primer paso, posiblemente uno de los más importantes, en el proceso del diagnóstico y manejo oportuno de este conjunto de entidades neurológicas que son causa de muerte o de discapacidades en la infancia. El identificar tempranamente uno de estos síndromes permite actuar rápidamente, bien ante la sospecha diagnóstica de una malformación cerebrovascular o con el tratamiento de urgencia y el posterior traslado a un centro asistencial, donde existan profesionales con experiencia y recursos para el tratamiento de los síndromes cerebrovasculares de los niños

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients.

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736.