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BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.
Subject(s)
Tauopathies , tau Proteins , Animals , Tauopathies/metabolism , tau Proteins/metabolism , Mice , Acetylation , Humans , Immunotherapy/methods , Disease Models, Animal , Mice, Transgenic , Brain Injuries, Traumatic/metabolism , Brain Injuries/metabolism , Brain/metabolism , Brain/pathology , Neuroprotective Agents/pharmacologyABSTRACT
BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.
Subject(s)
Embolization, Therapeutic , Hematoma, Subdural, Chronic , Meningeal Arteries , Recurrence , Humans , Hematoma, Subdural, Chronic/surgery , Male , Female , Embolization, Therapeutic/methods , Aged , Meningeal Arteries/surgery , Meningeal Arteries/diagnostic imaging , Retrospective Studies , Middle Aged , Aged, 80 and over , Reoperation/statistics & numerical data , Treatment Outcome , Secondary Prevention , Neurosurgical Procedures/methodsABSTRACT
INTRODUCTION: Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence-septated cSDH-remains undetermined. METHODS: From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation. RESULTS: Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59-77) with 20% females. Twenty-eight cSDHs (35%) had septations identified on imaging. Surgical evacuation with burr holes was performed in 45% and craniotomy in 18.8%. Baseline characteristics between no-septations (no-SEP) and septations (SEP) groups were similar except for median age (SEP vs no-SEP, 72.5 vs. 65.5, p = 0.016). The recurrence rate was lower in the SEP group (SEP vs. no-SEP, 3 vs. 16.7%, p = 0.017) with higher odds of response from MMAE for septated lesions even when controlling for evacuation strategy and antithrombotic use (OR = 0.06, CI [0.006-0.536], p = 0.012). MMAE resulted in higher mean absolute thickness reduction (SEP vs. no-SEP, -8.2 vs. -4.8â mm, p = 0.016) with a similar midline shift change. The rate of reoperation did not differ (6.2 vs. 3.1%, p = 0.65). CONCLUSION: MMAE appears to be equal to potentially more effective in preventing the recurrence of cSDH in septated lesions. These findings may aid in patient selection.
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BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment. OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma. METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in CSDH thickness, and midline shift. RESULTS: Fifty-seven patients met inclusion criteria. The median age was 66 years (IQR 58-76) with 21.1% females. Sixty-six embolizations were performed. The median length to follow-up was 20 days (IQR 14-44). Nineteen patients (33.3%) had rapid reinitiation of antithrombotics (5 antiplatelet, 11 anticoagulation, and 3 both). Baseline characteristics between the no antithrombotic (no-AT) and the AT groups were similar. The recurrence rate was higher in the AT group (no-AT vs AT, 9.3 vs 30.4%, P = .03). Mean absolute reduction in CSDH thickness and midline shift was similar between groups. Rate of reoperation did not differ (4.7 vs 8.7%, P = .61). CONCLUSION: Rapid reinitiation of AT after MMA embolization for CSDH leads to higher rates of recurrence with similar rates of reoperation. Care must be taken when initiating antithrombotics after treatment of CSDH with MMA embolization.
Subject(s)
Embolization, Therapeutic , Hematoma, Subdural, Chronic , Female , Humans , Aged , Male , Retrospective Studies , Hematoma, Subdural, Chronic/drug therapy , Hematoma, Subdural, Chronic/surgery , Meningeal Arteries/diagnostic imaging , Meningeal Arteries/surgery , ReoperationABSTRACT
BACKGROUND: In 2016, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan. The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. Given the public health burden of injuries to the central nervous system, neurotrauma was one of 11 panels formed to address this recommendation with a gap analysis and generation of high-priority research questions. METHODS: We recruited interdisciplinary experts to identify gaps in the neurotrauma literature, generate research questions, and prioritize those questions using a consensus-driven Delphi survey approach. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the importance of the questions on a 9-point Likert scale. Consensus was defined as 60% or greater of panelists agreeing on the priority category. We then coded research questions using an National Trauma Research Action Plan taxonomy of 118 research concepts, which were consistent across all 11 panels. RESULTS: Twenty-eight neurotrauma experts generated 675 research questions. Of these, 364 (53.9%) reached consensus, and 56 were determined to be high priority (15.4%), 303 were deemed to be medium priority (83.2%), and 5 were low priority (1.4%). The research topics were stratified into three groups-severe traumatic brain injury (TBI), mild TBI (mTBI), and spinal cord injury. The number of high-priority questions for each subtopic was 46 for severe TBI (19.7%), 3 for mTBI (4.3%) and 7 for SCI (11.7%). CONCLUSION: This Delphi gap analysis of neurotrauma research identified 56 high-priority research questions. There are clear areas of focus for severe TBI, mTBI, and spinal cord injury that will help guide investigators in future neurotrauma research. Funding agencies should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.
Subject(s)
Brain Injuries, Traumatic , Spinal Cord Injuries , Brain Injuries, Traumatic/epidemiology , Brain Injuries, Traumatic/therapy , Consensus , Humans , Public Health , Research DesignABSTRACT
BACKGROUND: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. METHODS: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. RESULTS: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. CONCLUSIONS: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.
Subject(s)
Hematoma, Subdural, Acute , Hypothermia, Induced , Hypothermia , Reperfusion Injury , Adult , Glial Fibrillary Acidic Protein/metabolism , Hematoma, Subdural/etiology , Hematoma, Subdural/therapy , Hematoma, Subdural, Acute/complications , Humans , Hypothermia/complications , Hypothermia, Induced/adverse effects , Reperfusion Injury/complicationsABSTRACT
Importance: Motor vehicle crashes (MVCs) are an important public health concern. Recent trends suggest that introducing rideshare services has decreased the incidence of MVCs. However, detailed analyses linking rideshare volume, convictions for impaired driving, and nonfatal MVC traumas remain inconclusive. Objective: To determine if there is an association between rideshare use and MVC traumas and convictions for impaired driving in Houston, Texas. Design, Setting, and Participants: This multicenter cohort study was conducted between January 2007 and November 2019 with hospital data from the Red Duke Trauma Institute within the Memorial Hermann Hospital-Texas Medical Center and Ben Taub General Hospital. Rideshare data from Uber and Google covered trips taken within Houston, Texas, from February 2014 (the date of deployment of Uber to Houston) to December 2018. Impaired driving convictions included all indictments made by the Harris County, Texas, District Attorney's office from January 2007 to December 2018. All adults with MVC traumas evaluated at both centers in the study population (individuals >16 years with a mechanism of injury classified under "motor vehicle collision") were included. Impaired driving incidents were included only if the final legal outcome was conviction. Main Outcomes and Measures: The primary study outcomes were the incident rate ratios for hourly MVC traumas and daily impaired driving convictions. Results: A total of 23â¯491 MVC traumas (involving patients with a mean [SD] age of 37.9 [17.8] years and 14â¯603 male individuals [62.1%]), 93â¯742 impaired driving convictions, and more than 24 million Uber rides were analyzed. Following the introduction of Uber in February 2014, MVC traumas decreased by 23.8% (from a mean [SD] of 0.26 [0.04] to 0.21 [0.06] trauma incidents per hour) during peak trauma periods (Friday and Saturday nights). The incident rate ratio of MVC traumas following Uber deployment was 0.33 (95% CI, 0.17-0.67) per 1000 indexed rides (P = .002). Furthermore, rideshare use was associated with a significant, geographically linked reduction in impaired driving convictions between January 2014 to December 2019 (incidence rate ratio, 0.76 [95% CI, 0.73-0.78]; P < .001). Conclusions and Relevance: In this study, introducing rideshare services in the Houston metropolitan area was associated with significant reductions in MVC traumas and impaired driving convictions. Increased use of rideshares may be an effective means of reducing impaired driving and decreasing rate of MVC traumas.
Subject(s)
Accidents, Traffic/statistics & numerical data , Driving Under the Influence/statistics & numerical data , Transportation/statistics & numerical data , Wounds and Injuries/epidemiology , Accidents, Traffic/prevention & control , Adult , Driving Under the Influence/legislation & jurisprudence , Female , Humans , Injury Severity Score , Male , Middle Aged , Retrospective Studies , Search Engine/statistics & numerical data , Seasons , Texas/epidemiology , Transportation/methods , Young AdultABSTRACT
Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.
Subject(s)
Alzheimer Disease/etiology , Alzheimer Disease/prevention & control , Brain Injuries, Traumatic/complications , Neuroprotection , tau Proteins/metabolism , Acetylation , Alzheimer Disease/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biomarkers/blood , Biomarkers/metabolism , Brain Injuries, Traumatic/metabolism , Cell Line , Diflunisal/therapeutic use , Female , Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) , Humans , Male , Mice , Mice, Inbred C57BL , Neurons/metabolism , Salicylates/therapeutic use , Sirtuin 1/metabolism , p300-CBP Transcription Factors/antagonists & inhibitors , p300-CBP Transcription Factors/metabolism , tau Proteins/bloodABSTRACT
BACKGROUND: Middle meningeal artery (MMA) pseudoaneurysms are rare but can occur secondary to trauma with an associated skull fracture and can present with a variety of hemorrhage patterns. Epidural, subdural, subarachnoid, and intraparenchymal hematomas have all been reported. Given the wide range of clinical presentations and radiographic findings, multiple treatment strategies have been employed, including surgical removal, endovascular intervention, and conservative treatment. MMA pseudoaneurysms typically range from 2 to 5 mm in size and have been shown to have unpredictable growth patterns. CASE DESCRIPTION: A 54-year-old male identifying as a Jehovah's Witness presented after a fall and was found to have an epidural hematoma with an accompanying temporal bone fracture. Imaging demonstrated a traumatic pseudoaneurysm of the MMA. Given the patient's religious preferences, the emphasis was made during surgical planning for the minimization of blood loss. The epidural hematoma was evacuated, and the MMA pseudoaneurysm was directly visualized and surgically excised after ligation of its tributaries. The patient tolerated the procedure well without significant blood loss and made a complete neurological recovery. CONCLUSION: A well-circumscribed hypodensity on CT within a surrounding hyperintense collection should raise suspicion of MMA pseudoaneurysm in the setting of overlying temporal bone fracture as supported by previous imaging findings of large MMA pseudoaneurysms. The early detection of MMA pseudoaneurysm is imperative, as the presence may dictate more urgent intervention and changes in operative technique. Although not much is known about the nature and progression of these lesions, surgical excision has remained a safe, reliable method of treatment.
ABSTRACT
OBJECTIVE: To determine whether machine learning (ML) algorithms can improve the prediction of delayed cerebral ischemia (DCI) and functional outcomes after subarachnoid hemorrhage (SAH). METHODS: ML models and standard models (SMs) were trained to predict DCI and functional outcomes with data collected within 3 days of admission. Functional outcomes at discharge and at 3 months were quantified using the modified Rankin Scale (mRS) for neurologic disability (dichotomized as good [mRS ≤ 3] vs poor [mRS ≥ 4] outcomes). Concurrently, clinicians prospectively prognosticated 3-month outcomes of patients. The performance of ML, SMs, and clinicians were retrospectively compared. RESULTS: DCI status, discharge, and 3-month outcomes were available for 399, 393, and 240 participants, respectively. Prospective clinician (an attending, a fellow, and a nurse) prognostication of 3-month outcomes was available for 90 participants. ML models yielded predictions with the following area under the receiver operating characteristic curve (AUC) scores: 0.75 ± 0.07 (95% confidence interval [CI] 0.64-0.84) for DCI, 0.85 ± 0.05 (95% CI 0.75-0.92) for discharge outcome, and 0.89 ± 0.03 (95% CI 0.81-0.94) for 3-month outcome. ML outperformed SMs, improving AUC by 0.20 (95% CI -0.02 to 0.4) for DCI, by 0.07 ± 0.03 (95% CI -0.0018 to 0.14) for discharge outcomes, and by 0.14 (95% CI 0.03-0.24) for 3-month outcomes and matched physician's performance in predicting 3-month outcomes. CONCLUSION: ML models significantly outperform SMs in predicting DCI and functional outcomes and has the potential to improve SAH management.
Subject(s)
Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Machine Learning/trends , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/epidemiology , Adult , Aged , Brain Ischemia/therapy , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Retrospective Studies , Subarachnoid Hemorrhage/therapy , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: This study aims to assess outcomes of pediatric patients with blunt traumatic brain injury (TBI) with a presenting Glasgow Coma Score (GCS) of 3. METHODS: After local institutional review board approval, we identified patients ages 0 to15 years with blunt TBI and a reported GCS of 3 between 2007 and 2017 from a pediatric level 1 trauma center prospective registry. Exclusion criteria were cardiac death on arrival and penetrating injury. We recorded clinical variables from patients with a non-pharmacologic GCS of 3 and pupillary exam documented by a neurosurgical attending or resident. The original Glasgow Outcome Scale (GOS) was used to compare with other studies. Importance of variables to survival was calculated. RESULTS: A total of 88 patients (mean age 6.9 years) were included with a mortality rate of 68%. Twelve percent had a poor long-term outcome (GOS 2 or 3) while 20% had a good long-term outcome (GOS 4 or 5). Median follow-up was 1.8 years. Initial group comparison revealed patients in group 1 (survivors) had less hypotension on arrival (14% SBP < 90 mmHg vs. 66%, p < 0.0001), higher temperatures on arrival (36.3 °C vs 34.9 °C, p = 0.0002), lower ISS (29.7 vs 39.5, p = 0.003), less serious injury to other major organs (34% vs 61%, p = 0.02), more epidural hematomas (24% vs 7%, p = 0.04), and less evidence of brain ischemia on CT (7% vs 39%, p = 0.002) or brainstem infarct, hemorrhage, or herniation (0% vs 27%, p = 0.002). Differences between the 2 groups in age, sex, race, MOI, AIS score, presence of midline shift > 5 mm, or time from injury to hospital arrival or time to surgery were not statistically significant. Classification tree analysis showed that the most important variable for survival was pupillary exam; mortality was 92% in presence of bilateral, fixed dilated pupils. The relative importance of initial temperature, MOI, and hypotension to survivability was 0.79, 0.75, and 0.47, respectively. CONCLUSION: Twenty percent of our pediatric non-pharmacologic GCS 3 cohort had a good functional outcome. Lack of bilaterally fixed and dilated pupils was the most important factor for survival. Temperature, MOI, and hypotension also correlated with survival. The data support selective aggressive management for these patients.
Subject(s)
Coma , Head Injuries, Closed , Adolescent , Child , Glasgow Coma Scale , Glasgow Outcome Scale , Humans , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Epidural hematomas (EDHs) involving the venous sinuses are uncommon and carry the risk of hemorrhage or venous infarction. We report the largest case series for superior sagittal sinus- and transverse sinus-related EDHs including surgical and nonsurgical management. We compare our findings to the relevant literature. METHODS: A retrospective review of the EDH cases at our center was performed from 2013-2018. Patients were analyzed by surgical versus conservative management, outcomes, and complications. RESULTS: Of the 268 EDH patients identified, 32 involved the venous sinuses (23 supratentorial and 9 infratentorial). Ten of the patients had surgery, and 22 were managed conservatively. No surgical complications occurred, and all had a Glasgow Outcome Scale score of 5 at follow-up. All of the nonsurgical patients had a Glasgow Outcome Scale score of 4 or 5 at follow-up except for 1 patient with prior disability. The literature search resulted in 39 infratentorial and 47 supratentorial EDHs involving venous sinuses. CONCLUSIONS: Surgical and nonsurgical management of EDHs involving the venous sinuses are both viable options with good outcomes. Surgical intervention is based on location, size, neurologic examination, expansion on serial imaging, and vascular imaging findings. Surgery has the potential for significant complications, but all surgical patients in our series had good outcomes at follow-up. Similarly, nonsurgically managed patients had good outcomes and our overall series demonstrates better outcomes with fewer complications than other similar series in the literature.
Subject(s)
Conservative Treatment , Hematoma, Epidural, Cranial/therapy , Neurosurgical Procedures , Adult , Conservative Treatment/methods , Cranial Sinuses/pathology , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Modern science and healthcare generate vast amounts of data, and, coupled with the increasingly inexpensive and accessible computing, a tremendous opportunity exists to use these data to improve care. A better understanding of data science and its relationship to neurosurgical practice will be increasingly important as we transition into this modern "big data" era. METHODS: A review of the literature was performed for key articles referencing big data for neurosurgical care or related topics. RESULTS: In the present report, we first defined the nature and scope of data science from a technical perspective. We then discussed its relationship to the modern neurosurgical practice, highlighting key references, which might form a useful introductory reading list. CONCLUSIONS: Numerous challenges exist going forward; however, organized neurosurgery has an important role in fostering and facilitating these efforts to merge data science with neurosurgical practice.
Subject(s)
Big Data , Neurosurgery , Neurosurgical Procedures , Humans , NeurosurgeonsABSTRACT
BACKGROUND: Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions. METHODS: Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24-48 h, 3-5 days, and 6-8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters. RESULTS: Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes. CONCLUSIONS: Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.
Subject(s)
Brain Ischemia/blood , Cytokines/blood , Inflammation/blood , Subarachnoid Hemorrhage/blood , Adult , Aged , Brain Ischemia/etiology , Female , Humans , Inflammation/etiology , Male , Middle Aged , Prospective Studies , Subarachnoid Hemorrhage/complicationsABSTRACT
The inflammatory processes following traumatic brain injury (TBI) have not been fully characterized. We hypothesize that differences in systemic cytokine/chemokine (CC) levels are associated with TBI clinical outcomes. To test this hypothesis, we examined systemic levels of CCs and their relationship with patient outcomes. Plasma from acute TBI subjects was collected at 24-48â¯h, and the CC levels were measured using a multiplex 41-plex-kit. Clinical outcomes were assessed using the modified Rankin scale (mRS) with good outcomes defined as mRSâ¯≤â¯3 and poor outcome as mRSâ¯≥â¯4. The differences in CC concentrations between groups were then compared using the Mann-Whitney U test. Seventy-six acute TBI subjects were included in this study. In the mRSâ¯≥â¯4 group, interleukin-6 (IL-6) and interleukin-10 (IL-10) were elevated, indicating early activation of immune reaction and modulation. Simultaneously, PDGFAA and RANTES were lower in the mRSâ¯≥â¯4 group. Poor outcomes after TBI were associated with elevated levels of IL-6 and IL-10 and lower levels of PDGFAA and RANTES within 24-48â¯h after injury.
Subject(s)
Brain Injuries, Traumatic/immunology , Inflammation/immunology , Adult , Brain Injuries, Traumatic/complications , Cytokines/immunology , Female , Humans , Male , Middle Aged , Recovery of Function/immunologyABSTRACT
OBJECTIVE: Anticoagulant therapy (ACT) after traumatic intracranial hemorrhage may lead to progression of hemorrhage, but in the presence of thromboembolic events, the clinician must decide if the benefits outweigh the risks. Currently, no data exist to guide therapy in the acute setting. METHODS: We retrospectively identified all patients admitted to our institution with traumatic intracranial hemorrhage that received intravenous heparin, full-dose enoxaparin, or warfarin during their initial hospitalization over a 3-year period. We reviewed their demographics, hospital course, clinical indication and timing for initiation of ACT, and complications. RESULTS: A total of 112 patients were identified. The median age and Glasgow Coma Scale score of these patients was 50.5 years and 9.5, respectively. Twenty-two patients required neurosurgical procedures for their presenting injury, including intracranial pressure monitors and/or open surgeries. Fifty-four patients had deep vein thrombosis or pulmonary embolism prior to initiation, and the remaining 20 patients had preexisting conditions or other indications for initiating ACT. The median time from injury to starting ACT was 8 days. Immediate complications occurred in 6 patients; however, none of these patients required a neurosurgical intervention. Delayed complications included progression of acute to chronic subdural hematoma that required intervention in 2 patients. One patient died from delayed hemorrhage. CONCLUSIONS: For this patient population, the risk of immediate and delayed intracranial hemorrhages from initiating ACT therapy in intracranial injury must be weighed against the morbidity of delaying treatment. Although further studies are needed, our review provides the first rates of complications for this patient population.
Subject(s)
Anticoagulants/administration & dosage , Intracranial Hemorrhage, Traumatic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Enoxaparin/administration & dosage , Female , Heparin/administration & dosage , Humans , Intracranial Hemorrhage, Traumatic/surgery , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Warfarin/administration & dosage , Young AdultABSTRACT
INTRODUCTION: Head injury and exsanguination are the leading causes of death in trauma patients. Hemorrhagic shock triggers systemic endothelial glycocalyx breakdown, potentially leading to traumatic endotheliopathy (EoT). Levels of syndecan-1, a main glycocalyx component, have been used to assess the integrity of the glycocalyx. In TBI patients, it remains unclear whether syndecan-1 shedding occurs and its correlation with outcomes. We aimed to determine the frequency of EoT+, defined as a syndecan-1 level of 40 ng/ml or higher, after TBI in isolated and polytraumatic injury. We also investigated how the presence of EoT+ affected outcomes in TBI patients. METHODS: Severely injured trauma patients were enrolled. From blood samples collected upon patients' arrival to the hospital, we measured syndecan-1 (main biomarker of EoT+), soluble thrombomodulin (sTM, endothelial activation) adrenaline and noradrenaline (sympathoadrenal activation), and assessed TBI patients' coagulation capacity. RESULTS: Of the enrolled patients (n = 331), those with TBI and polytrauma (n = 68) had the highest rate of EoT+ compared to isolated TBI (n = 58) and Non-TBI patients (n = 205) (Polytrauma-TBI 55.9% vs. Isolated-TBI 20.0% vs. non-TBI polytrauma 40.0%; p = 0.001). TBI patients with EoT+ exhibited marked increases in sTM, adrenaline and noradrenaline levels, and physiological and coagulation derangements. In isolated TBI patients, increasing syndecan-1 levels (ß for every 10 ng/ml increase: 0.14; 95% CI: 0.02, 0.26) and hypocoagulability were negatively associated with survival. CONCLUSIONS: This study provides evidence of syndecan-1 shedding after TBI supporting the notion that breakdown of the glycocalyx contributes to the physiological derangements after TBI.
Subject(s)
Brain Injuries, Traumatic/blood , Syndecan-1/blood , Adult , Aged , Biomarkers/blood , Brain Injuries, Traumatic/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Prospective Studies , Trauma Severity IndicesABSTRACT
OBJECTIVE The objective of this study was to assess the incidence, diagnosis, and treatment of pediatric blunt cerebrovascular injury (BCVI) at a busy Level 1 trauma center and to develop a tool for accurately predicting pediatric BCVI and the need for diagnostic testing. METHODS This is a retrospective cohort study of a prospectively collected database of pediatric patients who had sustained blunt trauma (patient age range 0-15 years) and were treated at a Level 1 trauma center between 2005 and 2015. Digital subtraction angiography, MR angiography, or CT angiography was used to confirm BCVI. Recently, the Utah score has emerged as a screening tool specifically targeted toward evaluating BCVI risk in the pediatric population. Using logistical regression and adding mechanism of injury as a logit, the McGovern score was able to use the Utah score as a starting point to create a more sensitive screening tool to identify which pediatric trauma patients should receive angiographic imaging due to a high risk for BCVI. RESULTS A total of 12,614 patients (mean age 6.6 years) were admitted with blunt trauma and prospectively registered in the trauma database. Of these, 460 (3.6%) patients underwent angiography after blunt trauma: 295 (64.1%), 107 (23.3%), 6 (1.3%), and 52 (11.3%) patients underwent CT angiography, MR angiography, digital subtraction angiography, and a combination of imaging modalities, respectively. The BCVI incidence (n = 21; 0.17%) was lower than that in a comparable adult group (p < 0.05). The mean patient was age 10.4 years with a mean follow-up of 7.5 months. Eleven patients (52.4%) were involved in a motor vehicle collision, with a mean Glasgow Coma Scale score of 8.6. There were 8 patients (38.1%) with carotid canal fracture, 6 patients (28.6%) with petrous bone fracture, and 2 patients (9.5%) with infarction on initial presentation. Eight patients (38.1%) were managed with observation alone. The Denver, modified Memphis, Eastern Association for the Surgery of Trauma (EAST), and Utah scores, which are the currently used screening tools for BCVI, misclassified 6 (28.6%), 6 (28.6%), 7 (33.3%), and 10 (47.6%) patients with BCVI, respectively, as "low risk" and not in need of subsequent angiographic imaging. By incorporating the mechanism of injury into the score, the McGovern score only misclassified 4 (19.0%) children, all of whom were managed conservatively with no treatment or aspirin. CONCLUSIONS With a low incidence of pediatric BCVI and a nonsurgical treatment paradigm, a more conservative approach than the Biffl scale should be adopted. The Denver, modified Memphis, EAST, and Utah scores did not accurately predict BCVI in our equally large cohort. The McGovern score is the first BCVI screening tool to incorporate the mechanism of injury into its screening criteria, thereby potentially allowing physicians to minimize unnecessary radiation and determine which high-risk patients are truly in need of angiographic imaging.
Subject(s)
Cerebrovascular Trauma/complications , Cerebrovascular Trauma/diagnosis , Trauma Severity Indices , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis , Adolescent , Angiography, Digital Subtraction , Child , Child, Preschool , Cohort Studies , Computed Tomography Angiography , Female , Humans , Infant , Infant, Newborn , Logistic Models , Male , ROC CurveABSTRACT
STUDY HYPOTHESIS: Traumatic brain injury (TBI) is a leading cause of mortality with penetrating TBI (p-TBI) patients having worse outcomes. These patients are more likely to be coagulopathic than blunt TBI (b-TBI) patients, thus we hypothesize that coagulopathy would be an early predictor of mortality. METHODS: We identified highest-level trauma activation patients who underwent an admission head CT and had ICU admission orders from August 2009-May 2013, excluding those with polytrauma and anticoagulant use. Rapid thrombelastography (rTEG) was obtained after emergency department (ED) arrival and coagulopathy was defined as follows: ACT≥128s, KT≥2.5s, angle≤56°, MA≤55mm, LY-30≥3.0% or platelet count≤150,000/µL. Regression modeling was used to assess the association of coagulopathy on mortality. RESULTS: 1086 patients with head CT scans performed and ICU admission orders were reviewed. After exclusion criteria were met, 347 patients with isolated TBI were analyzed-99 (29%) with p-TBI and 248 (71%) with b-TBI. Patients with p-TBI had a higher mortality (41% vs. 10%, p<0.0001) and a greater incidence of coagulopathy (64% vs. 51%, p<0.003). After dichotomizing p-TBI patients by mortality, patients who died were younger and were more coagulopathic. When adjusting for factors available on ED arrival, coagulopathy was found to be an early predictor of mortality (OR 3.99, 95% CI 1.37, 11.72, p-value=0.012). CONCLUSIONS: This study demonstrates that p-TBI patients with significant coagulopathy have a poor prognosis. Coagulopathy, in conjunction with other factors, can be used to earlier identify p-TBI patients with worse outcomes and represents a possible area for intervention.
Subject(s)
Blood Coagulation Disorders/epidemiology , Head Injuries, Penetrating/complications , Head Injuries, Penetrating/mortality , Adult , Blood Coagulation Disorders/etiology , Emergency Service, Hospital , Female , Head Injuries, Penetrating/diagnostic imaging , Humans , Incidence , Injury Severity Score , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prognosis , Thrombelastography , Tomography, X-Ray Computed , United States , Young AdultABSTRACT
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.